Sunil Kumar ’09GP, ’14Ph.D.

Assistant Professor
Ph.D., Pharmaceutical Sciences, St. John's University

I am a scientist with more than 10 years of experience in basic, as well as translational, research in the field of diabetes and obesity. As a Ph.D. student, I carried out research on insulin resistance in adipocytes using in-vitro as well as in-vivo models.

After completing my Ph.D. in Pharmaceutical Sciences with a concentration in Pharmacology at St. John’s, I devoted more than four years toward my postdoctoral work in diabetes and obesity research at NYU Langone Hospital—Long Island. I focused precisely on investigating the role of L-PGDS and its metabolite, PGD2 in diabetes and obesity using a L-PGDS knockout (L-PGDS KO) mouse model. I also characterized their phenotype and genotype on low- and high-fat diet.

Our research revealed that L-PGDS KO mice developed fatty liver disease accompanied with insulin resistance and weight gain on both diets. This interesting phenomenon originated numerous research avenues, but the incidence of nonalcoholic fatty liver disease (NAFLD) in these mice was one of the most fascinating and crucial as there is no US Food and Drug Administration-approved therapy for NAFLD.

My lab at St. John’s University is currently focused on investigating the role of L-PGDS, an unexplored protein in the field of glucose and lipid metabolism, in NAFLD and NASH (Nonalcoholic steatohepatitis). Precisely, we are interested in dissecting the mechanism of L-PGDS and its metabolite PGD2 receptor modulators, DP1 and D2 receptor agonist and antagonist, in NAFLD using insulin-resistant HepG2 cells and db/db mice subjected to a high-fat diet. Such a model would be a powerful tool for exploring the treatment of diabetes- and obesity-induced fatty liver disease by manipulating the PGD2 signaling pathway. Once hepatic regulation of L-PGDS signaling is understood, targets for NAFLD pharmacotherapy could be developed. Collectively, our research will shed new light on the role of L-PGDS in liver physiology and diabetes- and obesity-induced NAFLD and discover new therapeutic targets for future studies with my potential collaborators at NYU Langone, Columbia University, Albert Einstein College of Medicine, and St. John’s University.

My ability to contribute to scientific and academic community as a researcher and an educator have been the hallmarks of my career so far. Broadly, my area of research interest is diabetes, obesity, and fatty liver disease. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for type 2 diabetes mellitus, cardiovascular disease, and all-cause mortality.

Previously, we demonstrated that lipocalin-type prostaglandin D2 synthase (L-PGDS) knockout mice show increased glucose intolerance and accelerated atherosclerosis. In the present study, we investigated the role of L-PGDS in mediating NAFLD utilizing L-PGDS knockout (KO) and control C57BL/6 mice fed either a low-fat (LFD) or high-fat diet (HFD) for 14 weeks. Our research revealed that L-PGDS KO mice developed fatty liver disease accompanied with insulin resistance and weight gain on both diets. We found increased lipid accumulation in the liver of KO mice over time on both diets, as compared to control mice. The L-PGDS KO mice showed elevated fasting glucose and insulin levels and developed insulin resistance on both LFD and HFD. Lipogenesis marker proteins such as SREBP-1c and LXRα were increased in L-PGDS KO mice after 14 weeks on both diets, when compared to control mice. We replicated our in vivo findings in vitro using HepG2 cells treated with a combination of free fatty acids (oleic and palmitic acid) and exposure to a L-PGDS inhibitor and prostaglandin D2 receptor (DP1) antagonists.

We conclude that the absence or inhibition of L-PGDS results in dyslipidemia, altered expression of lipogenesis genes, and the acceleration of NAFLD to NASH, independent of diet and obesity. We propose L-PGDS KO mice as a useful model to explore the pathogenesis of NAFLD and NASH, and L-PGDS as a potential therapeutic target for treatment.

The proposed research will be innovative because once we elucidate the regulation and signaling of L-PGDS, new pharmacological agents that block these hepatic lipid accumulation pathways can be developed using DP1 and DP2, the PGD2 receptor modulators. Fatty liver disease is triggered through multiple pathways, but the most prominent cause is either diabetes or obesity, or a combination of the two. This work is impactful because it will uncover the novel role of L-PGDS and its metabolite, PGD2, in the pathogenesis of NAFLD. The pharmacological application of our research can discover novel targets as well as therapeutics for the treatment of NAFLD.

  1. Khairnar R (GRAD), Islam MA ((GRAD)), Fleishman J (UG), Kumar S. Shedding light on non-alcoholic fatty liver disease: Pathogenesis, molecular mechanisms, models, and emerging therapeutics. Life Sci. 2023 Jan 1; PMID: 36375569. 

