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Faculty Detail    
Name LALITA R SHEVDE-SAMANT
Director, Cancer Biology Theme
Associate Director for Education & Training, UAB O'Neal Comprehensive Cancer Center		  
Campus Address WTI 320D
Phone  (205) 975-6261
E-mail  lsamant@uab.edu
Other websites UAB Graduate Biomedical Sciences Cancer Biology Program
Metastasis Research Society
MRS ECAM
UAB Comprehensive Cancer Center
Shevde-Samant Lab website
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Center  UAB Immunology Institute  UAB Immunology Institute Professor
Primary  Joint Pathology  Molecular & Cellular Pathology Professor
Center  Ctr for Clinical & Translational Sci  Ctr for Clinical & Translational Sci Professor
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Biomatrix Eng Regen Med (BERM) Ctr  Biomatrix Eng Regen Med (BERM) Ctr 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’s graduate training from the Cancer Research Institute, University of Mumbai, India focused on studying the role of innate immunity in the regulation of breast cancer. She completed postdoctoral training at the Hershey Medical Center, Penn State University 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. Research in the Shevde-Samant laboratory is aimed at understanding aberrations intrinsic to tumor cells and those that are extrinsically manipulated as a result of interaction with cells in the tumor microenvironment.

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)      
The American Society for Cell Biology (ASCB)     
 



Research/Clinical Interest
Title
Investigating molecular signaling mechanisms that present as fundamental aberrations in tumor cells or their immune microenvironment
Description
Tumor metastasis, the movement of tumor cells from a primary site to progressively colonize distant organs, is a major contributor to the deaths of cancer patients. My research program aims to define molecular signaling mechanisms that impact tumor progression and metastasis. Our studies are focused on understanding tumor-intrinsic and tumor-extrinsic factors that influence breast cancer. Our discoveries have pivotally contributed to decoding the molecular crosstalk that enables breast cancer cells to re-program their microenvironment and facilitate metastatic progression. Our lab was the first to report that Merlin impedes attributes of tumor progression in breast cancer. Ongoing investigations are following leads from metabolomics and bioenergetics assessments to identify vulnerabilities that can be therapeutically targeted in tumor cells deficient for Merlin. Cancer co-opts developmental processes to favor tumor progression, metastasis, and drug resistance. As such, these signaling pathways are particularly attractive targets for efficient anticancer therapies, especially in metastatic cancers. By crafting novel methodology and adapting state-of-the-art technologies, we have demonstrated that by virtue of activated Hedgehog (Hh) signaling, breast cancer cells manipulate vasculature at the primary site and also exploit the metastatic site of bone. Our recent work has identified that by activating Hh signaling, breast cancer cells orchestrate the composition of the tumor immune microenvironment to be tumor-permissive; inhibition of Hh re-positioned the immune portfolio to be inflammatory and tumor-eradicating – characterized by a remarkable shift in the nature of tumor-infiltrating macrophages and T cells. Work is underway to investigate the impact of the mutually sustaining synergy between tumor and its immune microenvironment and how this promotes evolution of the malignant phenotype.

Selected Publications 
Publication PUBMEDID
Mota, M., Metge, B.M., Hinshaw, D.C., Alsheikh, H. A., Chen, D., Samant, R.S., Shevde, L.A. Merlin deficiency alters the redox management program in breast cancer. Mol Oncol. Jan 7. doi: 10.1002/1878-0261.12896.  33410252 
Lama-Sherpa, T. D., Lin, V. T. G., Metge, B. J., Weeks, S. E., Chen, D., Samant, R. S., Shevde, L. A. Hedgehog signaling enables repair of ribosomal DNA double-strand breaks. Nucleic Acids Res 48 (18): 10342-10352, 2020. PMCID: PMC7544215.  32894284 
Mota, M. and Shevde, L. A. Merlin regulates signaling events at the nexus of development and cancer. Cell Comm Signal 18(1): 63, 2020. PMCID: PMC7164249.
 		 32299434 
Lama-Sherpa, T.D. and Shevde, L. A. An emerging regulatory role for the tumor microenvironment in the DNA damage response to double-strand breaks. Molecular Cancer Research, 18 (2): 185-193, 2020. doi: 10.1158/1541-7786.MCR-19-06652.PMCID: PMC7002210.  31676722 
Hinshaw, D.C. and Shevde, L.A. The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res 78(18): 4557-4566, 2019.  31350295. 
Hanna, A., Metge, B. M., Bailey, S. K., Chen, D, Chandrashekar, D. S., Varambally, S., Samant, R.S., Shevde, L.A. Inhibiting Hedgehog signaling reprograms the dysfunctional immune microenvironment in breast cancer. OncoImmunology 8(3):1548241, 2018.  30723576 
Das, S., Bailey, S. K., Metge, B. J., Hanna, A., Hinshaw, D. C., Mota, M. M., Forero-Torres, A., Chatham, J. C., Samant, R.S., Shevde, L.A. O-GlcNAcylation of GLI Transcription Factors in Hyperglycemic Conditions Augments Hedgehog activity. Lab Invest. 99(2): 260-270, 2019. doi: 10.1038/s41374-018-0122-8.  30420690 
Mota, M. S., Jackson, W.P., Bailey, S. K., Vayalil, P., Landar, A., Rostas, J. H., III, Mulekar, M. S., Samant, R.S., Shevde, L.A. Deficiency of tumor suppressor Merlin facilitates metabolic adaptation by co-operative engagement of SMAD-Hippo signaling in breast cancer. Carcinogenesis 39 (9): 1165-1175, 2018.  29893810 
Lin, V., Pruitt, H.C., Samant, R.S., Shevde, L.A. Developing cures: Targeting Ontogenesis in Cancer. Trends in Cancer 3(2): 126-136, 2017; DOI: http://dx.doi.org/10.1016/j.trecan.2016.12.007.  28718443. 
Das, S., Jackson, W.P., Prasain, J. K., Hanna, A., Bailey, S. K., Tucker, J. A., Mulekar, M. S., Bae, S., Wilson, L., Samant, R. S., Barnes, S., Shevde, L. A. Loss of Merlin induces metabolomic adaptation that engages dependence on Hedgehog signaling. Accepted for publication in Scientific Reports 7: 40773, 2017.  28112165 
Morrow, K. A., Das, S., Meng, E., Menezes M. E., Bailey, S. K., Metge, B. M., Buchsbaum, D. J., Samant, R. S., Shevde, L. A. Loss of tumor suppressor Merlin results in aberrant activation of Wnt/beta-catenin signaling in cancer. Oncotarget doi: 10.18632/oncotarget.7494.  26908451 
Shevde, L. A.and Samant, R. S. Non-Classical Hedgehog-GLI Signaling and Its Clinical Implications. Int. J. Cancer-135(1): 1-6, 2014.   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-33(20): 2620-2628, 2014.  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, innate and adaptive immune microenvironment, signaling, cancer stem cells, chemoresistance, metabolism, osteolysis, Merlin, Hedgehog pathway, Wnt pathway