Forchheimer Building 505D
Associate Professor, Department of Medicine (Endocrinology)
Associate Professor, Department of Molecular Pharmacology
AUTOPHAGY AND INTEGRATIVE PHYSIOLOGY
Autophagy is a cellular recycling program that degrades unwanted cytoplasmic contents within lysosomes. Autophagy occurs at basal levels in all cells and is induced during starvation and stress. Autophagy requires the de novo formation 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 research focus of the laboratory is to examine the organ-specific roles of autophagy in the regulation of lipid metabolism and energy/ glucose homeostasis using biochemical, immunohisto- chemical, and image-based approaches in vitro and in conditional knockout mouse models. Our interests lie in the understanding of how hypothalamic autophagy controls energy expenditure in peripheral tissues by influencing lipid metabolism and tissue differentiation in peripheral tissues.
The second research focus of the laboratory is to examine the consequences of aging-associated reduction of autophagy on the development of the metabolic syndrome of aging. We are currently 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 understand how to activate autophagy to prevent diabetes and improve the health-span in the aging population.
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 2015 (in-press).
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 and aging. Martinez-Lopez N, Athonvarangkul D, Singh R. Advances in Experimental Medicine and Biology 2015; 847: 73-87. | PubMed
ATGs: Scaffolds for MAPK/ERK signaling. Martinez-Lopez N, Singh R. Autophagy 2014; 10(3): 535-537. | PubMed
Autophagy proteins regulate ERK phosphorylation. Martinez-LopezN, Athonvarangkul D, Mishall P, SahuS, 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, AthonvarangkulD, Sahu S, ColettoL, Zong H, Bastie CC, Pessin JE, SchwartzGJ, Singh R. EMBO Reports 2013; 14(9): 795-803. | PubMed
Alterations in glucose homeostasis in a murine model of chagas disease. Nagajyothi F, Kuliawat R, Kusminski CM, Machado FS, Desruisseaux MS, Zhao D, Schwartz GJ, Huang H, Albanese C, Lisanti MP, Singh R, Li F, Weiss LM, Factor SM, Pessin JE, Scherer PE, Tanowitz HB. American Journal of Pathology 2013; 182(3): 886-94. | PubMed
Guidelines for the use and interpretation of assays for monitoring autophagy. Klionsky DJ,… Singh R,…Zschocke J, Zuckerbraun B. Autophagy 2012; 8(4): 445-544. | PubMed
Mapping autophagy onto your metabolic radar. Yamada E, Singh R. Diabetes 2012; 61(2): 272-80. | PubMed
Autophagy in the control of food intake. Singh R. Adipocyte 2012; 1(2): 75-79. | 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. | PubMed
Issue Cover | Link
Recommended by Faculty of 1000
Hypothalamic lipophagy and energetic balance. Singh R. Aging (Albany NY) 2011; 3(10): 934-942. | PubMed
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 |Link
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, The Fox News, EurekAlert.com, Jay Leno, National Public Radio
Recommended by Faculty of 1000
Autophagy and regulation of lipid metabolism. Singh R. Volume: Sensory and Metabolic Control of Energy Balance. Springer-Verlag. 2010; 52: 35-46. | Link
Autophagic pathways and metabolic stress. Kaushik S, Singh R, Cuervo AM. Diabetes, Obesity and Metabolism 2010; 12 Suppl 2: 4-14. | PubMed
Macroautophagy regulates energy metabolism during effector T cell activation. Hubbard VM, Valdor R, Patel B, Singh R, Cuervo AM, Macian F. Journal of Immunology 2010; 185(12): 7349-7357. | PubMed
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. Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistance to oxidant stress. 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
Recommended by Faculty of 1000 Biology
Autophagy regulates lipid metabolism. Singh R,* Kaushik S,* Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo, A.M., Czaja, M.J. 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. | PubMed
Preview: Weidberg H, Shvets E, Elazar Z. Lipophagy: Selective catabolism designed for lipids. Dev Cell 2009; 16: 628-30. | PubMed
Hepatology Elsewhere: Kersten S, Müller M. Dropping liver fat droplets. Hepatology 2009; 50: 645-647. | PubMed
Recommended by Faculty of 1000 Biology
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. | PubMed
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