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Faculty Detail    
Name LALITA R SHEVDE-SAMANT
Co-Director, Cancer Biology Theme
 
Campus Address WTI 320D
Phone 205-975-6261
E-mail lsamant@uab.edu
Other websites UAB Graduate Biomedical Sciences Cancer Biology Program
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Molecular & Cellular Pathology Associate Professor
Center  Center for Metabolic Bone Disease  Center for Metabolic Bone Disease Associate Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Lalita Shevde-Samant graduated from the Cancer Research Institute, University of Mumbai, India. She completed her postdoctoral training at the Hershey Medical Center, Penn State University and at the University of Alabama at Birmingham in the laboratory of Prof. Danny Welch in the area of metastasis suppressors. She was a faculty at the Mitchell Cancer Institute, University of South Alabama (2004-2012) before joining UAB in 2012.

Society Memberships
Organization Name Position Held Org Link
AACR-Minorities in Cancer Research (AACR-MICR)      
AACR-Women in Cancer Research (AACR-WICR)      
AAMC-Group on Women In Medicine and Science (GWIMS)      
American Association for Cancer Research (AACR)     
Metastasis Research Society (MRS)      

Research/Clinical Interest
Title
Mechanisms that regulate tumor progression, metastasis and drug resistance; crosstalk between the tumor cells and their microenvironment
Description
Our research goals are to define mechanisms that regulate tumor progression and metastasis, to apply this knowledge to complement and extend current clinical applications and provide additional therapeutic strategies. The microenvironment surrounding the cancer cells is an active participant in regulating tumor cell behavior. We are investigating the dynamics of the interactions between tumor cells and their microenvironment, researching how tumor cells manipulate their milieu and, conversely, how the reactive tumor microenvironment influences tumor cell plasticity, invasion, metastasis, and response to therapy. Our work identified the tumor suppressor, Merlin, as an important modulator of breast cancer. Further, we have discovered that Merlin is modulated by factors extrinsic to the tumor itself. Work is underway to investigate the impact of the mutually sustaining synergy between tumor and stromal cells and how that impacts the molecular homeostasis and promotes evolution of the malignant phenotype with a focus on determining the mechanisms and implications of post-translation modifications of Merlin protein. Another exciting aspect involves investigations of Hedgehog signaling. We have determined that Hedgehog signaling in tumor cells upregulates the expression of microenvironment modulators that influence tumor vascularization and metastasis. Ongoing investigations are centered on understanding the mechanisms and implications of autocrine and paracrine Hedgehog signaling in influencing tumor progression, metastasis and resistance to therapy.

