WELCOME TO THE 2024
ANNUAL FORCED BASED MANIPULATION
INVESTIGATOR MEETING, I'M ADAM
AND I AM WITH THE PROGRAM AT THE
NAGGAL CENTER FOR COMPLIMENTARY
OR INTEGRATIVE HEALTH OR NCCIH
AT THE NATIONAL INSTITUTES OF
HEALTH.
THANK YOU SO MUCH FOR JOINING US
TODAY FOR THE NCCIH AND THE
NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND
STROKE OR NINDS FOR THE 2024
ANNUAL FORCED BASE MANIPULATION
INVESTIGATOR MEETING.
ON BEHALF OF DR. CHAN, DR. JIM
KNAPP, PROGRAM DIRECTOR OF
NEUROSCIENCE CLUSTER ON
NEUROTECHNOLOGY AND INTEGRATED
SYSTEMS AND DR. LESLIE OSBOURNE,
DIVISION OF NEUROSCIENCE CLUSTER
ON SYSTEMS AND COGNITIVE
NEUROSCIENCE, WE ARE ALL PLEASED
YOU COULD JOIN US TODAY.
JUST WANT TO MAKE SURE THESE
SLIDES ARE UP AND SHARED.
PERFECT.
ALL RIGHT, SO, BEFORE WE BEGIN,
THERE'S A FEW LOGISTICS FOR
TODAY'S MEETING.
FOR OUR NIH VIDEOCAST VIEWERS,
YOU ARE WELCOME TO SUBMIT
QUESTIONS AT ANY TIME THIS
MORNING USING THE VIDEO KOOOF
THE FEEDBACK FORUM, THE LISTEN
FOR THE FORM SHOULD BE LOCATED
BELOW YOUR SCREEN FOR VIEWING
THE LIVE STREAM.
WE WILL TRY TO GET AS MANY
QUESTIONS AS POSSIBLE DURING THE
QUESTION AND ANSWER SESSION THIS
MANNING BUT WE ARE UNLIKELY TO
GET TO EVERY QUESTION.
ANY QUESTION WE'RE NOT ABLE TO
ADDRESS LIVE WILL BE SHARED WITH
THE PLANNING TEAM FOR THE
MEETING.
FINALLY THIS EVENT WILL BE
RECORDED AND WILL BE ARCHIVED ON
THE NIH VIDEOCAST WEBSITE FOR
FUTURE VIEWING.
WITH THOSE REMINDERS COVERED I'M
PLEASED TO ANNOUNCE D
R. HELENE LANG EVIN, AND
DR. LYN JAKEMAN FOR INTRODUCTORY
REMARKS.
>> WELL, GOOD MORNING, I AM SORY
I CAPTAIN BE THERE IN PERSON
WITH YOU TODAY BUT I AM GLAD I
CAN SHARE A FEW REMARKS TO KICK
US OFF.
SO IT'S WORTH REMEMBERING THAT
BACK IN 2019 WE HELD A GREAT
WORKSHOP AND DISCUSSION THAT
ADENTIFIED A NUMBER OF RESEARCH
GAPS AND OPPORTUNITIES AND FROM
THIS, WE DEVELOPED THIS PROGRAM
FOCUSED ON THE FOLLOWING HIGH
PRIORITY RESEARCH AREAS.
FIRST, TERMINOLOGY AND
MEASUREMENT OF FORCED BASED
MANIPULATION.
SECOND, MECHANISTIC MULTISCALE
RESEARCH MEASURING THE
PHYSIOLOGICAL RESPONSE TO FORCED
BASE MANIPULATION, THIRD, THE
CONTEXTURAL EFFECTS OF FORCED
BASE MANIPULATION AND FINALLY,
TECHNOLOGY AND METHODOLOGY
STUDIES.
I KNOW IT'S TAKEN A WHILE TO GET
WHERE WE ARE TODAY BUT I KNOW WE
ALL APPRECIATE THE SCOPE OF THIS
PROGRAM AND THE IMPORTANCE OF
THE DATA THAT YOU'RE ALL
GENERATING SO I WOULD LIKE TO
TAKE A MEMORY CLONE TONIGHT
RECOGNIZE WHAT YOU HAVE
ACCOMPLISHED.
TOGETHER THE 3 RESEARCH NETWORKS
FORTH NET, NEURONS MATTER AND
SPINE WORK HAVE RECRUITED OVER
600 OUTSIDE MEMBERS.
EACH NETWORK HAS DEVELOPED A
SERIES OF WORKING GROUPS TO
SUPPORT THE HIGH PRIORITY
RESEARCH AREAS, SO WE'RE REALLY
BUILDING A COMMUNITY HERE TO
ADVANCE THIS RESEARCH, THIS IS
SO IMPORTANT.
THE 3 NETWORKS ARE ALSO
SUPPORTING THE KEY ACTIVITIES SO
FIRST THE COLLABORATIVE
ACTIVITIES SUCH AS MEETING, WORK
STOP, SHOPS, CONFERENCES,
TRAINING, FOR EXAMPLE, EACH
NETWORK WAS A KEY CONTRIBUTOR TO
TODAY'S PROGRAM AND ALL 3 OF THE
NETWORKS HOSTED OVER A DOZEN
SCIENTIFIC WORKSHOPS, WEBINARS
AND TRAINING COURSES FOCUSED ON
TOPICS RELATED TO FORCED BASED
MANIPULATION.
IN THE AREA OF PILOT RESEARCH
PROJECTS ALL 3 NETWOWORKS
PUBLISHED APPLICATION AND
RECEIVED MULTIPLE APPLICATIONS
FROM INDEPENDENT INVESTIGATORS.
FOUR PILOT AWARDEES ARE IN FACT
HERE IN PERSON TODAY AND I SEND
A WARM WELCOME TO ALL OF 4 OF
YOU.
ADDITIONAL APPLICATION RECEIPT
DATES ARE CURRENTLY POSTED
ACROSS ALL OF THE 3 NETWORKS.
ALSO IN THE AREA OF PUBLICATION
DISSEMINATION AND OUTREACH, THE
FORCED NETWORK HAS PUBLISHED
MULTIPLE PAPERS ON MANUEL
THERAPIES IN FRONT YEARS AND
REHABILATION AND FRONTIERS IN
PSYCHOLOGY AND MEMBERS OF ALL 3
NETWORKS WORKED COLLABORATIVELY
TO PUBLISH 11 PAPERS IN THE
JOURNAL OF MANUEL AND
MANIPULATIVE THERAPY AS PART OF
A SPECIAL ISSUE SEVERAL MONTHS
AGO THAT INCLUDED MULTIPLE
ARTICLES OUTLINING EFFORTS IN
DEFINING RESEARCH GAPS,
OUTLINING COMMON TERMS AND
MAPPING MECHANISTIC PROCESSES
INVOLVED IN FORCED BASE
MANIPULATION AND THE SPECIAL
ISSUE WAS LED BY DR. CHAD COOK
OF THE FORCE NETWORK AND COOK'S
CONTINUED TO PUBLISH CONTENT,
YouTUBE RESENTATION AND
HOSTING PRESENTATIONS AND
WEBINARS.
THE NETWORK WILL SHARE SPECIFIC
UPDATES ABOUT NETWORK ACTIVITIES
DURING UPDATES AS PART OF THE
OPEN SESSION.
I WOULD ALSO LIKE TO TOUCH ON
THE IMPORTANT PROGRESS AT THE
CONSORTIUM OR CROSS NETWORK.
THE U24 CONSORTIUM STEERING
COMMITTEE CO SHARES, DR. BILL
REED UNIVERSITY OF ALABAMA IN
BIRMINGHAM AND DR. ELEN LUNKIN
FROM UC BERKELEY HAVE MET
MONTHLY OVER THE YEARS TO
COORDINATE THE EFFORTS INCLUDING
COORDINATING PLANNING OF THE
ANNUAL INVESTIGATORS MEETING AND
COORDINATING WORK DONE ACROSS
THE 5 TRANSNETWORK WORKING
GROUPS.
THE WORKING GROUPS ARE COMPOSED
OF EVERY 20 MEMBERS, NETWORK
MEMBERS AND SPLIT INTO 3
SCIENTIFIC AND 2 LOGISTICS
GROUPS AND THEY WILL SHARE MORE
ABOUT THESE TRANSNETWORK WORKING
GROUP ACTIVITIES DURING THEIR
UPDATES AS PART OF THE OPEN
SESSION.
SO, BASICALLY, I WANT TO SAY HOW
THRILLED I AM WITH ALL THIS
PROGRESS AND RECOGNIZE THE TRULY
EXCELLENT WORK THAT HAS OCCURRED
WITH THESE--IN THESE NETWORKS SO
FAR AND I REALLY LOOK FORWARD TO
A GREAT MEETING.
>> THANK YOU DR. LANG EVIN, AND
WE APPRECIATE YOUR COMMENT THIS
IS MORNING.
DR. JAKEMAN WOULD YOU LIKE TO
GIVE A FEW OPENING WORDS?
>> SO I AM LYN YAKEMAN AND I AM
WITH NINDS AND ON BEHALF OF
EVERYONE AT NINDS, WE ARE
EXCITED TO WELCOME YOU ALL AND
HIGHLIGHT THIS COLLABORATION,
THIS IS ALL ABOUT COLLABORATION
AND I'M JUST SO EXCITED TO SEE
THE COLLABORATION OF THE
NETWORKS TOGETHER AND WITHIN
EACH 1 OF THESE NETWORKS.
BEFORE I GIVE ANYMORE REMARKS, I
DO WANT TO THANK THE PROGRAM
STAFF AND THE LOGISTICS GROUP
THAT HAS MADE THIS POSSIBLE.
I HOPE YOU ALL REALLY ENJOY THE
NEW HYBRID ENVIRONMENT THAT
NINDS AND NIH HAS EMBRACED THIS
IS AN OPPORTUNITY FOR THOSE OF
YOU WHO HAVE TAKEN THE TIME TO
COME ACROSS THE COUNTRY, I KNOW
ACROSS THE COUNTRY OR HALFWAY
ACROSS THE COUNTRY, I KNOW THAT
TRAVEL IS HARDER NOW, IT'S MORE
EXPENSIVE NOW, BUT IT REALLY
HELPS WHEN YOU COME.
BECAUSE THEN WE HAVE A CHANCE TO
INTERACT WITH YOU BUT IN A
HYBRID ENVIRONMENT WE CAN
INTERACT WITH THOSE WHO ARE
FARTHER AWAY OR UNABLE TO ATTEND
AND I AM EXCITED THAT
COLLABORATION ACTUALLY EXTENDS
ACROSS THE CYBERSPACE NOW.
THE PROGRAM STAFF I WANT TO
THANK NOT ONLY ALEX TUTTLE AND
JIM NAUT AND LESLIE OSBORN
PROGRAM OFFICERS WHO ORGANIZE
THIS BUT THE SUPPORT STAFF THAT
SUPPORT THEM IN THEIR DAY-TO-DAY
WORK AND AS WELL AS OUR
COLLABORATORS AT NCCIH INCLUDING
LYNN CHEN AND DR. SHERTLOFF.
SO WHAT I'M EXCITED ABOUT IS
THIS WHOLE AREA OF FORCED BASE
MANIPULATION BECAUSE I THINK
THAT AS HUMAN BEINGS AND AS
NEUROSCIENTISTS, WE KNOW THAT
VARIOUS FORCED BASE
MANIPULATIONS HAVE IMPACTS ON
OUR HEALTH AND IMPACTS ON HOW
OUR BRAIN WORKS AND OUR RESPONSE
IN RECOVERY FROM NEUROLOGICAL
CONDITIONS.
WHAT WE DON'T KNOW IS HOW, AND
WHAT WE DON'T KNOW REALLY IS A
LOT OF THE BIG QUESTIONS ABOUT
THE CONTEXT OF HOW THOSE
MANIPULATIONS IMPACT THE NERVOUS
SYSTEM AND IMPACT OUTCOMES AND
IMPACT BEHAVIORS THROUGH THE
DEVELOPMENTAL TIMELINE IN THE
PRESENCE OF OTHER PATHOLOGIES
WHETHER THEY'RE NUR -OLOGICAL
PATHOLOGIES OR WHOLE BODY
PATHOLOGIES, WE DON'T KNOW HOW
THE NERVOUS SYSTEM RESPONDS
DURING DIFFERENT AFFECT OR
MODLATTORY STATES AFTER TRAUMA.
WE HAVE SO MANY QUESTIONS TO
ANSWER AND THE ONLY WAY WE CAN
BUILD THIS FIELD AND REALLY GROW
THE SCIENCE OF FORCED BASE
MANIPULATION AND NEUROSCIENCE IS
TO DEVELOP THE RESOURCES THAT
YOU ARE ALL WORKING AND OVER A
COLLABORATED YEAR TO BEGIN TO
BUILD.
I'M REALLY EXCITED I PLAYED WITH
THE WEBSITE TO LOOK AT SOME OF
THOSE THINGS, I HOPE EVERYBODY
WHO'S HERE AND ONLINE PULL UP
YOUR SLEEPS BECAUSE THE
COLLABORATION IS NOT OVERWITH,
THIS ISN'T LIKE A HIGHLIGHT AND
WE'RE OUT OF HERE BUT WE WILL
START THE BIG WORK AND THANK YOU
VERY MUCH, ALEX AND THANK YOU
ALL FOR COMING.
>> THANK YOU DR. JAKEMAN, AND
THANK YOU FOR THOSE COMMENTS.
YES, WE ARE ONLY BEGINNING.
SO THANK YOU BOTH FOR YOUR
REMARKS, WE ARE PLEASED YOU CAN
JOIN US TODAY, NOW I'M PLEASED
TO TURN IT OVER TO THE 3
REPRESENTATIVES FROM THE U24
FORCED BASE LEADERSHIP AS THEY
OFFER PROGRESS IN THEIR NETWORKS
FIRST UP WE HAVE CHAD COOK
DIRECTOR OF DUKE UNIVERSITY'S
CLINICAL FACILITATION RESEARCH
AND HE WILL BE FOLLOWED BY
DR. BETH WINKELSTEIN, DEPUTY
PROVOST UNIVERSITY OF
PENNSYLVANIA SPINE-WORK UPDATES.
FINALLY DR. ELEN LUMPKIN
PROFESSOR OF CELL BIOLOGY FOR
THE UC BERKELEY WILL PRESENT
NEURONS MATTR UPDATES.
DR. COOK, WE INVITE TO YOU COME
UP TO THE PODIUM.
>> WELL, GOOD MORNING EVERYONE,
IT'S A PLEASURE TO BE HERE.
AND THANK YOU FOR THE KIND
INTRODUCTION.
I'M CHAD COOK, I'M WITH FORCE
NET, AND I AM PLEASED TO WORK
WITH SUCH A WONDERFUL GROUP OF
PEOPLE WHO HAVE BECOME CLOSE
FRIENDS, WE HAVE COLLEAGUES FROM
ALL OVER, AND [INDISCERNIBLE]
BILL REID AND I ARE NPIs, WE
WOULD BE REMISS IF WE DIDN'T
RECOGNIZE DAWN ELLIOTT, WE WANT
TO CONGRATULATE HER, SHE TOOK AN
ACADEMIC LEADERSHIP POSITION AND
HAD TO LEAVE FORCE NET BUT WE
WANT TO RECOGNIZE HER FOR ALL
HER EFFORTS OVER THE LAST 2 AND
HALF CAREERS.
AS A REMINDER FORCE NET'S VISION
HAS ALWAYS BEEN ABOUT
TRANSLATIONAL RESEARCH AND ABOUT
RECOGNIZING THE IMPORTANCE OF
MECHANISMS INTO CLINICAL
OUTCOMES OF PATIENTS, THAT'S
BEEN OUR VISION AND MOST OF OUR
OPERATIONS HAVE BEEN REFLECTIVE
OF THAT VISION.
THIS INCLUDED THE INCLUSION OF A
NUMBER OF WORKING GROUP MEMBERS
IN FORCE NET WHO HAVE BEEN
INSTRUMENTAL IN MEETING
OBJECTIVES WE'VE MADE AND MANY
FOLKS ARE IN THE ROOM AND WE
WANT TO SAY THANK YOU FOR THE
EFFORTS YOU PUT INTO THAT.
WE HAVE OVER 400 MEMBERS THAT
ARE PARTNERS OF FORCE NET AND
IT'S A DIVERSE GROUP OF
INDIVIDUALS BOTH ACADEMICS AND
CLINICIANS, INDIVIDUALS WITH
MULTIPLE DEFINITE TYPES OF
RESEARCH BACKGROUNDSAs WELL
AND OUR FORCE NET MEMBERSHIP IS
VERY ACTIVE AND THEY OFTEN
ARE--HAVE BEEN ACTIVE IN
SUBMITTING PILOT GRANTS AS WELL.
OVER THE LAST 2 YEARS WE'VE HAD
A NUMBER OF REALLY FANTASTIC
FORCE NET WEBINARS AND HERE ARE
SOME SLIDES OF THESE AND AGAIN,
A LOT OF THESE FOLKS ARE IN THE
ROOM THAT HAVE ACTUALLY
PRESENTED THIS WORK.
I WANT TO POINT OUT WE HAVE 2
MORE THAT ARE ACTUALLY COMING UP
THIS YEAR, 1 WAS WITH STEPHEN
GEORGE WHO IS A TRANSLATIONAL
RESEARCHER, WE WILL TALK ABOUT
BUILDING THE APPROPRIATE TEAMS
FOR GRANTSMANSHIP AND THEN
DR. LANG EVIN WHO WILL PRESENT
ON OCTOBER 21st, SO MAKE SURE
AND SAVE YOUR CALENDARS FOR
THAT.
WE WILL SPONSOR AN INTELLECTUAL
SUMMIT ON OCTOBER 5 AND 6.
THIS IS AN INVITATION ONLY
EVENT.
WE WILL BE WORKING ON BUILDING
TEAMS THAT ARE SUSTAINABLE OVER
THE YEARS INCLUDING THOSE
WRITING GRANTS TOGETHER,
DEVELOPING AIMS AND GETTING A
DIVERSE GROUP TOGETHER TO
RESEARCH FORCE BASED
MANIPULATIONS.
AND WE'RE ALSO LOOKING FOR IN
FEBRUARY 2025 FOR OUR VIRTUAL
CONFERENCE SPECIFICALLY BECAUSE
WE ARE COLLABORATING WITH THE
UU24s IN THIS CONFERENCE, WE
WILL USE VERBELLA AND IT WILL BE
OPEN FOR ALL OF THE WORLD TO
ATTEND AND WE'RE EXCITED ABOUT
THAT, THERE WILL BE 4 DIFFERENT
LINES OF RESEARCH.
I KNOW THAT FORCE NET WILL HAVE
2 LINES, 1 WILL BE ON IMAGING
AND MECHANISMS AND ANOTHER WILL
BE ON CLINICAL MECHANISMS.
OVER THE LAST 2 YEARS, WE'VE HAD
HAD 2 PILOT GRANT CYCLES.
WE'VE HAD A TOTAL OF 26 PILOT
SUBMISSIONS, 21 UNIQUE
POSITIONS, 5 REPEATS FROM THE
FIRST ROUND.
WE HAVE FUNDED 2 PILOT GRANTS
FROM THE FIRST ROUND AND THESE
FOLKS ARE IN THE ROOM RIGHT NOW,
DR. GERLING, DR. LEWIS, AND
DR. LOGHMANI, AND WE HOPE TO
HAVE A THIRD ROUND COMING UP
JUST A WICK SUMMARY OF OUR 2
YEAR ACCOMPLISHMENT AS DR. LANG
EVIN, WE HAD A SPECIAL ISSUE, I
WANT TO RECOGNIZE JIM WHO IS A
CO EDITOR ON THAT SPECIAL ISSUE.
IT INCLUDED 11 PAPERS, INCLUDING
SEVERALOT GAPS IN FORCED BASE
MANIPULATION RESEARCH.
WE HAVE AN INVITED PAPER FROM
THE TAXONOMY GROUP CHA I WILL
TALK ABOUT DURING THAT
PRESENTATION FOR THE FALL OF 24
AND THEN 2 PAPERS, 1 IN
FRONTIERS IN PSYCHOLOGY AND 1 IN
FRONTIERS IN REHABILATION SO THE
GROUP HAS BEEN VERY ACTIVE THIS
PUBLISHING.
