Maria Soledad Sosa, PhD Email Maria Soledad Sosa
- ASSISTANT PROFESSOR | Pharmacological Sciences
- ASSISTANT PROFESSOR | Oncological Sciences
Link to Sinai lab portal: http://labs.icahn.mssm.edu/sosalab.
Multi-Disciplinary Training Areas
Cancer Biology [CAB], Pharmacology and Therapeutics Discovery [PTD]
PhD, University of Buenos Aires/University of Pennsylvania
Early Dessimination Events in Breast Cancer
In 2012 I was awarded a DoD Breast Cancer Postdoctoral Grant to study the processes responsible for dissemination and target organ colonization by breast tumor cells. I found that before pre-malignant lesions can form a primary tumor they are constantly releasing cells into the blood stream and these pre-malignant DTCs although quiescent at the beginning could eventually proliferate into metastases at secondary sites. These pre-malignant cells may constitute, by themselves and/or in cooperation with later arriving DTCs, the sources of relapses. Thus, my future research will aim to understand how these cells very early in tumor progression disseminate, survive and cooperate with the microenvironment to form metastases. This program will strongly impact the way modern therapy is achieved and it will incorporate a new biology in metastasis disease.
Targeting Minimal Residual Disease
I am interested in exploring the intrinsic and extrinsic signaling pathways that allow the establishment and maintenance of minimal residual disease in cancer patients. I found that NR2F1 while lost in primary tumors is re-expressed upon surgical removal of the primary tumor in local and distant residual tumor cells and allows them to undergo dormancy. Importantly, I was able to demonstrate the re-expression of NR2F1 in dormant disseminated tumor cells (DTCs) derived from prostate cancer patients. This dormancy phase regulated by NR2F1 involved upregulation of cell cycle inhibitors and interestingly it also required the induction of stem cell genes. The latter result is surprising and important since it is the first time that a connection between pluripotency genes and quiescence programs has been established in tumor cells and dormancy. In addition, I also found a novel function for NR2F1 in regulating histone modifications during dormancy. These findings open a new field of investigation where epigenetics modulations may be responsible for the quiescence phase of minimal residual disease. In addition I developed a screening strategy to find agonists and antagonists of NR2F1 required for disseminated tumor cell reprogramming into dormancy. This work already identified molecules with these activities that we are optimizing. Importantly this work has been selected for a potential spin-off via the Accelerator program that Eli Lilly and other companies in NYC have in place.
Sosa MS, Parikh F, Maia AG, Estrada Y, Bosch A, Bragado P, Ekpin E, George A, Zheng Y, Lam HM, Morrissey C, Chung CY, Farias EF, Bernstein E, Aguirre-Ghiso JA. NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes. Nature communications 2015; 6.
Sosa MS, Bragado P, Aguirre-Ghiso JA. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nature reviews. Cancer 2014 Sep; 14(9).
Aguirre-Ghiso JA, Bragado P, Sosa MS. Metastasis awakening: targeting dormant cancer. Nature medicine 2013 Mar; 19(3).
Begley U, Sosa MS, Avivar-Valderas A, Patil A, Endres L, Estrada Y, Chan CT, Su D, Dedon PC, Aguirre-Ghiso JA, Begley T. A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-α. EMBO molecular medicine 2013 Mar; 5(3).
Curtis JJ, Walls JT, Schmaltz RA, Boley T, Landreneau R, Nawarawong W. Prognosis of hospital survivors after salvage from cardiopulmonary bypass with centrifugal cardiac assist. ASAIO transactions / American Society for Artificial Internal Organs; 36(3).
Bragado P, Estrada Y, Sosa MS, Avivar-Valderas A, Cannan D, Genden E, Teng M, Ranganathan AC, Wen HC, Kapoor A, Bernstein E, Aguirre-Ghiso JA. Analysis of marker-defined HNSCC subpopulations reveals a dynamic regulation of tumor initiating properties. PloS one 2012; 7(1).
Kim RS, Avivar-Valderas A, Estrada Y, Bragado P, Sosa MS, Aguirre-Ghiso JA, Segall JE. Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer. PloS one 2012; 7(4).
Wertheimer E, Gutierrez-Uzquiza A, Rosemblit C, Lopez-Haber C, Sosa MS, Kazanietz MG. Rac signaling in breast cancer: a tale of GEFs and GAPs. Cellular signalling 2012 Feb; 24(2).
Sosa MS, Avivar-Valderas A, Bragado P, Wen HC, Aguirre-Ghiso JA. ERK1/2 and p38α/β signaling in tumor cell quiescence: opportunities to control dormant residual disease. Clinical cancer research : an official journal of the American Association for Cancer Research 2011 Sep; 17(18).
Wen HC, Avivar-Valderas A, Sosa MS, Girnius N, Farias EF, Davis RJ, Aguirre-Ghiso JA. p38α Signaling Induces Anoikis and Lumen Formation During Mammary Morphogenesis. Science signaling 2011; 4(174).
Sosa MS, Lopez-Haber C, Yang C, Wang H, Lemmon MA, Busillo JM, Luo J, Benovic JL, Klein-Szanto A, Yagi H, Gutkind JS, Parsons RE, Kazanietz MG. Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer. Molecular cell 2010 Dec; 40(6).
Griner EM, Caino MC, Sosa MS, Colón-González F, Chalmers MJ, Mischak H, Kazanietz MG. A novel cross-talk in diacylglycerol signaling: the Rac-GAP beta2-chimaerin is negatively regulated by protein kinase Cdelta-mediated phosphorylation. The Journal of biological chemistry 2010 May; 285(22).
Sosa MS, Lewin NE, Choi SH, Blumberg PM, Kazanietz MG. Biochemical characterization of hyperactive beta2-chimaerin mutants revealed an enhanced exposure of C1 and Rac-GAP domains. Biochemistry 2009 Sep; 48(34).
Sosa MS, Girotti MR, Salvatierra E, Prada F, de Olmo JA, Gallango SJ, Albar JP, Podhajcer OL, Llera AS. Proteomic analysis identified N-cadherin, clusterin, and HSP27 as mediators of SPARC (secreted protein, acidic and rich in cysteines) activity in melanoma cells. Proteomics 2007 Nov; 7(22).
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Dr.Sosa did not report having any of the following types of financial relationships with industry during 2018 and/or 2019: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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