I received my B.S. in chemistry from the University of Tampa, FL, in 1987. In 1988 I moved 20 minutes across town to work on my doctorate in physical chemistry (Ph.D. awarded in 1994) at the University of South Florida, Tampa, in the laboratory of Eric Wickstrom. My research focused on the stereoselective synthesis of and spectroscopic characterization of methylphosphonate DNA derivatives. To complete my formal training I worked in the laboratory of Peter B. Moore within the Departments of Chemistry and Molecular Biophysics and Biochemistry at Yale University, New Haven, CT. There my research focused on the structure and function of several RNA molecules. In the fall of 1998, I joined VCU’s School of Pharmacy in the Department of Medicinal Chemistry.

My current work broadly focuses on ribosome biogenesis in bacteria and eukarya and specifically on the involvement of methyltransferases. The universally conserved KsgA/Dim1 enzyme dimethylates two adjacent adenosines in small subunit ribosomal RNA. In efforts to understand this family of enzymes we probe the structure and function of KsgA/Dim1 using a variety of biochemical and structural techniques (x-ray crystallography and NMR).

A second project focuses on the 16S rRNA methyltransferases ArmA/RmtA/RmtB/RmtC that confer high level aminoglycoside resistance when expressed by pathogenic bacteria. This is a newly discovered form of clinical antibiotic resistance, yet already has deep penetration into many hospitals throughout parts of the world. A sound biochemical and structural understanding of these enzymes will provide foundation for later drug discovery efforts. We are currently probing the structure and function of these critical resistance enzymes.

Recent publications

1. O’Farrell, H.C., Pulicherla, Desai, P.M., and Rife, J.P. (2006) Recognition of a complex substrate by the KsgA/Dim1 family of enzymes. RNA. 12, 725-33.

2. Desai, P.M. & Rife, J.P. (2006) The Dimethyladenosine Methyltransferase KsgA Recognizes a Specific Conformational State of the 30S Subunit. Archives of Biochemistry and Biophysics. 449, 57-63.

3. Johnson KK, Green DL, Rife JP, Limon L. (2005) Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother., 2, 290-301.

4. O’Farrell, H. C., Scarsdale, J. N., Rife, J.P. (2004) Crystal Structure of KsgA, a Universally Conserved rRNA Adenine Dimethyltransferase in Escherichia coli. Journal of Molecular Biology, 339, 337-353.

5. Cashman, D. J., Rife, J. P. and Kellogg, G. E. (2004) Docking and hydropathic analysis of Hoecsht 33258 in complex with double-stranded RNA. Med. Chem. Res. 12, 445-455.

6. O'Farrell, H.C., Musayev, F.N., Scarsdale, J.N., Wright, H.T., and Rife, J.P. (2003) Crystallization and preliminary x-ray diffraction analysis of KsgA, a universally conserved RNA adenine dimethyltransferase in Escherichia coli. Acta Cryst., D59, 1490-1492.

7. Kacer, V., Scaringe, S.A., Scarsdale, J.N., and Rife, J.P. (2002) Crystal Structures of r(GGUCACAGCCC)2. Acta Cryst., D59, 423-432.

8. Rife, J.P. (2002) Therapeutic agents acting on RNA targets. In: Burger’s Medicinal Chemistry, 6th Edition, Abraham, D.J., Ed.