R. Ariel Gomez. M.D.

R. Arial Gomez, M.D.

R. Ariel Gomez received his medical degree at the University of Buenos Aires School of Medicine in Argentina in 1975.  After completing his residency in Pediatrics at the Hospital de Ninos “Ricardo Gutierrez”, Buenos Aires, Argentina, he served as Chief Resident at the same hospital followed by fellowships in Pediatric Nephrology at the University of Iowa, Iowa City, Iowa, (1980-1983) where he pursued research in fetal physiology under the mentorship of Jean Robillard and at the University of California, San Francisco, (1983-1984) under the mentorship of Malcom Holliday and Donald Potter.

Dr. Gomez joined the Pediatrics Department at The University of Virginia School of Medicine in 1984 as an Assistant Professor and established an independent research program that has been continuously supported by NIH funding since 1988. From 1997-2000 Dr. Gomez served as Genentech Professor and Associate Chair for Research for the Department of Pediatrics. In 2001 he became Interim Vice President for Research and Public Service and then, in 2003, Vice President for Research and Graduate Studies. He returned to full time research in 2008 as the Harrison Distinguished Professor of Pediatrics and holds a courtesy appointment in the department Biology, School of Arts and Sciences.

Research in Dr.Gomez’s lab focuses on renin-synthesizing cells and kidney vascular development. Renin cells are crucial in the regulation of blood pressure and fluid and electrolyte homeostasis in the adult. In addition to their role in adult life, lineage tracing studies using a mouse generated  in his lab that expresses cre recombinase under the control of the renin locus, revealed that renin cells are also precursors for multiple cell types, including renal vascular smooth muscle, mesangial and tubular epithelial cells as well as extrarenal cells such as Leydig and adrenal cells. Current studies aim at defining the determinants of renin cell identity and the mechanisms that govern the development of the kidney vasculature.

To define the factors governing renin cell identity we are testing the hypothesis that renin cell identity is determined by the three-dimensional conformation of chromatin resulting from the interaction of renin gene regulatory sequences (enhancer and promoter) with other genes in the genome. We are using epigenetic approaches to build a map of chromatin modifications for the renin cell to define the active and inactive regions of chromatin responsible for the renin cell phenotype and chromosome conformation capture to identify key transcriptional factories/gene-gene interactions characteristic of the renin cell.

Since micro RNAs are known to have important functions in the regulation of many genes and gene pathways we are analyzing the role micro RNAs play in the differentiation of the renin cell and its descendants. We identified two unique renin cell specific micro RNAs (miR-330 and miR-125b-5p) that regulate crucial genes for the maintenance of the myoepithelioid renin cell phenotype and are currently determining whether these micro RNAs play a role in determining the temporal and spatial pattern of renin cell differentiation during development and regulate the identity and fate of renin cells and nephron morphogenesis.

The project for this Pediatric Center of Excellence in Nephrology addresses the development of the kidney vasculature. The proper and timely assembly of the arterioles with their respective nephrons is a crucial morphogenetic event leading to the formation of a functioning kidney necessary for independent extrauterine life. The mechanisms that govern the development of the kidney vasculature are poorly understood. Foxd1+ cells and their descendants, the Ren+ precursors, are the earliest metanephric progenitors for all the mural cells of the kidney arterioles. We recently showed that deletion of RBP-J (the final transcriptional effector for all Notch receptors) is required to maintain the number of renin-expressing cells, and that it is crucial in the plasticity of vascular SMCs to regain the renin phenotype in response to a threat to homeostasis. Using in vivo lineage tracing, time- and cell-specific conditional deletion, genome wide epigenetic and gene-expression profiling and cell identification with appropriate differentiation markers we are testing the overall hypothesis that RBP-J is necessary for the differentiation of Foxd1+ and Renin+ progenitor cells and the establishment of cell identity-specific epigenetic marks and gene-expression patterns that culminate with the emergence of the differentiated mural cells of the renal arterioles.

This work will fill an important gap in our knowledge by defining the precise cellular origin and mechanisms whereby early and intermediate stromal precursors lead to the successful formation of the renal arterial tree, without which there is no functioning kidney and could lead to a new understanding of vascular development and disease with eventual therapeutic applications.