Vivian Gama, Ph.D.

Assistant Professor

vivian.gama@vanderbilt.edu

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Faculty Appointments
Assistant Professor of Cell and Developmental Biology
Education
Ph.D., Pharmacology, Case Western Reserve University, Cleveland, OhioM.S., Clinical Lab Sciences, University of Wisconsin, Milwaukee, WisconsinB.S., Microbiology, Universidad de Los Andes, Bogota, Colombia
Research Description
Stem cells (both normal and cancerous) are defined by their ability to self-renew, in order to maintain their numbers, and their ability to differentiate into distinct cell types. Our lab is interested in uncovering new pathways regulating these stem cell properties. We are particularly interested in characterizing the functions of apoptotic proteins in maintaining self-renewal and pluripotency and in the regulation of differentiation and reprogramming. Using genetics, biochemistry, proteomics and live cell imaging we are uncovering the role of apoptotic proteins for the maintenance of the stem cell phenotype. We use embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and cancer stem cells (Glioblastoma and Medulloblastoma) as model systems. The lab focuses on three main lines of research:

1) Role of apoptosis proteins as modulators of stem cell self-renewal, pluripotency and differentiation.

2) Function of apoptosis proteins in maintaining the cancer stem cell pool.

3) Mechanisms by which mitochondrial network dynamics regulate normal and cancer stem cell fate.
Research Keywords
stem cells, apoptosis, mitochondria, Bcl-2 family
Publications
Rasmussen ML, Kline LA, Park KP, Ortolano NA, Romero-Morales AI, Anthony CC, Beckermann KE, Gama V. A Non-apoptotic Function of MCL-1 in Promoting Pluripotency and Modulating Mitochondrial Dynamics in Stem Cells. Stem Cell Reports [print-electronic]. 2018 Mar 3/13/2018; 10(3): 684-92. PMID: 29429957, PMCID: PMC5918190, PII: S2213-6711(18)30031-6, DOI: 10.1016/j.stemcr.2018.01.005, ISSN: 2213-6711.

Rasmussen ML, Ortolano NA, Romero-Morales AI, Gama V. Wnt Signaling and Its Impact on Mitochondrial and Cell Cycle Dynamics in Pluripotent Stem Cells. Genes (Basel). 2018 Feb 2/19/2018; 9(2): PMID: 29463061, PMCID: PMC5852605, PII: genes9020109, DOI: 10.3390/genes9020109, ISSN: 2073-4425.

Romero-Morales AI, Ortolano NA, Gama V. Apical polarization and lumenogenesis: The apicosome sheds new light. J. Cell Biol [print-electronic]. 2017 Dec 12/4/2017; 216(12): 3891-3. PMID: 29138252, PMCID: PMC5716292, PII: jcb.201710028, DOI: 10.1083/jcb.201710028, ISSN: 1540-8140.

Ortolano NA, Gama V. Chronicle of a Neuronal Death Foretold: Preventing Aging by Keeping MGRN1 at the Nucleus. Mol. Cell. 2017 May 5/4/2017; 66(3): 301-3. PMID: 28475865, PII: S1097-2765(17)30270-8, DOI: 10.1016/j.molcel.2017.04.014, ISSN: 1097-4164.

D'Angelo W, Gurung C, Acharya D, Chen B, Ortolano N, Gama V, Bai F, Guo YL. The Molecular Basis for the Lack of Inflammatory Responses in Mouse Embryonic Stem Cells and Their Differentiated Cells. J. Immunol [print-electronic]. 2017 Mar 3/1/2017; 198(5): 2147-55. PMID: 28130495, PMCID: PMC5321812, PII: jimmunol.1601068, DOI: 10.4049/jimmunol.1601068, ISSN: 1550-6606.

Garcia I, Crowther AJ, Gama V, Miller CR, Deshmukh M, Gershon TR. Bax deficiency prolongs cerebellar neurogenesis, accelerates medulloblastoma formation and paradoxically increases both malignancy and differentiation. Oncogene. 2015 Jul; 34(29): 3881. PMID: 26179456, PII: onc2015204, DOI: 10.1038/onc.2015.204, ISSN: 1476-5594.

Gama V, Deshmukh M. Life after MOMP. Mol. Cell. 2015 Apr 4/16/2015; 58(2): 199-201. PMID: 25884366, PMCID: PMC4879686, PII: S1097-2765(15)00256-7, DOI: 10.1016/j.molcel.2015.03.035, ISSN: 1097-4164.