OUR INITTIAIVE ITS FOR YEARS 3-5
WILL BE THE PROMOTION OF THE
IMPORTANCE OF MECHANISMS AND
UNDERSTANDING FORCED BASE
MANIPULATIONS.
I THINK WE'VE DONE A NICE JOB OF
REACHING OUT TO OUR MEMBERSHIP
AND OUR MEMBERSHIP BEING ACTIVE
ON THAT, TOO, CONTINUED IMROAG
AND DEVELOPMENT OF OUR
MEMBERSHIP, 1 MORE HOPEFULLY
PILOT FUNDING CYCLE UPON
APPROVAL, CONTINUE TO FOSTER THE
WORKING GROUP DELIVERABLES, I
KNOW THE FORCE NET FOLKS ARE
VERY ACTIVE IN THE 5 WORKING
GROUPS, TRANSLATIONAL TRAINING
INITIATIVES AND THE SUMMIT AND
CONFERENCE AND THEN TO
COLLABORATE WITH THE OTHER U24S
WHICH HAS REALLY SPOOLED UP
NICELY AND CREATED GREAT
RELATIONSHIPS.
WE WOULD LOVE FOR YOU TO JOIN.
THE QR CODE IS ACTIVE IF YOU ARE
OUT THERE AND WATCHING, YOU CAN
JOIN ON THE WEBSITE IF YOU WOULD
LIKE OR REACH OUT TO EITHER BILL
OR MYSELF.
THAT'S MY REPORT, THANK YOU VERY
MUCH.
>> THANK YOU VERY MUCH DR. COOK.
DR. WINKELSTEIN IF YOU WOULD
LIKE TO APPROACH THE PODIUM.
ALL RIGHT.
>> THANKS SO MUCH ALEX AND
THANKS EVERYBODY.
IT'S REALLY NICE TO BE IN THE
SAME ROOM TOGETHER, I WILL TART
WITH THAT AND ALSO FOLLOW THE
THREAD THAT CHAD SET UP AND AT
THE END OF HIS UPDATE TO SAY
THAT 1 OF THE--WHILE I'M HERE
REPRESENTING SPINE WORK 1 OF THE
ABSOLUTE THRILLS, BENEFITS AND
JOYS OF THIS WORK HAS BEEN
WORKING ACROSS THE NETWORKS.
SPINE WORK AS YOU CAN SEE IS
FROM OUR TITLE IS VERY SPECIFIC
AND PERHAPS THE MOST FOCUSED IN
TERMS OF BODY PART AND SYNDROME.
SO FOR US IT'S REALLY VERY, VERY
BENEFICIAL TO BE PARTNERED WITH
FORCE NET AND NEURONS MATTER IN
THIS LARGER ENDEAVOR.
I'M HERE REPRESENTING MY CO PI
AS WELL VICTOR BAROCAS WHO WAS
UNABLE TO BE HERE BUT I WANTED
TO WALK THROUGH SOME OF THE
SPECIFIC PROBLEMS THAT WE'RE
TRYING TO ADDRESS IN SPINE WORK
AND THEY'RE HIGHLIGHTED HERE IN
RED, WE'RE VERY FOCUSED ON THOSE
FORCED BASE MANIPULATIONS THAT
WORK TO OR TRY TO ALLEVIATE
SPINE PAIN AND TO BRING FOLKS
FROM VERY DESPERATE OR DISTANT
OR SEPARATE FIELDS TOGETHER TO
PERFORM EVERYONE THAT BRIDGES
THOSE GAPS.
SO OUR GOALS ARE TO CREATE AN
INTEGRATED PROFESSIONAL NETWORK
OF RESEARCHERS, INTERESTED IN
SPINE PAIN AND FBM AND TO REALLY
PROVIDE FACILITATION OF THEIR
MECHANISTIC RESEARCH TO COME
FORWARD IN THIS AREA.
AND OUR GOALS WERE AROUND 4
DIFFERENT AREAS AND THIS IS WHAT
WE FOCUS ON, INTERSECTING SPACES
AND EDUCATION OF SORT OF PARTNER
GROUPS IF YOU WILL,
NEUROMECHANICAL MECHANISMS,
IMAGING AND EXPERIMENTAL
COMPUTATIONAL MODELS, SO THAT
IS--OUR GROUP HAS A LOT OF
EDUCATIONAL OPPORTUNITIES AROUND
FOR DISSEMINATION.
LASTLY I THINK IT'S REALLY
IMPORTANT TO TALK ABOUT IS 1 OF
THE THINGS WE'RE INTENTIONAL
ABOUT WRITING IN OUR PROPOSAL
AND WILL BE A FOCUS OF OUR
FORWARD LOOKING WORK IS THE
HEALTH EQUITY LENS, BOTH AROUND
THE RESEARCH ITSELF, BUT ALSO
ABOUT REPRESENTATION IN OUR
NETWORK.
SO OUR PRIORITY RESEARCH AREAS
ARE VERY SIMILAR TO OTHERS AS
THEY WERE A SUBSET OF THE
ORIGINAL CALL TERMINOLOGY AND
MEASUREMENT, MECHANISTIC
MULTISCALE RESEARCH INTO
MECHANISMS, BIOMARKERS FROM
IMAGING TO MOLECULES, DIVERSITY
AND HEALTH DISPARITY.
I'M REALLY, REALLY THRILL THAD
WE HAVE SUCH A TIGHT KNIT AND
REALLY COLLABORATIVE GROUP OF
SORT OF WHAT I WOULD CALL SENIOR
LEADERS ON OUR TEAM AS I
MENTIONED, MY COLLABORATOR
VICTOR BAROCAS, IS UNABLE TO BE
HERE, HE'S ACTUALLY DOING
STUDIES TODAY, SO HE'S IN
THEMEATIC SERVICE.
WE HAVE MANY FOLKS IN THE ROOM
THEY WANT TO DO A SPECIAL CALL
OUT TO ARIN WHO IS AT MIN MEN
WITH VECTOR AND ELEN, AND LISA
LEWIS SITTING NEXT TO ME IN THE
BACK OF THE ROOM AND RONI EVANS
AND CATALIN PICU HAVE BEEN
REALLY TREMENDOUS.
WE HAVE A SMALLER NETWORK
BECAUSE WE'RE SOMEWHAT FOCUSED
WITH ONLY ABOUT A HUNDRED PLUS
MEMBERS AT THIS TIME, CAN YOU
SEE A DISTRIBUTION OF THEIR
RESEARCH INTEREST, PAIN BEING
FIRST AND FOREMOST, SPINE COMING
UP A LOT AND DIFFERENT REGIONS
OF SPINE ALSO COMING UP.
OUR NETWORK MEMBERSHIP INCLUDES
ALL SORTS OF PRACTITIONERS,
NEUROSCIENTISTS AND ENGINEERS
FROM A RANGE ACROSS THE GLOBE
AND IN A RANGE OF PROFESSIONAL
INTERESTS AS YOU CAN SEE HERE.
IN THE LAST YEAR WE'VE BEEN
PRETTY ACTIVE IN OUR EDUCATIONAL
CAMPAIGN, I WOULD LIKE TO THANK
BILL REID WHO CAME TO OUR
COMMUNITY TO LEAD AN EDUCATIONAL
EFFORT IN WHAT IS NEEDED AND HOW
CAN ENGINEERS HELP TAKE THIS UP?
WE HAD SMALL BREAK OUTS, SIMON
TANG HAS BEEN AND HE'S HERE AS
WELL, THANKS TO SIMON FOR ALL OF
YOUR HELP, WE'VE HAD A CONSTANT
PRESENCE AT ACCRAC, OVER THE
YEARS, SIMON WAS OUR
REPRESENTATIVE LAST YEAR AND
BECAUSE OF THE WORK HE DID IN
MAKING--IN OUTREACH THERE, WE
ARE WORKING TOGETHER WITH THAT
COMMUNITY TO PLAN A RESEARCH
METHODS WORKSHOP THAT WILL
EITHER BE A HALF DAY RIGHT
BEFORE THAT CONFERENCE OR AN
ONGOING WORKSHOP DURING THAT
MEETING.
SO WE'RE REALLY EXCITED ABOUT
THAT IN THE COMING YEAR.
WE'VE HAD 1 PILOT GRANT FUNDING
CYCLE, AND I'M HAPPY SO FAR AND
I'M HAPPY TO REPORT THAT WE HAVE
GREAT PROJECTS THAT WILL BE
FEATURED LATER THIS AFTERNOON
AND SO, REALLY THRILLED ABOUT
THOSE FROM 2 DIFFERENT VERY
DIFFERENT PERSPECTIVES, SO WE'VE
OFFERED SEVERAL REALLY IMPACTFUL
TRAVEL AWARDS FOR CONFERENCES.
ADDITIONAL TRAVEL AWARDS TO
ESTABLISH COLLABORATIONS WHICH
WAS EXACTLY OUR INTENT AND
SUPPORT FOR PUBLICATIONS.
WE HAVE ALREADY RELEASED OUR
NEXT ROUND OF PILOT GRANTS.
OUR LETTER OF INTENTS ARE NOT
DUE UNTIL SEPTEMBER, SO ANYONE
OUT THERE WHO'S INTERESTED,
PLEASE, PLEASE, PLEASE, CONTACT
US THROUGH THE MATERIALS AND WE
ARE ALSO VERY COLLABORATIVE WITH
THE OTHER GROUPS, SO IF IT'S NOT
APPROPRIATE FOR OUR CALL, WE
WILL MAKE SURE IT ENDS UP IN 1
OF THE RIGHT OTHER NETWORKS.
WE HAVE THE SMALL AJUSTMENT
GRANTS, THOSE ARE ROLLING SO
PLEASE, PLEASE, REACH OUT TO US
IF YOU HAVE ANY IN THAT.
MOVING FORWARD, WE ARE REALLY
HAPPY TO BE PARTNERING WITH
FORCE NET AND NEURONS MATTEROT
VIRTUAL CONFERENCE YOU JUST
HEARD ABOUT.
WE'RE PLANNING IN ADDITION TO
THE WORKSHOP WITH ACCRAC, WE'RE
ALSO PLANNING A WORKSHOP ON
RESEARCH METHODS, WE HAVE 2
PUBLICATIONS HIGHLIGHTED HERE
THAT WE HAVE FORTH COMING THAT
ARE IN DEVELOPMENT, WE WANT TO
CONTINUE OUR WORK WITH FUNDING
OPPORTUNITIES AND REALLY FOCUS
AS A SAID ON THE HEALTH EQUITY
LENS.
SO WE INVITE TO YOU JOIN US.
WE OFFER UP EDUCATIONAL
RESOURCES, MAKING CONNECTIONS
AND INTRODUCTIONS, FUNDING AND
MONEY AND AN ENTRÉE TO WHAT I
CONSIDER A REALLY MEANINGFUL
PARTNERSHIP BOTH WITHIN OUR
NETWORK AND ACROSS THE OTHERS.
THANK YOU.
>> THANK YOU VERY MUCH, BETH.
LAST BUT NOT LEAST ELEN LUMPKIN
TO GIVE AN UPDATE ON NEURONS
MATTR.
>> THANK YOU ALEX, WHO CONTROLS
THE SLIDES?
ME?
OKAY.
THAT DOESN'T WORK.
THIS?
OKAY, I WAS TRYING TO USE THIS
MASSIVE THING.
WELL, IT'S A PLEASURE TO BE HERE
TODAY TO SEE FAMILIAR FACES AND
I HOPE TO HAVE TIME TO MEET
PEOPLE I HAVEN'T YET MET IN
PERSON.
THE FOCUS OF NEURONS MATTR IS TO
ESTABLISH A INCLUSIVE RESEARCH
NETWORK TO IDENTIFY MECHANISMS
THROUGH WHICH SOFTTISSUE
MANIPULATION AND IN PARTICULAR
MASSAGE EXERTS BIOLOGICAL
EFFECTS ON NEURAL AND NONNEURAL
CELLS.
THE HIGH PRIORITY AREAS WE'VE
CHOSEN TO FOCUS ON ARE LISTED
HERE.
WE'RE INTERESTED IN MECHANISTIC
MULTISCALE RESEARCH, MEASURING
BOTH PHYSIOLOGICAL RESPONSES TO
FORCED BASE MANIPULATIONS, AS
WELL AS UNDERSTANDING THE
NEUROBIOLOGICAL BASES OF
EFFECTIVE TOUCH.
WE'RE ALSO INTERESTED IN
DEVELOPING TECHNOLOGY,
METHODOLOGY AND COMPUTATIONAL
APPROACHES, FOR MECHANISTIC
STUDIES AND THEN, IN YEAR 1 WE
ADDED A FOURTH PRIORITY AREA
WHICH IS TO DEVELOP FRAMEWORKS
AND LEXICON FOR DESCRIBING
MECHANISTIC STUDIES AND WE'RE
EXCITED ABOUT THIS AREA BECAUSE
IT'S A FOCUS ON A LOT OF OUR
TRANSU24 NETWORK ACTIVITY.
OUR NETWORK ACTIVITIES ARE
ORGANIZED THROUGH 3 PROGRAMS, A
CONFERENCE PROGRAM, A PILOT
PROJECTS PROGRAM AND
DISSEMINATION ACTIVITIES.
OKAY, THAT'S NOT THE RIGHT
BUTTON.
THIS PICTURE SHOWS OUR TEAM,
MANY OF WHOM YOU HEARD ABOUT
ALREADY, OUR TEAM SPANS OUR CORE
DISCIPLINES WHICH INCLUDE
NEUROSCIENTISTS, ENGINEERS,
CLINICIANS AND MANUEL THERAPISTS
AS WELL AS PHYSIOLOGISTS.
I WOULD LIKE TO HIGHLIGHT FROM
OUR CONFERENCE PROGRAM OUR
VIRTUAL SPEAKER SERIES THIS YEAR
THAT SPANNED ALL OF THE--ALL 4
OF THESE TARGET GROUPS.
SO WE HAD--WE'RE AIMING FOR 4
VIRTUAL SEMINARS A YEAR AND THIS
YEAR WE HAD 5 ALREADY AND WE
HOPE YOU'LL STAY TUNED FOR YOUR
UPCOMING SERIES THAT WILL
KICKOFF IN THE FALL.
OTHER EVENTS THAT WE HAVE
SCHEDULED FOR THE CONFERENCE
PROGRAM IS A SOPHISTICATED MAT O
SENSORY GANGLION AND
NOMENCLATURE WORKSHOP AND WE
HAVE AN ACTIVE WORKING GROUP
HOPING TO COME UP WITH A UNIFIED
NOMENCLATURE FOR THE DIVERSITY
OF SOPHISTICATED MAT O SENSORY
CELL TYPES.
WE WILL ALSO FAR TIS PARTICIPATE
IN A TRIAL IN THE--PARTICIPATE
IN THE FORCE NET VIRTUAL
CONFERENCE AND WE'RE ACTIVELY
WORKING ON A SUMMER SCHOOL THAT
WILL HAPPEN IN JUNE OF NEXT YEAR
WHICH WILL FOCUS ON
INTERROGATING THE HUMAN NERVOUS
SYSTEM DURING STM THERAPIES.
ONE THING WE'VE BEEN STRUGGLING
WITH, LIKE ALL OF THE NETWORKS
IS HOW TO ASSESS THE IMPACT OF
OUR PROGRAMS AND WE'VE STARTED
TO DO THIS THROUGH SURVEYS,
PARTICULARLY AROUND OUR YEAR 2
SUMMER SCHOOL WHICH OCCURRED IN
INDICATORS UNIVERSITY AND
INDIANAPOLIS, THE RESULTS OF OUR
EXIT SURVEY, I AM DELIGHTED TO
SAY WE HAD A HIGH RESPONSE RATE,
AT 66 PSYCHOFIZZISTS AND IT
INCLUDED QUANTITATIVE AND
QUALITATIVE OPEN ENDED
QUESTIONS, OUR QUANTITATIVE
SCALES SHOWED THAT ALL
RESPONDENTS AGREED OR STRONGLY
AGREED THAT THE EVENT HAD
EXCELLENT CONTENT.
IT WAS VALUABLE AND WAS
SUCCESSFUL AT FOSTERING BOTH NEW
COLLABORATIONS AND NETWORKING
OPPORTUNITIES.
OUR QUALITATIVE RESULTS WERE
ALSO REALLY INTERESTING.
WE FOUND THAT THE REASONS THAT
PEOPLE CAME TO THE SUMMER SCHOOL
WERE TO ESTABLISH COLLABORATIONS
AND NETWORKING AND THE IMPACTFUL
OUTCOME OF THEIR ATTENDANCE WAS
IN FACT NEW CONNECTIONS AND
COLLABORATIONS.
WE'RE IN THE MIDST OF OUR FIRST
EVALUATION OF PILOT PROJECT
APPLICATIONS, OUR NOTICE OF
FUNDING OPPORTUNITY WAS RELEASED
IN SPRING, AND MORE THAN HALF
THE APPLICATIONS MRI KABTS WERE
FROM SUMMER SCHOOL ATTENDEES.
WE'RE NOW--WE INVITED 2/3RDS OF
THE APPLICATIONS TO GO TO FULL
APPLICATION STAGE AND THEN THEY
WILL BE REVIEWED.
WE PLANNED 2 MORE ROUNDS IF
THEY'RE APPROVED BY NCCIH.
WE ALSO HAVE A MINISEBATICLE
PROGRAM.
THESE ARE EVALUATED ON ROLLING
BASIS, THEY'RE SIMILAR TO FORCE
NETS ADJUSTMENT AWARDS AND THAT
THE GOAL IS TO JUMP START NEW
COLLABORATIONS OR ALLOW OUR
MEMBERS TO,A QUIRE NEW TECHNICAL
SKILLS OR TO PERFORM
PRELIMINARY STUDIES.
WE ALSO HAVE TRAVEL GRANTS FOR
INCLUSIVE EXCELLENCE, AND THE
GOAL IS TO PROMOTE AN INCLUSIVE
COMMUNITY BY FUNDING TRAINEES,
EARLY STAGE INVESTIGATORS AND
RESEARCHERS FROM GROUPS USHED
REPRESENTED IN STEM TO PRESENT
RELEVANT NETWORK RESEARCH AT A
CONFERENCE OF THEIR CHOICE AND
WE WELCOME YOUR APPLICATIONS
AGAIN ON A ROLLING BASIS.
HIGHLIGHTS OF OUR DISSEMINATION
PROGRAM INCLUDE PUBLICATIONS,
THE TRANS-U24 NETWORK
PUBLICATION INCLUDED A POSITION
PAPER DEFINING SOME OF THE
IMPORTANT TOPICS THAT NEED TO BE
THE FOCUS OF RESEARCH AS WELL AS
PUBLICATIONS THAT HIGHLIGHT NEW
TECHNOLOGIES.
FINALLY, LIKE THE OTHER
SPEAKERS, I WELCOME YOU TO JOIN
OUR NETWORK, WE CURRENTLY HAVE
200 + MEMBERS, ACROSS
NEUROSCIENCE, ENGINEERING,
PHYSIOLOGY AND CLINICIANS, AND
WE HOPE THAT YOU WILL WELCOME
US, THAT YOU'LL JOIN US IF
YOU'RE RESEARCH INTERESTS MATCH
WITH OUR NETWORK PRIORITIES,
THANKS SO MUCH.
>> THANK YOU VERY MUCH
DR. LUMPKIN AND THANK YOU TO ALL
THE PRINCIPLE INVESTIGATORS OF
FORCE NET, NEURONS MATTR, AND
SPINE WORK UPDATES THIS MORNING.
I'M NOW PLEASED TO INVITE OUR
TRANS-NETWORK SCIENTIFIC WORKING
GROUP TO GIVE UPDATES OF THE
WORK THEY DID.
ONCE AGAIN IS CHAD COOK WHO WILL
PRESENT THE FRAMEWORK AND
TAXONOMY FOR THE GROUP.
