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.