Susan M. Mendrysa

Susan M.  Mendrysa Profile Picture

Associate Professor of Basic Medical Sciences
Ph.D., University of Wisconsin-Madison, 2001

Contact Info:

Training Group(s):
Cancer Biology

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

The unifying theme of the research in the Mendrysa laboratory is the role of the p53 tumor suppressor protein in development, tissue homeostasis, and disease. The regulation of p53 must be tightly controlled as loss of p53 function is a major driver of tumor formation and aberrantly elevated p53 function contributes to the neuro-degeneration associated with human disease including Parkinson’s and Alzheimer’s Disease. A major focus of our current research is to delineating the mechanisms by which p53 function is regulated by the MDM2 protein in cerebellar granule neuron progenitors (GNPs). Disruption of GNP maturation can result in defects in motor coordination and learning, or in medulloblastoma, the most common childhood brain tumor. We primarily use genetically modified mice as a model system in which to place MDM2 and p53 within the molecular pathways that govern the proliferation, differentiation, and cell death of GNPs in cerebellar development and tumorigenesis. Our in vivo genetic studies with mice are complimented by in vitro molecular biology and biochemistry approaches in mammalian cells to delineate the functional and mechanistic relationship of cellular signaling molecules. Using this multi-disciplinary approach, the Mendrysa lab is able to perturb the level of proteins of interest (e.g. p53, MDM2) in the whole animal in order to investigate their physiological roles in normal and pre-cancerous tissues and conduct hypothesis-driven experiments in vitro for follow up analyses.

Selected Publications:

Wang G., Fulkerson C.M., Malek R., Ghassemifar S., Snyder P.W., and Mendrysa S.M. (2012) Mutations in Lyar and p53 are Synergistically Lethal in Female Mice. Birth Defects Research Part A: Clinical and Molecular Teratology - in press

Ghassemifar S., and Mendrysa, S.M. (2012) MDM2 Antagonism by Nutlin-3 Induces Death in Human Medulloblastoma Cells. Neuroscience Letters 513, 106-110.

Malek, R., Matta, J., Taylor, N., Perry, M.E., and Mendrysa, S.M. (2011) The p53 Inhibitor MDM2 Facilitates Sonic Hedgehog-Mediated Tumorigenesis and Influences Cerebellar Foliation. PLoS One.

Mendrysa, S.M. Ghassemifar, and Malek, R., (2011) Role of p53 in the CNS: perspectives on development, stem cells, and cancer. Genes&Cancer 2:431-442.

McGowan, K.A., Park, C.Y., Perez, M., Glader, B.E., Wong, C., Malek, R., Mendrysa, S.M., Weissman, I.L., and Barsh, G.S. (2011) Activation of p53 links ribosomal protein mutations to bone marrow failure in mice. Blood 118, 3622-3633.

Mendrysa, S.M., Akagi, K., Roayaei, J., Copeland, N.G., Jenkins, N.A., and Eisenman RN. (2010) An Integrated Genetic-Genomic Approach for the Identification of Novel Cancer Loci in Mice Sensitized to c-Myc-Induced Apoptosis. Genes&Cancer. 1, 465-479.

Laurie, N., Donovan, S., Zhang, J., Shih,C.S., Mills, N., Fuller,C., Teunisse,A., Mohan,A., Johnson, D., Wilson, M., Rodriguez-Galindo,C., Quarto, M., Marine, J.C., Jochemson, A.G., Guy, R.K., Mendrysa, S.M., and Dyer, M.A. (2006). Inactivation of the p53 pathway in retinoblastoma. Nature 444, 61-66.

Mendrysa, S.M. and Perry, M.E. (2006). Tumor suppression by p53 without accelerated aging. Just enough of a good thing? Cell Cycle 5, 714-717.

Mendrysa, S.M., O'Leary, K.A., McElwee, M.K., Michalowski, J., Eisenman, R.N., Powell, D., and Perry, M.E. (2006). Tumor Suppression and Normal Aging in Mice with Constitutively High p53 Activity, Genes & Dev. 20, 16-21.

Cowley, S.M., Iritani, B.M., Mendrysa, S.M., Xu, T., Cheng, P.F., Yada, J., Queva, C., and Eisenman, R.N. (2005) The mSin3a Chromatin-Modifying Complex is Essential for Embryogenesis and T Cell Development, Mol. Cell. Biol. 25, 6990-7004.

O'Leary, K.A., Mendrysa, S.M., Vaccaro, A., and Perry, M.E. (2004) Mdm2 Regulates p53 Independently of p19ARF in Homeostatic Tissues, Mol. Cell. Biol. 24, 186-191.

Mendrysa, S.M., McElwee, M.K., Michalowski, J., O'Leary, K. Young, K.M. and Perry, M.E. (2003) Inhibition of p53 by mdm2 is Critical for Lymphopoiesis and Resistance to Whole Body Ionizing Irradiation, Mol. Cell. Biol. 23, 462-473.

Michalowski, J., Seavey, S.E., Mendrysa, S.M., and Perry, M.E. (2001) Defects in Transcription Coupled Repair Interfere with Expression of p90MDM2 in Response to Ultraviolet Light. Oncogene 20, 5856-5864.

Mendrysa, S.M., McElwee, M.K., and Perry, M.E . (2001) Characterization of the 5 and 3 Untranslated Regions in murine mdm2 mRNAs, Gene, 264, 139-146.

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