Marius Sudol, PhD
Staff Scientist
LOCATION
Weis Center for Research
100 North Academy Avenue
Danville, PA 17822
Phone: 570-271-6677
Fax: 570-271-6701
msudol1@geisinger.edu
EDUCATION
PhD, The Rockefeller University, 1983
Postdoctoral Training, The Rockefeller University, 1983-1987
RESEARCH FOCUS
Protein-Protein Interaction, Cancer, Signal Transduction, Cellular Regulation, Genomics
EXPERTISE
Modular Domains, WW Domains, Hippo Signaling Pathway, SRC Oncogene, ERBB4 Receptor Signaling
RESEARCH INTERESTS
Molecular Function of the WW Domain in Signaling and DiseasesOur goal is to elucidate signaling pathways that use a small, modular protein domain known as the WW domain. This domain mediates well-defined protein-protein interactions and has been implicated in several human diseases through missense mutations mapped within the domain or its ligand. We aim to characterize genetic lesions that affect the domain and/or its ligand and result in human disease. We also employ high-throughput strategies to illuminate contribution of the WW domain to the function of the human proteome. Our ultimate goal is to predict and design molecular tools for interventions in WW domain-mediated pathways to correct pathological states.
Recently, we started to explore laboratory models of oncogenic transformation as sources of biomarkers of human cancers.
Two major projects are being pursued.
We investigate the role of YAP protein in the Hippo signaling pathway. In Drosophila, the Hippo pathway controls the size of organs. Activation of this pathway in the fly conveys growth inhibitory signals and promotes apoptosis. We "reconstituted" the Hippo pathway in a human epithelial cell line and showed that, in contrast to flies, the activation of this pathway results in anti-apoptotic signals. We have shown that the complex formation between transcriptional co-activator YAP and Lats kinases requires intact WW domains of YAP, as well as intact Proline-Proline-[Any Amino Acid]-Tyrosine (PPxY) motifs in Lats kinases. The entire Hippo pathway is rich in multiple WW domain-PPxY complexes.The apoptotic "read-out" of the Hippo pathway in embryonic kidney cells represents a useful experimental system for the identification of putative upstream receptors or extracellular factors that initiate the entire signaling cascade and ultimately control organ size. In contrast to its pro-apoptotic activity, YAP was recently shown to be an oncogene of breast and liver cancer. We are now trying to identify molecular determinants of the duality of YAP action.
- Core Components of the Hippo Signaling Pathway
- Functional Network of v-src Induced & Repressed Genes
RECENT PUBLICATIONS
Oka, T., Mazack, V., and Sudol, M.,. (2008). Mst2 and Lats kinases regulate apoptotic function of YAP.. J. Biol. Chem., 283, 27534-27546.
Masker, K., Golden, A., Gaffney, C., Mazack, V., Schwindinger, W., Zhang,W., Wang, L-H., Carey, D.J., and Sudol, M.,. (2007). Transciptional profile of Rous Sarcoma Virus transformed chicken embryo fibroblasts reveals new signaling targets of viral-src.. Virology, 364.10-20.
Aqeilan, R.E., Donati, V., Palamarchuk, A., Kaou, M., Trapasso, F., Pekarsky, Y., Sudol, M., Croce, M.C.. (2005). WW domain-containing proteins, WWOX and YAP compete for interaction with ErbB-4 and modulate its transcriptional function.. Cancer Research, 65, 6764-6772.
Hu, H., Columbus, J., Zhang, Y., Wu, D., Lian, L, Carter, M., Davis, R., Sudol, M., Rodwell, J., Herrero, J.. (2004). A map of WW domain family interactions.. Proteomics, 4, 643-655.
Komuro, A., Nagai, M., Navin, N., and Sudol, M.,. (2003). WW Domain-containing Protein YAP Associates with ErbB-4 and acts as a co-transcriptional activator for the carboxy-terminal fragment of ErbB4 that translocates to the nucleus.. J. Biol.Chem., 278, 33334-33341.