AFTER THAT WE WELCOME MARY
BARBE, AT TEMPLE UNIVERSITY WHO
WILL GIVE AN UPDATE FOR THE
MIC
MECHANISMS WORKING GROUP FINALLY
WE LOOK FORWARD TO HEARING AN
UPDATE FROM THE MOTHOLOGY AND
TECHNOLOGY GROUP FROM DR. GREG
KAWCHUK FROM THE UNIVERSITY OF
ALBERTA, BUT FIRST DR. COOK.
NTHANK YOU DR. TUTTLE, I'M CHAD
COOK, PRECEPTING ON THE
FRAMEWORK AND TAXONOMY.
SO IN THE TOWER OF BABEL, THE
IDEA IS THAT THE CHRISTIAN GOD
STRUCK ALL OF THE WORKERS WITH
DIFFERENT LANGUAGES AND THAT'S
HOW ALL OF DIFFERENT LANGUAGES
ARE IN THE WORLD THAT'S THE
THOUGHT BEHIND THAT BUT THAT'S
ACTUALLY NOT TRUE, THE REAL
REASON IN THE BIBLE IS THAT HE
WANTED TO CONFUSE THE WORKERS SO
THAT THEY WERE UNABLE TO
COMPLETE THE TOWER OF BABEL AND
BY THE WAY, THAT'S A PERFECT
AFTEREFFECT CONSEQUENCE TO WHAT
WE'RE DEALING WITH TODAY.
THERE ARE SO MANY DIFFERENT
TAXONOMIES AND TERMINOLOGIES
AROUND FORCED BASED MANIPULATION
THAT IT'S ACTUALLY CREATED A LOT
OF CONFUSION AMONG CLINICIANS,
AMONG BASIC SCIENTISTS AND AMONG
COLLABORATORS AND THAT'S THE
IDEA BEHIND THIS COMMITTEE IS TO
HARMONIZE THE LANGUAGE AND SHARE
THESE WITH KEY STAKEHOLDERS AND
WE HAVE MANY KEY STAKEHOLDERS
THAT REALLY NEED THIS
HARMONIZATION INCLUDING BASIC
SCIENTIST, MOVEMENT SCIENTISTS,
IMAGING SPECIALISTS,
BIOMECHANICAL ENGINEERS, PUBLIC,
CLINICAL SCIENTISTS, PHYSIOS
ACCIDENT KHIHIGH ROWS, OFTIO
PATHS AND CERTAINLY EVEN THE
NIH.
THAT WAS THE PREMISE BEHIND THIS
COMMITTEE AND THESE ARE THE
WONDERFUL INDIVIDUAL WHO IS
WORKED TIRELESSLY IN THIS
COMMITTEE.
WE MEET EVERY MONTH AND SOME
MONTHS WE ACTUALLY MET TWICE AND
ALL OF THESE INDIVIDUALS FROM
MANY DIFFERENT BACKGROUNDS HAVE
BEEN RESPONSIBLE FOR PUTTING A
LOT OF PRODUCT TOGETHER AND I
HOPE TO SHARE THAT WITH YOU
TODAY.
WE WERE GIVEN A CHARGE AND WE
WERE GIVEN THIS DIAGRAM THAT WAS
FROM 2019 AND WHAT HAPPENS WHEN
A PRACTITIONER PLACES FORCE ON
TISSUE AND WE WERE TO DESCRIBE
THE PHYSIOLOGICAL RESPONSES TO
THAT FORCE USING STANDARDIZED
LANGUAGE AND BUILDING TAXONOMY,
OUR FIRST MEETING WAS
MARKETPLACE 102023, AND AT THAT
MEETING WE CREATED 3 CHARGES,
THE FIRST WAS TO CREATE A MODEL
TO GUIDE FORCED BASE
MANIPULATION RESEARCH, THE
SECOND WAS TO CREATE A FORCED
DOCUMENT, AND THE THIRD IS TO
CREATE A MASTER TERMINOLOGY FORM
THAT CAN BE USED IN AN
OPERATIONS MANUEL FOR THE
COMMUNITY OF RESEARCHERS AT
LARGE.
WE WERE CHARGED WITH HAVING AT
LEAST 2 DELIVERABLES, WE'LL
ACTUALLY HAVE MORE THAN THAT BUT
THOSE WOULD BE PUBLICATION ON
TAXONOMY AND TERMINOLOGY FOR
THAT FORCED DIAGRAM AND THE
SECOND WOULD BE TERMS USED FOR
AN OPERATIONS MANUEL.
SO, LET ME PRESENT FIRST ON
PROJECT 1 WHICH IS A MODEL TO
GUIDE FORCED BASE MANIPULATION
RESEARCH, BUT I WANT TO CALL
SOMEBODY OUT WHO'S IN THE ROOM
THIS, IS TERRY LOMANI'S WORK,
SHE'S BEEN INSTRUMENTAL IN THIS
AND I THINK YOU WILL AGREE
THAT--SHE'S FROM NEURONS MATTR,
I THINK YOU WILL AGREE THE END
PRODUCT IS QUITE GOOD.
THIS IS A 3 DIMENSIONAL MATRIX
INVOLVED FORCE APPLIED TO THE
TISSUE THAT HAS 3 AREAS.
THERE'S CONTEXTURAL FACTORS,
STRUCTURE AND FUNCTION, AND
FORCED PARAMETERS.
AND BASIC SCIENTISTS
TRANSLATIONAL RESEARCHERS,
CLINICIANS ALL KNOW THERE ARE
MULTIPLE VARIABLES INVOLVED IN
THOSE 3 PRIMARY AREAS.
THE TEAM HAS PUT TOGETHER THIS
INTERACTIVE DIAGRAM THAT ALLOWS
LEVELS TO BE OPENED UP AND
DISCUSSED SO THAT 1 CAN
UNDERSTAND THAT THESE FACTORS
CAN CHANGE REMARKABLY WHICH IS
PROBABLY WHY WE SEE SUCH
DIFFERENCES IN CLINICAL OUTCOMES
WITH THEIR PATIENTS.
THERE ARE SO MANY INTERACTIVE
VARIABLES IN, WHEN FORCE IS
APPLIED TO THE BODY.
IT IS QUITE INTEGRATIVE AND IT
REFLECTS ALL THE INTERACADEMYS
OF ALL THE DIFFERENT MECHANISMS
AND THEN 1 CAN SEE THEN HOW MANY
RESPONSES CAN CHANGE BASED ON
THIS.
IT HAS THE POTENTIAL TO BE
TRANSLATIONAL TO ACTUALLY SHOW
HOW THESE INTERACTIONS CAN ALSO
INFLUENCE CLINICAL OUTCOMES.
AND MOST IMPORTANTLY IT'S
DYNAMIC.
IN THIS MODEL WHICH WAS
COMPLETED JUST RECENTLY HAS BEEN
TRANSFERRED TO MECHANISMS GROUP
AND ALSO THE MEASUREMENT GROUP
WHERE THEY WILL ADD TO IT, WE
WERE CHARGED WITH CREATING A
SCAFFOLDING AND IT WAS WONDERFUL
WORK--WE HAD AN ILLUSTRATOR FOR
THIS AND THEN THERE'S A SUBGROUP
OF US, JEFF, BETH, AND ME WERE
WORKING ON A PAPER WHERE ABOUT
60% OF THE PAPER RIGHT NOW, AND
THEN WE HOPE TO PUBLISH THE
MANUSCRIPT TO GET THIS
INFORMATION OUT THERE.
PROJECT 2 WAS TO CREATE A FORCED
DOCUMENT.
SO WE'RE USING THE DIAGRAM, WE
WERE TO STANDARDIZE THE LANGUAGE
AROUND FORCE AND THE FORCE
DOCUMENT IS AN EFFORT TO
HARMONIZE CONCEPTS AND
TERMINOLOGY ASSOCIATED WITH THE
APPLICATION OF FOURS AND WAS
COLLECTED WITH THE NUMEROUS
SCIENTISTS FROM DIFFERENT
BACKGROUNDS AS WELL AS
CLINICIAN.
WE WERE ABLE TO COMPLETE THIS
PROJECT AFTER 2 CYCLES ON
JUNE 6th IN 2024, AND NOW WE
HAVE AN END PRODUCT AND WILL BE
WORKED WITH NIH AND THE OTHER
U24S ON HOW TO DISSEMINATE THIS
INFORMATION.
THE THIRD CHARGE IS CREATE A
MASTER TERMINOLOGY FORM THAT CAN
BE USED IN OPERATIONS MANUEL AND
THE COMMUNITY AT LARGE.
AT PRESENT WE HAVE APPROXIMATELY
360 DURANNENT DEFINITIONS AND
WE'RE CURRENTLY GOING THROUGH
AND HARMONIZING THESE, GETTING
INPUT FROM THE MEMBERS AND THEN
WE WILL SHARE THESE WITH OTHER
WORKING GROUP MEMBERS AND THE
U24 LEADS.
AND I WOULD LIKE TO ALSO GIVE A
SHOUT OUT TO BRIAN DAGENHEART IN
THIS WORK, WE USE HIS WORK FROM
RECENT PUBLICATION, THIS IS
COMING ALONG QUITE NICELY AND
THERE'S A LOT OF HARMONY, I
THINK WITHIN THE TERMINOLOGY
THAT WE'VE PUT TOGETHER.
COMPREHEND.
WE WERE CHARGED WITH COMPLETING
THIS WORK BY SPRING OF 2025 AND
HEIM HAPPY TO SAY THAT MOST
LIKELY OUR TEAM WILL BE FINISHED
BY SEPTEMBER OF 2024.
BUT WE DON'T WANT ANY ARK
DITIONAL WORK SO ONCE WE'RE
DONE, WE'RE GOOD.
I WANT TO FINISH UP WITH JUST
DISCUSSING OTHER DELIVERABLES
THAT THIS TEAM HAS EITHER
DIRECTLY OR INDIRECTLY BURN PART
OF.
THE FIRST 1 WAS A STANDARDIZED
DEFINITION OF CONTEXTURAL
FACTORS.
THIS PAPER WAS RECENTLY
PUBLISHED IN 2023.
THIS WAS AN INDIRECT INPUT FROM
THE TAXONOMY GROUP.
YOU WILL RECOGNITION A NUMBER OF
INDIVIDUALS THAT ARE ACTUALLY
FROM THE U24S THAT ARE PART OF
THIS PARTICULAR PROJECT.
CONTEXTURAL FACTORS HAVE BEEN
CALLED A THOUSAND DIFFERENT
THINGS IN THE LITERALLURE AND
USING A NOMINAL GROUP TECHNIQUE
THIS GROUP HARMONIZED AN
INTERNATIONAL DEFINITION AND IT
CAME OUT IN LATE 2023 AND IT'S
ALREADY BEEN CITED 17 TYPES SO I
THINK THERE WAS A PRETTY
SUBSTANTIAL NEED FOR THIS
PARTICULAR PAPER.
THIS IS RYAN DAGENHART'S WORK, A
GROUP THAT HARMONIZED
NOMENCLATURE, THIS WAS PUBLISHED
IN FORCE NET'S SPECIAL ISSUE IN
2024 SPRING.
AND THEY REALLY DO A WONDERFUL
JOB IN THE SUPPLEMENTS OF
INCLUDING A NUMBER OF THE MOST
IMPORTANT TERMINOLOGY VARIABLES
AROUND FORCED BASE MANIPULATION.
YOU WILL ALSO RECOGNIZE A NUMBER
OF U24 INDIVIDUALS EITHER
WORKING GROUP MEMBERS OR
OTHERWISE THAT ARE PART OF THIS
PROJECT AS WELL.
THIS WAS AN INDIRECT PUBLICATION
THAT WAS RELATE THE TO OUR
GROUP.
AND THIS WAS AROUND HOW DO WE
TALK TO PATIENTS AROUND
MECHANISMS, SO IT HARMONIZE THE
WAY THAT THAT CONVERSATION FOR
THOSE CLINICIANS AND THAT
PATIENTS IN FRONT OF YOU, HOW DO
YOU ACTUALLY DISCUSS WHAT FORCED
BASE MANIPULATIONS ACTUALLY DO
EMPLOY THIS WAS PUBLISHED IN
2024.
IN THE SPECIAL ISSUE, THIS
WONDERFUL WORK BY DAMON KEITER,
WHO IS IN THE ROOM ON
INTERNATIONAL GAPS IN FORCED
BASE MANIPULATION USING A DEL-PH
I STUDY, OR EXCUSE ME, A NOMINAL
GROUP TECHNIQUE, THAT IDENTIFY
GAPS IN RESEARCH MECHANISMS AND
THIS PAPER WAS PUBLISHED THEN
AND YOU WILL NOTICE A NUMBER OF
NAMES ALSO AFFILIATED WITH MANY
OF THE U24s.
THERE'S ALSO AN INTERNATIONAL
GAPS AND CONACCIDENTURAL FACTORS
RESEARCH IN FORCED BASE
MANIPULATION.
THIS WAS LED BY DAVID GRISWALD
BUT YOU WILL NOTICE OTHER
INDIVIDUALS AGAIN INCLUDING
JENNIFER BENT WITH THE U24s
AND THE LAST PARTNERSHIP I WILL
HEIGHT LIGHT IS THE INVITED
MANUSCRIPT AND THIS 1 WAS
PROBABLY THE LARGEST
COLLABORATION AMONG THE U24s
WITH RESPECT TO PUBLISHING, A
HIGHLIGHTED ALL THE NAMES.
YOU WILL RECOGNIZE MEMBERS FROM
FORCE NET, SPINE WORKS AND FROM
NEURONS MATTER AND WHAT WE'VE
DONE IS WE'VE ACTUALLY
CATEGORIZED TREATMENT MECHANISMS
AT A HIERARCHY SO THEY
UNDERSTAND WHAT THESE ACTUALLY
ARE, BUT ALSO DISCUSS THESE IN
TERMS OF ARE THEY CAUSAL, ARE
THEY SOCIAATIVE AND I THINK THIS
WAS GREATLY NEEDED IN THE
LITERATURE, AND WE HOPE THIS
WILL CLEAR UP THINGS MOVING
FORWARD.
THAT'S MY REPORT AND THANK YOU
VERY MUCH.
NTHANK YOU VERY MUCH DR. COOK.
NEXT UP WE ARE BEING JOINED
VIRTUALLY BY DR. MARY BARBE FROM
TEMPLE UNIVERSITY, MARY ARE YOU
ON THE LINE IN.
>> I AM, DO I SHARE MY SLIDES OR
DO YOU SHARE THEM?
>> I THINK WE MIGHT HAVE YOU
SHARE YOUR SLIDES DIRECTLY MIGHT
BE THE BEST--
>> OKAY.
>> LET ME JUST BRING UP--SHIFT
GEARS HERE.
WE HAVE OUR AV TECH JOSHUA
HELPING US TODAY.
THANK YOU JOSHUA.
>> OKAY.
CAN YOU SEE MY SLIDES?
>> YES, YES WE CAN.
>> OKAY.
SO LET ME TURN OFF THE--JUST A
SECOND--I'LL JUST KEEP GOING.
SO, THANK YOU.
THIS IS THE MECHANISMS WORKING
GROUP AND LET ME--IT'S LIKE
GOING BACKWARDS FOR A SECOND.
THERE.
I'M SPEAKING ON BEHALF OF THE
MECHANISM WORKING GROUP, I'M
SORRY I CAN'T BE THERE, SERIES
OF UNEXPECTED THINGS PREVENTED
BY ATTENDANCE.
WE HAVE SEVERAL MEMBERS OF THIS
WORKING GROUP CURRENTLY, WE HAVE
DR. ELLEN LUMPKIN, WITH
NEUROKNOWS MATTR, JEN
[INDISCERNIBLE] JOINED US FROM
NEURONS MATTR AND MYSELF AND
SPINE WORKS AND DR. SIMON TANG
FROM WASH-U IS PART OF OUR
GROUP, HE'S FROM SPINE WORKS AND
THEN WE HAVE 2 MEMBERS FROM
FORCE NET, DR. BILL REED FROM
UAB AND DR. NAPP A DOW FROM
HARVARD MEDICAL SCHOOL.
WE ARE ACTIVELY RECRUITING.
WE NEED ADDITIONAL MEMBERS TO
HANDLE ALL THE WRITING WE HAVE
PLANNED AND IF YOU ARE
INTERESTED PLEASE SPEAK TO SIMON
TANG TODAY.
HE IS THERE AT THE CONFERENCE
AND WILL HELP US WITH THE
RECRUITING.
WE HAVE SEVERAL GOALS.
WE HAVE THE GOALS OF OUR
MECHANISM WORKING GROUP IS THAT
THE MECHANISMS THEMSELVES ARE
NOT WELL KNOWN AS YOU JUST HEARD
FROM THE FRAMEWORK AND AXON ME
WORKING GROUP LEADER CHAD COOK,
THEREFORE OUR GROUP'S GOALS ARE
TO COLLABORATE WITH THE
FRAMEWORK AND TAXONOMY WORKING
GROUP TO FURTHER REFINE THE
CLASSIFICATIONS OF MECHANISTIC
TARGETS OF FORCE-BASED
MANIPULATIONS.
TO EVALUATE CURRENT
UNDERSTANDINGS OF MECHANISMS OF
ACTION AND TO IDENTIFY IMPORTANT
KNOWLEDGE GAPS AND POTENTIAL
CUTTING-EDGE RESEARCH
OPPORTUNITIES TO ADVANCE
MECHANISTIC UNDERSTANDING OF
DIFFERENT TYPES OF FORCED BASE
MANIPULATIONS AND TO COLLABORATE
WITH THE DISSEMINATION WORKING
GROUP TO PRODUCE LIVING
DOCUMENTS AND RELATED RESOURCES.
OUR COLLABORATIONS HAVE BEEN
EXTENSIVE THIS YEAR WITH THE
FRAMEWORK AND TAXONOMY WORKING
GROUP, WE WERE THANKFUL FOR THE
OPPORTUNITY.
WE PROVIDED INPUT TO THE FORCED
ASSUMPTIONS DOCUMENT, TAXONOMY
DIAGRAM, THE PRIMARY TAXONOMY
DIAGRAM, THE TERMINOLOGY
DOCUMENT, AND THE WRITE UP FOR
CONSIDERATIONS FOR FORCES AND
FORCE-BASED MANIPULATION.
OUR OTHER MAIN GOAL IS TO
DEVELOP LITERATURE REVIEWS WITH
A KEY GOAL TO EVALUATE THE
CURRENT UNDERSTANDINGS OF
MECHANISM ACTION IN RESPONSE TO
FORCED-BASED MANIPULATIONS FROM
THE LITERATURE.
THESE ARE MECHANISMS IN THE
TISSUES THEMSELVES.
OUR INITIAL DOCUMENT WILL FOCUS
ON EXEMPLAR FORCE-BASED
MANIPULATIONS AND TECHNIQUES
IDENTIFIED IN THESE VARIOUS
PUBLICATIONS.
WE ALSO STRIVE TO IEE, AUDIENCE
DENTIFY POTENTIAL KNOWLEDGE GAPS
AND POTENTIAL CUTTING-EDGE
RESEARCH OPPORTUNITIES TO
ADVANCE MECHANISTIC
UNDERSTANDING.
WE HAVE UTILIZE THE FRAMEWORK
TAXONOMY WORKING GROUP AS YOU
CAN SEE HERE.
THUS FAR WE'VE IDENTIFIED OVER
160 PAPERS IN THE LITERATURE AND
THERE WILL BE MORE BEING
IDENTIFIED IN WHICH FORCED BASE
MANIPULATIONS ON TISSUES WERE
EXPLORED.
INITIALLY WE SUBDIVIDED THESE
INTO TISSUE LAYERING TYPE
TARGETED BY THE FORCED BASED
MANIPULATION METHOD THAT WAS
UTILIZED.
SO FOR EXAMPLE, IN BONE
CARTILAGE AND JOINT, IF WE JUST
LOOK AT MANUAL THERAPIES ON
THESE TISSUES, 5 PAPERS WERE
IDENTIFIED, HOWEVER, IF WE MOVE
ON TO THE IN VIVO MODELS AND THE
PILOT STUDY ON THIS BUT THERE
ARE SEVERAL IN VIVO MODELS
EXAMINING OFTIO SIGHTS FOR
EXAMPLE THEN THE AMOUNT OF
PAPERS EXPAND CONSIDERABLY.
