Department of Genetics
Beth Israel Deaconess Medical Center - Nephrology
330 Brookline Ave., RN 304
Boston, MA 02215
Tel: (617) 667-0461
Fax: (617) 667-0495
Web Page: The Pollak Lab Page
3 postdoctoral fellows, 1 graduate student, 2 technicians, 1 genetic counselor
My laboratory studies the genetic basis of kidney disease. We are particularly interested in kidney disease characterized by proteinuria and glomerulosclerosis because this phenotype is common and is often seen as a response to forms of injury such as hypertension, diabetes, and HIV infection. We have identified a gene ACTN4 (alpha-actinin-4) which when mutated causes an autosomal dominant form of proteinuria, kidney failure, and glomerulosclerosis ("focal segmental glomerulosclerosis" or FSGS). We have developed ACTN4 mutant (knockin) and knockout mice to help us understand the underlying disease mechanisms. We are exploring the role of mutations in the alpha-actinin-4 protein in altering the biomechanical properties of the actin cytoskeleton. In addition, we are studying the human genetics and biology of other inherited forms of FSGS and working to identify other FSGS genes. We have a large collection of human DNA samples from subjects with kidney disease which forms the basis of many of these studies. Another interest of our laboratory is the biology of the extracellular calcium receptor. Our present focus is on understanding the role of this receptor in regulating kidney function and calcium metabolism using mouse models.
Potential rotation projects:
1) Examine role of candidate genes in human kidney disease
2) Perform human linkage studies
3) Develop new mouse models
4) Examine cell signaling at the glomerular slit-diaphragm
5) Develop kidney cell-based assays to help identify drugs and drug targets
- 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 Genetics. 2000 Mar;24(3):251-6.
- Kos C, Karaplis A, Peng J-B, Hediger, Goltzman D, Mohammad K, Guise T, Pollak MR. The calcium sensing receptor is required for normal calcium homeostasis independent of parathyroid hormone, J Clinical Investigation, 2003, 111(7):1021-1028
- Kos CK, Le TC, Sinha S, Henderson J, Kim SH, Sugimoto H, Kalluri, R., Gerszten RE, Pollak, MR, alpha-actinin-4 deficient mice have severe glomerular disease. J. Clinical Investigation, 2003, 111(11):1683-90.
- Yao J, Le TC, Kos CH, Allen PG, Denker BM, Pollak MR. ?-actinin-4 mediated FSGS: an inherited kidney disease caused by an aggregated and rapidly degraded cytoskeletal protein. Public Library of Science Biology, 2004, 2(6):787-794.
BBS webpage updated 12/02/2009