  2. Das A, Vartak R (GRAD), Islam MA (GRAD), Kumar S, Shao J, Patel K. Arginine-Coated Nanoglobules for the Nasal Delivery of Insulin. Pharmaceutics. 2023 Jan 20;15(2):353. doi: 10.3390/pharmaceutics15020353. PMID: 36839674; PMCID: PMC9965127. 

  3. Islam MA, Khairnar R, Fleishman J, Thompson K, Kumar S. Lipocalin-Type Prostaglandin D2 Synthase Protein- A Central Player in Metabolism. Pharm Res. 2022 Nov;39(11):2951-2963. doi: 10.1007/s11095-022-03329-4. Epub 2022 Jul 8. PMID: 35799081.

  4. Kumar S, Srivastava A, Palaia T, Hall C, Lee J, Stevenson M, et al. Lipocalin-type prostaglandin D2 synthase deletion induces dyslipidemia and non-alcoholic fatty liver disease. Prostaglandins Other Lipid Mediat. 2020;149:106429. 

  5. Kumar S, Palaia T, Hall C, Ragolia L. DP1 receptor agonist, BW245C inhibits diet-induced obesity in ApoE(-/-) mice. Obes Res Clin Pract. 2018;12(2):229-41

  6. Amin RP, Patel SN, Kumar S, Zito WS, Barletta MA (2018) Effects of Usnic Acid on Hyperglycemia and Renal Function in Streptozotocin-Induced Diabetic Rats. Arch Nat Med Chem ANMC-119.

  7. Kumar S, Lau R, Palaia T, Hall C, Lee J, Hall K, et al. Selective beneficial cardiometabolic effects of vertical sleeve gastrectomy are predominantly mediated through glucagon-like peptide (GLP-1) in Zucker diabetic fatty rats. Ann Med Surg (Lond). 2016;12:65-74. 

  8. Kumar S, Lau R, Hall CE, Palaia T, Rideout DA, Brathwaite CE, et al. Lipocalin-type prostaglandin D2 synthase (L-PGDS) modulates beneficial metabolic effects of vertical sleeve gastrectomy. Surg Obes Relat Dis. 2016;12(8):1523-31. 

  9. Lau RG, Kumar S, Hall CE, Palaia T, Rideout DA, Hall K, et al. Roux-en-Y gastric bypass attenuates the progression of cardiometabolic complications in obese diabetic rats via alteration in gastrointestinal hormones. Surg Obes Relat Dis. 2015;11(5):1044-53.

  10. Kumar S, Palaia T, Hall CE, Ragolia L. Role of Lipocalin-type prostaglandin D2 synthase (L-PGDS) and its metabolite, prostaglandin D2, in preterm birth. Prostaglandins Other Lipid Mediat. 2015;118-119:28-33.

  11. Kumar S, Lau R, Hall C, Palaia T, Brathwaite CE, Ragolia L. Bile acid elevation after Roux-en-Y gastric bypass is associated with cardio-protective effect in Zucker Diabetic Fatty rats. Int J Surg. 2015;24(Pt A):70-4.

  12. Davani D, KumarS, Palaia T, Hall C, Ragolia L. Lipocalin-type prostaglandin D2 synthase reduces glucagon secretion in alpha TC-1 clone 6 cells via the DP1 receptor. Biochem Biophys Rep. 2015;4:224-227.

  13. Hu B, Amin R, Kumar S, Kunaparaju N, Graham SM, et al. (2014) Bioassay-guided Isolation of the Antidiabetic Active Principle from Salvia miltiorrhiza and its Stimulatory Effects on Glucose Uptake Using 3T3-L1 Adipocytes. Med chem 4: 592-597. 

  14. Amin, R.P., Kunaparaju, N., Kumar S., Taldone, T. Barletta, M.A., and Zito, S.W. (2013). Structure elucidation and inhibitory effects on human platelet aggregation of chlorogenic acid from Wrightia tinctoria. Journal of Complementary and Integrative Medicine, 10(1), 1-8. 

  15. Avella, J., Kunaparaju, N., Kumar S., Lehrer, M., Zito, S.W., and Barletta, M.A. (2010). Uptake and distribution of the abused inhalant 1, 1-difluoroethane in the rat. Journal of Analytical Toxicology,34, 381-388. 

  16. Kumar S., Kunaparaju, N., Zito, S.W., and Barletta, M.A. (2011). Effect of Wrightia tinctoria and Parthenocissus quinquefolia on blood glucose and Insulin levels in the Zucker Diabetic Rat Model. Journal of Complementary and Integrative Medicine, 8(1). 

  17. Shinde, J., Taldone, T., Barletta, M.A. Kunaparaju, N., Hu, B., Kumar S., Placido, J., and Zito, S.W., (2008) Alpha-Glucosidase inhibitory activity of Syzygium cumini (Linn.) Skeels seed kernel in vitro and in Goto-Kakizaki (GK) rats. Carbohydrate Research. 343,1278-1281.