AMOUNT MUCH PAPERS EXAMINING
MECHANISMS OF ACTION ARE
INTERVERTEBRAL DISKS ARE 40
RIGHT NOW AND LET'S NOT FORGET
FASCIA, SKIN AND SUBCUTANEOUS
TISSUES THAT CONNECT OUR SKIN
TOGETHER AND THERE ARE 23 TODAY.
THERE ARE ALSO 60 PAPERS
EXAMINING MUSCLES ACCIDENT MUSD
ARTERIESS AND THEN WE HAVE
SOMATIC AND CENTRAL NEURON
SYSTEMS WITH 20 OR MORE TO GO.
WE ARE TRYING TO SINNER UTILIZE
WITH THE WORKING GROUP TOW THAT
WE CAN HAVE A NICE HARMONY
ACROSS OUR GROUPS.
NOW I PERCEIVE THAT THAT WILL BE
A SEPARATE VIEW PAPER THAN THIS
NEXT 1 I WILL DISCUSS WHERE
WE'RE LOOKING AT THE BODY
SYSTEMS IMPACTED LIKE ARTERIOLE
LYMPHATIC, IMMUNE, INFLAATORY,
NERVOUS SYSTEM LIKE PAIN AND
NEUROIMMUNE, THE PSYCHOSOCIAL
SECTION WILL BE ABBREVIATED.
DR. CASE FROM NEURONS MATTR ARE
WORKING ON A FULL REVIEW OF THE
PSYCHOSOCIAL ASPECTS AND HOPE TO
FINISH THAT IN THE FALL.
WE'RE ALSO STRIVING TO
CATEGORIZE THE LITERATURE BY
SPECIFIC FORCED BASE
MANIPULATION METHOD UTILIZED
THAT THEN CREATES THESE CHANGES
IN THE TISSUES, LIKE JOINT
MOBILIZATION, INSTRUMENTED,
MASSAGE, MY O FACIAL THERAPY,
SPINAL MANIPULATION AND MORE AND
SPECIFIC PARADIGMS WILL BE
DELINEATED ACCORDING TO THE
SCAFFOLD, THIS WILL HAVE TO BE
INCLUDED IN EACH OF OUR REVIEWS
AND YOU CAN SEE ALREADY THAT
THERE IS SYNERGY WITH THE FORCED
BASED--FORCED TAXONOMY GROUPS
DIAGRAMS THEY HAVE PRESENTED.
WE ALSO SEE THE--A CHANCE TO
EXPAND ON THE LIMA ET ALL IN
2020 WHERE 1 CAN LOOK AT THE
DIFFERENT TYPES OF PARAMETERS
USED, HOW MANY PAPERS HAVE BEEN
PUBLISHED ON EACH 1 AND
DIFFERENT SORT OF IDEAS THAT WE
CAN EXPAND ON AND OUR ABILITY TO
IDENTIFY GAPS.
WE'RE HOPING TO USE ALL OF THIS
TO IDENTIFY THERAPIES FOR WHICH
UNDERLYING MECHANISMS ARE
UNCLEAR.
THERAPIES FOR WHICH MORE
RESEARCH IS NEEDED.
FOR THIS WE WILL PUT OUT A CALL
FROM OUR NETWORKS TO IDENTIFY
THE LEAST STUDIED MECHANISMS OF
MECHANO THERAPIES.
WE ALSO STRIVE TO IDENTIFY OR
SUGGEST POTENTIAL CUTTING EDGE
RESEARCH OPPORTUNITIES TO
ADVANCE MECHANISTIC
UNDERSTANDING IN COLLABORATION
WITH A METHODOLOGY AND
TECHNOLOGY WORKING GROUP.
WE WILL COLLABORATE WITH THE
DISSEMINATION WORKING GROUP TO
PRODUCE LIVING DOCUMENTS AND
RELATED SOURCES.
SINCE THE LITERATURE EXPANDS
REGULARLY AND WE HOPE
EXTENSIVELY BASED ON ALL OF OUR
EFFORTS, WE SEE THIS OR ALL OF
THESE HAS LIVING DOCUMENTS WE
NEED TO BE UPDATED REGULARLY.
WE ENVISION USING VARIOUS OPGS
FOR DISSEMINATION TO THE PUBLIC
AS A PLACE FOR A LIVING
DOCUMENT, UPDATING IT REGULARLY
INCLUDING OF THE PREPRINT SERVER
FROM BIOLOGY, SUGGESTIONS
INCLUDED LIKE AN ENCYCLOPEDIA
MBPI JOURNALS, INTERNATIONALLY
PEER REVIEWED OPEN ACCESS
JOURNAL THAT RECORDS QUALIFIED
REVIEWS THAT OFFER COMPREHENSIVE
ANALYSIS OF THE EXTANT
LITERATURE, IEKS DENTIFYING
CURRENT GAPS OR PROBLEMS,
THEREFORE MATCHING OUR GOALS AND
THEN WE RECEIVED SOME WHITE
PAPERS.
THIS IS ALL IN ADDITION TO
PUBLISHED PEER REVIEWED PAPERS.
COME OUR WORKING GROUP
MEMBERS--AND OUR WORKING GROUP
MEMBERS HAVE BEEN ENGAGED WITH
SEVERAL DIFFERENT PEER REVIEWED
PUBLICATIONS AS YOU CAN SEE ON
THIS LIST HERE.
SEE IF I CAN GET RID OF SOME OF
THESE THINGS IN THE WAY SO THAT
YOU CAN SEE THE LOWER CASE WAS
WITH REDUCED HEAT PAIN IN A
RANDOMIZED CONTROL TRIAL AND WE
HAVE OTHER 1S LIKE IF YOU LOOK
AT NUMBER 4, DR. COOK EXPLAINED
THE INTERNATIONAL CONSENSUS
DEFINITION OF CONTEXTURAL
FACTORS WHICH IS VERY USEFUL FOR
OUR GROUP AS WELL.
AND THEN NUMBER 5 THE MANUEL
THERAPY AND EXERCISE EFFECTS OF
ON INFLAMMATORY CYTOKINES A
NARRATIVE OVERVIEW, WELL WE HAVE
DISCOVERED THIS FAR WITH OUR
TABLE THIS IS FAR IS THAT A
REDUCTION IN INFLAMMATORY
PROCESS SEEMS TO BE 1 KEY
MECHANISM INVOLVED THAT THE
TISSUES'RE UNDERGOING WITH THE
FORCED BASE MANIPULATION.
AND THEN THERE'S MAYBE OTHER
THEMES, WE'VE ALL BEEN QUITE
BUSY.
THERE'S AN IASP-PAIN THERAPY
REPORT AND SO THAT'S MY REPORT
AND THANK YOU VERY MUCH.
>> THANK YOU VERY MUCH
DR. BARBE, LAST BUT NOT LEAST WE
HAVE DR. GREG KAWCHUK WHO WILL
GIVE AN UPDATE ON THE METHOLOGY
AND TECHNOLOGY WORKING GROUP
PROGRESS.
GREG, ARE YOU ON THE LINE?
>> HI, EVERYBODY, ABLE TO HEAR
MY AUDIO NOW.
>> YES, WE CAN HEAR YOU NOW.
>> YEAH, MY APOLOGIES FOR THE
TECHNICAL DIFFICULTY RIGHT
THERE, THERE IS NO 1 MORE
DISAPPOINTED THAN ME BY NOT
BEING AT THIS EVENT TODAY.
MANY OF YOU WE NEVER MET AND
STARTED THIS WORK REMOTELY AND
IT WAS REALLY SOMETHING THAT I
WAS HIGHLY LOOKING FORWARD TO
AND MY APOLOGIES FOR NOT BEING
ABLE TO MAKE IT THERE TODAY.
SO THIS IS MY REPORT FROM THE
METHODOLOGY AND TECHNOLOGY
WORKING GROUP AND I'LL JUST
BEGIN BY INTRODUCING THE MEMBERS
OF THE GROUP WHO MANY OF WHOM
YOU HEARD FROM OR HAVE SEEN
MENTIONED TODAY ALREADY.
ARIN ELLING SON, GREG, GARY AND
KARL LEWIS WHO ARE FROM OTHER OF
THE U24 PROJECTS AND THIS IS A
COMBINATION OF COURSE OF THE
WORKING GROUP OF DIFFERENT
PEOPLE WITH THE COMMON INTEREST
IN THIS TOPIC, NOW, THIS TOPIC'S
A LITTLE DIFFERENT FROM THE 1S
THAT YOU HEARD PREVIOUSLY IN
THAT THERE'S A LOT OF DISCUSSION
THAT NEEDS TO HAPPEN WHEN YOU'RE
TRYING TO DEFINE TAXONOMY.
A LOT OF--I'M SURE VERY
INTERESTING DISCUSSIONS ABOUT
HOW TO DEFEIGN CERTAIN WORDS,
WHAT WORDS ARE INCLUDED OR NOT,
ET CETERA.
AND SIMILARLY WITH MECHANISMS
THAT'S A PRETTY FLUID TOPIC AS
WELL THAT DESERVES A LOT OF
DISCUSSION TO BE ABLE TO GET TO
THE POINT OF WHAT'S INCLUDED IN
THE DISCUSSION.
OUR MANDATE IS A BIT DIFFERENT.
OUR MANDATE IS TOCCATA LOG OR
WAREHOUSE ALL THE DIFFERENT
METHLOGICAL TECHNIQUES,
TECHNOLOGIES, PROTOCOLS THAT
COULD BE USED IN THE STUDY OF
FORCED BASE MECHANISMS AND
THAT'S SOMETHING THAT ISN'T
REALLY CONTROVERSIAL IN TERMS OF
HAVING TO DEFINE WORDS OR
DEFINITIONS OR TAXONOMIES, BUT
IT IS A TREMENDOUS AMOUNT OF
WORK AND YOU CAN IMAGINE THE
SCOPE OF THE DIFFERENT
TECHNIQUES THAT CAN BE USED TO
ACHIEVE THIS.
SO WE USED A NUMBER OF DIFFERENT
TECHNIQUES THAT I WILL SHOW YOU
ABOUT IN A SECOND, BUT REALLY WE
SPLIT THIS UP INTO 2 DIFFERENT
DOMAINS, THE FIRST WAS TO
CAPTURE THOSE METHODOLOGIES AND
TECHNOLOGIES THAT ARE CURRENTLY
USED OR AT LEAST HAVE PAPERS
THAT WERE PUBLISHED DIRECTLY
RELATING TO METHODOLOGIES AND
TECHNOLOGIES TO OUTCOMES THAT
WERE DIRECTLY ASSOCIATED WITH
FORCED BASE MECHANISMS AND THEN
A LITTLE MORE, I GUESS FORWARD
THINKING IN THAT TRYING TO
IESHES DENTIFY THESE DIFFERENT
METHOLOGYS AND TECHNOLOGIES THAT
HAD POTENTIAL TO BE INVOLVED IN
THIS AREA.
SO IF THERE WAS ANY AREA FOR
CONTROVERSY OR DISAGREEMENT IT
WOULD BE IN THIS AREA BUT
BECAUSE IN 1 SENSE INTERESTING
CAN BE USED AS A POTENTIAL
METHOD, WHO KNOWS WHAT'S OUT
THERE AND WHAT CAN BE DISCOVERD
SO THAT'S HOW WE HYBRIDIZE THIS
AND THEN THERE'S A LITTLE BIT OF
AN OPPORTUNITY HERE TO
CATEGORIZE OR KEEP UP TO DATE
THE OPPORTUNITIES THAT WE HAVE
WITHIN THE COMMUNITY TO EITHER
APPLY FOR FUNDING OR TO NETWORK
AND ATTEND CONFERENCES AND OTHER
THINGS LIKE THAT IN THIS AREA.
SO WITH THAT, WE USED A COUPLE
OF TECHNIQUES TO ACQUIRE THESE
DIFFERENT TECHNOLOGIES AND 1 OF
THEM WAS TO SIMPLY CREATE THIS
ROADMAP.
AND THIS WAS TO INVITE EVERYONE
IN THE NETWORKS, INCLUDING
MEMBERSHIPS ISSUES NOT JUST
LEADERSHIP BUT TO INVITE THEM
AND ASK, WHAT HAVE YOU USED IN
YOUR WORK OR IF YOU WOULD LIKE
TO EVEN GO FURTHER, PUT DOWN
SOME OF THE THINGS THAT YOU
CONSIDER TO BE THE IMPORTANT
METHODOLOGIES AND TECHNOLOGIES
AND WE WERE ABLE TO ACCUMULATE
QUITE A LIST, THERE'S A LOT OF
DUPLICATION AS YOU CAN IMAGINE,
THERE'S A LOT OF CONDENSING THAT
HAS TO HAPPEN TO MAKE THIS
REALLY SOMETHING THAT YOU CAN
NAVIGATE IN A WAY THAT IS EASY
AND ACCESS CLINICAL COMMUNITY
AND WE WILL GET ON IT THAT IN A
SECOND EMPLOY AND THEN WE'VE GOT
SOME--A LIST THAT SPLITS INTO
OTHER TECHNOLOGIES THAT HAVE
POTENTIAL BAH MAYBE HAVEN'T BEEN
USED IN THIS FIELD YET AND
IT'S--BESIDES THE GROUP
VOLUNTEERING THIS INFORMATION
THROUGH OUR DIRECT INVITATION,
WE WERE ALSO FORTUNATE ENOUGH TO
HIRE A MASTERS OF SCIENCE
LIBRARIAN STUDENT WHO WAS ABLE
TO GO THROUGH THE LITERATURE AS
WELL AND PULL THE DEFINITE
MOTHOLOGYS FROM THE PAPERS THAT
ARE IDENTIFIED AS ASSOCIATED
WITH FORCED-BASED
INTERVENTIONED.
THAT AS WELL AS ADVANCES IN
LARGE LANGUAGE MODELS INCLUDING
SOME OF THE SPECIFIC LITERATURE
SEARCH TOOLS THAT CHAT GPT
OFFERS SUCH AS CONSENSUS ARE
REALLY HELPFUL IN FINDING
GENERAL FEEDS THAT MAYBE WE HAD
OVERLOOKED AND THEN EXPLORING
THOSE THEMES FOR PARTICULAR
EXAMPLES.
SO WITH THAT WE REALIZE THIS IS
A PRETTY FLUID AREA, 1 WHERE
PAPERS ARE BEING PUBLISHED
CONSTANTLY WITH MAYBE NEW IDEAS,
TECHNOLOGIES, ET CETERA BUT YOU
HEARD A LOT TODAY ABOUT CREATING
UPDATES TO DOCUMS, LIVING DOCUMS
AND WE WANT TO REALLY TAKE THAT
TO HEART AND SAY THAT WE NEEDED
TO HAVE SOMETHING THAT WASN'T
NECESSARILY JUST A MARK IN ITS
END AS A PUBLICATION BUT
SOMETHING THAT COULD BE USED IN
AN ONGOING BASIS.
SO WITH THAT WE CREATED A
WEBPAGE AND I'LL SHOW YOU IN
JUST A SECOND, BASED ON THE
CREATION OF THIS PEB PAGE, WOULD
BE THE FORMULATION OF OUR FIRST
ACADEMIC PAPER OF HOW ALL THIS
HAPPENED.
SO IN THE CHAT, I'VE ACTUALLY
PUT THE WEBSITE SO YOU CAN
ACCESS IT DIRECTLY, THE QR CODE
DOESN'T SEEM TO GIVE YOU THE
FULL WEBPAGE EXPERIENCE BUT YOU
CAN CERTAINLY USE IT.
BUT THE CHAT SHOULD HAVE THE
URL.
SO THIS WEBPAGE IS A NICE 1.
VERY SIMPLE TO MAKE ON 3
PLATFORM GOOGLE SITES AND
THERE'S A LOT OF STUFF YOU CAN
IMAGINE A WEBSITE SHOULD HAVE,
BUT THE KEY FEATURE THAT BRINGS
TOGETHER A LISTING OF ALL THE
METHODOLOGIES AND TECHNOLOGIES
IS THIS INTERACTIVE MINE MAP, SO
ON THE WEBSITE YOU CAN INTERACT
WITH THE MINE MAP, IT'S A MUCH
BETTER EXPERIENCE ON A LAPTOP
RIGHT NOW THAN IT IS ON A HAND
HELD DEVICE AND WE HAVE TO DO A
BIT OF WORK THERE TO MAKE THAT
EASIER TO USE.
IT'S USEABLE, BUT IT'S A LITTLE
TINY.
SO IN THIS MIND MAP, WE SEE ON
THE LEFT THE GENERAL CATEGORIES
OF METHODOLOGIES AND CATEGORIES
THAT WE IDENTIFIED AND ON THE
RIGHT, THESE ARE SOME OF THE
NEWER OR PROMISING TECHNOLOGIES
AND METHODOLOGIES THAT MAY BE
INVOLVED IN FORCED BASED
INTERVENTION RESEARCH AND THAT,
I'M SURE WE'VE ALL USED MIND
MAPS BEFORE BUT OF COURSE IF YOU
HAVEN'T, YOU CAN TOUCH ON ANY OF
THESE POINTS AND CONTINUOUSLY
BLOW THEM UP UNTIL YOU REACH
TERMINUS OF THE BRANCH AND HERE
YOU WILL SEE DIFFERENT SPECIFIC
METHODOLOGIES.
AND NOT ONLY DO YOU SEE THE
SPECIFIC METHODOLOGIES, BUT IF
YOU CLICK ON THEM, YOU WILL BE
GIVEN AN EXAMPLE OF THAT
METHODOLOGY THROUGH A PUBLISHED
PAPER.
SO YOU CAN CLICK ON THAT AND
SOMETIMES WE HAVE MULTIPLES OF
THESE EXAMPLES, AND YOU WILL BE
TAKEN DIRECTLY TO THE WEBPAGE
WHERE THAT PAPER APPEARS, WHICH
I THINK THE JOURNAL PUBLISHERS
REALLY APPRECIATE RATHER THAN
GOING THROUGH SOME OF THE OTHER
CITATION SOURCES.
SO THAT'S SOMETHING THAT YOU CAN
INTERACT AND PLAY WITH NOW.
IF YOU DON'T LIKE THE MIND MAPS,
THERE ARE LISTS OF BOTH OF THOSE
CITATIONS EITHER THE CURRENT 1S
OR THE PROMISING 1S THAT YOU CAN
USE FROM THE WEBSITE AS WELL.
AND I JUST HAVE AN EXAMPLE OF
THAT HERE.
YOU CAN EVEN DO THIS WITHIN THE
MIND MAP AS WELL.
CAN YOU CHANGE THE STRUCTURE OF
THE MIND MAP TO JUST GIVE THE
CITATIONS.
AND FINALLY WE WANTED TO USE THE
WEBSITE AS A WAY TO CONTINUOUSLY
UPDATE THE INFORMATION.
SO OF COURSE WE'RE KAN--KANAING
FOR THAT ALL THE TIME BUT IF YOU
USE THE WEBSITE OR HAPPEN ON IT,
THERE'S A FEEDBACK FORM YOU CAN
FILL OUT IF THERE IS MAYBE A GAP
IF WHAT WE'RE DISPLAYING OR
SHOWING OR SOMETHING THAT YOU
THINK IS MISARRANGED AND SHOULD
FOLLOW UNDER ANOTHER BRANCH IN
THE HIERARCHY, ET CETERA AND
THAT FEEDBACK FORM IS NICE
BECAUSE INSTEAD OF AN E-MAIL
ADDRESS WHICH SOMEONE HAS TO
MONITOR AND KEEP UP TO DATE
WITH, WE CAN USE THIS FEEDBACK
FORM TO KEEP CONTINUAL RUNNING
LIST THAT EVERYONE CAN ACCESS TO
SEE WHAT HAS BEEN SUGGESTED IN
THE PAST AND WHAT THE MORE
RECENT SUGGESTIONS HAVE BEEN.
SO WITH THAT THE DISSEMINATION
OF THAT IS PRETTY STRAIGHT
FORWARD, IT'S JUST A MATTER OF
GETTING THE URL OUT TO
EVERYBODY, WHICH WILL HAPPEN
THROUGH THE WORKING GROUPS,
THROUGH THE U24 GROUPS AND THEIR
600 OR SO MEMBERS BUT OF COURSE
THE WEBPAGE IS OPEN TO ANYONE.
