Research in our laboratory centers on the functions of the SUMO family of small ubiquitin-related proteins. The covalent conjugation of SUMOs to other cellular proteins regulates a wide range of essential processes that include the replication and repair of DNA, the control of transcription initiation, trafficking of proteins and RNA between the nucleus and the cytoplasm and progression of cells through mitosis. Because all of these processes are essential for normal cell growth and differentiation, defects in SUMO conjugation are associated with a variety of human diseases, including cancer, Alzheimer’s disease and diabetes.

Studies in the lab are focused on characterizing the enzymes, and defining the molecular mechanisms, that regulate the conjugation of SUMO to specific proteins in the cell. We are also working to define and characterize the molecular effects that SUMO conjugation has on the functions of modified proteins. Specific projects include understanding how the conjugation of SUMO to mitotic chromosome-associated proteins is coordinated with progression through mitosis, and understanding how SUMO conjugation regulates the segregation of sister chromatids. We are also studying how the conjugation of SUMO to proteins at the nuclear pore complex functions to regulate the transport of proteins and RNAs between the nucleus and the cytoplasm and how modification of the Bloom syndrome DNA helicase, BLM, affects DNA repair. Specific sub-projects in the lab are focused on characterizing the SUMO pathway in malaria-causing parasites and on defining requirements for SUMO conjugation during HIV-1 replication in human cells.

Biochemistry and molecular biology, cell biology, SUMO, nuclear pore complexes, mitosis, malaria, HIV, ubiquitin

1984 PSU Department of Biochemistry Gilman Science Award

1988 Amoco Foundation Pre-doctoral Research Fellowship

1994 American Cancer Society Amgen Postdoctoral Fellowship

1998 JHSPH Faculty Innovation Award

1999 American Cancer Society Research Scholar Award

2003 March of Dimes Research Award

2003 JHMRI Pilot Grant

2005 CFAR Pilot Grant

Ouyang, K.J., L.L. Woo, J. Zhu, D.Huo, M.J. Matunis and N.A. Ellis. 2009. SUMO modification regulates BLM and RAD51 interaction at damaged replication forks. PLoS Biology. In press.

Zhu, S., J. Goeres, K.M. Sixt, M. Békés, X.D. Zhang, G.S. Salvesen and M.J. Matunis. 2009. Protection from isopeptidase-mediated deconjugation regulates paralog-selective SUMOylation of RanGAP1. Mol. Cell. 33:570-580.

Zhu, J., S. Zhu, C.M. Guzzo, N.A. Ellis, K.S. Sung, C.Y. Choi and M.J. Matunis. 2008. SUMO binding determines substrate recognition and paralog-selective SUMO modification. J. Biol. Chem. 283:29405-29415.

Zhang, X.-D., J. Goeres, H. Zhang, T.J. Yen, A.C.G. Porter, and M.J. Matunis. 2008. SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis. Mol. Cell. 29:729-741.

La Salle, S., F. Sun, X.-D. Zhang, M.J. Matunis and M.A. Handel. 2008. Developmental control of sumoylation pathway protein in mouse male germ cells. Dev. Biol. 321:227-237.