Department of Genetics
Life Sciences Building, Room 124
Piscataway, NJ 08854
FAX - (732) 445-1147
Adenine phosphoribosyltransferase deficiency, chronic
renal failure, microchimerism and organ transplantation, Alzheimers disease, molecular
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.