SO WITH THAT, IT'S 1 THING TO
CREATE THAT TOOL, THAT
CATALOGING, THAT INTERACTIVE
MIND MAP, WHAT CAN YOU DO WITH
IT?
THE HOPE HAS ALWAYS BEEN THAT
CATEGORIZING THIS, WE CAN BEGIN
TO IDENTIFY WHERE THERE ARE
GAPS.
THIS IS THE RIGHT HAND SIDE OF
THE MIND MAP, THE PROMISING
AREAS COMING INTO PLAY.
BUT YOU HEARD IT SPOKEN ABOUT
BEFORE WITH THE OTHER WORKING
GROUPS BUT IT'S REALLY THE
INTEGRATION OF THE WORK, GROUPS
THAT CAN CREATE SOME OF THE
OPPORTUNITIES, I THINK IN TERMS
OF IDENTIFYING GAPS AND OTHER
PRIORITIES.
SO YOU'VE SEEN ALREADY FROM THE
OTHER WORKING GROUPS, THEIR
OUTPUTS WHETHER IT'S FROM
FRAMEWORK AND TAXONOMY OR
MECHANISMS AND NOW IT'S TIME TO
TIE ALL THIS TOGETHER.
SO IF YOU LOOK AT THE DIFFERENT
MECHANISMS THAT WILL BE LISTED
BY THE GROUPS, THE WORDING THAT
IS USED AND THE DIFFERENT
MOTHOLOGIES AND TECHNOLOGIES
THAT EXIST, HOW DO YOU PUT THOSE
THINGS TOGETHER BECAUSE MAYBE
THERE'S OPPORTUNITIES OF
TECHNOLOGIES THAT AREN'T BEING
USED IN THE MECHANISM SIDE OR
MECHANISMS THAT ARE PROPOSED
THAT DON'T HAVE TECHNOLOGIES
THAT MAY NOT BE IDENTIFIED IN
TERMS OF STUDYING THOSE.
SO WE'RE EXPLORING NOW SOME
IDEAS OF USING 3D VISUALIZATION
TOOLS THAT WE'VE ALL SEEN BEFORE
THAT CAN TAKE SOME PRETTY
COMPLEX 3 DIMENSIONAL IDEAS AND
MAKE SENSE OUT OF THEM, RIGHT?
SO WHICH LAYERS OF WHICH GROUPS
MAY BE ARE MAKING SUFFICIENT
CONNECTIONS AND WHERE ARE THERE
NODES THAT ARE NOT MAKING
CONNECTIONS AND HOW CAN WE USE
THESE TYPES OF VISUALIZATION
TECHNIQUES BETWEEN THE WORKING
GROUPS TO IDENTIFY THE GAPS OR
LATENT IDEAS MIGHT BE LURKING
WITHIN ALL OF THIS CONTENT.
SO WITH THAT, THAT'S REALLY THE
REPORT FROM ME.
WE LOOK FORWARD TO GOING NOW TO
MAKING THIS AN ACADEMIC PRODUCT
BUT REALLY THAT'S A SLICE IN
TIME WHEN THAT PAPER COMES OUT.
THE REAL KEY I THINK IS MAKING
THIS AN ONANYTHING UP TO DATE
LIVING DOCUMENT THAT CAN BE USED
ON A WEBSITE SO THANK YOU VERY
MUCH.
>> THANK YOU VERY MUCH TO ALL OF
OUR SCIENTIFIC WORKING GROUP
CHAIRING FOR YOUR UPDATES THIS
MORNING.
I LOVED GREG YOUR NETWORK
VISUALIZATION MAP AT THE END,
I'M ACTUALLY CURIOUS AS TO
WHETHER YOU IDENTIFIED ANY GAPS
YET OR WHETHER THAT'S JUST A
PROOF OF CONCEPT?
YOU'RE MUTED AGAIN, SORRY,
UNMUTE, PLEASE.
NYOU THINK YOU WOULD KNOW BY
NOW, RIGHT?
THAT'S JUST A DREAM AT THIS
STAGE LOOKING FORWARD TO
ACTUALLY TACKLING THAT WITH
EVERYBODY THERE.
>> PERFECT, THERE THIS IS A
DPRAIT EXAMPLE OF HOW THE
TRANSNETWORK GROUPS ARE WORKING
WITH 1 ANOTHER TO REALIZE THESE
VERY, YOU KNOW COMPLEX AND WELL
REALIZED PRODUCTS SO WE
APPRECIATE ALL OF YOUR UPDATES
THIS MORNING.
IT'S NOW MY HONOR TO INTRODUCE
OUR KEY NOTE SPEAKER FOR THIS
MEETING DR. VALERIA VAZQUEZ AND
IS A PROFESSOR AT UT HEALTH AND
SHE'S STUDYING THE ION CHANNELS
RESPONSIBLE FOR PAIN AND
PROPRIMATES O ACCEPTION, SHE
RECEIVED HER Ph.D. IN UVA, AND
IS ITED SENSITIVE CHANNELS IN
E.COLI, SHE COMPLETED POST
DOCTORAL TRAINING AT STANFORD
UNIVERSITY WHERE SHE STUDIED HOW
PHOSPHOLIPIDS ARE ESSENTIAL FOR
NORMAL TOUCH SENSATION, WE ARE
EXTREMELY PLEASED TO HAVE
DR. VASQUEZ PRESENT TODAY ON
FINE TUNING MECHANO SENSITIVE
ION CHANNELS EMPLOY.
FROM BASIC SCIENCE TO
TRANSLATIONAL RESEARCH.
>> GOOD MORNING EVERYONE EMPLOY
THANK YOU VERY MUCH FOR THIS
OPPORTUNITY, IT'S VERY
REMARKABLE WHAT YOU GUYS HAVE
BEEN DOING FOR THE LAST COUPLE
OF YEARS AND I AM VERY HONORED
TO BE INVITED TO THIS PART OF
YOUR MEETING ESPECIALLY BECAUSE
I'M CONSIDER A BASIC SCIENTIST
AND ALSO I WANT TO TELL YOU THAT
I DIDN'T RECEIVE THE MEMO ABOUT
THE TERMINOLOGY, SO PARDON MY
LACK OF PRIOR TERMINOLOGY.
SO AS THE TITLE SAYS STUDYING
ION CHANNELS BY FATTY ACIDS,
FATTY ACIDS ARE THE BUILDING
BLOCKS OF THE PLASMA MEMBRANE,
SO BEAR WITH ME, OH THIS IS NOT
WORKING.
OKAY.
THIS IS NOT WORKING EITHER,
OKAY.
IS IT?
OH, PERFECT.
OKAY.
GREAT.
SO WE'RE CURRENTLY WORKING WITH
NONSELECTIVE CAT ION CHANNELS
LIKE PIEZ1 AND PIEZ 2, THAT
ALLOW THE CALCIUM INSIDE
NONEXCITABLE CELLS AS WELL, WE
ALSO WORK WITH MECHANO SENSITIVE
ION CHANNELS FROM BACTERIA IN
WHICH WE TRY TO TEST HYPOTHESIS
THAT ARE RELATED TO THE MEMBRANE
AND WE ALSO WORK WITH MECHANO
SENSITIVE ION CHANNELS IN
C.ELEGANS.
AND ULTIMATELY NOW OR LATELY WE
HAVE BEEN TRYING TO DO MORE
TRANSLATIONAL WORK, TRYING TO
IDENTIFY HOW WE CAN IMPROVE OR
AMELIORATE PAIN OR PIEZ02
DISORDERS.
SO MY TALK WILL CONSIST OF 4
PARTS I WILL TALK ABOUT MECHANO
SENSITIVE ION CHANNELS IN WARM,
AND INTRODUCING YOU TO THE
TOPIC.
HOW MEMBRANE COMCISION CAN BE
MODULATED TO MECHAN COPROPERTIES
AND IN TURN MORE MECHANO
SENSITIVE ION CHANNELS, DESCRIBE
HOW WE FOUND A TOOL KIT OF FATTY
ASITS TO MODULATE FUNCTION OF
PIEZO1 FUNCTION AND PIEZO
FUNCTION, AND A COUPLE EMPLOY
ANDS OF HOW WE ARE USING FATTY
ACIDS TO AMELIORATE PIEZ02
RELATED DISORDERS.
SO I FORGOT, THIS IS NEW, I HAVE
TO DISCLOSE I HAVE A CONFLICT OF
INTEREST BECAUSE MY LAB HAS
FILED FOR A PATENT A COUPLE
YEARS AGO RELATED TO THE USE OF
[INDISCERNIBLE] TO AMELIORATE
PAIN.
SO MECHANO SENSATION IS VERY OLD
IN THE EVOLUTIONARY SENSE.
WHEN YOU--IF YOU IMAGINE HAVING
A MEMBRANE VESICLE AND THERE IS
A CHANGE OF [INDISCERNIBLE], IF
YOU ONLY HAVE THAT MEMBRANE, THE
MEMBRANE WILL BURST WHEN THERE
IS A CHANGE IN [INDISCERNIBLE].
BUT IF YOU HAVE A MECHANO
SENSITIVE ION CHANNEL SITTING AT
THAT MEMBRANE, YOU HAVE THE
OPPORTUNITY OF HAVING
THAT--AVOIDING RUPTURE OF THE
MEMBRANE BECAUSE THE ION CHANNEL
COULD OPEN EMPLOY SO I WAS VERY
LUCKY BECAUSE FOR MY GRADUATE
STUDIES, I STUDIED 1 OF THOSE
CHANNELS THAT SEE IN THEINER
MEMBRANE OF [INDISCERNIBLE] A
GRAM NEGATIVE BACTERIA IN
RESTING CONDITIONS, THIS ION
CHANNEL IS CLOSED BUT THERE IS A
SUDDEN CHANGE IN
[INDISCERNIBLE], THEN THE
MEMBRANE OF THIS E.COLI WILL
SENSE THE PRESSURE AND IT'S
GOING TO BECOME THINNER, THE
INNER MEMBRANE AND THE
[INDISCERNIBLE] WILL EVOKE A
CONFIRMATIONAL CHANGE IN THE
MECHANO SENSITIVE ION CHANNEL.
BY DOING THIS, THIS ION CHANNEL
CAN CONDUCT ION CHANNEL--SORRY
IONS AND SOLIDS AND IS GOING TO
CALIBRATE THE LOCAL ENVIRONMENT
AND THIS WILL ALLOW THE BACTERIA
TO SURVIVE.
SO THIS PRESENTATION NOT ONLY
FOLLOWS THE FAKE DENDRITIC CELL
ROW GRAM BUT ALSO FOLLOWS MY
CAREER MORE OR LESS BECAUSE THEN
FOR MY POST DOCTORAL OF--BEFORE
MOVING TO MY POST DOCTORAL
RESEARCH PROJECT I WAS--REALIZED
THAT BY STUDYING MECHANO
SENSITIVE ION CHANNELS IN
BACTERIA, WHEN YOU DO
[INDISCERNIBLE]
ELECTROPHYSIOLOGY EXPERIMENTS
CAN YOU OPEN THESE CHANYS BY
APPLYING NEG5 PRESSURE TO THE
PATCH PIPETTE.
BY DOING THIS, YOU GO FROM THE
CLOSE CONFIRMATION TO THE OPEN
CONFIRMATION AND THEN THE
CHANNEL ENACT VAIOF THES.
BUT IF YOU HAVE THESE
ACCOUNTERIAL MECHANO SENSITIVE
ION CHANNEL IN THE PIPETTE YOU
SHOULD THE SAME CONFIGURURATION
BUT INSTEAD OF APPLYING NEG5
PRESSURE, NOW YOU ADD A
DETERGENT LIKE MOLECULE LIKE
E.COLI, THESE DETERGENT MOLECULE
WILL INSERT INTO THE MEMBRANE
AND WILL CHANGE THE MECHANO
PROPERTIES AND INSTEAD OF
WALKING INACTIVATION, NOW THE
CHANNELS BECOME MORE AND MORE
OPEN UNTIL THE SEAL BREAKS.
INDICATING THAT THE SAME CHANNEL
CAN SENSE DIFFERENT
PERTURBATIONS DONE TO THE
MEMBRANE.
SO I HAD IN IDEA THEN THAT I
WANT TO TEST ALL THE MECHANO
SENSITIVE ICON CHANNELS IN MORE
COMPLEX ORGANISMS LIKE SIMILAR
TO C.ELEGANNINGS, SO FOR THAT I
JOINED THE LAB OF
[INDISCERNIBLE] AS ALEX SAID AND
I USED ALL THE MEMBRANE--I
STUDIED HOW THE MEMBRANE
MODULATES THE MECHANO SENSITIVE
ION CHANYS THAT ARE RESPONSIBLE
FOR TOUCH SENSATION IN WORMS.
LET ME JUST SHOW YOU AGAIN.
SO UNLIKE WHAT WE DO,--I CANNOT
RUN THIS VIDEO AGAIN, SORRY.
SO PAY ATTENTION BECAUSE IT'S
GOING TO BE VERY FAST.
NO, NOT TODAY.
IN ANY CASE.
WELL, SO IN C.ELEGANS TO EVOKE
RESPONSES FROM THESE ANIMALS WE
USED OUR EYE LASHES ANY IF YOU
TOUCH THE HEAD OR TAIL OF THE
ANIMAL, THE ANIMAL WILL
CERTAINLY--CERTAINLY VOAK AN
AVOIDANCE RESPONSE.
THESE AS YOU CAN SEE FROM THE
MANAGENITUDE OF THE NUMBERS IS
VERY SMALL, SO THE SENSITIVITY
OF THE ANIMAL SYSTEM QUITE HIGH
IN COMPARISON TO MAMMALS AND
HUMANS.
SO WHEN I YOINED MIRIAM'S LAB,
BACK IN THE DAY, THE MECHANO
RECEPTOR GENES THAT WERE
RESPONSIBLE FOR THESE DEHAD A
FEWIAL RESPONSE WERE ALREADY
RECOGNIZED AND I'M JUST
HIGHLIGHTING HERE A FEW THAT ARE
MEMBRANE PROTEINS PART OF
MECHANO RECEPTOR CHANNEL COMPLEX
THAT ALLOWS AFTER A MECHANICAL
STIMULATION, THESE CAT IONS WILL
FLOW IN THE NEURONS AND WILL
EVOKE THIS DEHAD A FEWIAL
PRESPONSE QUANTIFIED HERE IN THE
[INDISCERNIBLE] PLOT.
ANIMALS LACKING THE POOR UNIT
HAVE A DRASTIC DEFICIENCY IN
TOUCH RESPONSE.
SO WHAT I DID WHEN I YOINED THE
LAB, WAS PLAY WITH MUTANTS THAT
WERE LACKING THE [INDISCERNIBLE]
FATTY ACIDS BECAUSE OF MY
BACKGROUND IN BIOPHYSICS I KNEW
THAT POLYUNSATURATED FATTY ACIDS
WILL HAVE THE PROPERTIES FOR THE
PLASMA MEMBRANE AND WHAT I FOUND
WITH MIRAKA WRAM IS THAT ANIMALS
THAT LACK [INDISCERNIBLE] THEY
BECOME DEFICIENT IN DOSE
RESPONSE, [INDISCERNIBLE] IN THE
ION CHANNEL WITH DRAMATIC IN
COMPARISON TO THE WILD-TYPE.
THEN WE DECIDED TO FIND OUT THE
MECHANISM FOR THESE AND WE
MEASURE THE MECHANICAL
PROPERTIES OF THE TOUCH RESEARCH
IN THE PLASMA MEMBRANES BY USING
ATOMIC FORCE MICROSCOPY AND WE
DETERMINED THAT THOSE NEURONS
THAT LACK ARCHIINDONIC SPARKS
ACID ARE MORE WITH THE FATTY
ACID TOOLS.
SO I'M SUMMARIZING HERE THAT TO
HAVE PROPER TOUCH SENSITIVITY,
YOU HAVE TO HAVE A BALANCE OF
POLYUNSATURATED FATTY ACIDS IN
C-ELEGANS, I HOPE YOU CAN
APPRECIATE BY THIS SHORT
INTRODUCTION THAT THE SENSITIVE
ION CHANNELS I HAVE BEEN TALKING
ABOUT, THE 1 IN BACTERIA AND THE
1 IN C.ELEGANS ARE VERY
DIFFERENT.
OKAY?
SO THIS IS A VERY PECULIAR
FAMILY OF ION CHANNELS BECAUSE
THEY DON'T SHARE SEQUENCE, THEY
DON'T SHARE TOPOLOGY, THEY DON'T
SHARE ORGANIZATION.
I'M ONLY SHOWING 4 EXAMPLES HERE
OF 4 DIFFERENT MEMBERS OF THE
FAMILY.
SO THEY WANT IN BACTERIA FOR
EXAMPLE, [INDISCERNIBLE], THEY
ASSEMBLE A PENTAMEROR A
HETEROGENEOUSA MER, THEY WANT TO
SEE PLANS FOR EXAMPLE, THEY
ASSEMBLE AS DIMERS AND THE
PIEZO1 OR 2 ARE DIMERS AND THEY
HAVE 38 TRANSMEMBRANE SEGMENTS.
SO YOU CAN IMAGINE STUDYING
THESE CHANNELS FROM THE
BIOPHYSICAL POINT OF VIEW IS A
NIGHTMARE BECAUSE THEY DON'T
HAVE ANYTHING IN COMMON, MORE
THAN THEIR ABILITY TO SENSE
MEMBRANE TENSION.
SO IF YOU AS I SHOW IN THE
EXPERIMENT, A FEW SLIDES,
MODULATE OR INCREASE THE LATERAL
TENSION OF THESE MEMBRANES WHERE
THESE MECHANO SENSITIVE ION
CHANNELS SIT, YOU INCREASE THE
OPEN PROBABILITY AND NOW HAVE
YOU MORE CURRENT PATTERN TO THE
[INDISCERNIBLE] OF THESE
CHANNELS.
SO IF YOU HAVE A BIOLOGICAL
MEMBRANE THAT IS DESCRIBED BY
THIS PRESSURE PROFILE, YOU HAVE
DIFFERENT LIPID COMPONENTS LIKE
FATTY ACIDS, HEAD GROUPS,
CHOLESTEROL THAT RISE TO THESE
CARTOONISH EXPRESSION PROFILE
THAT GIVES THE CHANNELS OR THESE
MECHANO SENSITIVE ION CHANNELS
IN THE CLOSEST STATE.
SO CAN YOU IMAGINE THAT ANY
PERTURBATION OF THE MOTION OF
THE PLASMA MEMBRANE CAN INVOKE
CHANGES IN THE OPEN PROBABILITY
OF THESE MECHANO SENSITIVE ION
CHANNELS INCLUDING MODULATION AS
WE CAN IMAGINE WITH TOUCH, AND
INTORPERATION WITH
[INDISCERNIBLE] MOLECULES, ET
CETERA.
SO JUST LIKE IN WORMS, WE HUMAN
ANDS MAMMALS WE NEED TO EAT
FATTY ACID SO WE ARE WHAT WE EAT
AND WE INCORPORATE THIS AND
CLEAR MAZ MA IN NOT ONLY PLASMA
MEMBRANES BUT CELL MEMBRANES BY
USING THE [INDISCERNIBLE] CYCLE
WHICH HAD SPREAD MANY YEARS AGO.
SO CAN YOU APPRECIATE HERE THAT
FATTY ACIDS ARE A POWERFUL
[INDISCERNIBLE] CHAINS COMPARED
WITH A GROUP WHEN THEY ARE
TERRIFIED THEY JOIN THE LINEUP
EDUCATIONALS AND THEY BOTTOM
PART OF PLASMA MEMBRANE.
SO, YOU CAN IMAGINE THAT IF WE
MODIFY THE MEMBRANE COMCISION,
WE CAN MODEL LATE THE SENSITIVE
ION CHANNELS IN CHARGE.
SO WHEN I STARTED MY LAB, I
DECIDED TO STUDY A MAMMALIAN
SPECIFIC ION CHANNEL,
APPROXIMATE SPECIFICALLY PIEZO 1
AND 2.
