Steven L. Gonias, M.D., Ph.D.
- Distinguished Professor and Chair
- Ph.D. - Duke University, 1983
- M.D. - Duke University, 1984
- Residency Training: Anatomic and Clinical Pathology
- Board Certifications: Clinical Pathology
- Clinical Specialty: Disorders of hemostasis and thrombosis
Our laboratory is interested in identifying and characterizing novel pathways by which proteases and their cell-surface receptors regulate cell physiology. We are particularly interested in the function of proteases in cancer but also have active projects related to peripheral nerve injury, Alzheimer’s disease and cardiovascular biology. One focus involves urokinase-type plasminogen activator (uPA), a serine protease and plasminogen activator that binds with high affinity to a GPI-anchored receptor called uPAR. This event activates multiple cell-signaling pathways that affect cell migration, survival, and phenotype. We are actively working to elucidate mechanisms by which uPAR-initiated cell-signaling promotes cancer metastasis. We are particularly interested in breast cancer, but also work on prostate cancer and cancers of the central nervous system.
The complex of uPA with its inhibitor, PAI-1, is a ligand for a receptor called LRP-1. LRP-1 also is the receptor for other ligands, including extracellular matrix proteins, growth factors and foreign toxins. Our laboratory elucidated a pathway in which LRP-1 regulates cell-signaling indirectly, by regulating the cell-surface level of uPAR. However, recent studies suggest that LRP-1 also directly regulates cell-signaling by binding adaptor proteins, such as Shc and JIP. By this mechanism, LRP-1 regulates cell survival and gene transcription. Our current research is aimed at determining the role of LRP-1 in cancer and peripheral nerve injury, using in vitro and in vivomodel systems. Using proteomics approaches, we also are actively investigating the ability of LRP-1 to model the composition of the plasma membrane.
Our third area of focus concerns the plasma protease inhibitor, alpha2M. Our laboratory has demonstrated that this protein functions as a conformation-dependent carrier of growth factors. Alpha2M may also function in cell-signaling by binding to LRP-1. By site-directed mutagenesis, we have isolated and individually modified various functional sites in this multifunctional protein. This work enables us to determine the mechanism by which alpha-2M regulates cell physiology and the response to injury in vivo.
Click here for information on the Gonias Lab.
- Shi, Y., Mantuano, E., Inoue, G., Campana, W., and Gonias, S. (2009) Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase-dependent pathway. Sci Signal 2, ra18
- Jo, M., Eastman, B., Webb, D., Stoletov, K., Klemke, R., and Gonias, S. (2010) Cell signaling by urokinase-type plasminogen activator receptor induces stem cell-like properties in breast cancer cells. Cancer Res 70, 8948-8958
- Hu, J., Jo, M., Cavenee, W. K., Furnari, F., VandenBerg, S. R., and Gonias, S. L. (2011) Crosstalk between the urokinase-type plasminogen activator receptor and EGF receptor variant III supports survival and growth of glioblastoma cells. Proc Natl Acad Sci U S A 108, 15984-15989
- Stiles, T. L., Dickendesher, T. L., Gaultier, A., Fernandez-Castaneda, A., Mantuano, E., Giger, R. J., and Gonias, S. L. (2013) LDL receptor-related protein-1 is a sialic-acid-independent receptor for myelin-associated glycoprotein that functions in neurite outgrowth inhibition by MAG and CNS myelin. J Cell Sci 126, 209-220
- Staudt, N. D., Jo, M., Hu, J., Bristow, J. M., Pizzo, D. P., Gaultier, A., Vandenberg, S. R., and Gonias, S. L. (2013) Myeloid cell receptor LRP1/CD91 regulates monocyte recruitment and angiogenesis in tumors. Cancer Res
- Mantuano, E., Lam, M. S., and Gonias, S. L. (2013) LRP1 assembles unique co-receptor systems to initiate cell signaling in response to tissue-type plasminogen activator and myelin-associated glycoprotein. J Biol Chem 288, 34009-34018 Click here to search for Dr. Gonias' publications
Dr. Gonias received his B.S. as valedictorian in Biochemistry at the State University of New York, Stony Brook. He then received his M.D. and Ph.D. degrees with a scholarship from the Medical Scientist Training Program at Duke University. Dr. Gonias completed residency training in Anatomic and Clinical Pathology at Duke University and is currently board-certified in Clinical Pathology.
As a young investigator in the Departments of Pathology and Biochemistry at the University of Virginia, Dr. Gonias was selected for a Pew Scholarship in the Biomedical Sciences and was the recipient of a Research Career Development Award from the NHLBI. His research on protease regulation, cancer invasion and metastasis, blood coagulation, and vascular biology has received continuous funding from the NIH. At the University of Virginia, Dr. Gonias served as Director of the Medical Scientist Training Program, Vice Chair for Research in Pathology, and Associate Director for Translational Research in the NCI-funded Cancer Center.
At UCSD, in addition to his role as Chairperson of Pathology, Dr. Gonias remains highly active as a scientist. He has held multiple positions in the peer review process and contributes in the organization of international meetings.Click here to contact me
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