Biographical Sketch

Dr. Leis earned his Ph.D. from Cornell University in 1970 and completed postdoctoral training at Albert Einstein College of Medicine in 1973 working on reverse transcription. From 1974 to 1979 he was at the Duke Medical Center working on replication of retroviruses. He then joined the CWRU faculty as a Professor of Biochemistry and co-director of the Molecular Virology Graduate Training Program.  He became a Northwestern faculty member in 1999 where is is also the Executive Associate Dean of the Medical School.

Research Description

Multidisciplinary molecular genetics and biochemical approaches are being used to study replication of avian and human retroviruses.  Areas of particular interest are in reverse transcription, viral DNA integration, and virion assembly.      

Specific projects include studying 1) the role of viral RNA secondary structures in initiation of reverse transcription, 2) the mechanism of concerted integration of viral DNA into the host chromosome by integrase (IN) using an in vitro reconstituted system and identification of the amino acids of tIN responsible for specificity for the LTR ends, 3) the mechanism of processing of Gag and Pol polyproteins into mature viral proteins by the virus-specific protease (PR), and 4) the role of a Gag polyprotein assembly domain in budding of virus particles from cells.

In many of these studies, amino acid substitutions have been placed at biochemically or structurally important residues and the effect these changes have on viral replication and on the properties of the mutant proteins have been defined.

Research Abstract

Specific projects include studying:

In many of these studies, amino acid substitutions have been placed at biochemically or structurally important residues and the effect these changes have on viral replication and on the properties of the mutant proteins have been defined.

The first structure of a retroviral enzyme, the structure of Rous sarcoma virus protease, was solved by Leis' lab in colloration with Dr. Wlodawer's lab in NIH.

Publications

VerPlank, L., Agresta, B., Grassa, T., Kikonyogo, A., Leis, J., and Carter, C.   Tsg101, the prototype of a class of dominant-negative ubiquitin regulators, binds human immunodeficiency virus type 1 Pr55^Gag: the L domain is a determining of binding.  Proc. Natl. Acad. Sci. USA 98:7724-7729 (2001).

Kinonyogo, A., Bouamr, F., Vana, M., Xiang, Y., Aiyar, A., Carter, C., and Leis, J.  Proteins related to the Nedd4 family of ubiquitin protein ligases interact with the L domain of Rous sarcoma virus and are required for Gag budding from cells.  Proc. Natl. Acad. Sci. USA. 98: 11199-11204 (2001).

Brin, E. and Leis, J.  Changes in the mechanism of DNA integration in vitro induced by base substitutions in the HIV-1 U5 and U3 terminal sequences.  J. Biol. Chem., 277:10938-10948 (2002).

Morris, S., Johnson, M., Stavnezer, E., and Leis, J. Replication of Avian Sarcoma Virus In Vivo Requires an Interaction Between the Viral RNA and the TyC loop of the tRNA^Trp Primer. J. Virol.  76: 7571-7577 (2002).

Johnson, M., Morris, S., Chen, A., Stavnezer, E., and Leis, J.   Biological Selection of Functional Mutations in the U5-IR Stem and Loop Regions of the Rous Sarcoma Virus Genome.   BMC Biology, 2:8 (2004).

Vana, M. L.,  Tang, Y., Chen, A., Medina, G., Carter, C., and Leis, J. The Role of Nedd4 and Ubiquitination of RSV Gag in Budding of Virus-Like Particles from Cells. J. Virol. 78, 13943-13953 (2004).

Medina, G., Zhang, Y., Tang, Y., Gottwein, E., Vana, M. L., Bouamr, F., Leis, J., and Carter, A.   The Functionally Exchangeable L Domains in RSV and HIV-1 Gag Direct Particle Release Through Pathways Linked by Tsg101.  Traffic 6: 880-894 (2005). 

Vana, M. L., Boross, P., Chen, A., Weber, I., Colman, D., Barklis, E. and Leis J. Mutations Affecting Cleavage at the p10-Capsid Protease Cleavage Site Block Rous Sarcoma Virus Replication.   Retrovirology 2:58 (2005).

Chen, A., Weber, I., Harrison, R., and Leis, J.   Identification of Amino Acid Residues in HIV-1 and ASV Integrase Subsites Required for Specific Recognition of the LTR Termini.  J. Biol. Chem.  281, 4173-4182 (2006).

Medina, G., Pincetic, A., Zhang, Y., Ehrlich, L. S., Tang, Y., Leis, J., and Carter, C.  Tsg101 can replace Nedd4 function in ASV Gag release but not membrane targeting.  Virology  377: 30-38 (2008).