The candidate is a junior researcher with considerable experience in studies of nonalcoholic fatty liver disease (NAFLD), metabolic syndrome and autophagy. However, in order for the applicant to transition into a fully independent investigator, an additional supervised training period is imperative. Dr. Mark J. Czaja has extensive research experience in the study of liver physiology, NAFLD and autophagy, will serve as an ideal mentor for this additional training. The research project will be carried out in the Marion Bessin Liver Research Center at the Albert Einstein College of Medicine which offers a scientifically motivating and inspiring environment and has a well-established liver research facility ideally suited to study altered cellular metabolism and physiology. The proposed five year career development plan is focused on: i) conferring upon the candidate a strong background in liver research, ii) improving his research skills and fundamentals as well as the learning of new experimental approaches, iii) facilitating productive collaborations with established researchers and iv) developing his teaching, training, and group leadership skills. The main goal of the current research project is to understand the mechanisms by which macroautophagy functions as a critical regulator of cellular lipid content through organ specific effects which lead to manifestations of the metabolic syndrome. We propose to test the hypothesis with studies in hepatocyte, adipocyte and a hypothalamic cells and autophagy knockout mouse models to delineate the function of autophagy in three interrelated organs that regulate whole body energy content and hepatic lipid accumulation. The studies are divided into three specific aims. First, we will determine whether macroautophagy regulates the development of steatohepatitis and hepatic insulin resistance. Second, we will establish that autophagy regulates adipose tissue mass and lipid content through effects on adipocyte differentiation. Third, we will demonstrate that autophagy regulates hypothalamic lipid metabolism in response to circulating nutrients, which then modulates orexigenic peptide secretion and food intake. The ultimate goal of these investigations is to better understand basic cellular mechanisms in three interrelated organs that regulate lipid metabolism and lipid accumulation in order to design new strategies for the prevention and treatment of human NAFLD.

Public Health Relevance

Metabolic syndrome and NAFLD are prevalent clinical conditions that have no known treatment. Attempts to understand the mechanisms of lipid metabolism in three interrelated organs that crosstalk with each other to regulate lipid metabolism are critical to the development of new strategies for the prevention and treatment of NAFLD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK087776-04
Application #
8457134
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
2010-05-01
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$98,474
Indirect Cost
$7,294
Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Martinez-Lopez, Nuria; Garcia-Macia, Marina; Sahu, Srabani et al. (2016) Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver. Cell Metab 23:113-27
Ward, Carl; Martinez-Lopez, Nuria; Otten, Elsje G et al. (2016) Autophagy, lipophagy and lysosomal lipid storage disorders. Biochim Biophys Acta 1861:269-84
Martinez-Lopez, Nuria; Athonvarangkul, Diana; Singh, Rajat (2015) Autophagy and aging. Adv Exp Med Biol 847:73-87
Martinez-Lopez, Nuria; Singh, Rajat (2015) Autophagy and Lipid Droplets in the Liver. Annu Rev Nutr 35:215-37
Martinez-Lopez, Nuria; Singh, Rajat (2014) ATGs: Scaffolds for MAPK/ERK signaling. Autophagy 10:535-7
Nagajyothi, Fnu; Kuliawat, Regina; Kusminski, Christine M et al. (2013) Alterations in glucose homeostasis in a murine model of Chagas disease. Am J Pathol 182:886-94
Martinez-Lopez, Nuria; Athonvarangkul, Diana; Mishall, Priti et al. (2013) Autophagy proteins regulate ERK phosphorylation. Nat Commun 4:2799
Martinez-Lopez, Nuria; Athonvarangkul, Diana; Sahu, Srabani et al. (2013) Autophagy in Myf5+ progenitors regulates energy and glucose homeostasis through control of brown fat and skeletal muscle development. EMBO Rep 14:795-803
Singh, Rajat; Cuervo, Ana Maria (2012) Lipophagy: connecting autophagy and lipid metabolism. Int J Cell Biol 2012:282041
Klionsky, Daniel J (author list too long to display - see original citation for additional authors) (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445-544

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