THESE CHANNELS ARE IMPORTANT FOR
SENSING MOLARITY, VOLUME, TOUCH,
PROPRIMATES O ACCEPTION AND
CHALLENGE.
I PUT CHOSE THIS PICTURE HERE
BECAUSE IT DESCRIBES VERY WELL
WHAT WE STUDY WHICH IS A SENSE
OF TOUCH AND ALSO PROPRIMATES O
ACCEPTION OF COURSE YOU ALLOW US
TO SENSE WHERE OUR LIMBS ARE @
ANY TIME.
SO IN THE LAB, TO MODULATE
MEMBRANE COMCISION WHAT WE DO IS
EITHER DISSECT OR TAKE PRIMARY
CELLS IN THIS CARTOON, PRIMARY
NEURONS FROM MICE OR WE TAKE
PRIMARY NEUROONS FROM THE
ENDOTHELIAL CELLS FROM THE
ARTERIES AND WE INCUBATE
OVERNIGHT WITH PARTICULAR FATTY
ACID TO ENRICH THAT FATTY ACID
IN THE PLASMA MEMBRANE.
WE ALSO HAVE OPTIMIZED AN
APPROACH IN WHICH WE FEED
ANIMALS WITH A FATTY ACID
ENRICHED DIET FOR--LET'S SAY FOR
5-8 WEEK ANDS WE DISSECTED
NEURONS AND MADE SURE HOW THESE
CHANNELS BEHAVIOR AND LITELY
WE'VE BEEN DOING SOMETHING MORE
REEL KEEPSAKES VAPT TO YOU
PERHAPS THAT IS USED IN THIS
AREA OF FATTY ACIDS TO ENRICH
LOTIONS AND TESTED IN MICE TO A
CHANGE THEIR RESPONSES TO
MECHANICAL INDENTATION.
SO MOST OF THE SLIDES I WILL
SHOW YOU NOW HAVE THIS PROTOCOL
IN THE RESULT.
SO WHAT WE REGULARLY DO IS USE
AN ATTACHED PIPETTE AND WE DO
PHYSIOLOGY IN THE WHOLE CELL
[INDISCERNIBLE] AT THE TOP.
WE HAVE A MECHANICAL PROBE TO
LOOK AT MICROMETERS AND BY DOING
THIS WE CAN AT LEAST SEE ION
CHANNEL CURRENTS BUT AS YOU CAN
SEE PIEZO1 AND 2 HAVE MORE OR
LESS THE SAME PROFILE, THEY
CLOSE AND THEY OPEN AND THEY
ENACTIVATE.
EVERY TIME THEY OPEN, THEY PASS
CAT ION CHANNELS AND IF THEY'RE
EXPRESSED IN NEURONS, THIS IS
GOING TO EXCITE THE NEURONS AND
IT WILL ACTION POTENTIALS.
SO THE FIRST PART OF WHAT WE DID
IN MY LAB A FEW YEARS AGO WAS TO
THE USE TO ENJOY CELLS, THE
NEUROBLASTOMA CELL LINE, WHERE
IT WAS DISCOVERED BY THE
LABORATORY FOR THE
[INDISCERNIBLE].
THE REASON WHY WE USE THIS CELL
CULTURE, IS BECAUSE THE
ENDOGENOUS EXPRESS PIEZO 1, SO
IF WE WANT TO CHANGE THE FATTY
ACID COMPOSITION, WE DON'T HAVE
TO PUT A PLAY WITH THE TRANSIENT
EXPRESS A-CELLS.
SO, I TOOK--I SEARCH OR ACTUALLY
WE DETERMINED THE FATTY ACID OF
THE NEURO NEUROBLASTOMA CELL LID
THE REASON I DID THIS WAS
BECAUSE I WANTED TO SEE WHICH
ACIDS WERE OF LOW FATTY CONTENT
SO WE COULD ENRICH THEM.
HERE I'M SHOWING YOU A FEW.
I HOPE YOU NOTICE THEY ARE
SATURATED FATTY ACIDS BECAUSE
THEY DON'T HAVE [INDISCERNIBLE]
POINTS THAT'S WHAT THE
[INDISCERNIBLE] STANDS FOR AND
THE NUMBER FOLLOWING THE C16,
THOSE ARE THE NUMBERS OF
[INDISCERNIBLE] IN THE CHAIN.
AS YOU CAN SEE, I APPRECIATE
HERE THESE ARE VERY LOW, THE
SEPARATED FATTY ACIDS, I'M
HIGHLIGHTS HERE THAT IS CALLED
[INDISCERNIBLE] OR
[INDISCERNIBLE] ACID BECAUSE
MARGORIE [INDISCERNIBLE] WAS
USED TO MAKE MARGARINE BACK IN
THE 19th CENTURY SO I CHOSE
THIS 1 BECAUSE I ASSUME IF IT
DIDN'T KILL PEOPLE IN THE 19th
CENTURY THEN IT SHOULDN'T KILL
OUR CELLS IN THE PLATE.
SO WE ENRICH OUR CELL CULTURE,
INTO A CELL CULTURE WITH MAR
JORRINE ACID OVERNIGHT USING
CONITRATIONS, I ALSO FORGOT TO
MENTION THAT A GROUP, A COUPLE
OF YEARS BEFORE WE WORK WITH
THIS PHARMACOKINETICS ANDORRINE
ACID, THAT THE ENRICHED
MAJORRINE ACID WILL INCREASE
SYNDROMES IN DORPHINS AND DUCKS.
SO HERE ARE THE RESULTS IF WE
INCREASE PHARMACOKINETICS
ANDARRIC ACID OVERNIGHT IN THESE
CELLS WE INHIBIT PIEZO1 FUNCTION
AND THESE CAN BE SUMMARIZED
REALLY WELL HERE IN THE DOSE
RESPONSE PROFILE, THE MORE
MARGARIC ACID, THE LESS PIEZO 1
YOU HAVE IN THOSE CURRENTS.
AT THE TIME WE DIDN'T KNOW IF
THIS WAS DUE TO GENE EXPRESSION
OR TRAFFICKING, SO TO ANSWER
THAT, WE USE AGONIST OR
SENSITIZER OF PIEZO1 CALLED
UDAILY BASIS 1, AT LEAST IN THE
[INDISCERNIBLE] AND WHAT WE
DEMONSTRATED WITH THESE IS THAT
EVEN IN THE HIGH PRESENCE OF
MARGARIC ACID IN THOSE MEMBRANES
BY 1, WE COULD SEE ALL THE
CHANNELS IN THE PLASMA MEMBRANE,
INDICATING WE WERE INHIBITING
FUNCTION BUT NOT TRAFFICKING OUR
EXPRESSION.
I ALSO LIKE TO SHOW NEGATIVE
RESULTS SO NO FATTY ACIDS DO
SOMETHING, SO WE ALSO ENRICH
MEMBRANES WITH FATTY ACID CALL
PENTINE REGIMEN OMATIC CARBON,
AND YOU CAN SEE THERE'S NO
DIFFERENT BETWEEN THE CONTROLS
AND THE CELLS WITH THE PANT O
TEMMIC ACID, EVEN THOUGH WE WERE
ABLE TO SEE AN INCREASE IN THE
MASS SPEC., SO THIS INDICATES
AND ACTUALLY I FORGOT TO INCLUDE
HERE, WE ALSO HAVE POSITIVE DATA
FOR A FATTY ACIDS ARE LONGER
THAN 17 INDICATING THERE IS A
[INDISCERNIBLE] FOR THE AMOUNT
OF CARBONS NEEDED TO CHANGE THE
MECHANICAL PROPERTIES OF THE
PLASMA MEMBRANES AT LEAST IN
NEEZ CELLS.
SO WE USE ATOMIC MICROSCOPY JUST
LIKE IN WORMS BUT THIS TIME WE
DID IT IN N2A CELLS IN THE SAME
WE WE DO THE [INDISCERNIBLE]
PHYSIOLOGY AND WE DETERMINE THAT
THOSE CELLS N2A CELLS THAT WERE
ENRICHED--SORRY, I'M STRUGGLING
WITH MARGARIC ACID HAD A LARGER
STIFFNESS OR CONTROL, THE
CONTROL OF THE PERCENT OF THE
BLACK LINE.
ALSO I'M GOING TO JUMP AHEAD AND
GIVE YOU--I'M GOING TO SKIP
AHEAD AND TELL YOU THAT IF WE
HAVE MEMBRANE [INDISCERNIBLE]
MEMBRANES AND RICH
POLYUNSATURATED FATTY ACIDS NOW
WE HAVE LESS [INDISCERNIBLE]
FORCERS, THOSE MEMBRANES ARE
LEAD READ.
SO LUCKY FOR US POLYSUN
SATURATED FATTY,A SIDS ARE
ALMOST ALWAYS A LOW CONTENT IN
EVERY CELL, SO IT'S VERY EASY TO
ENRICH THEM AND THAT'S 1 OF THE
REASONS WHY WE HAVE TO GIVE
[INDISCERNIBLE] ACID TO INCREASE
THIS POLY[INDISCERNIBLE] OR
POLYUNSATURATED FAT ACID IN OUR
TISSUES.
SO AGAIN, THEY ARE VERY LOW AND
WE TOOK ADVANTAGE OF THESE AND
WE SET UP THE EXPERIMENT VERY
SIMILAR TO WHAT WE DID WITH
MARGARIC ACID SO HERE I'M
SHOWING THE CONTROL IN GREEN AS
A REFERENCE AND MARGARIC ACID TO
BE THE EXTREME VISION OF PIEZO1.
ON THIS 1 THE CURRENT DENSITY SO
WE CAN DETERMINE WHETHER THE
CURRENTS INCREASE OR DECREASE,
HERE WE'RE MEASURING TAU OF
ACTIVATION, HOW LONG DOES IT
TAKE FOR THESE CHANNELS TO BE
PRESENCE IN THE MECHANISTIC
DEVICE, SO WE EXPECT THAT IF WE
REACH MEMBERS IN THE BOTH, THE 1
THAT MAKE THE MEMBRANES LESS
READ WE WOULD HAVE MORE FUNCTION
BUT THIS IS NOT WHAT HAPPENED.
WHAT HAPPENED IS IF WE INCREASE
THE PANTANOIC ACID WE DO NOT
CHANGE THE CURRENT PLASMA
MEMBRANES ABOUT YOU WE ENHANCE
INACTIVATION.
THE CHANNELS BECOME LESS
FUNCTIONAL AND THIS IS VERY
REPRODUCIBLE.
IF WE USE INSTEAD THE FATTY
ACID, OMEGA 3 FATTY ACID THAT
HAVE 22 CARBONS BUT THEY DO NOT
CHANGE FOR NOW THE CHANNEL IT
STAYS LONGER, IT STAYS OPEN
LONGER.
AND SURPRISINGLY THE ACID WHICH
IS INNATE IN CARBON
[INDISCERNIBLE] AFFECTS BOTH,
THE AMOUNT OF CURRENT IN THE
PLASMA MEMBRANES OF PIEZO 1 AND
SLOWS DOWN INACTIVATION.
SO YOU CAN APPRECIATE THAT WE
HAVE A REALLY NICE, I HOPE TO
SAY REALLY NICE, TOOL KIT FOR
THE FUNCTION OF THESE MECHANO
SENSITIVE ION CHANNEL.
WE KNEW THIS WAS NECESSARY TO
INCUBATE THESE CELLS OVERNIGHT
BUT WE HAVE, YOU KNOW REVIEWERS
AND WE WONDER OURSELVES IF THIS
WAS A DIRECT INTERACTION, MAYBE
THIS FATTY ACIDS ARE BINDING TO
PIEZO 1 AND TO EXPLORE THAT, WE
PERFORM THE SAME TYPE OF
EXPERIMENTS BUT INSTEAD OF
INCUBATING OVERNIGHT, WE PROFUSE
THE FATTY ACIDS FOR A COUPLE OF
MINUTES AND MEASURE THE
MECHANICAL RESPONSE AGAIN.
BY DOING THIS FOR EXAMPLE WITH
MARGARIC ACID, WE DID NOT SEE
ANY CHANGES IN CURRENT O
INACTIVATION EMPLOY WE ACTUALLY
HAD TO INCLUDE A NEGATIVE,
INHIBITOR OF PIEZO1, BUT
NEVERTHELESS ALLOWED US TO
DETERMINE THAT THE PROFUSION WAS
WORKING.
THIS IS SUMMARIZING A PLOT.
AND WHAT WE FOUND IS THAT NONE
OF THE FATTY ACIDS UNDER THESE
CONDITIONS WERE ABLE TO CHANGE
PIEZO FUNCTION INDICATING THAT
PLASMA MEMBRANE REMODELING WHAT
MODULATES A FUNCTION OF PIEZO 1.
SO IN IT ONLY RAISED FROM THE
MECHAN O PROPERTIES OF THE
PLASMA MEMBRANE, WE HYPOTHESIZE
THAT OTHER MECHANO SENSITIVE ION
CHANNELS THAT DO NOT LOOK ALIKE
AT THE BEGINNING SHOULD HAVE
SIMILAR RESPONSES LIKE PIEZO 1.
FOR THESE EXPERIMENTS WE USE THE
CHANNEL OF LARGE CONDUCT ANT
MSCL THAT IS IN E.COLI AS YOU
CAN SEE FROM THESE PARTS IS VERY
DIFFERENT.
SO WE TRANSFECT INTO A SOURCE
THAT NOW HAVE INCREASED
[INDISCERNIBLE] KNOCK OUT PIEZO1
AND WHAT WE DETERMINE IS THAT IF
WE INCUBATE MARGIARIC ACID
OVERNIGHT NOT ONLY WE DIMINISH
AMOUNT OF CURRENTS WITH MSCL BUT
ALSO NOW WE REQUIRE MORE MECHAN
O SENSITIVE ACID.
IF WE USE MSCL IN CELLS THAT
HAVE ACID OVER NIGHT, NOW WE
HAVE LARGER CURRENTS AND WE
REQUIRE LESS MECHANICAL STIMULI
TO OPEN THESE CHANNELS.
SO OUR RESULTS SO FAR CONFIRM
THAT THE FATTY ACIDS MOTTIFY
PIEZO1 BY MODIFYING PROPERTIES
OF THE PLASMA MEMBRANE AND
DIRECTLY TO THE [INDISCERNIBLE].
SO NOW WE HAD A TOOL KIT OF
FATTY ACIDS THAT WILL ALLOW US
TO MODIFY THE FUNCTION OF
PIEZO1, WE CAN HAVE MORE
MARGARIC ACID AND PLAY WITH THAT
TO INHIBIT CHANNEL FUNCTION OR
WE CAN USE THE DHA OR
[INDISCERNIBLE] ACID TO ENHANCE
CHANNEL FUNCTION.
THIS IS FOR PIEZO1.
WITH PIEZO2, WITH MANY PAPERS
BUT I DON'T HAVE TIME TO DISCUSS
BUT IT'S A CHANNEL YOU CARE
ABOUT BECAUSE IT IS
IMPORTANT--OOPS, OKAY, IT IS
IMPORTANT FOR WOUND DEVELOPMENT
FOR PROPRIMATES O ACCEPTION,
TOUCH, MECHANICAL DEEMIA,
EXPRESS INDEED SENSORY NEURONS
THAT INVIGORATE OUR SKIN, ALSO
INTERNAL ORGANS, CELLS, IT'S
IMPORTANT FOR [INDISCERNIBLE]
RIGHT?
SO I WILL SHOW YOU A COUPLE OF
EXAMPLES WHERE IT GOES TO
TRANSLATION AND HOW WE CAN USE
THESE FATTY ACIDS TO AMELIOR 8
THESE PIEZO 2 DISORDERS.
SO AS I SAID PIEZO2 IS EXPRESSED
IN SENSORY NEURONS IN THIS
PARTICULAR EXAMPLE, I'M
HIGHLIGHTING THAT IS EXPRESSED
IN PROPRIMATES O SEPTORSOR
NEURONS WHERE IT MODULATES
SUSCEPTIBILITY OR CONTROLS
MUSCLE--I FORGOT CONTRACTION
ALSO IMPORTANT FOR MUSK LO
SKELETAL DEVELOPMENT.
SO [INDISCERNIBLE] SEVERAL YEARS
AGO FOUND A FAMILY HA HAD A
PIEZO2 GAIN OF FUNCTION MUTATION
THAT HAD DISTAL [INDISCERNIBLE]
TYPE 5.
SO THIS GAIN OF FUNCTION OF
PIEZO2, THE CORRELATION WAS VERY
SIGNIFICANT AND THEY PROPOSE
FROM HIS LAB THAT THIS GAIN OF
FUNCTION OF PIEZO2 CAUSED THIS
PHENOTYPE.
A FEW YEARS AGO, WE COLLABORATED
WITH [INDISCERNIBLE] BECAUSE
THEY MADE A MOUSE MODEL OF
PIEZO2 GAIN OF FUNCTION IN WHICH
THEY DETERMINE THAT BY
EXPRESSING THIS GAIN OF FUNCTION
MUTATION IN SENSORY NEURONS OR
PROPRIMATES O SEPTORSOR NEURONS
THEY WERE ABLE TO RECAPITULATE
THOSE PHENOTYPES FOUND IN THE
HUMAN FAMILY WITH THE
[INDISCERNIBLE].
THEY ALSO DETERMINED THAT IT'S
VERY IMPORTANT WHEN IN TIME YOU
EXPRESS GAIN OF FUNCTION
MUTATION SO IF THEY EXPRESS THE
PIEZO2 FUNCTION MUTATION DURING
ADULTHOOD, THEN THOSE ANIMALS
ARE NORMAL JUST LIKE THE
WILD-TYPE [INDISCERNIBLE].
SO THERE IS A VERY NARROW WINDOW
DURING DEVELOPMENTAL STAGE THAT
GAIN OF FUNCTION MUTATION CAUSES
THE PHENOTYPE ASSOCIATE WIDE OUR
HYPOTHESIS.
THOSE PHENOTYPES ARE SHOWN HERE
SO THIS THERE IS A VERY DRAMATIC
CHANGE IN THE ANGLES BETWEEN THE
BONES, THEY GO FROM TO RIGHT
ANGLES, THEY ARE SHORTER, THE
ANIMALS BEHAVIOR DIFFERENTLY,
THEY SPEND LESS TIME ACROSSING
THE HANGING WIRE AND THEY ALSO
SPEND LESS TIME WHEN THEY--WHEN
SHANNON AND COLLABORATORS
[INDISCERNIBLE] THE ANIMALS WITH
THE SCREEN TEST.
TURNS OUT AT THE SAME TIME WITH
THE GAIN OF FUNCTION MUTATION
THEY REPORTED A FEW YEARS BACK,
THEY REPORTED THIS AS WELL, OF
COURSE, THAT THE DECEASED MIGHT
BE CAUSED BECAUSE ONLY LIKE THE
WILD-TYPE CHANNEL, THE GAIN OF
FUNCTION MUTATIONS THAT
[INDISCERNIBLE] NOW THEY TAKE
LONGER TO ENACTIVATE.
THIS MEANS THERE IS MORE CALCIUM
GOING INTO THE CELL, RIGHT, INTO
THE NEURONS, ACTUALLY THE MUSEUM
AT THAT POINT OF THE PAPER IS
THIS 1, I JUST ADDED THIS
BECAUSE I FIND IT REMARKABLE
THAT MOW MATTER WHERE THE
MUTATIONS ARE, THEY MAKE THIS
INACTIVATION TO GO SLOWER, BUT
WHAT WE FOUND THAT I THINK WAS
VERY IMPORTANT IS THAT IF WE
INCUBATE THOSE CELLS, EXPRESSING
THE PIEZO2 GAIN OF FUNCTION
MUTATION, AND MEMBRANES THAT ARE
REACHED WITHIN PEN TANOIC,A SID
WE CAN MAKE THESE MUTANT
CHANNELS BEHAVE LIKE
WILD-TYPE'VE TYPE AND THIS IS
SUMMARIZED IN THE WILD-TYPE PLOT
AND YOU CAN APPRECIATE THE GREEN
AND THE [INDISCERNIBLE] BECOME
VERY FAST WHEN THERE'S
[INDISCERNIBLE] PENTINE
REGIMENANOIC ACID IN THE
MEMBRANE.
