Dr. Randhawa's laboratory research has four specific aims:

  1. To characterize the complete clinical spectrum of PV infection in man: It is hypothesized that the spectrum of human renal disease associated with PV BK is wider than presently recognized. Quantitation of viral DNA in the kidney, urine and blood will uncover currently unrecognized forms of PV disease in cases currently being classified as acute cellular rejection or chronic allograft nephropathy.

  2. To delineate the host and viral factors that affect PV replication: It is hypothesized that the progression of asymptomatic BKV infection to clinical disease is a function of multiple factors that include (a) viral genotype, (b) mutations and genetic rearrangements in the PV genome, (c) sex hormones, glucocorticoids, and prednisone, (d) injury to host cells (mediated by calcineurin inhibitors, anoxia or cytokines such as tumor necrosis factors, perforin, granzyme), and (e) concurrent infection with other viruses ( JCV, SV40, CMV).

  3. To analyze PV infection associated cellular gene expression in cultured cells, blood, and urine of kidney transplant patients, and tissue specimens with urogenital carcinoma: It is hypothesized that distinctive patterns of host gene expression are associated with specific stages of the viral life cycle (for example, binding of virus to cell surface, intracellular entry, and initiation of cell proliferation/lysis). Delineation of these patterns will (a) enhance our understanding of the pathogenesis of PVAN, (b) suggest potential biomarkers to follow the clinical course of this disease, (c) identify metabolic pathways to target in future drug discovery studies, and (d) generate data that will help explore a possible role for PV in human carcinogenesis.

  4. To perform in-vitro testing of anti-BKV drugs for possible future use in the clinical arena: The testing currently in progress seeks to evaluate the clinical relevance of compounds shown to have anti-viral activity against other polyomaviruses and laboratory strains of BKV.