We are testing a new system for linking grants to scientists.
The funding information displayed below comes from the
NIH Research Portfolio Online Reporting Tools and the
NSF Award Database.
The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
You can help! If you notice any innacuracies, please
sign in and mark grants as correct or incorrect matches.
Sign in to see low-probability grants and correct any errors in linkage between grants and researchers.
High-probability grants
According to our matching algorithm, Jonathan Z. Long is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2021 |
Long, Jonathan Zhong |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Chemical Control of Energy Metabolism by N-Acyl Amino Acids
We are in the midst of an epidemic of obesity and type 2 diabetes. The discovery of new pathways of energy metabolism is critically needed to address this pressing medical problem. Using untargeted metabolomics, we have identified a new pathway of energy expenditure mediated by family of bioactive lipids called N-acyl amino acids. Certain N-acyl amino acids and stimulate mitochondrial respiration by promoting proton leak. We have also de-orphanized a novel upstream enzyme, PM20D1 (peptidase M20 domain containing 1), that functions as an extracellular N-acyl amino acid synthase/hydrolase. Pharmacological or genetic elevation of circulating N-acyl amino acids increases energy expenditure, reduces adiposity, and improves glucose homeostasis in mouse models of diet-induced obesity. However, we are still early in our understanding of N-acyl amino acids. What remains unknown is how N-acyl amino acids promote proton conductance across the inner mitochondrial membrane, what other extracellular mechanisms regulate N- acyl amino acid levels, and whether this pathway could be useful for the treatment of obesity-associated disorders. Answers are critically needed to understand the biology and therapeutic potential of this energy expenditure pathway in metabolic disease. The long-term goal of this project is to harness energy expenditure pathways for the treatment of obesity and type 2 diabetes. The overall objective of this proposal is to mechanistically dissect the regulators of the N-acyl amino acid pathway and to assess the therapeutic potential of these bioactive lipids. Our central hypothesis is that N-acyl amino acid bioactivity is regulated by both intracellular and extracellular proteins, and that this pathway can be pharmacologically leveraged for the treatment of obesity and type 2 diabetes. We will test this hypothesis via three Specific Aims: 1) Determine how N-acyl amino acids stimulate uncoupled respiration; 2) Determine the mechanisms that control circulating N-acyl amino acid levels; and 3) Evaluate the bioactivity of synthetic N-acyl amino acid analogs in diet-induced obesity mouse models. Successful completion of this proposal will provide a detailed, mechanistic understanding of the regulation and function of N-acyl amino acids in energy metabolism, as well as a pharmacological evaluation of this pathway for the treatment of obesity-associated dis- eases such as type 2 diabetes.
|
1 |