Einstein/Montefiore Department of Medicine

Department Faculty

Dr. Rajat Singh, M.D.,  M.B.B.S.

Rajat Singh, M.D., M.B.B.S.

Associate Professor, Department of Medicine (Endocrinology)

Associate Professor, Department of Molecular Pharmacology

Areas of Research: We are interested in studying the roles of autophagy in metabolic regulation in physiology, during obesity, and with age.

Professional Interests

AUTOPHAGY AND INTEGRATIVE PHYSIOLOGY

Macroautophagy (or autophagy) is a cellular recycling program that degrades unwanted cytoplasmic contents in lysosomes.  Autophagy occurs at basal levels in all cells and is induced during starvation and stress.  Autophagy requires the de novformation of a double-walled limiting membrane that sequesters cargo destined for degradation and seals upon itself to form an autophagosome.  The delivery of the engulfed cargo to lysosomes by autophagosome-lysosome fusion results in cargo degradation.  We demonstrated a role for autophagy in mobilization and degradation of intracellular lipid stores by a process we termed lipophagy, thus mapping autophagy to metabolic regulation.  We have recently shown that lipophagy in  hypothalamic neurons generates neuron-intrinsic free fatty acids that drive neuronal feeding mechanisms.  The primary  focus of the laboratory is to examine the organ-specific roles of autophagy in the regulation of lipid metabolism and energy homeostasis using biochemical, immunohistochemical, and image-based approaches in vitro and in conditional knockout mouse models. More specifically, our interests lie in understanding how autophagy in the CNS and peripheral tissues controls energy, glucose, and lipid metabolism in a time-, diet-, and age-dependent manner.  The second focus of the laboratory is to examine the consequences of aging-associated reduction of autophagy on the development of the metabolic syndrome.  We are interested in understanding how autophagy decreases with age, and whether restoration of autophagy prevents the metabolic syndrome of aging. Our long term goals are to develop ways to activate autophagy and improve healthspan in the obese and aging population.

 

Selected Publications

 

Blocking p62/SQSTM1-dependent SMN degradation ameliorates Spinal Muscular Atrophy disease phenotypes.
Rodriguez-Muela N, Parkhitko A, Grass T, Gibbs RM, Norabuena EM, Perrimon N, Singh R, Rubin LL.
Journal of Clinical Investigation. 2018; Epub ahead of print. PubMed  

System-wide benefits of intermeal fasting by autophagy.
Martinez-Lopez N, Tarabra E, Toledo E, Garcia-Macia M, Sahu S, Coletto L, Batista-Gonzalez A, Barzilai N, Pessin JE, Schwartz GJ, Kersten S, Singh R.
Cell Metabolism. 2017; 26: 856-871. PubMed
Highlighted: Nature Reviews in Endocrinology  

Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance.
Ito K, Turcotte R, Cui J, Zimmerman SE, Pinho S, Mizoguchi T, Arai F, Runnels JM, Alt C, Teruya-Feldstein J, Mar JC, Singh R, Suda T, Lin CP, Frenette PS, Ito K.
Science. 2016; 354: 1156-1160. PubMed  

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky DJ, … Singh R, … Zughaier SM.
Autophagy. 2016; 12: 1-222. PubMed

Autophagy in the CNS and periphery coordinate lipophagy and lipolysis in the brown adipose tissue and liver.
Martinez-Lopez N, Garcia-Macia M, Sahu S, Athonvarangkul D, Liebling E, Merlo P, Cecconi F, Schwartz GJ, Singh R.
Cell Metabolism. 2016; 23: 113-127. PubMed

Autophagy and lipid droplets in the liver.
Martinez-Lopez N, Singh R.
Annual Review of Nutrition. 2015; 35: 215-237. PubMed   

Loss of the RNA polymerase III repressor MAF1 confers obesity resistance.
Bonhoure N, Byrnes A, Moir RD, Hodroj W, Preitner F, Praz V, Marcelin G, Chua SC Jr, Martinez-Lopez N, Singh R, Moullan N, Auwerx J, Willemin G, Shah H, Hartil K, Vaitheesvaran B, Kurland I, Hernandez N, Willis IM.
Genes & Development. 2015; 29: 934-947. PubMed

