Marcus Pezzolesi
Associate Professor of Nephrology and Adjunct Assistant Professor of Human Genetics
Diabetes and Metabolism Research Center
Diabetes, Diabetic Nephropathy, Chronic Kidney Disease, Genetics, Next-generation Sequencing, microRNAs
Molecular Biology Program
Education
B.S. University of Massachusetts Amherst
Ph.D. Ohio State University
M.P.H. Harvard School of Public Health
Research
The primary focus of my research is to understand the etiology of diabetes, diabetic complications, and chronic kidney disease using high-throughput next-generation sequencing technology and integrated ‘omics’-based approaches. We know that genetic factors contribute to the susceptibility of diabetic kidney disease, the major complication facing patients with diabetes and the leading cause of end-stage renal disease in the United States. However, despite intense effort, few predisposing genes and/or variants for this disease have been identified. To accelerate these efforts, my laboratory is integrating large data resources, including electronic medical record data from the University of Utah Hospital and genealogical data from the Utah Population Database, and combining this with next-generation sequencing to perform whole genome sequencing-based gene discovery in families enriched for diabetic kidney disease. This same approach is being applied to accelerate our search for genes that contribute to diabetes and chronic kidney disease. Additionally, my laboratory is also investigating circulating microRNAs as novel biomarkers of kidney disease, including progressive renal function decline in patients with diabetes.
References (Selected Publications)
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van Zuydam NR, Ahlqvist E, Sandholm N, Deshmukh H, Rayner NW, Abdalla M, Ladenvall C, Ziemek D, Fauman E, Robertson NR, McKeigue PM, Valo E, Forsblom C, Harjutsalo V; Finnish Diabetic Nephropathy Study (FinnDiane), Perna A, Rurali E, Marcovecchio ML, Igo RP Jr, Salem RM, Perico N, Lajer M, Käräjämäki A, Imamura M, Kubo M, Takahashi A, Sim X, Liu J, van Dam RM, Jiang G, Tam CHT, Luk AOY, Lee HM, Lim CKP, Szeto CC, So WY, Chan JCN; Hong Kong Diabetes Registry Theme-based Research Scheme Project Group, Ang SF, Dorajoo R, Wang L, Clara TSH, McKnight AJ, Duffy S; Warren 3 and Genetics of Kidneys in Diabetes (GoKinD) Study Group, Pezzolesi MG; GENIE (GEnetics of Nephropathy an International Effort) Consortium, Marre M, Gyorgy B, Hadjadj S, Hiraki LT; Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, Ahluwalia TS, Almgren P, Schulz CA, Orho-Melander M, Linneberg A, Christensen C, Witte DR, Grarup N, Brandslund I, Melander O, Paterson AD, Tregouet D, Maxwell AP, Lim SC, Ma RCW, Tai ES, Maeda S, Lyssenko V, Tuomi T, Krolewski AS, Rich SS, Hirschhorn JN, Florez JC, Dunger D, Pedersen O, Hansen T, Rossing P, Remuzzi G; SUrrogate markers for Micro- and Macrovascular hard endpoints for Innovative diabetes Tools (SUMMIT) Consortium, Brosnan MJ, Palmer CNA, Groop PH, Colhoun HM, Groop LC, McCarthy MI. A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes. Diabetes. 2018 Jul;67(7):1414-1427. doi: 10.2337/db17-0914. Epub 2018 Apr 27. PMID: 29703844
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Satake E, Pezzolesi MG, Md Dom ZI, Smiles AM, Niewczas MA, Krolewski AS. Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes. Diabetes. 2018 May;67(5):1013-1023. doi: 10.2337/db17-1207. Epub 2018 Feb 16. PMID: 29453204
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Sandholm N, Van Zuydam N, Ahlqvist E, Juliusdottir T, Deshmukh HA, Rayner NW, Di Camillo B, Forsblom C, Fadista J, Ziemek D, Salem RM, Hiraki LT, Pezzolesi M, Trégouët D, Dahlström E, Valo E, Oskolkov N, Ladenvall C, Marcovecchio ML, Cooper J, Sambo F, Malovini A, Manfrini M, McKnight AJ, Lajer M, Harjutsalo V, Gordin D, Parkkonen M; FinnDiane Study Group, Jaakko Tuomilehto., Lyssenko V, McKeigue PM, Rich SS, Brosnan MJ, Fauman E, Bellazzi R, Rossing P, Hadjadj S, Krolewski A, Paterson AD; DCCT/EDIC Study Group, Jose C. Florez., Hirschhorn JN, Maxwell AP; GENIE Consortium, David Dunger., Cobelli C, Colhoun HM, Groop L, McCarthy MI, Groop PH; SUMMIT Consortium. The Genetic Landscape of Renal Complications in Type 1 Diabetes. J Am Soc Nephrol 2017 Feb; 28(2):557-574. PubMed PMID: 27647854; PubMed Central PMCID: PMC5280020.
- Pezzolesi MG, Satake E, McDonnell KP, Smiles AM, Krolewski AS. TGF-β-regulated microRNAs are differentially expressed in type 1 diabetic patients at high risk of renal function decline and progression to ESRD. Diabetes 2015 Sep; 64(9):3285-93. PubMed PMID: 25931475.
- Martini S, Nair V, Patel SR, Eichinger F, Nelson RG, Weil EJ, Pezzolesi MG, Krolewski AS, Randolph A, Keller BJ, Werner T, Kretzler M. From SNP to Transcriptional Mechanism: A Model for FRMD3 in Diabetic Nephropathy. Diabetes 2013 Jul; 62(7):2605-12. PubMed PMID: 23434934; PubMed Central PMCID: PMC3712052.
- Pezzolesi MG, Jeong J, Smiles AM, Skupien J, Mychaleckyj JC, Rich SS, Warram JH, Krolewski AS. Family-based association analysis confirms the role of the chromosome 9q21.32 locus in the susceptibility of diabetic nephropathy. PLoS One. 2013; 8(3):e60301. PubMed PMID: 23555951; PubMed Central PMCID: PMC3612041.
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Skupien J, Warram JH, Smiles AM, Niewczas MA, Gohda T, Pezzolesi MG, Cantarovich D, Stanton R, Krolewski AS. The early decline in renal function in patients with type 1 diabetes and proteinuria predicts the risk of end-stage renal disease. Kidney Int. 2012 Sep;82(5):589-97. PubMed PMID: 22622493; PubMed Central PMCID: PMC3425658.
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Pezzolesi MG, Poznik GD, Mychaleckyj JC, Paterson AD, Barati MT, Klein JB, Ng DPK, Placha G, Canani LH, Bochenski J, Waggott D, Merchant ML, Krolewski B, Mirea L, Wanic K, Katavetin P, Kure M, Wolkow P, Dunn JS, Smiles A, Walker WH, Boright AP, Bull SB, DCCT/EDIC Research Group, Doria A, Rogus JJ, Rich SS, Warram JH, Krolewski AS. Genome-wide association scan for diabetic nephropathy susceptibility genes in type 1 diabetes mellitus. Diabetes 2009 Jun; 58(6):1403-1410. PubMed PMID: 19252134; PubMed Central PMCID: PMC2682673.