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Faculty Detail    
Name SUSHANT BHATNAGAR
Assistant Professor 		 
Campus Address SHEL 1203 Zip 0012
Phone  (205) 996-0164
E-mail  sushantb@uab.edu
Other websites
     

Education
Graduate  West Virginia University, West Virginia     2008  Ph.D. 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Med - Endocrinology, Diabetes & Metabolism  Med - Endocrinology, Diabetes & Metabolism Associate Professor
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Associate Professor
Center  Nutrition Sciences Research  Nutrition Obesity Res Ctr (NORC) Associate Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Post-graduate Training Post Doctoral Fellow, 2009–12, Department of Biochemistry, University of Wisconsin, Madison, WI Project: Positional cloning and initial functional characterization of tomosyn-2 gene underlying diabetes susceptible quantitative trait locus in an F2 mouse cross between obese diabetes resistant, C57BL/6 and diabetes susceptible, BTBR mice. Assistant Scientist, 2012–15, Department of Biochemistry, University of Wisconsin, Madison, WI Project 1: Identification of the mechanism by which beta cells regulate insulin secretion by modulating phosphorylation and ubiquitination-dependent degradation of tomosyn-2. Identification of an E3-ubiquitin ligase that regulates the abundance of tomosyn-2 protein. Project 2: Developed a high through-put bioinformatic method to identify novel proteins that are involved in regulating metabolic processes as a function of obesity, age, and diabetes. Honors And Awards 1. Oral presentation award (3rd place), Midwest Islet Club conference, Mentor (with Trung Huynh), 2017 2. UAB Honors College Experimental Fellowship Program, Mentor (with Trung Huynh), 2017 3. Young Investigator Travel Grant Award to the American Diabetes Association, San Diego, CA, 2017 4. Certificate of participation for receiving a top scoring abstract at the ADA Scientific Sessions, San Diego, CA, 2017 5. Keystone Scholarship, Pathogenesis of Diabetes, Santa Fe, NM; Jan 29–Feb 3, 2012 6. Best Poster Award, FASEB Summer Conferences: Molecular Mechanisms Involved in the Nutrient Control of Cellular Function, Carefree, Arizona; July, 20–25, 2008 7. Best Poster Award, E. J. Van Liere Convocation and Research Day, WVU, WV, 2008 8. Top 10 Abstracts for Oral Presentation, E. J. Van Liere Convocation and Research Day, West Virginia University, 2008 9. Pfizer Global Research and Development Scholarship Award: Keystone Symposia on Diabetes Mellitus, Insulin Action, and Resistance, Breckenridge,CO, 2008 10. Graduate Student Travel Award, School of Medicine, West Virginia University Funding 1. UAB DRC Pilot and Feasibility award, 5P30DK079626-10, 2017 2. NIH NIDDK, 4 R00 DK95975-03, 2016 3. NIDDK K99 NIH Pathways to Independence Award Grant #1K99DK095975-01, 2014 4. American Diabetes Association Mentor-Based Fellowship 7-11-MN-03 07/01/11-06/30/12 Press 1. Work featured “ Diabetes gene identified: tomosyn-2 regulates insulin secretion” in several national and international media (Science Daily, USA; Press Association, UK; Times of India, India; etc.), October 2011 2. Work featured, “WVU research shows new class of hormones may reverse diabetes and obesity: Graduate student’s presentation wins international award” Pittsburgh Post-Gazette, October 2008. Service Ad Hoc reviewer for Diabetologia, PLoS One, and Lipids in Health and Disease journals

Society Memberships
Organization Name Position Held Org Link
ASBMB   Menber   
American Diabetes Association  Member   
Endocrinology Society     
Lab Website    https://www.bhatnagarlab.com 
UAB Center for Excercise and Medicine   Associate Scientist   
UAB Diabetes Research Center (DRC)  Member    
UAB Nutritional and Obesity Research Center (NORC)  Member   http://www.norc.uab.edu/people/sbhatnagar 
 



Research/Clinical Interest
Title
Identification and characterization of novel factors in insulin secretion in obesity and type 2 diabetes
Description
Type 2 diabetes is a serious public health problem in the United States that affects more than 29 million individuals. Obesity is the leading cause of type 2 diabetes. During obesity, individuals develop resistance to insulin, which leads to increase in blood glucose levels. It is critical to maintain normal blood glucose levels. Therefore, to compensate for elevated blood glucose levels, pancreatic beta cells increase secretion of insulin to maintain euglycemia. When beta cell function fails, predominately during obesity, insulin secretion decreases and this leads to type 2 diabetes. It is well established that greater than 80% of type 2 diabetic individuals are obese, however, not all obese individuals are diabetic. This suggests that the reduction of insulin secretion from pancreatic beta cells leads to type 2 diabetes in obese individuals. Therefore, identifying factors that cause reduction in insulin secretion will improve our understanding of mechanisms underlying progression to type 2 diabetes. We employ genetics, bioinformatics, and proteomics approaches to identify novel regulators of beta-cell function. Our lab is currently focused on the following projects: Project 1: The role of tomosyn in insulin secretion. I positionally cloned tomosyn-2 by using a forward genetics approach as a gene that increases susceptibility to type 2 diabetes. Tomosyn-2 is an inhibitor of insulin secretion. It works by limiting the formation of the SNARE-mediated fusion of insulin granules to the plasma membrane. However, the mechanism of tomosyn-2 action still remains relatively uncharacterized. We are utilizing biochemical, cell biological, and physiological approaches to investigate the mechanism of tomosyn-2 in beta-cells. Currently, we are using knockout mouse models to understand the role of tomosyn-2 and its closely related protein tomosyn-1 in beta cell function. Project 2: The role of complement 1q-like 3 (C1ql3) protein in beta-cell function. Using bioinformatics approaches, our laboratory has identified a novel signaling pathway in pancreatic beta cells. We showed that C1ql3, which is a secreted protein signals in an autocrine-dependent manner via its G-protein coupled receptor to inhibit insulin secretion from pancreatic beta cells. By using knockout mice, we are identifying the mechanism by which C1ql3 and its receptor inhibits beta cell function. Understanding the role of these proteins will provide insight to the mechanism by which insulin secretion is reduced in obesity that leads to type 2 diabetes.