SO AT THE TIME WE STARTED
COLLABBUATION WITH DAMON AND HIS
LAB MEMBERS SO THEY START
FEEDING PANT AN OHIC ACID
FEEDING THE MICE AND MATING AND
PREGNANT AND 5 WEEKS AFTER
RECEIVING THIS DIET, THEY
PERFORMED BEHAVIORIAL ASSAYS AND
WE ALSO LOOKED AT THE MIEWRONS
THAT HAD MORE ACID IN THE PLEM
BRAINS WHICH IS THE CASE.
--MEMBRANES WHICH IS THE CASE.
WE ALSO USED A HIGH FATTY DIET
TO HAVE PROPER CONTROL AND WHAT
THEY DETERMINED WITH OUR DIET IS
THAT OUR ANIMALS ARE NOT LIKE
WILD-TYPE BUT THEY'RE BETTER
THAN THEY GAIN OF FUNCTION
MUTATION EMPLOY SO BY FEEDING A
DIET ENRICHED IN PANTANOIC ACID,
NOW THE ANIMALS ARE MORE USE CAN
LESS RIGHT, NOW THE ANIMALS
SPEND MORE TIME ON THE WIRE AND
THEY SPEND MORE TIME DURING THE
SCREEN TEST AND NEEDLESS TO SAY,
THESE ANIMALS WERE IN LINE TO
TREATMENT.
SO NOW THAT I IMPART THAT TO YOU
DIRECTLY, I HOPE, SO I SHOW THAT
YOU PIEZOWAS INHIBITED BY
MARGARIC ACID BUT WE ALSO FOUND
THAT PIEZO2 ENDORSE GANGLION
NEURONS FROM MICE, RATS AND
HUMANS ARE INHIBITED BY THE
MARGARIC ACID, AND YOU CAN SEE
THAT DATA HERE, CAN YOU
APPRECIATE THAT THE GANGLION
NEURONS BECOME SMALLER WHEN
THEY'RE INCUBATED OVERNIGHT WITH
MARGARIC ACID, THIS IS THE PLOT,
ALSO YOU CAN APPRECIATE THAT YOU
REQUIRE MORE MECHANICAL
STIMULATION TO ILISOTOPEIT THESE
AS SMALL BIEZO2 CORRELATES.
THE COOL THING ABOUT DOING THE
SPRMS IN THE NEURONS WHICH I
DIDN'T APPRECIATE BEFORE IS THAT
YOU CAN ALSO ELICIT MECHANO
ACTION POETIC TEBTIALS.
SO INSTEAD OF INJECTS
[INDISCERNIBLE], WE IN DOSE
[INDISCERNIBLE] NEURONS IN
CULTURE AND WE CAN ILLICIT
ACTION POTENTIALS.
SO THESE ARE THE CONTROL NEURONS
AND THESE ARE THE 1S INCUBATED
WITH MARGARIC ACID.
THEY'RE THE SAME MECHANICAL
STIMULI BUT IF YOU KEEP POKES
AND POKES, NOW HAVE YOU MECHANO
ACTION POETIC TEBTIALS AND THIS
IS SUMMARIZED HERE AND I THINK
IT'S VERY SIGNIFICANT WHEN YOU
SEE HOW MUCH A MECHANICAL
STIMULI WE NEED TO ACTIVATE THIS
ACTION POTENTIALS.
SO [INDISCERNIBLE] AND HIS LAB
YEARS AGO ALREADY DEMONSTRATE
THAD PIEZO2 WAS PART OF THE
CASCADE OF THE INFLAMMATORY
SOUP, PIE ZOFUNCTION IS ENHANCED
DIRECTLY BY [INDISCERNIBLE]
KININES THE [INDISCERNIBLE], SO
AT THE TIME WE WERE PREPARING
THIS PAPER THAT WE PUBLISHED WE
WONDER IF MARGARIC ACID WOULD BE
ABLE TO FIGHT BACK THE
INFLAMMATION SO WE DID THIS IN
CULTURE, THE NEURONS HAVE THE
[INDISCERNIBLE] RECEPTOR SO WE
ESSENTIALLY REPLICATE ITEMS AND
THE RESPONSE IN OUR LAB BY
PRODUCING BRADYKININ EMPLOY SO
WHAT WE DID WAS USE THESE
NEURONS AND THEY INCUBATE OVER
NIGHT WITH MARGARIC ACID AND YOU
CAN SEE THE SMALL LEVEL.
INDICATING WE CAN DECREASE
PIEZO2 INFLATION TO
NONINFLAMMATORY.
AND THEN WHEN IT BECAME OBVIOUS
THEY HAD TO BECOME MORE
TRANSLATIONAL AND USE THIS BASIC
KNOWLEDGE, THIS HAS BEEN VERY,
VERY NICE BUT THERE IS A LOT OF
[INDISCERNIBLE].
I WAS LUCKY BECAUSE I STARTED A
COLLABORATION WITH ALEX
CHESSENER WHEN --WHO IS ALSO AT
NIH AND WE WROTE A TINY GRAPT,
INTRAMURAL, EXTRAMURAL FROM
BENCH TO BEDSIDE AND BACK ASK WE
EVEN APPLIED FOR THIS PATENT
THAT I HAVE TO DISCLOSE ALL THE
TIME SO THE GOAL WAS TO MAKE A
MARGARIC ACID LOTION THAT
TARGETS PIEZO 2 AT THE PERIPHERY
AND THAT WE CAN MODULATE OR
INHIBIT PAIN WITHOUT INHIBITING
ANONSPECIFIC SIDE EFFECTS
THEY--THEICIZING.
THAT WAS THE GOAL, RIGHT?
AGAIN I'M A BASIC SCIENTIST SO
THIS IS VERY NEW TO ME SO I
APOLOGIZE FOR ANY BIG MISTAKES
OR ERRORS, BUT WE,A PROACHED
THIS NAIVELY, WE USED 2 GROUPS
OF WILD-TYPE MICE, HEALTHY MICE
AND WE DECIDED TO DIVIDE THESE
GROUPS AND APLOY A PLACEBO
LOTION AND A MARGARIC ARK SID
ENRICHED LOTION, WE WOULD RUB
THE PAWS OF THE ANIMAL ONCE A
DAY, USING A MECHANICAL SO YOU
CAN HOLD THEM WITHOUT CAUSING
ANY DAMAGE, WE DIDN'T WANT TO
USE ANESTHESIA BECAUSE WE DIDN'T
WANT TO, YOU KNOW, DIRTY UP THE
RESULTS SO EVERY SINGLE DAY MY
PEOPLE WOULD GO TO THE FACILITY,
RUB THE PLACEBO LOTION OR THE
MARGARIC LOTION, WE LEFT 1 PAW
CONTROL NOT TOUCHING THAT.
AND EVERY 7 DAYS WE DECIDED TO
DO A BONE-FREE ASSAY AND MEASURE
HOW MANY--HOW MUCH FORCE WAS
NEAT NEEDED TO EVOKE A RESPONSE
ON THESE PAWS.
SO THE HYPOTHESIS WAS IF THE
LOTION WORKS THEN WE WOULD
REQUIRE MORE FORCE TO
ILISOTOPEIT WITH THE RESPONSES
IN THESE MICE.
AND THIS IS WHAT HAPPENED SO I'M
SHOWING YOU HERE, DAY 14, 21 AND
28.
I'M NOT SHOWING YOU 7 BECAUSE
NOTHING HAPPENED AT DAY 7.
SO THE BLUE DOTS ARE PLACEBO, SO
CAN YOU SEE A TINY INCREASE IN
THE FORCES BUT IT'S NOT
SIGNIFICANT.
HOWEVER WHEN YOU COMPARE WITH
THE RED COUNTERPART WHICH WAS
THE 1S THAT WERE THE ANIMALS,
THAT HAD THE CONTROL PAW WITH
THE MARGARIC ACID LOTION, SORRY,
CAN YOU LOOK--I DON'T WANT TO
RUIN THE SURPRISE, I'M SORRY.
FORGET I SHOW YOU THIS.
OKAY, SO YOU CAN APPRECIATE THAT
THE FORCES BECOME LARGER AND
LARGER AND 28 DAYS IS WHEN IT
BECOMES A PEAK THAT YOU REQUIRE
MORE A FORCE TO ILLICIT A
RESPONSE.
WE ALSO DID AN EXPERIMENT--SO
THESE EXPERIMENTS WERE DONE IN
3D IN BATCHES OF MICES WITH 3 3D
BATCHES OF LOTION SO WE'RE
REALLY CONFIDENT WE CAN
REPRODUCE THESE, BUT PEOPLE IN
MY LAB HATE ME FOR IT BECAUSE
THEY HAVE IT GO DO MICE PAWS OR
MASSAGE OR GENTLE SOFT
STIMULATION, SO WHEN WE STOP
APPLYING THE MARGARIC LOTION TO
THESE MICE, WE FOUND THERE WAS A
DECREASE WITH TIME SO THE EFFECT
IS NOT GOING TO STAY THERE
FOREVER WHICH I THINK IS VERY
IMPORTANT.
ALSO WE MAKE SURE THE ABILITY OF
THESE MICE TO RESPONSE TO HEAT
BECAUSE THE IDEA IS IF WE ARE
ONLY AFFECTING MECHANO SENSITIVE
ION CHANNELS, CHANNELS LIKE 3
D 1 FOR EXAMPLE SHOULD NOT BE
AFFECTED BY THE PRESENCE OF
MARGARIC ACID, AND WE DIDN'T SEE
ANY DIFFERENCE BETWEEN THE MA
SEEB O AND THE MICE.
ALSO WE TOOK THE BLOOD OF THE
MICE AT THE END OF THE
EXPERIMENTS JUST TO MAKE SURE WE
WERE NOT CAUSING SYSTEMIC
INFLAMMATION AND THAT WAS NOT
THE CASE SO WE EVALUATED WITH A
KIT FOR THE CYTOKINES AND
CHEMOKINES THAT ARE MARKERS OF
INFLAMMATION AND WE DID NOT SEE
ANY DIFFERENCE.
THE MICE JUST LOOK NORMAL.
SO NOW WE ARE HOPING TO GRAB
MORE COLLABORATION, PEOPLE THAT
WORK WITH PAIN AND WE CAN USE
MAYBE THIS LOTION TO AMELIORATE
FOR EXAMPLE, RHEUMATOID
ARTHRITIS PAIN OR ANYTHING THAT
IS CHRONIC.
THIS IS NOT ANYTHING TO HELP IF
YOU GET IT YOURSELF TODAY, AND
YOU PUT IT, IT'S NOT GOING TO
HAPPEN BECAUSE IN CULTURE IT
TAKES AT LEAST 18 HOURS TO BE
REMODELED.
SO I HAVE MANY CONCLUSIONS BUT I
DECIDED TO GIVE YOU TAKE HOME
MESSAGES, SO I WANT YOU TO
REMEMBER THAT THE BASAL CHANNEL
FUNCTION CAN BE FINE TUNED BY
MODELING THE MEMBRANE
COMPOSITION, THE PANTANOIC ACID
CAUSED BY GAIN OF FUNCTION
MUTATIONS IN MICE, THAT THE
MARGARIC LOTION HAS THE ABILITY
TO AMELIOR 8 HYPER SENSITIVITY.
SO I WOULD LIKE TO ACKNOWLEDGE
THE PEOPLE IN OUR GROUPS THAT
DID THE WORK, MISS ROMMER O,
WHICH IS GRADUATING A COUPLE
MONTH AGO, POST DOCS WHO DID ALL
THE ANIMAL WORK, MY
COLLABORATORS, CHECKISTS AND HE
WAS IMPLEMENTAL TO THE SCIENTIST
LOTION THAT DO NOT BURN THE SKIN
OF ANIMALS AND WE CAN HAVE
POSITIVE RESULTS AND WITH THIS I
WOULD LIKE TO THANK YOU FOR YOUR
ATTENTION.
ANY QUESTIONS?
>> THANK YOU DR. VASQUEZ,
EXCITING TALK EMPLOY WE WILL NOW
OPEN UP TO GENERAL Q&A, BOTH
RECEIVING QUESTIONS FROM THE
PUBLIC WHO ARE ATTENDING
VIRTUALLY AND AS WELL AS THOSE
IN THE ROOM.
>> NICE TALK AND SUPER
INTERESTING WORK.
REFERRING TO THE DIFFERENCES YOU
SAW IN MODULATING SPECIFIC FATTY
ACIDS, I WONDER IF THERE'S ANY
DATA SHOWING PREFERRED
ASSOCIATION BETWEEN THOSE FATTY
ACIDS AND DIFFERENT CHANNELS?
>> SO YES THERE ARE CHANNELS
THAT ARE DIRECTLY MODULATED BY
FATTY ACIDS FOR EXAMPLE FOR
POTASSIUM CHANNELS BECAUSE
THEY'RE ACTIVATED BY
[INDISCERNIBLE] ACID, THERE IS
ALSO LIGAND GATED ION CHANNELS
WHICH HAS RECEPTORS ARE ALSO
MOTIVATED BY DHA IN THEIR
PARTICULAR CASE IT SEEMS TO BE
AGE RELATED TO DIRECT BINDING
AND ACTUALLY THERE ARE
STRUCTURES OF THOSE CHANNELS
WITH THOSE FATTY ACIDS BOUND TO
A POCKET.
IN THE CASE OF MECHANO SENSITIVE
ION CHANNELS, I'M NOT DISCARDING
100% THEY DO NOT BIND BUT WHAT
IT SEEMS BASED ON OUR DATA THAT
IS SOMETHING OF THE MECHANICAL
PROPERTIES OF THE MEMBRANE
BECAUSE WE SEE THE SAME EFFECT
ON PRO CARIOTIC MECHANO
SENSITIVE ION CHANNELS AS I SAID
THEY LOOK COMPLETELY DIFFERENT.
SO ACTUALLY IT LOOKS LIKE
[INDISCERNIBLE] BUT I WROTE A
FEW YEARS AGO IN WHICH WE TALK
ABOUT DIRECT AND INDIRECT
ACTIONS AND I THINK THOSE THINGS
COULD BE POSSIBLE AND THEY CAN
CO EXIST AS WELL.
BUT RIGHT NOW WE DON'T HAVE ANY
EVIDENCE AT LEAST IN MY LAB THAT
SUGJEFFS JEFF--SUGGESTS DIRECT
BINDING.
>> IF I MAY ASK 1 FOLLOW UP
QUESTION, WITH RESPECT TO
MECHANICAL PROPERTIES OF THE
MEMBRANE YOU THINK IT'S A
STRAIGHT AHEAD STIFFNESS
RELATIONSHIP OR DO YOU THINK
THERE ARE VISITINGICAL ELASTIC
COMPONENTS THAT ALSO
DIFFERENTIALLY IMPACT
NABSOLUTELY.
YEAH, I DIDN'T INCLUDE THIS DOSE
SLIDES IN MY TALK BUT NOT ONLY
THAT, BECAUSE FOR EXAMPLE,
[INDISCERNIBLE] ACID, THEY
ENACTIVATE THE CHANNEL FASTER,
AND THEY MAKE THE MEMBRANE LESS
RIGID.
THE [INDISCERNIBLE] ACID HAVE
THE SAME EFFECT ON MECHANICAL
PROPERTIES BUT THEY HAVE A
DIFFERENT EFFECT ON CHANNEL
FUNCTION.
WE HAVE THE [INDISCERNIBLE] THAT
DEMONSTRATE THAT THAT IS NOT
ONLY THE STIFFNESS BUT ALSO HOW
COMPARATIVE ARE THE MEMBRANES SO
YOU CAN IMAGINE MEMBRANES WITH
MARGARIC ACID, FOR EXAMPLE ARE
ORGANIZED LIKE THIS, MORE LIKE
THAT, RIGHT, SO THOSE PROPERTIES
ARE DIFFERENT AND ALSO IF YOU
FOR EXAMPLE, APPLY HIT, THE
RESPONSE TO THOSE OF COURSE ARE
DIFFERENT AND BASED ON THE
SCHOLASTIC PROPERTIES, ALSO
ANOTHER PARAMETER I DIDN'T
MENTION BECAUSE WE DON'T HAVE
ANY ON IT, YOU CAN IMAGINE THAT
YOU HAVE A MEMBRANE DOMAINS IN
WHICH FOR EXAMPLE, MEMBRANES IN
WHICH DHA WOULD HAVE OR NOT HAVE
[INDISCERNIBLE] CHANNELS AND
THEN HAVE YOU A PROBLEM OF
LOCATION, BUT WE HAVEN'T
EXPLORED THAT.
>> THANK YOU.
WE HAVE A QUESTION FROM DR. LANG
EVIN?
>> WE HAD A QUESTION OVER THERE,
NO?
>> YES, SORRY CAN YOU HEAR ME?
>> YES, WE CAN HEAR YOU, YEAH,
WELL, THANK YOU SO MUCH.
WHAT ELEGANT WORK AND I HAVE A
QUESTION THAT REALLY A FOLLOW UP
TO THE PREVIOUS QUESTION ABOUT
THAT VISITINGICAL ELASTIC
PROPERTIES OF THE MEMBRANE SO WE
TYPICALLY TALK ABOUT CHANNELS,
LIKE CHANNELS FOR EXAMPLE, ARE
FORCED SENSORS THAT THEY SENSE
MECHANICAL FORCE BUT THERE'S THE
FUNDAMENTAL RELATIONSHIP OF
STRESS AND STRAIN BY FORCE,
STRESS BEING THE FORCE DIVIDED
BY THE CROSS SECTIONAL AREA AND
STRAIN BEING THE CHAIN OF LENGTH
OVER THE INITIAL LENGTH.
AND STIFFNESS IS WHAT RELATES
THOSE 2, RIGHT?
IT'S THE RELATIONSHIP BETWEEN
FOR STRESS AND STRAIN IS THROUGH
STIFFNESS, SO IF YOU'RE--IF YOUR
CHANNEL IS--YOU'RE DEMONSTRATING
REALLY NOT JUST THE STIFFNESS
BUT THE MECHANICAL PROPERTIES OF
THE MEMBRANE SOUND LIKE THEY ARE
AFFECTING THE CHANNEL, DO YOU
THINK THIS WOULD SUGGEST THAT
WITH THE CHANNEL IS RESPONDING
TO IS MORE THE STRING OR
DEFORMATION OF THE STRAIN RATHER
THAN ITSELF?
IT MATTERS BECAUSE AS YOU'RE
DEMONSTRATING THE MEMBRANE
ITSELF WILL CHANGE HOW THE--HOW
THE--THE SAME FORCE IS GOING TO
BE FELT AND RESPONDED TO TOO BY
THE CHANNEL.
IT SOUNDED A LITTLE ACADEMIC BUT
I THINK THIS IS IMPORTANT?
>> YEAH, IT IS VERY IMPORTANT.
UNFORTUNATELY WE DON'T HAVE THE
TOOLS IN THE LAB TO STUDY THAT
BUT WE'RE VERY FORTUNATE THAT
OUR COLLEAGUES IN THE MECHANO
SENSITIVE ION CHANNEL FIELD, FOR
EXAMPLE, FROM THE LABORATORY OF
BORIS MARTIN AT CHARLES COX
[INDISCERNIBLE] AT DUKE, THEY
HAVE DETERMINE THAD PIEZO1 AND
2, TO A CERTAIN EXTENT THEY DO
RESPOND TO CHANGES IN LATERAL
TENSION THEY HAVE DONE ALL OF
THE QUANTIFICATION TO
CHARACTERIZE THE--AS YOU CALL IT
THE ACADEMIC PART OF THIS
MODULATION OF PIEZO-CHANNELS.
SO IN MY LAB UNTIL RECENTLY WAS
VERY SMALL SO WE HAD ONLY
OPPORTUNITY TO USE THIS
PLACEMENT CLAMP IN WHICH
ESSENTIALLY JUST INDENTED THE
NEURONS OR THE CELLS BUT IMEAN
WE DID NOT STUDY CHANGES IN THE
STRAIN SO WE WERE MORE
CONCENTRATED ON THE CONTENT OF
THESE FATTY ACIDS IN THE PLASMA
MEMBRANE BUT WE CAN, YOU KNOW
MAYBE DISCUSS LATER AND TALK
ABOUT OTHER PEOPLE'S WORK THAT
HAVE FED OUR STORIES.
