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Professional Profile
Research Interests: -Investigation of the molecular mechanisms and signaling pathways that regulate malignant behavior and drug resistance of breast cancer and melanoma. Honors and Academic Achievements: -Principal Investigator, Basic, Clinical & Translational Research grant (BCTR0402317), Susan G. Komen Breast Cancer Foundation, 2005-07. -Principal Investigator, American Cancer Society-IRG, (IRG-60-001-44 and CA 13148-31) University of Alabama at Brimingham, 2003-2004. -Principal Investigator, UAB Breast SPORE-Pilot Grant (CA89019), University of Alabama at Birmingham, 2003-2004. -AACR- Genentech, Inc. Scholar-in-Training Award, 92nd Annual Meeting of the American Association of Cancer Research, 2001. -Susan G. Komen Breast Cancer Foundation, Fellowship Award, 2000-2003. Education: -Ph.D., Applied Biology (Tumor Immunology), University of Mumbai, India. (1999) -M.S., Microbiology, University of Baroda, India. (1994) -B.S., Microbiology, University of Mumbai, India. (1992) Professional Appointments: -Research Instructor, Department of Pathology/ Molecular and Cellular Pathology University of Alabama, Birmingham, AL (2003-2004). -Associate Scientist, Women’s Cancer Section, Comprehensive Cancer Center, University of Alabama at Birmingham, AL (2002-2004). -Assistant Professor, Mitchell Cancer Institute, University of South Alabama, Mobile, AL (2004-present). -Assistant Professor, Department of Cell Biology & Neurosciences, University of South Alabama, Mobile, AL (2007-present). Service: -Scientific Reviewer, Department of Defense, Breast Cancer Research Program, 2004-2009 -Scientific Reviewer, Komen Foundation, 2005-2009 -Scientific Reviewer, Cancer Research UK -Scientific Reviewer, Prostate Cancer Foundation of Australia Scientific Focus: Our laboratory is investigating the role of the oncoprotein, osteopontin (OPN). The focus on OPN research is at two levels: 1) understanding mechanisms that regulate OPN 2) elucidating the signaling pathways that OPN participates in, to potentiate malignant behavior. We are also investigating mechanisms that contribute to chemoresistance of breast cancer with an emphasis on Nuclear Protein 1 (NUPR1). 1. Understanding mechanisms that regulate OPN We have published our work showing that the Breast Cancer Metastasis Suppressor 1 gene regulates OPN via a novel NF-?B site (Molecular Cancer 6: 6, 2007). We have investigated the role of the Hedgehog pathway in regulating the expression of OPN in melanoma and have found a clinically relevant relationship between the transcription factor, GLI1 and OPN. We have also identified and characterized an miRNA that targets OPN. This miRNA is upregulated in spheroid-cultures (classically used to study chemoresistance) of breast cancer cells. Intuitively, the expression of OPN is increased in the spheroid-forming breast cancer cells ( J Cell Mol Med 2009 Jun 16). Studies are in progress to determine the role of this miRNA in breast cancer and melanoma. 2. Elucidating the signaling pathways that OPN participates in, to potentiate malignant behavior. We have investigated the role of OPN in influencing the behavior of breast cancer cells when cultured as spheroids under conditions of low attachment. Specifically, we find that OPN expression under these conditions is critical to their ability to form vascular, lumen-bearing structures that express endothelial markers, in response to nutritional limitation. Studies are underway to elucidate the role of OPN in allowing the breast cancer cells to metamorphose into cells that resemble an endothelial-like phenotype. Further research is underway to determine the downstream effects of Hedgehog-initiated osteopontin-mediated signaling that enhance melanoma and breast tumor metastasis. 3. In the last couple of years, my laboratory has been studying the role of NUPR1 in chemoresistance. We have published our work showing that NUPR1 mediates resistance to conventional chemotherapeutic drugs, likely through the involvement of p21 (Cancer Metastasis Rev (1-2):225-32, 2009 and Curr Cancer Drug Targets 8(5):421-30, 2008.). Studies are in progress to determine the role of p21 in the signaling downstream of NUPR1, with a focus on chemoresistance. Selected Publications: 1. Das S., Harris L.G., Metge B.J., Liu S., Riker A.I., Samant R.S., Shevde L.A. (2009) The Hedgehog pathway transcription factor, GLI1 promotes malignant behavior of cancer cells by upregulating osteopontin. J Biol Chem. 284(34): 22888-22897. 2. Shevde, L.A., Metge, B. M., Mitra, A., Ju, J., King, J.A., Samant, R.S. (2009) Spheroid-forming sub-population of breast cancer cells demonstrates vasculogenic mimicry via hsa-miR-299-5p regulated de novo expression of osteopontin. J Cell Mol Med. June 16, 2009 (Doi: 10.1111/j.1582-4934.2009.00821.x). 3. Clark D.W., Mitra A., Fillmore R.A., Jiang W.G., Samant R.S., Fodstad O., Shevde L.A. (2008) Nupr1 interacts with p53, transcriptionally regulates p21 and rescues breast epithelial cells from doxorubicin-induced genotoxic stress. Current Cancer Drug Targets 8(5): 421-430. 4. Samant R.S., Clark D.W., Fillmore R.A., Cicek M., Metge B.J., Chandramouli K.H., Chambers A.F., Casey G., Welch D.R., Shevde L.A. (2007) Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-Kappa B activation. Mol. Cancer 6: 6 (doi: 10.1186/1476-4598-6-6). 5. Shevde L.A., Samant R.S., Paik J.C., Metge B.J., Chambers A.F., Casey G., Frost A.R., Welch D.R. (2006) Osteopontin knockdown suppresses tumorigenicity of human metastatic breast carcinoma. Clin Exp Metastasis 18(8): 683-693. Active Grants: -BC0601257 Department of Defense (06/01/07-05/31/10) Crosstalk between cancer cells and bone via the Hedgehog pathway determines bone metastasis of breast cancer Goals: To investigate the role of the hedgehog pathway in mediating metastasis of breast cancer to bone. Role: Principal Investigator |
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Lalita R. Shevde-Samant, Ph.D.University of South Alabama - Mobile Alabama 36688-0002 Appointments: Medical, Surgical and Gynecologic Oncology: (251) 665-8000 Radiation Oncology: (251) 445-9615 Administration: (251) 460-6993 For questions or comments Contact Us Date last changed: October 15, 2009 9:39 AM http://www.southalabama.edu/mci/lsamant.html |
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