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Beta Cell Regeneration by Reprogramming of Adult Pancreatic Cells

Award Number: U01DK089566
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2010
PERIOD OF PERFORMANCE END DATE: 06/30/2015

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Beta Cell Regeneration by Reprogramming of Adult Pancreatic Cells - DESCRIPTION (provided by applicant): The overall goal of this proposal is to identify means for improving ?-cell regeneration in the adult pancreas. With previous BCBC funding we have developed a transgenic model of inducible total or partial ?-cell ablation (RIP-DTR). In these mice, ?-cell regeneration occurs after near total ?-cell loss, and this relies on the transdifferentiation of adult mature ?-cells to ?-cells. In this proposal we will test, among different aspects, i) whether ?-cell regeneration in RIP-DTR mice can be enhanced by promoting the observed spontaneous ?-to-?-cell conversion. ?-cell regeneration occurs by ?-cell replication in other diabetes models of less severe ?-cell ablation. Regeneration in RIP-DTR mice is less efficient than in these mouse models probably because DT treatment leaves almost no ?-cells (DT stands for diphtheria toxin, the agent used to induce ?-cell ablation in these mice). Accordingly, ?-cell repopulation principally occurs in RIP-DTR mice by a mechanism of ?-cell reprogramming. One of our objectives will be ii) to determine if age plays a role in ?-cell regeneration / ?-cell reprogramming , since proliferation in islets has been shown to profoundly decline in older rodents and humans. In addition, we will examine the molecular mechanisms controlling ?- to ?-cell transdifferentiation in RIP-DTR mice. These analyses will be performed in parallel with studies aimed at iii) exploring whether cell fate reprogramming is a common feature of different adult pancreatic cell types, and is not restricted to ? - cells only. The heterologous origin of new ?-cells is particularly interesting, since the almost complete ?-cell depletion achieved in RIP-DTR mice recreates a condition very similar to the situation found in Type 1 diabetic patients.


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: 2014 ( Subtotal = $100,000 )
2014	2014	UNIVERSITY OF GENEVA SCHOOL OF MEDICINE	1 RUE MICHEL-SERVET	GENEVA				CHE	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	7/30/2014	NON-COMPETING CONTINUATION	$100,000
														Subtotal = $100,000

Issue Date FY: 2013 ( Subtotal = $218,123 )
2013	2013	UNIVERSITY OF GENEVA SCHOOL OF MEDICINE	1 RUE MICHEL-SERVET	GENEVA				CHE	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	8/8/2013	EXTENSION WITH OR WITHOUT FUNDS	$218,123
														Subtotal = $218,123

Issue Date FY: 2012 ( Subtotal = $235,008 )
2012	2012	UNIVERSITY OF GENEVA SCHOOL OF MEDICINE	1 RUE MICHEL-SERVET	GENEVA				CHE	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/3/2012	NON-COMPETING CONTINUATION	$235,008
														Subtotal = $235,008

Issue Date FY: 2011 ( Subtotal = $234,048 )
2011	2011	UNIVERSITY OF GENEVA SCHOOL OF MEDICINE	1 RUE MICHEL-SERVET	GENEVA		00000		CHE	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/18/2011	NON-COMPETING CONTINUATION	$0
2011	2011	UNIVERSITY OF GENEVA SCHOOL OF MEDICINE	1 RUE MICHEL-SERVET	GENEVA				CHE	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/8/2011	NON-COMPETING CONTINUATION	$234,048
														Subtotal = $234,048

Issue Date FY: 2010 ( Subtotal = $234,048 )
2010	2010	UNIVERSITY OF GENEVA SCHOOL OF MEDICINE	1 RUE MICHEL-SERVET	GENEVA				CHE	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/10/2010	NEW	$234,048
														Subtotal = $234,048

Grand Total All Awards = $1,021,227

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Beta Cell Regeneration by Reprogramming of Adult Pancreatic Cells

Award Number: U01DK089566

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/10/2010

PERIOD OF PERFORMANCE END DATE: 06/30/2015

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