Selected Publications 
Publication PUBMEDID
Shevde, L. A.and Samant, R. S. Non-Classical Hedgehog-GLI Signaling and Its Clinical Implications. Int. J. Cancer-In Press. doi: 10.1002/ijc.28424.   23929208 
Devine, D. J., Rostas, J. W., Metge, B. J., Das, S., Mulekar, M. S., Tucker, J. A., Grizzle, W. E., Buchsbaum, D. J., Shevde, L. A., Samant R. S. Loss of N-Myc interactor promotes epithelial-mesenchymal-transition by activation of TGF-beta/SMAD signaling. Oncogene-In Press  23770854 
Das, S., Samant, R. S., Shevde, L.A. Non-Classical Activation of Hedgehog Signaling Enhances Multidrug Resistance and Makes Cancer Cells Refractory to SMOH-Targeting Hedgehog Inhibition. J. Biol. Chem. 288(17): 11824-11833, 2013.   23508962 
Vincent, A. J., Ren, S., Harris, L.G., Devine, D. J., Samant, R.S., Fodstad, O., Shevde, L.A. Cytoplasmic translocation of p21 mediates NUPR1-induced chemoresistance. FEBS Letters 586: 3429-3434, 2012.   22858377 
Morrow, K.A. and Shevde L.A. Merlin: The wizard requires protein stability to function as a tumor suppressor. BBA-Reviews on Cancer. 1826(2): 400-406, 2012.   22750751 
Meng, E., Long, B., Sullivan, P., McClellan, S., Finan, M.A., Reed, E., Shevde, L.A., Rocconi, R.P. CD44+/CD24- ovarian cancer cells demonstrate cancer stem cell-like properties and correlate to survival. Clin. Exp. Metastasis 29(8): 939-948, 2012.  22610780 
Frost, A.R., Hurst, D.R., Shevde L.A. and Samant, R.S. The Influence of the Cancer Microenvironment on the Process of Metastasis (Editorial) Int J Breast cancer, 2012: 756257, 2012.  22570792 
Das, S., Samant, R.S., Shevde, L.A. The Hedgehog Pathway Conditions the Bone Microenvironment for Osteolytic Metastasis of Breast Cancer. Int. J. Breast Cancer. 2012: 298623, 2012.   22295244 
Kudo, K., Amable, L., Gavin, E., Das, S., Denny, W., Shevde, L.A., Reed, E. Inhibition of Gli-1 results in altered c-Jun activation, inhibition of cisplatin-induced up-regulation of ERCC1, XPD, and XRCC1, and inhibition of platinum-DNA adduct repair. Oncogene 31 (44): 4718-4724, 2012.   22266871 
Mitra, A., Menezes, M.E., Pannell, L.K., Mulekar, M.S., Honkanen, R.E., Shevde, L.A., Samant, R.S. DNAJB6 chaperones PP2A mediated dephosphorylation of GSK3β to down regulate β-catenin transcription target, osteopontin. Oncogene 31 (41): 4472-4483, 2012.   22266849 
Harris, L.G., Pannell, L.K., Singh, S., Samant, R.S., Shevde, L.A. Hedgehog signaling promotes breast cancer vascularity and spontaneous hematogenous metastasis by upregulating CYR61. Oncogene 31(28): 3370-3380, 2012.   22056874 
Morrow, K. A., Das, S., Metge, B.M., Ye, K., Mulekar, M.S., Tucker, J.A., Samant, R.S., Shevde, L.A. The tumor suppressor Merlin is lost in breast cancer by osteopontin-induced degradation. J Biol Chem 286(46): 40376-40385, 2011.   21965655 
Harris, L.G., Samant, R.S., Shevde, L.A. Hedgehog signaling: Networking to nurture a pro-malignant tumor microenvironment. Mol. Cancer Res. 9(9): 1169-1174, 2011.   21775419 
Ray, A., Meng, E., Reed E., Shevde, L.A., Rocconi, R.P. Hedgehog signaling pathway regulates the growth of ovarian cancer spheroid forming cells. Int. J. Oncol 39(4): 797-804, 2011.   21701772 
Das, S., Samant, R.S., Shevde, L.A. Hedgehog signaling induced by breast cancer cells promotes osteoclastogenesis and osteolysis. J. Biol. Chem. 286(11): 9612-9622, 2011.   21169638 
Mitra, A., Menezes, M.E., Shevde, L.A., Samant R. S. DNAJB6 induces degradation of β-catenin and causes partial reversal of mesenchymal phenotype. J. Biol. Chem. 285(32): 24686-24694, 2010.   20522561 
Shevde, L.A., Das, S., Clark, D. W., Samant, R.S. Osteopontin: An effector and an effect of tumor metastasis. Curr Mol Med 10(1): 71-81, 2010.   20205680 
Das S., Harris L.G., Metge B.J., Liu S., Riker A.I., Samant R.S., Shevde L.A.* The Hedgehog pathway transcription factor, GLI1 promotes malignant behavior of cancer cells by upregulating osteopontin. J Biol Chem 284(34) 22888-22897, 2009.  19556240 
Shevde, L.A., Metge, B. M., Mitra, A., Xi, Y., Ju, J., King, J.A., Samant, R.S. 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 14(6B): 1693-1706, 2010  19538464 
Chowdhury, U.R., Samant, R.S., Fodstad, O., Shevde, L.A. Emerging role of Nuclear Protein 1 (NUPR1) in Cancer Biology. Cancer and Metastasis Rev 28: 225-232, 2009.   19153668 
Mbeunkui F., Metge B.M., Shevde L.A.*, Pannell L. K.* Identification of differentially secreted biomarkers using LC-MS/MS in isogenic cell lines representing a progression of breast cancer. J Proteome Res 6(8): 2993-3002, 2007.   17608509 

Keywords
Tumor progression, metastasis, signaling, cancer stem cells, chemoresistance, microenvironment, metabolism, osteolysis, Merlin, Hedgehog pathway, Wnt pathway