Amrik Sahota Research Professor Rutgers University Department of Genetics Life Sciences Building. Room 124 Piscataway. NJ 08854 (732) 445-7185 FAX - 1147 sahota@biology.rutgers.edu

Adenine phosphoribosyltransferase deficiency. chronic renal failure. microchimerism and organ transplantation. Alzheimers disease. molecular diagnostics

Summary of Research Interests

• Adenine phosphoribosyltransferase (APRT) deficiency: Germline mutations in APRT are a cause of kidney stone disease and. in some cases. acute or chronic renal failure. We have identified nearly all the known mutations in this gene and are using these data to infer genotype-phenotype and structure-function correlations.
  

• Molecular pathophysiology of kidney stone disease: The interaction of crystals with renal epithelial cells is an important event in the initiation of cellular injury in kidney stone disease. We are investigating. in Aprt knockout mice and in cell culture systems. the pathological bases of renal injury induced by crystals of 2,8-dihydroxyadenine. the material that accumulates in APRT deficiency. We have also developed an Aprt/Opn double knockout mouse to study the effects of osteopontin (OPN) on stone disease. OPN has multiple cellular functions. including its' effects as an inhibitor of crystal aggregation and a promoter of inflammation.
  

• Chronic rejection of kidney allografts: Chronic rejection remains a major problem in kidney transplantation. We are using microarray and related technologies to identify genes that may act as surrogate markers for early diagnosis of chronic rejection. Early diagnosis may facilitate early intervention by changes in immunosuppressant regimens. before the onset of irreversible scarring in the kidney allograft.
  

• Molecular diagnostics: Recent advances in molecular biology and genetics have revolutionized our understanding of inherited disorders. cancer. and infectious diseases. We have developed and/or implemented into clinical practice many molecular diagnostic assays based on these advances. A number of highly productive research collaborations have resulted from these endeavors.

Selected Publications

Liang L. Chen J. Vittal R. Selvanayagam ZE. McAteer JA. Deng L. Tischfield J. Chin KV. Sahota A. (2006) Expression profiling of crystal-induced injury in human kidney epithelial cells. Nephron Physiol. 103(1):p53-62.

Vernon HJ. Osborne C. Tzortzaki EG. Yang M. Chen J. Rittling SR. Denhardt DT. Buyske S. Bledsoe SB. Evan AP. Fairbanks L. Simmonds HA. Tischfield JA. Sahota A. (2005) Aprt/Opn double knockout mice: osteopontin is a modifier of kidney stone disease severity. Kidney Int. 68(3):938-47.

Tzortzaki EG. Tischfield JA. Sahota A. Siafakas NM. Gordon MK. Gerecke DR. (2003) Expression of FACIT collagens XII and XIV during bleomycin-induced pulmonary fibrosis in mice. Anat Rec A Discov Mol Cell Evol Biol. 275(2):1073-80.

Tzortzaki EG. Yang M. Glass D. Deng L. Evan AP. Bledsoe SB. Stambrook PJ. Sahota A. Tischfield JA (2003). Impaired expression of an organic cation transporter. IMPT1. in a knockout mouse model for kidney stone disease. Urol Res 31: 257-261.

Wang L. Raikwar N. Yang M. Deng L. McAteer JA. Stambrook PJ. Sahota A. Tischfield JA (2002). Induction of α-catenin. integrin α3. integrin β6. and PDGF-B by 2,8-dihydroxyadenine crystals in cultured kidney epithelial cells. Exp Nephrol 10: 365-373.

Tzortzaki EG. Glass D. Yang M. Evan AP. Bledsoe SB. Stambrook PJ. Sahota A. Tischfield JA (2002). Gender- and age-dependent changes in kidney androgen protein mRNA expression in a knockout mouse model for nephrolithiasis. J Histochem Cytochem 50: 1663-1669.

Evan AP. Bledsoe SB. Connors BA. Deng L. Liang L. Shao C. Fineberg N. Grynpass MD. Stambrook PJ. Sahota A. Tischfield JA (2001). Sequential analysis of kidney stone disease in the Aprt knockout mouse. Kidney Int 60: 910-923.

Deng L. Yang M. Fründ S. Wessel T. De Abreu RA. Tischfield JA. Sahota A (2001). Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT. Mol Genet Metab 72: 260-264.

Evans RM. Emsley CL. Gao S. Sahota A. Hall KS. Farlow MR. Hendrie H (2000). Serum cholesterol. APOE genotype. and the risk of Alzheimer's disease: a population-based study of African Americans. Neurology. 54: 240-24.

Sahota A. Gao S. Hayes J. Jindal RM (2000). Microchimerism and rejection: A meta-analysis. Clin Transplant 14: 346-351.

Wang L. Raikwar N. Deng L. Yang M. Liang L. Shao C. Evan AP. Stambrook PJ. Sahota A. Tischfield JA (2000). Altered gene expression in kidneys of mice with 2,8-dihydroxyadenine nephrolithiasis. Kidney Int 58: 528-536.