Andres J.P. Klein-Szanto, MD, PhD
Director, Histopathology Facility
- PhD, Pathology, University of Buenos Aires, School of Medicine, Argentina, 1970
- MD, Medicine, University of Buenos Aires , School of Medicine, Argentina, 1965
- American Association for the Advancement of Science
- American Association for Cancer Research
- US and Canadian Academy of Pathology
- European Society of Pathology
- Associate Editor, Acta Odontologica Latinoamericana, 1984-present.
- Associate Editor, Molecular Carcinogenesis, 1994-present.
- Member, External Advisory Committee, Wistar/Penn Skin SPORE, 2001-2004
- Ad Hoc Reviewer for the Cancer Etiology Study Section Section, National Institutes of Health, Division of Research Grants, Bethesda, MD, 2004-2008
Role of the Pro-protein convertases furin and PACE-4 in cancer progression.
Pathobiology and pathogenesis of skin, oral mucosa and esophageal cancer.
Tumor progression is a chain of cellular and molecular events that occur gradually during the development of neoplasia. We are studying the role of pro-protein convertases (PCs) such PACE-4 and furin during the early and late stages of tumor progression. These enzymes activate cancer related biomolecules that regulate cell proliferation, cell adhesion and invasion. Over-expression of PCs correlates with aggressive tumor features both in mouse models and in human tumors. This has been demonstrated in our laboratory using tumor cells derived from lung, esophagus, ovarian and oral malignant tumors. Inhibition of PCs can be obtained by using competitive inhibitors such as chloro-methyl-ketone (CMK). This inhibitor decreases and even abolishes the invasive/malignant phenotype of tumor cells by inhibiting the activation of invasion and metastasis-associated gene products such as MT1-MMP, stromelysin 3, TGF-β and IGFR1. CMK was also used in vivo by topical skin administration. Using this modality we were able to decrease 40% the number of chemically-induced mouse skin cancers as well as diminish 60% the respective tumor volumes.
My laboratory collaborates with a multidisciplinary team from the University of Pennsylvania, Harvard University and the the Medical University of South Carolina that had join forces to study mechanisms of esophageal carcinogenesis. We focus on the histopathology and immunohistochemistry of several projects. For example, in vitro/invivo experiments have shown the role of cyclin D1 regulation and Fbx4 mutations in esophageal carcinogenesis. Specifically, SCFFBX4-aB crystallin E3 ligase maintains threshold levels of the cyclin D1/CDK4 kinase critical for esophageal cell growth and homeostasis. Other studies on mechanisms of esophageal cancer include the role of periostin, Notch-1, Notch-3, WNT10A as well as several other biomolecules involved in autophagy and tumor microenvironment.
Bassi D.E., Fu J., Zhang J., and Klein-Szanto A.J. The Role of Proprotein convertases in animal models of skin carcinogenesis. Colloquium Series on Protein Activation and Cancer, 1 (1): 1-60, 2012, San Rafael (CA): Morgan & Claypool Life Sciences. DOI: 10.4199/C00060ED1V01Y201206PAC001. ISBN: 9781615045099.
Klein-Szanto A.J., Zhang J., and Bassi D.E. Proprotein Convertases in gynecological cancers. Colloquium Series on Protein Activation and Cancer, 1 (2): 1-43, 2012, San Rafael (CA): Morgan & Claypool Life Sciences. DOI: 10.4199/C00065ED1V01Y201208PAC002, ISBN: 9781615044658.
Li Y, Chitnis N, Nakagawa H, Kita Y, Natsugoe S, Yang Y, Li Z, Wasik MA, Klein-Szanto AJ, Rustgi AK, Diehl JA, PRMT5 is required for lymphomagenesis triggered by multiple oncogenic drivers. Cancer Discov. 5:288-303, 2015. PMC4355177.
Bassi D.E., Cenna J., Zhang J., Cukierman E. and Klein-Szanto A.J. Enhanced aggressiveness of benzopyrene-induced squamous carcinomas in transgenic mice overexpressing the proprotein convertase PACE4 (PCSK6). Molec. Carcinogenesis (published on line) 2015.