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POLARIZATION OF ADULT STEM CELLS, THE ROLE OF VANGL IN SKIN HOMEOSTASIS AND CANCE

Award Number: F32AR060166
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2010
PERIOD OF PERFORMANCE END DATE: 08/31/2013

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POLARIZATION OF ADULT STEM CELLS, THE ROLE OF VANGL IN SKIN HOMEOSTASIS AND CANCE - DESCRIPTION (provided by applicant): This proposal aims to investigate the role of the Planar Cell Polarity pathway in regulating epithelial homeostasis and cancer progression. The skin is a fundamental human organ that is continually shedding and making new cells and hairs. Adult stem cells orchestrate this cycle of self renew via a complex set of molecular signals. Understanding precisely what these signals do to the cells is an extremely active area of research. One signaling pathway that remains unexplored during skin homeostasis is the Planar Cell Polarity Pathway (PCP). All multicellular organisms exhibit some degree of polarity, and use conserved sets of genes to establish it. Two such conserved genes are Vangl1 and Vangl2, members of the PCP pathway. These genes can regulate a variety of cellular outputs from migration to the production of stereocillia. Both Vangl1 and Vangl2 are expressed in the adult epidermis. This proposal will define the precise epidermal compartments that express each gene. It will also explore the function of these genes during normal skin activity by knocking-out the genes in mice. The effect on the cells will be explored, from changes in the differentiation state of the stem cells to altered expression or localization patterns of adhesion molecules. Different mechanisms are likely employed for the production of new skin cells versus the production of a new hair. Cancer is a major health concern worldwide and one of the most brutal killers of all human diseases. Understanding the molecular switch from a normal to a cancer cell, the mechanisms that allow metastasis, and the precise causes of death by these aberrant cells are essential to finding a cure. The Vangl genes have recently been implicated in metastatic cancers. The Watt lab has a number of tumor models that will facilitate the study of Vangl genes during skin cancer progression. Changes in localization or activity of these genes may promote metastasis via increased migration or loss of adhesion. These possibilities will be explored. PUBLIC HEALTH RELEVANCE: The aim of this grant is to explore the basic biology of skin and hair self- renewal. These processes may be disrupted in skin related disease such as psoriasis, alopecia and chronic ulcers. This grant will also investigate the mechanisms underlying the causes of skin cancer metastasis.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2012 ( Subtotal = $7,850 )
2012	2012	CANCER RESEARCH UNITED KINGDOM	61 Lincolns Inn Fields	CAMBRIDGE				GBR	Arthritis, Musculoskeletal and Skin Diseases Research	002	3	9/4/2012	NON-COMPETING CONTINUATION	$7,850
														Subtotal = $7,850

Issue Date FY: 2011 ( Subtotal = $7,850 )
2011	2011	CANCER RESEARCH UNITED KINGDOM	61 Lincolns Inn Fields	CAMBRIDGE				GBR	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	8/17/2011	NON-COMPETING CONTINUATION	$7,850
														Subtotal = $7,850

Issue Date FY: 2010 ( Subtotal = $7,850 )
2010	2010	CAMBRIDGE RESEARCH INSTITUTE	LI KA SHING CENTRE	CAMBRIDGE				GBR	Arthritis, Musculoskeletal and Skin Diseases Research	003	1	9/14/2010	NEW	$0
2010	2010	CANCER RESEARCH UNITED KINGDOM	61 Lincolns Inn Fields	CAMBRIDGE				GBR	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	8/16/2010	NEW	$7,850
														Subtotal = $7,850

Grand Total All Awards = $23,550

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POLARIZATION OF ADULT STEM CELLS, THE ROLE OF VANGL IN SKIN HOMEOSTASIS AND CANCE

Award Number: F32AR060166

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2010

PERIOD OF PERFORMANCE END DATE: 08/31/2013

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