Nadine Nagy, PhD, Instructor, Department of Medicine, Stanford University School of Medicine
Research Description: Dr. Nagy studies how immune responses are regulated in inflamed tissues with a particular focus on autoimmune, type 1 diabetes (T1D). In her research, she has identified a critical role for hyaluronan (HA), an extracellular matrix polymer abundant in inflamed tissues, in the development of T1D. She has found that HA accumulates in pancreatic islets during the progression to autoimmune insulitis in T1D as well as in mouse models of the disease. Further, she has identified that a drug called 4-methylumbelliferone (4-MU), known to inhibit HA production, can reverse the progression to autoimmune diabetes in animal models. Dr. Nagy has found that oral 4-MU reduces accumulation of HA in pancreatic islets, restores normal glycemic control, and suspends the progression to autoimmunity in mouse models of T1D. She was recently awarded a Pilot and Feasibility Award from the Stanford DRC for 2017-2018. Her research goals are to understand the biology of insulitis and to develop novel tools to prevent T1D. Her plans are to become an independent investigator in an academic setting in the next 1-2 years.
Selected relevant publications (Stanford DRC Members in BOLD):
Nagy N, Sunkari VG, Kaber G, Hasbun S, Lam DN, Speake C, Sanda S, McLaughlin TL, Wight TN, Long SR, Bollyky PL. Hyaluronan levels are increased systematically in human type 2 but not type 1 diabetes independently of glycemic control. Matrix Biol. 2019 Jul; 80: 46-58. PMID: 30196101. [Cites SDRC support]
Nagy N, Gurevich I, Kuipers HF, Ruppert SM, Marshall PL, Xie BJ, Sun W, Malkovskiy AV, Rajadas J, Grandoch M, Fischer JW, Frymoyer AR, Kaber G, Bollyky PL. 4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition. J Biol Chem. 2019 May; 294(19): 7864-7877. PMID: 30914479. [Cites SDRC pilot funding support]
Nagy N, de la Zerda A, Kaber G, Johnson PY, Hu KH, Kratochvil MJ, Yadava K, Zhao W, Cui Y, Navarro G, Annes JP, Wight TN, Heilshorn SC, Bollyky PL, Butte MJ. Hyaluronan content governs tissue stiffness in pancreatic islet inflammation. J Biol Chem. 2018 Jan; 293(2): 567-578. PMID: 29183997. [Cites SDRC support and grant P30DK116074]
HF Kuipers*, N Nagy*, SM Ruppert, VG Sunkari, PL Marshall, JA Gebe, HD Ishak, SG Keswani, J Bollyky, AR Frymoyer, TN Wight, L Steinman, PL Bollyky. The pharmacokinetics and dosing of oral 4-methylumbelliferone for inhibition of hyaluronan synthesis in mice. Clin Exp Immunol. 185:372-81, 2016 *authors contributed equally
N Nagy, G Kaber, PY Johnson, JA Gebe, A Preisinger, BA Falk, VG Sunkari, MD Gooden, RB Vernon, M Bogdani, HF Kuipers, AJ Day, DJ Campbell, TN Wight, PL Bollyky. Inhibition of hyaluronan synthesis restores immune tolerance during autoimmune insulitis. J Clin Invest 125:3928-40, 2015.
M Bogdani, PY Johnson, S Potter-Perigo, N Nagy, AJ Day, PL Bollyky, TN Wight. Hyaluronan and hyaluronan-binding proteins accumulate in both human type 1 diabetic islets and lymphoid tissues and associate with inflammatory cells in insulitis. Diabetes 63:2727-43, 2014.