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Targeting Oncogenic Pathways in Head and Neck Cancer

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Air date: Wednesday, December 12, 2012, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 230, (70 Live, 160 On-demand)
Category: WALS - Wednesday Afternoon Lectures
Runtime: 00:50:27
Description: Margaret Pittman Lecture

Dr. Jennifer R. Grandis was born and raised in Pittsburgh, Pa. She earned her BA in art history and biology from Swarthmore College and her medical degree with high honors from the University of Pittsburgh School of Medicine. She completed her internship in general surgery and her residency in otolaryngology at the University of Pittsburgh.

During her training she began to focus her studies on the biology of head and neck tumor growth. She has dedicated her research career to the study of the critical genetic alterations that characterize these cancers, with the ultimate goal of improving patient treatment and survival. Her laboratory was among the first to validate the epidermal growth factor receptor(EGFR) and Signal Transducers and Activators of Transcription (STATs) as therapeutic targets in head and neck cancer (HNC), thus paving the way for studies in other cancers.

EGFR serves as a central integration point for coordination of a broad array of cellular signals. She demonstrated that G-protein-coupled receptors(GPCRs) “transactivate” EGFR contributing to HNC progression. Each of these basic science observations has been translated into clinical trials. She developed an antisense gene therapy approach targeting EGFR and completed a phase 1 study that found a high clinical response rate (35%), which correlated with decreased EGFR expression in the post-treatment biopsies, suggesting that modulation of the target protein may identify a subset of patients who will respond to therapy. A phase 2 trial is now open to accrual. She completed a pharmacodynamic study comparing the effects of an EGFR inhibitor, alone or in combination with a GPCR inhibitor, on biomarker expression profiles in HNC patients. She developed a transcription factor decoy approach to block STAT3 and demonstrated antitumor efficacy in preclinical HNC models. A phase 0 trial of this first inhuman STAT3 inhibitor was recently completed and future studies will optimize this approach to enable systemic administration.

Dr. Grandis is dedicated to training the next generation of physician scientists as demonstrated by her role as PI on two NIH T32 grants. She has personally trained dozens of predoctoral and postdoctoral students and is the recipient of the2011 University of Pittsburgh Provost’s Award for Excellence in Mentoring. Dr. Grandis was elected to the Institute of Medicine of the National Academies in 2012.

The NIH Director's Wednesday Afternoon Lecture Series, colloquially known as WALS, is the highest-profile lecture program at the NIH. Lectures occur on most Wednesdays from September through June from 3:00 to 4:00 p.m. in Masur Auditorium, Building 10 on the NIH Bethesda campus.

Each season includes some of the biggest names in biomedical and behavioral research. The goal of the WALS is to keep NIH researchers abreast of the latest and most important research in the Unites States and beyond. An added treat is the annual J. Edward Rall Cultural Lecture, which features top authors and other cultural icons. All speakers are nominated by the NIH community.

For more information, visit:
The NIH Director's Wednesday Afternoon Lecture Series
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NLM Title: Targeting oncogenic pathways in head and neck cancer [electronic resource] / Jennifer R. Grandis.
Series: NIH Wednesday afternoon lecture
Author: Rubin Grandis, Jennifer.
National Institutes of Health (U.S.)
Publisher:
Other Title(s): NIH Wednesday afternoon lecture
Abstract: (CIT): Margaret Pittman Lecture Dr. Jennifer R. Grandis was born and raised in Pittsburgh, Pa. She earned her BA in art history and biology from Swarthmore College and her medical degree with high honors from the University of Pittsburgh School of Medicine. She completed her internship in general surgery and her residency in otolaryngology at the University of Pittsburgh. During her training she began to focus her studies on the biology of head and neck tumor growth. She has dedicated her research career to the study of the critical genetic alterations that characterize these cancers, with the ultimate goal of improving patient treatment and survival. Her laboratory was among the first to validate the epidermal growth factor receptor(EGFR) and Signal Transducers and Activators of Transcription (STATs) as therapeutic targets in head and neck cancer (HNC), thus paving the way for studies in other cancers. EGFR serves as a central integration point for coordination of a broad array of cellular signals. She demonstrated that G-protein-coupled receptors(GPCRs) "transactivate" EGFR contributing to HNC progression. Each of these basic science observations has been translated into clinical trials. She developed an antisense gene therapy approach targeting EGFR and completed a phase 1 study that found a high clinical response rate (35%), which correlated with decreased EGFR expression in the post-treatment biopsies, suggesting that modulation of the target protein may identify a subset of patients who will respond to therapy. A phase 2 trial is now open to accrual. She completed a pharmacodynamic study comparing the effects of an EGFR inhibitor, alone or in combination with a GPCR inhibitor, on biomarker expression profiles in HNC patients. She developed a transcription factor decoy approach to block STAT3 and demonstrated antitumor efficacy in preclinical HNC models. A phase 0 trial of this first inhuman STAT3 inhibitor was recently completed and future studies will optimize this approach to enable systemic administration. Dr. Grandis is dedicated to training the next generation of physician scientists as demonstrated by her role as PI on two NIH T32 grants. She has personally trained dozens of predoctoral and postdoctoral students and is the recipient of the2011 University of Pittsburgh Provost"s Award for Excellence in Mentoring. Dr. Grandis was elected to the Institute of Medicine of the National Academies in 2012. The NIH Director's Wednesday Afternoon Lecture Series, colloquially known as WALS, is the highest-profile lecture program at the NIH. Lectures occur on most Wednesdays from September through June from 3:00 to 4:00 p.m. in Masur Auditorium, Building 10 on the NIH Bethesda campus. Each season includes some of the biggest names in biomedical and behavioral research. The goal of the WALS is to keep NIH researchers abreast of the latest and most important research in the Unites States and beyond. An added treat is the annual J. Edward Rall Cultural Lecture, which features top authors and other cultural icons. All speakers are nominated by the NIH community. For more information, visit: The NIH Director's Wednesday Afternoon Lecture Series.
Subjects: Drug Delivery Systems
Head and Neck Neoplasms--drug therapy
Protein Transport
Publication Types: Lectures
Webcasts
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Caption Text: Download Caption File
NLM Classification: WE 707
NLM ID: 101599122
CIT Live ID: 12037
Permanent link: http://videocast.nih.gov/launch.asp?17717

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