Sam Thiagalingam, Ph.D.
Ph.D. The Johns Hopkins University
Post-doctoral Fellowship: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
General field of research:
Molecular basis of cancer metastasis and biomarkers for diagnosis, prognosis and therapy of cancer and psychiatric disorders.
Affiliations other than medicine:
Evans Center for Interdisciplinary Biomedical Research
Genetics & Genomics
Pathology & Laboratory Medicine
Evans L320 and E323
Phone: (617)-638 6013
Phone: (617)-638 6022
Fax: (617)-638 4275
Research group information
Sait Ozturk, B.S., Pre-doctoral Fellow – firstname.lastname@example.org
Arthur W. Lambert, B.S., Pre-doctoral Fellow – email@example.com
Panos Papageorgis, Ph.D., Post-doctoral Fellow – firstname.lastname@example.org
Sahab Yaqubi, M.D., Post-doctoral Fellow – email@example.com
Hamid M. Abdolmaleky, M.D., Research Associate/Visiting Professor – firstname.lastname@example.org
Cancer genetics; Cancer epigenetics; Cancer metastasis; Epigenetics of schizophrenia and bipolar disorder; Biomarkers for cancer and psychiatric disorders; Smad signaling
Summary of research interest:
Our major research focus is on the use cancer genomics, employing primarily breast, colon and lung cancers as model systems, to shed light on genomic instability, genetic and epigenetic aberrations and metastasis of cancer. Furthermore, we are also interested in unravelling the role of the epigenome in the pathogenesis of major psychiatric disorders such as schizophrenia and bipolar disorder.
Our pioneering studies showed that SMAD4 is the major target tumor suppressor gene localized to the minimally lost region on chromosome 18q. Currently, we are testing the hypothesis that the direct/indirect inactivation of Smad4 is a major switch for benign to metastatic form of colon cancer.
TGF-beta levels are increased in advanced breast cancers and believed to induce epithelial mesenchymal transition (EMT), a critical process during cancer progression. We exploited a model system and found that TGF-beta regulates promoter DNA methylation of genes during the acquisition of the EMT phenotype. We are extending these studies to examine other modes of epigenetic regulation and the molecular basis of these effects.
We have also proposed a simplified scheme to explain the complexity in cancer progression as alternations that accrue in a series of a cascade of sub-network modules and elicited as events in a multi-modular molecular network (MMMN) of cancer progression.
Gao, F., J. F. Ponte, P. Papageorgis, M. Levy, S. Ozturk, A.W. Lambert, H. Pan, D. Chinnappan, K-h. Cheng, A. Thiagalingam, H. M. Abdolmaleky and S. Thiagalingam. 2009. hBub1 deficiency triggers a novel p53 mediated early apoptotic checkpoint pathway in mitotic spindle damaged cells. Cancer Biology & Therapy 8(7): 627-35.
Gao, F., J. F. Ponte, M. Levy, P. Papageorgis, N.M. Cook, S. Ozturk, A.W. Lambert, A. Thiagalingam, H. M. Abdolmaleky, B. A. Sullivan and S. Thiagalingam. 2009. hBub1 negatively regulates p53 mediated early cell death upon mitotic checkpoint activation. Cancer Biology & Therapy 8(7): 636-44. (Accompanied with cover illustration).
Pan, H., F. Gao, P. Papageorgis, H. Abdolmaleky, D.V. Faller and S. Thiagalingam. 2007. Aberrant activation of g-catenin promotes genomic instability and oncogenic effects during tumor progression. Cancer Biology & Therapy 6:1638-43.
Thiagalingam, S. 2006. A cascade of modules of a network defines cancer progression. Cancer Res. 66: 7379-7385.
Abdolmaleky, HM., K-h. Cheng, S.V. Faraone, M. Wilcox, S. J. Glatt, F. Gao, C.L. Smith, R. Shafa, B. Aeali, H. Pan, P. Papageorgis, J.F. Ponte, V. Sivaraman, M. Tsuang and S. Thiagalingam. 2006. Hypomethylation of MB- COMT Promoter is a major risk factor for Schizophrenia and Bipolar Disorder. Human Mol. Genet. 15: 3132-3145.
Cheng, K-h., J. F. Ponte and S. Thiagalingam. 2004. Elucidation of epigenetic inactivation of SMAD8 in cancer using Targeted Expressed Gene Display. Cancer Res. 64: 1639-1646.
Thiagalingam, S., S. Laken, J. K. V. Willson, S. Markowitz, K. W. Kinzler, B. Vogelstein and C. Lengauer. 2001. The mechanisms underlying losses of heterozygosity in human colorectal cancers. Proc. Natl. Acad. Sci. USA. 98: 2698-2702.
Thiagalingam, S., C. Lengauer, F. S. Leach, M. Schutte, S. A. Hahn, J. Overhauser, J. K. V. Willson, S. Markowitz, S. R. Hamilton, S. E. Kern, K. W. Kinzler and B. Vogelstein. 1996. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nature Genet. 13: 343-346.
Technologies available for sharing upon request:
Methylation Specific PCR; Standard Molecular and Cell Biology techniques