Research Interest

We are interested in understanding the mechanisms whereby the renin-angiotensin system (RAS) specify phenotypic differientiation, cell diversity and positional information in the developing kidney.

Three different cell types are being studied:
1) the juxtaglomerular cell, a highly specialized cell, associated with the development and branching of the kidney vasculature and regulation of blood pressure via renin secretion.
2) embryonic ureteric cells that induce the metanephric mesenchyme to undergo epithelial transformation, and
3) proximal tubular cells.
Using lineage markers and micorinjected green flourescent protein DNA we are investigating the embryonic origin and fate of precursor cells along the nephron in an in vitro embryonic kidney culture model. To understand the molecular mechanisms regulating cell diversity, we are clonig the genes involved in cell differentiation. One of these genes, termed Ziss (for Zinc finger, splicing stability) is likely involved in JG cell differentiation. We are in tha process of testing whether Ziss regulates JG cell development. A similar approach is being used with genes cloned from ureteric bud and proximal tubular cells.

In related studies, we are trying to understand the mechanisms whereby angiotensin regulates kidney development. We have found that inhibition of angiotensin receptor (subtype 1-AT1) results in marked nephorvascular developmental abnormalities. However, inhibition of the AT2 receptor results in increased glomerulogenesis suggesting a balance of function between the two receptors. In addition, knock-out of the angiotensin converting enzyme gene in mice or its pharmacological inhibition in rana castabeiana tadpoles undergoing metamorphosis result in striking morphological_developmental renal abnormalities. These experiments demonstrate the importance of renin-angiotensin system in kidney development and suggest that the morphogenetic function of the RAS is cinserved throughout the phylogenetic scale.

Publications

Gomez RA, Chevalier RL, Everett AD, Elwood JP, Peach MJ, Lynch KR, Carey RM: Recruitment of renin gene expressing cells in adult rat kidney. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F660-F665, 1990.

Norwood VF, Gomez RA. Bridging the gap between physiology and molecular biology: New approaches to perpetual questions. Am. J Physiol 267: R865-R878, 1994 (invited review)

Gomez RA, Norwood VF. Developmental consequences of the RAS. Am. J Kid Dis 26: 409-431, 1995 (invited review)

Tufro-McReddie A, Romano LM, Harris JM, Ferder L, Gomez RA. Angiotensin II regulates nephrogenesis and renal vascular development. Am J Physiol 269: F110-F115, 1995.

Takahashi N, Chernavvsky DR, GomezRA, Igarashi P, Gitelman HJ, Smithies O: Uncompensated polyuria in a model of Bartter's syndrome. Proc. Natl.Acad. Sci 97:5434 - 5439, 2000.

Baker LA, GomezRA: Tmp21-I, a vesicular trafficking protein, is differentially expressed during induction of the ureter and metanephros. J Urol 164(2): 562-566, 2000.

Sequeira Lopez MLS, Pentz ES, Robert B,Abrahamson DR, Gomez RA. Embryonic origin and lineage of juxtaglomerular cells. Am J Physiol 281(2): F345-F356, 2001.

Pentz ES, Sequeira Lopez MLS,Kim HS, Carretero O, Smithies O, Gomez RA. Ren1d and Ren2 cooperate to preserve homeostasis: evidence from mice expressing GFP in place of Ren1d. Physiol Genomics 6(1):45-55,2001.

Hilgers KF, Veelken R, Muller DN, Kohler H, Hartner A, Botkin SR, Stumpf C, Schmieder E, Gomez RA. Renin uptake by the endothelium mediates vascular angiotensin formation. Hypertension 38: 243-248, 2001.

For more information email rg@virginia.edu.