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Stem Cells of the Skin: Their Biology and Clinical Potential

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Air date: Wednesday, April 30, 2008, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
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Category: WALS - Wednesday Afternoon Lectures
Runtime: 01:14:15
Description: Stem cells can self-renew and differentiate along multiple lineages to generate different tissues. In the embryo, multipotent stem cells respond to various cues to undergo morphogenesis and produce these tissues. The epidermis of the skin is an excellent model to explore how multipotent stem cells are able to respond to different cues to generate three functional tissues: epidermis, sebaceous gland and hair follicles. In the adult, stem cells reside in the epidermal basal layer, at the base of the sebaceous gland and in a niche within the hair follicle known as the bulge. Despite intensive studies, we still know very little about how stem cells and these niches become established and maintained. Genetic marking and molecular approaches stem cells within the bulge typically cycle infrequently. In response to a skin injury, these stem cells can be mobilized to move upward, proliferate and repair epidermal wounds or replenish the sebaceous gland. In normal homeostasis, these stem cells fuel the hair cycle, where they become activated to proliferate and regenerate the hair follicle with each new anagen phase. It has been known for nearly a decade that that the transition from dormant to activated follicle stem cells involves changes in signaling by Wnts, BMPs, and other factors but the molecular details of the activation and commitment steps are still unfolding. My laboratory has used a combination of molecular, cellular continues to study the molecular mechanisms that underlie follicle stem cell activation, and in so doing have begun to realize that when sustained through genetic mutations, the pathways involved in stem cell activation lead to tumo igenesis and skin cancers

Elaine Fuchs is internationally recognized for her contributions to skin biology and its human genetic disorders, including skin cancers and life-threatening genetic syndromes such as blistering skin disorders. For nearly three decades, Fuchs has focused on the molecular mechanisms that underlie the morphogenesis of the epidermis and its appendages, and how perturbations of these mechanisms result in disease. She has systematically and skillfully devised innovative molecular approaches to tackle these problems. She is credited for her pioneering use of “reverse genetics,” an approach to start with a specific protein, study its biology and then use mice as a means to ultimately identify the genes responsible for inherited human disorders. A classical geneticist would start with a specific genetic disorder. Instead, Fuchs has employed this creative cell biological strategy to solve the genetic bases of a number of dermatological disorders in humans. The method has since broadly benefited human medical genetics. Fuchs is widely recognized as having brought the field of dermatological research into modern day science. Her contributions range from the identification of proteins and signal transduction pathways important in epidermal and hair functions to uncovering of the molecular nature of skin diseases in humans. Fuchs and coworkers identified genetic defects in several disorders from perturbations of cytoskeletal proteins related to those present in the skin, but whose expression resides outside the skin, particularly in the muscle and the nervous system. An elegant example is reverse genetics to uncover the underlying genetic basis of blistering human skin disorder that arises from defects in epidermal keratin genes. Her 10 years of prior research set the groundwork for this discovery, which uncovered a key function of intermediate filament (IF) proteins as mechanical integrators of the cytoskeleton. The work also set the paradigm for >20 different human disorders of IF genes that affect many different tissues of the body. Her ground-breaking research is often used in biolgy and medical textbooks as a landmark

http://www.hhmi.org/research/investigators/fuchs_bio.html

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NLM Title: Stem cells of the skin : their biology and clinical potential [electronic resource] / Elaine Fuchs.
Series: NIH director's Wednesday afternoon lecture series
Author: Fuchs, Elaine.
National Institutes of Health (U.S.)
Publisher:
Other Title(s): NIH director's Wednesday afternoon lecture series
Abstract: (CIT): Stem cells can self-renew and differentiate along multiple lineages to generate different tissues. In the embryo, multipotent stem cells respond to various cues to undergo morphogenesis and produce these tissues. The epidermis of the skin is an excellent model to explore how multipotent stem cells are able to respond to different cues to generate three functional tissues: epidermis, sebaceous gland and hair follicles. In the adult, stem cells reside in the epidermal basal layer, at the base of the sebaceous gland and in a niche within the hair follicle known as the bulge. Despite intensive studies, we still know very little about how stem cells and these niches become established and maintained. Genetic marking and molecular approaches stem cells within the bulge typically cycle infrequently. In response to a skin injury, these stem cells can be mobilized to move upward, proliferate and repair epidermal wounds or replenish the sebaceous gland. In normal homeostasis, these stem cells fuel the hair cycle, where they become activated to proliferate and regenerate the hair follicle with each new anagen phase. It has been known for nearly a decade that that the transition from dormant to activated follicle stem cells involves changes in signaling by Wnts, BMPs, and other factors but the molecular details of the activation and commitment steps are still unfolding. My laboratory has used a combination of molecular, cellular continues to study the molecular mechanisms that underlie follicle stem cell activation, and in so doing have begun to realize that when sustained through genetic mutations, the pathways involved in stem cell activation lead to tumo igenesis and skin cancers Elaine Fuchs is internationally recognized for her contributions to skin biology and its human genetic disorders, including skin cancers and life-threatening genetic syndromes such as blistering skin disorders. For nearly three decades, Fuchs has focused on the molecular mechanisms that underlie the morphogenesis of the epidermis and its appendages, and how perturbations of these mechanisms result in disease. She has systematically and skillfully devised innovative molecular approaches to tackle these problems. She is credited for her pioneering use of "reverse genetics," an approach to start with a specific protein, study its biology and then use mice as a means to ultimately identify the genes responsible for inherited human disorders. A classical geneticist would start with a specific genetic disorder. Instead, Fuchs has employed this creative cell biological strategy to solve the genetic bases of a number of dermatological disorders in humans. The method has since broadly benefited human medical genetics. Fuchs is widely recognized as having brought the field of dermatological research into modern day science. Her contributions range from the identification of proteins and signal transduction pathways important in epidermal and hair functions to uncovering of the molecular nature of skin diseases in humans. Fuchs and coworkers identified genetic defects in several disorders from perturbations of cytoskeletal proteins related to those present in the skin, but whose expression resides outside the skin, particularly in the muscle and the nervous system. An elegant example is reverse genetics to uncover the underlying genetic basis of blistering human skin disorder that arises from defects in epidermal keratin genes. Her 10 years of prior research set the groundwork for this discovery, which uncovered a key function of intermediate filament (IF) proteins as mechanical integrators of the cytoskeleton. The work also set the paradigm for >20 different human disorders of IF genes that affect many different tissues of the body. Her ground-breaking research is often used in biolgy and medical textbooks as a landmark http://www.hhmi.org/research/investigators/fuchs_bio.html WALS.
Subjects: Skin--cytology
Stem Cells--physiology
Publication Types: Lectures
Webcasts
Download: To download this event, select one of the available bitrates:
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NLM Classification: QU 325
NLM ID: 101475695
CIT Live ID: 6221
Permanent link: http://videocast.nih.gov/launch.asp?14468

 

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