Michael J. Matunis,
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, neurodegenerative diseases 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 properties and functions of modified proteins. Specific projects include: (1) 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. (2) Understanding how SUMO modification of BLM, the protein mutated in Bloom syndrome, affects its role in DNA repair and the maintenance of genome integrity. (3) Understanding how sumoylation of proteins functions to protect cells from the effects of cytotoxic stress using S. cerevisiae as a model system.
Lastly, projects in the lab are also focused on characterizing the SUMO pathway in malaria-causing parasite, P. falciparum, with the goal of developing parsite-specific inhibitors of SUMO conjugation that could be used treat malaria.
Honors and Awards
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
Biochemistry and molecular biology, cell biology, SUMO, nuclear pore complexes, mitosis, malaria, HIV, ubiquitin
Goeres, J., P.-K. Chan, D. Mukhopadhyay, H. Zhang, B. Raught and M.J. Matunis. 2011. The SUMO-specific isopeptidase, SENP2, associates dynamically with nuclear pore complexes through interactions with karyopherins and the Nup107-160 nucleoporin subcomplex. Mol. Biol. Cell. In press.
Kelley, J.B., S. Datta, C.J. Snow, M. Chatterjee, L. Ni, A. Spencer, C.S. Yang, C. Cubeña-Potts, M.J. Matunis, B.M. Paschal. 2011. The defective nuclear lamina in Hutchinson-gilford progeria syndrome disrupts the nucleocytoplasmic ran gradient and inhibits nuclear localization of ubc9. Mol. Cell Biol. 31:3378-3395.
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.