Renal

Clinical Interests

Glomerulosclerosis

We are working to identify genes involved in the development of focal segmental glomerulosclerosis (FSGS). FSGS is a common form of renal disease, seen both as an isolated entity and as a consequence of HIV infection, diabetes, obesity, and hypertension. Towards this goal, blood for DNA extraction and clinical analyses have been performed on members of approximately 90 families with an inherited form of this condition. We identified the first FSGS locus on chromosome 19q13. We subsequently refined this locus and demonstrated genetic heterogeneity of FSGS. By analysis of genomic sequence databases, we were able to identify a number of candidate genes in the FSGS-1 interval. We have recently found mutations in ACTN4, encoding alpha-actinin-4, in FSGS-1 linked families. We have demonstrated altered actin binding activity in the mutant protein. Because FSGS is also a cause of renal dysfunction secondary to multiple other diseases, we are examining the role of this FSGS gene as a candidate renal dysfunction susceptibility gene. Current efforts are underway to understand the function of ACTN4 and the mechanism of this form of kidney disease using mouse models and cell biologic approaches. We are also working to identify additional human FSGS genes.

Extracellular calcium metabolism

Another interest of the lab is the function of the extracellular calcium receptor. Previously, we showed that mutations in the calcium receptor gene (CaR) cause inherited disturbances of calcium metabolism. We are using several mouse models with altered CaR to study the function of CaR in mammalian physiology.

Recent publications

1. Mathis B, Kim SH, Calabrese K, Haas M, Seidman JG, Seidman CE, Pollak, MR. Rapid Communication: A locus for inherited focal segmental glomerulosclerosis. Kidney International, 53:282-286, 1998.
   
   
2. Kaplan JM, H Kim S, North KN, Rennke H, A Correia L, Tong HQ, Mathis BJ, Rodriguez-Perez JC, Allen PG, Beggs AH, Pollak MR. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nature Genet. 2000 Mar;24(3):251-6.
   
   
3. Olszak IT, Poznansky MC, Evans RH, Kos C, Pollak MR, Brown EM, Scadden DT. Extracellular calcium elicits a chemokinetic response from monocytes in vitro and in vivo. J. Clinical Investigation, .2000, 105(9):1299-1305.
   
   
4. Tsukaguchi H, Yager H, Dawborn J, Jost L, Cohlmia J, Abreu P, Pereira A, Pollak MR. A locus for adolescent and adult onset focal segmental glomerulosclerosis on chromosome 1q25-31. J. Amer. Soc. Nephrol. 2000, 11:1674-1680.

For more information on Dr. Pollak's Lab visit his other web site at www.fsgs.bwh.harvard.edu