Autophagy proteins regulate ERK phosphorylation.
Martinez-Lopez N, Athonvarangkul D, Mishall P, Sahu S, Singh R.
Nature Communications. 2013; 4: 2799. PubMed   

Autophagy in Myf5+ progenitors regulates energy and glucose homeostasis through control of brown fat and skeletal muscle development.
Martinez-Lopez N, Athonvarangkul D, Sahu S, Coletto L, Zong H, Bastie CC, Pessin JE, Schwartz GJ, Singh R.
EMBO Reports. 2013; 14(9): 795-803. PubMed

Mapping autophagy onto your metabolic radar.
Yamada E, Singh R.
Diabetes. 2012; 61: 272-280. PubMed  

Loss of autophagy in hypothalamic POMC neurons impairs lipolysis.
Kaushik S, Arias E, Kwon H, Martinez-Lopez N, Sahu S, Schwartz GJ, Pessin JE, Singh R.
EMBO Reports. 2012; 13(3): 258-265. PubMed
Comment: Rubinsztein DC. Autophagy-alias self-eating-appetite and ageing. EMBO Reports 2012;13(3):173-174.   

Issue Cover  
Recommended by F1000 Prime

Autophagy in the cellular energetic balance. 
Singh R, Cuervo AM.
Cell Metabolism. 2011; 13: 495-504. PubMed
Cell Metabolism: Top 10 Reviews, 2005-2014, as chosen by the readers 

Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. 
Kaushik S, Rodriguez-Navarro, JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, Cuervo AM, Singh R
Cell Metabolism. 2011; 14: 173-183. PubMed
Featured: The Scientist magazine, The Los Angeles Times, Fox News, EurekAlert.com, Jay Leno, National Public Radio  
Recommended by F1000 Prime

Nuclear factor κB up-regulation of CCAAT/enhancer-binding protein β mediates hepatocyte resistance to tumor necrosis factor α toxicity.
Wang Y, Singh R, Xiang Y, Greenbaum LE, Czaja MJ. 
Hepatology. 2010; 52: 2118-2126. PubMed 

Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistance to oxidant stress.
Wang Y, Singh R, Xiang Y, Czaja MJ. 
Hepatology. 2010; 52: 266-277. PubMed

Autophagy regulates adipose mass and differentiation. 
Singh R, Xiang Y, Wang Y, Baikati K, Cuervo AM, Luu YK, Tang Y, Pessin JE, Schwartz GJ, Czaja MJ.
Journal of Clinical Investigation. 2009; 119(11): 3329-3339. PubMed
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Autophagy regulates lipid metabolism. 
Singh R,* Kaushik S,* Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo, AM, Czaja, MJ.
Nature. 2009; 458: 1131-1135. *co-first authors PubMed  
Nature News and Views: Zechner R, Madeo F. Cell biology: Another way to get rid of fat. Nature 2009; 458: 1118-1119.   
Preview: Weidberg H, Shvets E, Elazar Z. Lipophagy: Selective catabolism designed for lipids. Dev Cell 2009; 16: 628-30. 
Hepatology Elsewhere: Kersten S, Müller M. Dropping liver fat droplets. Hepatology 2009; 50: 645-647. 
Featured in communication media: ABC, BBC, Discover Magazine, Science Central, Science Daily, Washington Post
Recommended by F1000 Prime

Differential effects of JNK1 and JNK2 inhibition on insulin resistance and steatohepatitis.
Singh R, Wang Y, Xiang Y, Tanaka KE, Gaarde WA, and Czaja MJ. 
Hepatology. 2009; 49: 87-96. PubMed
Comment: c-Jun N-terminal kinase signaling in the pathogenesis of nonalcoholic fatty liver disease: Multiple roles in multiple steps. Kodama Y, Brenner DA. Hepatology 2009; 49: 6-8.

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Research Information

In the News

The Los Angeles Times's "Booster Shots" blog reports on new research by Dr. Rajat Singh that shows dieting causes certain brain cells to start eating small portions of themselves — triggering a hunger response.

More media coverage