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REGULATION OF EPIDERMAL DIFFERENTIATION ON ENGINEERED POLYMER SUBSTRATES

Award Number: F32AR056182
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: 12/01/2008
PERIOD OF PERFORMANCE END DATE: 09/30/2010

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REGULATION OF EPIDERMAL DIFFERENTIATION ON ENGINEERED POLYMER SUBSTRATES - DESCRIPTION (provided by applicant): Integrin-mediated adhesion plays a central role in numerous cellular processes including proliferation, migration, and differentiation. Within the epidermis of the skin, integrin receptors are known to influence stem cell differentiation; however, the mechanism by which cues from the ECM coordinate with other signaling pathways to determine cell fate remains unclear. The overall goal of this research proposal is to investigate the interaction between integrin-mediated adhesion and beta-catenin related signaling pathways in the regulation of epidermal differentiation. The proposed studies will employ engineered polymer substrates to control the type, density, and spatial organization of cell-adhesive ligands presented to the cells. The influences of these defined cell-matrix interactions on epidermal differentiation will be examined using keratinocytes isolated from wild type mice and transgenic mice with inducible beta-catenin, Notch, and c-Myc expression. The central hypothesis for this work is that integrin-mediated adhesion to the extracellular matrix regulates keratinocyte differentiation and that these responses are modulated by the strength of beta-catenin signaling and other related pathways. This research will be carried out in three specific aims: Aim 1: Develop poly-(OEGMA) substrates presenting controlled densities and patterns of cell adhesive ligands to modulate keratinocyte adhesion and morphology. Aim 2: Examine the effects of integrin-mediated adhesion to engineered substrates on keratinocyte proliferation and in vitro differentiation. Aim 3: Investigate the interactions between integrin-mediated adhesion and beta-catenin related pathways in the regulation epidermal differentiation. The successful completion of this research proposal will provide significant insights into the interacting roles of multiple pathways involved in the regulation of epidermal differentiation. The long term objective is to establish novel experimental systems that will improve the fundamental understanding of stem cell lineage selection, differentiation, and self renewal. This research has important implications in the field of cancer cell biology. Since integrin and beta-catenin signaling also influence tumor development and invasion, insights into the behavior of epidermal stem cells will advance the current understanding of skin cancer pathology and aid in the development of therapeutic agents.


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: 2011 ( Subtotal = -$6,966 )
2011	2010	CANCER RESEARCH UK CAMBRIDGE RES INST	INSTITUTE LI KA SHING CENTRE, ROBINSON WAY	CAMBRIDGE				GBR	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/23/2010	NON-COMPETING CONTINUATION	-$6,966
2011	2010	IMPERIAL CANCER RESEARCH FUND	LINCOLNS INN FIELDS	LONDON		00000		GBR	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	12/23/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = -$6,966

Issue Date FY: 2010 ( Subtotal = $49,646 )
2010	2010	CANCER RESEARCH UK CAMBRIDGE RES INST	INSTITUTE LI KA SHING CENTRE, ROBIN	Cambridge				GBR	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	1/11/2010	NON-COMPETING CONTINUATION	$41,796
2010	2010	IMPERIAL CANCER RESEARCH FUND	LINCOLNS INN FIELDS	LONDON				GBR	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	1/13/2010	NON-COMPETING CONTINUATION	$7,850
														Subtotal = $49,646

Issue Date FY: 2008 ( Subtotal = $46,826 )
2008	2008	IMPERIAL CANCER RESEARCH FUND	LINCOLNS INN FIELDS	LONDON		00000		GBR	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	8/13/2008	NEW	$7,850
2008	2008	CANCER RESEARCH UK CAMBRIDGE RES INST	INSTITUTE LI KA SHING CENTRE, ROBINSON WAY	CAMBRIDGE				GBR	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/11/2008	NEW	$38,976
														Subtotal = $46,826

Grand Total All Awards = $89,506

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REGULATION OF EPIDERMAL DIFFERENTIATION ON ENGINEERED POLYMER SUBSTRATES

Award Number: F32AR056182

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: 12/01/2008

PERIOD OF PERFORMANCE END DATE: 09/30/2010

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