Selected Publications 
Publication PUBMEDID
Ren G, Kim T, Kim HS, Young ME, Muccio DD, Atigadda VR, Blum SI, Tse HM, Habegger KM, Bhatnagar S, Coric T, Bjornsti MA, Shalev A, Frank SJ, Kim JA. (2020). A Small Molecule, UAB126, Reverses Diet-Induced Obesity and its Associated Metabolic Disorders. Diabetes. 2020 Jul 1:db191001. doi: 10.2337/db19-1001.   32782332  
Kim HS, Ren G, Kim T, Bhatnagar S, Yang Q, Bahk YY, Kim JA. (2020). Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells. Sci Rep. 2020 Aug 11;10(1):13523. doi: 10.1038/s41598-020-70347-w.   32782332  
Bethea, M., Liu, Y., Wade, A. K., Mullen, R., Gupta, R., Gelfanov, V., DiMarchi, R., Bhatnagar, S., Behringer, R., Habegger, K.M., Hunter, C (2018). Lhx1 is required for β-cell function via regulation of Glp1 receptor expression.Am J Physiol Endocrinol Metab. 2019 Mar 1;316(3): E397-E409  30620636 
Koltes JE, Arora I, Gupta R, Nguyen DC, Schaid M, Kim JA, Kimple ME, Bhatnagar S. (2019). A gene expression network analysis of the pancreatic islets from lean and obese mice identifies complement 1q-like-3 secreted protein as a regulator of beta-cell function. Sci Rep. 2019 Jul 12;9(1):10119. doi: 10.1038/s41598-019-46219-3.   31300714  
Gupta R, Nguyen DC, Schaid MD, Lei X, Balamurugan AN, Wong GW, Kim JA, Koltes JE, Kimple ME, Bhatnagar S. (2018). The C1ql3 secreted protein inhibits insulin secretion by cell adhesion G-protein coupled receptor, BAI3 from pancreatic beta-cells. J Biol Chem. 2018 Nov 23;293(47):18086-18098. doi: 10.1074/jbc.RA118.005403. Epub 2018 Sep 18.  30228187  
ASF1B Chaperones Histone 3.3 to the beta-cell cycle dance.
Banerjee RR, Bhatnagar S.
Cell Cycle. 2016 Nov 18:0. 		 27860543 
Phosphorylation and degradation of tomosyn-2 de-represses insulin secretion.
Bhatnagar S, Soni MS, Wrighton LS, Hebert AS, Zhou AS, Paul PK, Gregg T, Rabaglia ME, Keller MP, Coon JJ, Attie AD.
J Biol Chem. 2014 Sep 5;289(36):25276-86. doi: 10.1074/jbc.M114.575985. Epub 2014 Jul 7. 		 25002582  
Downregulation of carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretion.
Soni MS, Rabaglia ME, Bhatnagar S, Shang J, Ilkayeva O, Mynatt R, Zhou YP, Schadt EE, Thornberry NA, Muoio DM, Keller MP, Attie AD.
Diabetes. 2014 Nov;63(11):3805-14. doi: 10.2337/db13-1677. Epub 2014 Jun 26. 		 24969106  
Positional cloning of a type 2 diabetes quantitative trait locus; tomosyn-2, a negative regulator of insulin secretion.
Bhatnagar S, Oler AT, Rabaglia ME, Stapleton DS, Schueler KL, Truchan NA, Worzella SL, Stoehr JP, Clee SM, Yandell BS, Keller MP, Thurmond DC, Attie AD.
PLoS Genet. 2011 Oct;7(10):e1002323. doi: 10.1371/journal.pgen.1002323. Epub 2011 Oct 6. 		 21998599  
Fibroblast growth factor-19, a novel factor that inhibits hepatic fatty acid synthesis.
Bhatnagar S, Damron HA, Hillgartner FB.
J Biol Chem. 2009 Apr 10;284(15):10023-33. doi: 10.1074/jbc.M808818200. Epub 2009 Feb 20. 		 19233843 
Chenodeoxycholic acid suppresses the activation of acetyl-coenzyme A carboxylase-alpha gene transcription by the liver X receptor agonist T0-901317.
Talukdar S, Bhatnagar S, Dridi S, Hillgartner FB.
J Lipid Res. 2007 Dec;48(12):2647-63. Epub 2007 Sep 6. 		 17823458  
 

Keywords
Obesity, Type 2 Diabetes, Beta Cell Biology, Insulin Secretion, SNARE Biology, Secreted Proteins, Insulin Granule Trafficking, Tomosyn Proteins, Post-translational Modifications