>> THANK YOU.
IF I COULD JUST QUICKLY FOLLOW
UP.
I THINK THIS IS SO FUNDAMENTA
AND IF THERE ARE OTHER--FOR
EXAMPLE, CHANGES IN THE EXTRA
CELLULAR MATRIX, RIGHT, RIGHT
OUTSIDE OF THE CELL COULD ALSO
HAVE THE SIMILAR EFFECT BY
STIFFENING, RIGHT?
>> ABSOLUTELY.
SO I DIDN'T HAVE TIME TO SHOW IT
BUT THE WAY THAT PIEZO2, SO IT
REQUIRES FOR EXAMPLE MORE
MAGARIC ACID THAT BE INHIBITED
THAN PIEZO 1.
AND WE HAVE DATA DEMON TRAIT
THAGOREAN IT'S VERY IMPORTANT
INTERACTION WITH THE
CYTOSKELETON, WE AND OTHERS, NOT
ONLY US.
BUT WE HAD TO START SOMEWHERE,
RIGHT?
WE HAD TO FIND AN EXCUSE TO KEEP
STUDYING THESE BECAUSE AS FAR AS
I KNOW NO 1 DEMONSTRATED THIS
BEFORE AND I AGREE WITH YOU,
THIS IS SOMETHING THAT
FUNDAMENTAL AND WE NEED TO KNOW
BUT I DON'T HAVE THE ANSWER
RIGHT NOW.
>> THANK YOU.
>> QUICK QUESTION.
GREAT TALK.
I HAD A QUESTION ABOUT, YOU SAY
THAT THE MARGARIC ACID INCREASES
FORCE THRESHOLDS--
>> INCREASES WHAT, I'M SORRY?
>> INCREASES THE FORCE
THRESHOLDS REQUIRED DO YOU THINK
IT'S BECAUSE IT'S SOFTENING THE
CELL TISSUE OR IT'S STIFFENING?
>> IT'S STIFFENING.
>> SO IF YOU PUT THIS ON THE
SKIN NONNEURONNAL SKIN, WILL IT
SOFTEN THE SKIN OR WILL IT
STIFFEN THE SKIN?
>> I DON'T KNOW THAT'S AN
EXCELLENT QUESTION.
I CAN HYPOTHESIZE, THESE
EXPERIMENTS WE ALSO HAVE DONE IT
IN [INDISCERNIBLE] CELL
CARCINOMA CELL LINES MCC13 CELL
LINES WHICH I KNOW IS NOT SKIN,
IT'S JUST A CULTURE BUT WE HAVE
THE SAME EFFECT THAT WE SEE IN
NEURONS WE HAVEN'T MEASURED THE
STIFFNESS OF THE SKIN OF THE
ANIMALS AFTER 28 DAYS OF
MARGARIC ACID, I WOULD ASSUME
THEY HAVE THE SAME EFFECT
BECAUSE IT'S FATTY ACIDS AND
IT'S WELL REPORTED IS WE SEE
EVERYWHERE WE USE THAT MAKES THE
MEMBRANES MORE STIFF BUT I DON'T
KNOW, I CANNOT GUARANTEE THAT'S
GOING TO HAPPEN.
>> OKAY, THANK YOU.
WELL THE'S TAKE A QUESTION FROM
THE VIDEOCAST AUDIENCE,
DR. VASQUEZ DO YOU HAVE ANY
THEORIES AS TO WHERE THE MECHANO
SENSITIVE CHANNELS DON'T SHARE
ANY HOMOLOGYYS OR CONSERVATIONS
ACROSS SPECIES?
>> OH MY GOD, YEAH, I AM
REPRESENTING MYSELF SO THESE ARE
ONLY MY OPINIONS.
SO I DON'T THINK IT'S KNOWN.
YOU CAN GO BOTH WAYS.
YOU CAN SAY THERE'S CONVERGENCE
OR DIVERGENCE, RIGHT?
YOU CAN THINK ALL MEMBRANE
PROTONES WERE MECHANO SENSITIVE
AND THEY WERE LOSING THAT--DON'T
QUOTE ME ON THIS, SO THEY LOST
THAT ABILITY WITH TIME OR THE
OTHER WAY AROUND.
I DON'T KNOW.
BUT IT'S PUZZLING BECAUSE AGAIN
THEY LOOK TO IMPORTANTLY, THE
POTASSIUM CHANNELS OR THEY DON'T
LIKE LIKE MSCL, OR
[INDISCERNIBLE] SO YES.
NMAYBE JUST TO FOLLOW UP ON THAT
QUESTION, IS THERE ANY CONSERVED
MOTIFS ACROSS THOSE--
>> NO.
NOT AT ALL NTHEY LOOKED VERY
DIFFERENT IN THE DIAGRAM SHE
SHARED, YEAH.
>> SO THERE IS NO GENE WIDE GGOR
DD, OR SOMETHING, NOTHING.
WE TRIED AND WE REALLY LOOKED
FOR IT, WHEN I SAY WE THE
COMMUNITY BUT THERE IS NO, NOT
WHATSOEVER.
AND IN THE CASE OF C.ELEGANS
BECAUSE IT'S 1 CHANNEL COMPLEX.
SO INDICATING YOU CAN HAVE THE
SAME FUNCTION TO PUT TOGETHER
WITH VARIOUS MEMBRANE PROTEINS.
>> DR. LANG EVIN.
>> YEAH, THANK YOU, VERY
INTERESTING TALK, COULD YOU
CERTAINLY--CERTAINLY LABERATEOT
RELATIONSHIP BETWEEN THE
SENSITIVITY OF THE PIEZO2
CHANNEL AND INFLAMMATION?
BECAUSE IT SOUNDS LOAMACYIC IF
THERE IS AN INFLAMMATORY
ENVIRONMENT THEN DOES IT
MATTER--IT SEEMS LIKE THEN THE
ION CHANNEL WILL BE MORE
SENSITIVE, RIGHT?
AND HOW DOES THAT INTERACT WITH
THE AMOUNT OF [INDISCERNIBLE]?
>> OOH, OKAY, OKAY.
SO, THE SENSITIZATION AFTER
INFLAMMATION ACARDING TO OUR
PAPER WITH [INDISCERNIBLE] WITH
OUR OWN RESULTS REPLICATING HIS
HAPPENED REGARDLESS OF THE FATTY
ACID.
WE THEN DOO [INDISCERNIBLE] FOR
THAT 1 BUT--SO AS I UNDERSTAND
BRADYKINEIN ENHANCES PIEZOR 2,
THE FORMULATION OF THE PKCA AND
PC K, I DON'T KNOW IF PEOPLE
KNOW ALREADY WHICH IS POPULATED
OR WHICH AMINO ACIDS BUT THE
MARGARIC ACID ENRICHMENT HAPPENS
IN THE PLAZ MIDS MIDDOMAIN.
SO IT'S 2 DIFFERENT DOMAINS, I
DON'T KNOW ANY INTERACTION
BETWEEN THAT AND THE PKC, PKA
PHOSPHORYLATION SITES.
>> GOT IT.
THE REASON FOR THIS QUESTION WAS
IN GENERAL THERE ARE POPULATIONS
LIKE DIABETIC POPULATIONS WHERE
THERE'S A LOT OF INFLAMMATION
AND THEY HAVE GREATER PAIN
SENSITIVITY, GREATER STIFFNESS
AND I WAS JUST WONDERING IF SOME
OF THE MECHANISMS THAT YOU HAVE
BEEN STUDYING CAN SHED SOME
LIGHT ON WHY?
>> NOT YET, BUT YEAH.
I KNOW WHERE YOU'RE COMING FROM,
THERE ARE CERTAIN AGING
POPULATIONS THAT BECOME EITHER
LESS SENSITIVE OR MORE SENSITIVE
TO PAIN.
AND I CAN IMAGINE THEIR FATTY
ACID METABOLISM CHANGING WITH
TIME ALSO NEURONS, SO MANY
THINGS COULD HAPPEN, BUT I DON'T
HAVE THE ANSWER TO THAT BUT I
CAN SEE THAT HAPPENING OF
COURSE.
>> THANK YOU.
>> OKAY, LET'S GO TO ANOTHER
QUESTION FROM THE VIDEOCAST.
SO YOUR TRANSLATIONAL WORK IS
VERY INTERESTING AND HAS BROUGHT
IMPLICATIONS.
DO YOU HAVE ANY PLANS FOR FUTURE
EXPERIMENTS COMPARING MARGARIC
LOTIONS TO CAP ASSESSINGIN
CREAMS OR OTHER LOTION FOR PAIN
MANAGEMENT IN HUMAN TRIALS.
AND GIIVE YOUR LAB'S BACKGROUND
DO YOU PLAN TO USE IT IN ANIMAL
STUDIES FIRST?
WHAT'S YOUR PLAN ARE IF
EVALUATING THE MODELS OF THESE
LOTIONS ON HEAT MODELS?
>> YES, SO I DON'T HAVE ANY
PLANS BUT I'M ALWAYS LOOKING FOR
WORK TO HAVE COLLABORATIONS.
I DON'T HAVE THE MIND SET TO DO
THOSE EXPERIMENTS IN HUMANS,
ACTUALLY.
WE WERE APPROACHED BY A COUPLE
COMPANIES WHEN WE FILE THE PAD
PATENT AND WE HAVE A LICENSE
[INDISCERNIBLE] I DON'T THINK I
CAN CLAIM THIS BUT ANYWAYS,
PEOPLE ARE WORKING WITH THE
LOTION.
I WOULD LIKE TO TRY CBD AND
MAGARIC AND I WOULD LIKE TO TRY
ALL THOSE THINGS SO I DON'T HAVE
EXPERTISE SO IT WOULD REQUIRE
SOMEONE WHO WANTS TO DO WORK
WITH SOMEONE WHO KNOWS PHYSICS
AND PHYSIOLOGY TO,A PLIE IT, I
DON'T EVEN KNOW HOW TO RECRUIT
HUMANS FOR A CLINICAL TRIAL FOR
THAT MATTER.
SO THAT'S 1 OF THE REASONS WHY
ALEX AND I STARTED THIS SHORT
COLLABORATION.
I THINK HE WAS AROUND FOR 2
YEARS AND I THINK WE ACCOMPLISH
A LOT BUT WE DON'T HAVE MORE
GAS.
>> CAN I ASK A VERY TECHNICAL
QUESTION, FDA, SO DOES THIS
REQUIRE FDA APPROVAL BEFORE?
>> I THINK SO, THAT'S 1 OF THE
THINGS THAT WAS PUZZLING TO ME
BECAUSE I THOUGHT BEING A
NATURAL PRODUCT WOULDN'T NEED
BUT I THINK IT DOES.
AGAIN, I NEVER--MAY BE I DON'T
KNOW HOW TO ASK BUT I NEVER HAVE
RECEIVED 100 PERCENT YES, NEED
IT OR YOU DON'T NEED IT BUT IT'S
A NATURAL PRODUCT SO I'M NOT
SURE.
>> YEAH, USUALLY IT'S SAFE IF
THE FDA THINKS THERE'S ENOUGH
HISTORICAL INFORMATION CAN IT
CAN BE CATEGORIZED AS GRASS BUT
THAT'S AN FDA QUESTION, I GUESS
THAT WOULD BE SOMETHING TO ASK
THE FDA.
NYEAH, YEAH, WELL IF YOU KNOW
SOMEONE THAT WOULD BE GREAT.
>> SO THE OTHER THING TO THINK
ABOUT PIEZO2 IS I THINK IS ALSO
INVOLVED, IT IS INVOLVED IN
GENTLE TOUCH AND [INDISCERNIBLE]
TOUCH AND MAYBE YOU CAN MAKE A
LOTION THAT HAS POTENTIAL FOR
OTHER THING THAT CONNECT WITH
PEOPLE THAT LACK TOUCH,
RESPONSES, RIGHT?
>> YES, BACK TO YOUR MICE JUST
FOR 1 MORE QUESTION AND MAYBE
YOU COVERED THIS AND I MISSED
IT, BUT HAVE YOU LOOKED AT OR DO
YOU PLAN TO LOOK AT THE ACTIVITY
OF THE RECEPTORS IN THE PRESENCE
AND ABSENCE OF INFLAMMATION.
SO, YOU KNOW CREATING AN
INFLAMMATORY VERSUS
NONINFLAMMATORY ENVIRONMENT
EITHER IN VIVO OR INVITRO AND
LOOKING TO SEE THE IMPACT OF THE
MANIPULATIONS AND THE LOTION
OR--
>> YEAH, WE HAVEN'T DONE IT BUT
THAT'S SOMETHING WE WOULD LIKE
TO DO.
ACTUALLY, SO, MAYBE THIS IS A
LAME EXCUSE BUT I MOVE MY LAB 1
YEAR AGO, SO NOW I'M STARTING
ALL OVER AGAIN IN A NEW PLACE.
AND I'M--I THINK I'M IN A BETTER
PLACE FOR THOSE TYPE OF SPRMS
BECAUSE THERE IS MORE PEOPLE
WORKING WITH PAIN AT THE
UNIVERSITY OF TEXAS HOUSTON.
SO THAT'S THE HOPE.
THANK YOU.
>> GO AHEAD PETER.
>> I COULDN'T RESIST.
I WAS WONDERING WHAT YOUR
THOUGHTS ARE ON THESE ELEGANT
EXPERIMENTS YOU'VE DONE INVITRO
WITH ISOLATED CELLS COMPARED TO
THE IN VIVO ENVIRONMENT IN
PARTICULAR WHEN YOU HAVE NEURONS
WITHIN AN EXTRA CELLULAR MATRIX
SO THIS IS SOMEWHAT OF A FOLLOW
UP TO THE QUESTION THAT DR. LANG
EVIN AND DR. [INDISCERNIBLE]
ASKED ABOUT HOW THE
PIEZO-CHANNELS ARE RESPOND
NOTHING A MEMBRANE BUT WHAT WAS
REALLY IN AN EXTRA CELLULAR
MATRIX AND I WAS SPECIFICALLY
INTERESTED IN THE ROLE THAT
INTEGRINS PLAY IN THAT BECAUSE
WE HAVE DATA ALONG TIME AGO NOW
WHERE IF YOU--SINCE YOU BLOCK
THE INTEGRINS FROM THEIR
FUNCTION, YOU CHANGE
DRAMATICALLY, YOU INHIBIT THE
NEURONS THAT THESE ARE TOUCH
NEURONS, YOU INHIBIT THEIR
RESPONSE, AND SO I'M JUST
WONDERING WHERE YOU GO FROM
THESE ELEGANT INVITRO ISOLATED
CELLS TO I REALIZE YOU'RE DOING
THAT WITH [INDISCERNIBLE] HERE
BUT YOUR THOUGHTS ON THAT?
>> SO I AGREE WITH YOU.
I HAVE COLLEAGUES THAT HAVE
MEASURE THE MOBILITY OF
PIEZO2,--SORRY OF PIEZO1, NOT 2,
IN MEMBRANE RESIDENT REACH WITH
MARGARIC ACID, THEY SEEM TO MOVE
LESS AS WELL SO IMAGINE NOT
ONLY--YOU ARE EVOKING LESS
RESPONSES BY INDENTATION BUT
ALSO HAVE YOU HAVE INTEGRINS AND
PROTEINS AS A BUILDING
MICRODOMAINS WHERE THE
PIEZO-CHANNELS SIT, I CAN
IMAGINE ALL OF THAT ENVIRONMENT
BEING MORE RIGID AS WELL.
I'M NOT MEASURING THAT, I DON'T
HAVE ANY PLANS TO MEASURE THAT
YET BUT I COULD SEE THAT
HAPPENING AND I HOPE SOMEONE
GETS INSPIRED AND STARTS DOING
THOSE EXPERIMENTS BUT YEAH, I
DON'T HAVE ANY DATA FOR IT.
>> OKAY, I THINK WE HAVE TIME
FOR 1 MORE QUESTION.
OH YES, DOCTOR?
>> MAYBE KIND OF A TIEWP
--STUPID
QUESTION, I DEAL WITH PATIENTS
DALELY, I DO NOT KNOW ANYTHING
ABOUT ION RECEPTORS OR ION
CHANNELS SO DO YOUR FINDINGS
HAVE THE ABILITY TO SAY TO THEM
YOU SHOULD THEREFORE EAT THESE
KINDS OF FOODS AND NOT EAT THESE
OTHER KINDS OF FOODS?
>> YOU ENCOUNTER EVERY DAY
PEOPLE TOO, THEY PROBABLY WANT
TO KNOW, THAT'S EXCITING WHAT
CAN YOU TELL ME ABOUT WHAT I
SHOULD DO ON A DAILY BASIS?
>> YEAH, YEAH, SO I DON'T KNOW
IF YOU REMEMBER THE SLIDE WITH
THE DOLPHIN SO THOSE GUYS MADE A
COMPANY THAT CELLS PEELS WITH
PANTHETIC ANONAPOPTOTICKIC ACID,
AND AS I SHOW YOU IT DID NOT DO
ANYTHING FOR MECHANO SENSITIVE
ION CHANYS ON THE CONCENTRATION
THAT WE USE, BUT THEY'RE USING
THAT ACID, I DON'T KNOW IF DID A
LOT OF GOOD THINGS IN THE BODY,
I DON'T KNOW EXACTLY BUT THEY'RE
SELLING THAT OVER THE COUNTER, I
BELIEVE LIKE YOU FIND DHA AND
[INDISCERNIBLE] SO I CAN TELL
PEOPLE, LET'S SAY LIKE MY MOM
FOR EXAMPLE, OR MY DAD, YOU KNOW
IF YOU FIND--IF YOU'RE NOT
EATING ENOUGH EACH OR IF YOU
DON'T HAVE ENOUGH SOURCES OF THE
PANTANOIC ACID AND YOU HAVE
CHRONIC PAIN, MIGHT BE A GOOD
IDEA TO START HAVING THOSE FISH
OIL PEELS, BUT I DON'T KNOW.
I DON'T DEAL WITH PATIENTS AND
ACTUALLY THIS WOULD BE VERY
HELPFUL TO COMMUNICATE SCIENCE
BETTER, RIGHT THROUGH OUTREACH
AND CONVEY THE MESSAGE I GUESS.
>> OKAY, WELL, THANK YOU VERY
MUCH DR. VASQUEZ, WE APPRECIATE
YOUR KEY NOTE.
IT WAS VERY INTERESTING.
>> THANK YOU.
>> SO YES, I THINK AS AN ADYU
VENT CONSIDERING DIET AND
LOTIONSAsA I WAY TO CHANGE THE
CENTER FOR EXCELLENCE ON AGINGS
OF FORCED BASE MANIPULATIONS IS
VERY INTERESTING AND A POTENTIAL
AVENUE TO EXPLORE AND HOPEFULLY
THERE'S SOME INTEREST IN THE
ROOM AS WELL AS PEOPLE JOINING
US TO MAYBE EXPLORE THESE AREAS
FURTHER.
SO I WANT TO WRAP UP THIS
MEETING TODAY.
THANK YOU TO OUR VIDEOCAST
AUDIENCE AND OUR ATTENDEES FOR
YOUR QUESTIONS AND THANK TO YOU
EVERYONE FOR JOINING US TODAY
EITHER IN PERSON OR VIRTUALLY
AND I WANT TO GIVE SPECIAL
THANKS ONCE AGAIN TO OUR KEY
NEAT SPEAKER DR. VALERIA
VESQUESTIONS FOR HER VERY
INTERESTING TALK.
YEAH.
I JUST WANT TO REMIND EVERYONE
THAT THIS MEETING WAS RECORDED
AND WILL BE POSTED ON THE NIH
VIDEOCAST WEBSITE FOR FUTURE
VIEWING AND WITH THAT I WILL
CLOSE OUR BROADCAST BY THANKING
MY COLLEAGUES FROM NINDS AND
NICCH WHO HELPED MAKE TODAY'S
MEETING POSSIBLE AND I WISH
EVERYONE A WONDERFUL DAY.
THANK YOU.