Marcus Pezzolesi

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, chronic kidney disease, and cardiovascular disease in other datasets and populations.  As part of our work, we have established the Utah Diabetes Database (UDDb), a population-based resource that includes ~400,000 diabetic patients and more than 130 million clinical and laboratory records. Additionally, we have established the community-engaged Utah Pacific Islander Study (UPIS) and a biorepository to investigate the basis of metabolic disease in Native Hawaiians and Pacific Islanders. We are leveraging UPIS to develop novel genetic resources, i.e., the first Pacific Ancestry Pangenome Reference and the first Pacific Islander Imputation Reference Panel, to facilitate genetic research in Native Hawaiians and Pacific Islanders. Through collaborative efforts, we have assembled genetic cohorts of Native Hawaiians or Pacific Islanders totaling more than 10,000 individuals.  Additionally, we have cryopreserved PBMCs from ~500 UPIS participants and established patient-derived iPSC lines to further expand functional studies of variants and genes identified from these analyses and, in doing so, have established a discovery-to-mechanism pipeline to advances precision medicine while addressing longstanding disparities in genomic research.