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Integrating Computational and Experimental Models to Predict Toxicity of the Pancreas

Award Number: R21DK134931
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Integrating Computational and Experimental Models to Predict Toxicity of the Pancreas - PROJECT SUMMARY The CDC SEARCH for Diabetes in Youth study found that Type I Diabetes (T1D) incidence increased by 1.8% each year between 2002-2012, and Type II Diabetes (T2D) increased by 4.8%. The Environmental Determinants of Diabetes in the Young (TEDDY) study has attributed a substantial burden of T1D and T2D to environmental contaminants. Due to the increasing prevalence of diabetes and metabolic diseases (especially among youth), computational models for developmental pancreatic toxicity are needed. Understanding how multiple factors such as chemical structure, gene expression and target tissue cytotoxicity integrate and impact pancreatic health is vital. However, an integrated analysis of multiple factors at multiple scales poses great challenges due to the inherent complexity, high-dimensionality, uncertainty, and heterogeneity. Multilayer networks have emerged as a novel methodology in network science that combines multiple networks, called “layers”, into one mathematical object. Multilayer networks are able to represent multiple factors across multi- scales for a rigorous computational analysis of their interactions. Thereby, uncovering novel relations between key factors on a multi-scale. The overarching goal of this research is to create multilayer network models by which we can predict the magnitude and mechanisms of pancreatic developmental toxicity based on chemical structure in a zebrafish (Danio rerio) model. Aim 1 will build a Quantitative Structure-Activity Relationship (QSAR) model to predict mechanisms of toxicity resulting from pharmacological and toxicological exposures in the developing pancreas. The goal of Aim 1 is to utilize a multilayer network and topological clustering model to predict the relationship between exposures and pancreatic developmental toxicity based on chemical structure. Aim 2 will utilize multi-scale modeling to create an Adverse Outcome Pathway (AOP) using molecular, structural, and pathological criteria for pancreatic developmental toxicity. The goal of Aim 2 is to characterize the processes by which exposures may disrupt pancreas development and early diabetic pathogenesis. We will develop a rigorous predictive model that can be used to better inform a priori testing and expected outcomes of small molecules in the context of pancreatic developmental diseases, and we will construct a framework to connect peroxisome proliferator-activated receptor (PPAR) modulation (pharmacological & toxicological) with aberrant pancreatic development and early function.


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: 2025 ( Subtotal = $164,201 )
2025	2025	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/6/2025	NON-COMPETING CONTINUATION	$164,201
														Subtotal = $164,201

Issue Date FY: 2024 ( Subtotal = $175,148 )
2024	2024	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/15/2024	NON-COMPETING CONTINUATION	$10,947
2024	2024	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR MC1947	SAN DIEGO	CA	92182	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/25/2024	NON-COMPETING CONTINUATION	$164,201
														Subtotal = $175,148

Issue Date FY: 2023 ( Subtotal = $182,446 )
2023	2023	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR MC1947	SAN DIEGO	CA	92182	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/3/2023	NEW	$182,446
														Subtotal = $182,446

Grand Total All Awards = $521,795

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Integrating Computational and Experimental Models to Predict Toxicity of the Pancreas

Award Number: R21DK134931

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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