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Faculty Profile

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

Dr. Rajat Singh

Assistant Professor, Department of Medicine (Endocrinology)

Assistant Professor, Department of Molecular Pharmacology

 

Professional Interests

Autophagy or “self-eating” is an in-bulk lysosomal degradative pathway that plays a crucial role in cellular homeostasis through protein and organelle turnover. Autophagy occurs at basal levels in all cells and is induced following conditions such as stress or nutrient-deprivation. Briefly, the process of autophagy requires the de novo formation of a double-walled limiting membrane that engulfs cellular cargo destined for degradation and then seals upon itself to form an autophagosome. The delivery of the engulfed cargo to the lysosome occurs by fusion of the autophagosome with the lysosome leading to degradation of the cargo. We have recently demonstrated a novel role of autophagy in the mobilization and degradation of intracellular lipid stores in the liver, thus pointing to a possible function of autophagy in energy homeostasis. We have also recently shown that this lipophagic role of autophagy functions in hypothalamic neurons to generate neuron-intrinsic free acids that, in turn, drive neuronal feeding mechanisms.

The primary focus of the lab is to examine the organ-specific roles of autophagy in the regulation of lipid metabolism and energy homeostasis using biochemical, immunochemical, and image-based approaches in vitro and in conditional knockout mouse models.

We are interested in understanding:

1. How autophagy in discrete hypothalamic neurons controls food intake and energy expenditure in peripheral tissues?

2. The signaling mechanisms that regulate autophagy in response to nutrient signals

3. Physiological roles for autophagy in adipocytes and adipose progenitors, for instance, myogenic Myf5+ progenitors 

Aging is considered to reduce autophagic activity. The second focus of the laboratory is to examine the effect of aging-induced reduction of hypothalamic and adipose autophagy on the development of the metabolic syndrome of aging. 

 

Selected Publications

Martinez-Lopez N, Athonvarangkul D, Mishall P, Sahu S, Singh R. Autophagy proteins regulate ERK phosphorylation. Nature Communications 2013 Nov 18;4:2799. doi: 10.1038/ncomms3799.

Martinez-Lopez N*, Athonvarangkul D*, Sahu S, Coletto L, Zong H, Bastie CC, Pessin JE, Schwartz GJ, Singh R. Autophagy in Myf5+ progenitors regulates energy and glucose homeostasis through control of brown fat and skeletal muscle. EMBO Reports 2013 Aug 2. doi: 10.1038/embor.2013.111. 

 

Kaushik S, Arias E, Kwon H, Martinez-Lopez N, Athonvarangkul D, Sahu S, Schwartz GJ, Pessin JE, Singh R. Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO Reports 2012 Jan 17. doi: 10.1038/embor.2011.260. 

- Recommended by Faculty of 1000

 

Yamada E, Singh R. Mapping autophagy on to your metabolic radar. Diabetes. 2012 Feb;61(2):272-80.

 
Kaushik S, Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, Cuervo AM, Singh R. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metabolism 2011 Aug 3;14(2):173-83.
- Recommended by Faculty of 1000

Singh R*, Cuervo AM*. Autophagy in the cellular energetic balance. Cell Metabolism 2011;13(5):495-504.
 
Wang Y, Singh R, Xiang Y, Greenbaum LE, Czaja MJ. Nuclear factor κB up-regulation of CCAAT/enhancer-binding protein β mediates hepatocyte resistance to tumor necrosis factor α toxicity. Hepatology 2010;52(6):2118-26. 

Singh R. Autophagy and regulation of lipid metabolism. Results Probl. Cell Differentiation 2010;52:35-46. 
 
Wang Y,* Singh R,* Xiang Y, Czaja MJ. Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistant to oxidative stress. Hepatology 2010;52(1):266-77. 

Singh R, Xiang Y, Wang Y, Baikati K, Cuervo AM, Luu YK, Tang Y, Pessin JE, Schwartz GJ, Czaja MJ. Autophagy regulates adipose mass and differentiation in mice. J. Clin. Investigation 2009; 119(11):3329-39.
- Recommended by Faculty of 1000

Singh R,* Kaushik S,* Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ.  Autophagy regulates lipid metabolism. Nature 2009; 458:1131-1135.
- Recommended by Faculty of 1000
 
Singh R, Wang Y, Xiang Y, Tanaka KE, Gaarde WA, Czaja MJ. Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology 2009; 49:87-96. 

 

 

Research Images

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More Information About Dr. Rajat Singh

http://www.einstein.yu.edu/departments/molecular-pharmacology/our-researchers.asp?rid=9820

http://rajatsinghlab-com.webs.com

Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.

Contact

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 505D
Bronx, NY 10461

Tel: 718.430.4118
rajat.singh@einstein.yu.edu

 
Pubmed Search
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Media Coverage

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