Gama V, Swahari V, Schafer J, Kole AJ, Evans A, Huang Y, Cliffe A, Golitz B, Sciaky N, Pei XH, Xiong Y, Deshmukh M. The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells. Sci Signal. 2014 Jul 7/15/2014; 7(334): ra67. PMID: 25028717, PMCID: PMC4182917, PII: 7/334/ra67, DOI: 10.1126/scisignal.2005309, ISSN: 1937-9145.

Crowther AJ, Gama V, Bevilacqua A, Chang SX, Yuan H, Deshmukh M, Gershon TR. Tonic activation of Bax primes neural progenitors for rapid apoptosis through a mechanism preserved in medulloblastoma. J. Neurosci. 2013 Nov 11/13/2013; 33(46): 18098-108. PMID: 24227720, PMCID: PMC3828463, PII: 33/46/18098, DOI: 10.1523/JNEUROSCI.2602-13.2013, ISSN: 1529-2401.

Gama V, Deshmukh M. Adenosine: essential for life but licensed to kill. Mol. Cell. 2013 May 5/9/2013; 50(3): 307-8. PMID: 23664374, PMCID: PMC3682465, PII: S1097-2765(13)00325-0, DOI: 10.1016/j.molcel.2013.04.020, ISSN: 1097-4164.

Garcia I, Crowther AJ, Gama V, Miller CR, Deshmukh M, Gershon TR. Bax deficiency prolongs cerebellar neurogenesis, accelerates medulloblastoma formation and paradoxically increases both malignancy and differentiation. Oncogene [print-electronic]. 2013 May 5/2/2013; 32(18): 2304-14. PMID: 22710714, PMCID: PMC3449008, PII: onc2012248, DOI: 10.1038/onc.2012.248, ISSN: 1476-5594.

Gama V, Deshmukh M. Human embryonic stem cells: living on the edge [editorial]. Cell Cycle [print-electronic]. 2012 Nov 11/1/2012; 11(21): 3905-6. PMID: 23032268, PMCID: PMC3507477, PII: 22233, DOI: 10.4161/cc.22233, ISSN: 1551-4005.

Dumitru R, Gama V, Fagan BM, Bower JJ, Swahari V, Pevny LH, Deshmukh M. Human embryonic stem cells have constitutively active Bax at the Golgi and are primed to undergo rapid apoptosis. Mol. Cell [print-electronic]. 2012 Jun 6/8/2012; 46(5): 573-83. PMID: 22560721, PMCID: PMC3372694, PII: S1097-2765(12)00268-7, DOI: 10.1016/j.molcel.2012.04.002, ISSN: 1097-4164.

Londono C, Osorio C, Gama V, Alzate O. Mortalin, apoptosis, and neurodegeneration. Biomolecules. 2012 Mar 3/1/2012; 2(1): 143-64. PMID: 24970131, PMCID: PMC4030873, PII: biom2010143, DOI: 10.3390/biom2010143, ISSN: 2218-273X.

Leskov KS, Araki S, Lavik JP, Gomez JA, Gama V, Gonos ES, Trougakos IP, Matsuyama S, Boothman DA. CRM1 protein-mediated regulation of nuclear clusterin (nCLU), an ionizing radiation-stimulated, Bax-dependent pro-death factor. J. Biol. Chem [print-electronic]. 2011 Nov 11/18/2011; 286(46): 40083-90. PMID: 21953454, PMCID: PMC3220538, PII: M111.252957, DOI: 10.1074/jbc.M111.252957, ISSN: 1083-351X.

Gomez JA, Chen J, Ngo J, Hajkova D, Yeh IJ, Gama V, Miyagi M, Matsuyama S. Cell-Penetrating Penta-Peptides (CPP5s): Measurement of Cell Entry and Protein-Transduction Activity. Pharmaceuticals (Basel). 2010 Dec 12/15/2010; 3(12): 3594-613. PMID: 21359136, PMCID: PMC3045100, DOI: 10.3390/ph3123594, ISSN: 1424-8247.

Gomez JA, Sun W, Gama V, Hajkova D, Yoshida T, Wu Z, Miyagi M, Pink JJ, Jackson MW, Danielpour D, Matsuyama S. The C-terminus of interferon gamma receptor beta chain (IFNgammaR2) has antiapoptotic activity as a Bax inhibitor. Cancer Biol. Ther [print-electronic]. 2009 Sep; 8(18): 1771-86. PMID: 19657228, PMCID: PMC2927208, PII: 9323, ISSN: 1555-8576.

Gama V, Gomez JA, Mayo LD, Jackson MW, Danielpour D, Song K, Haas AL, Laughlin MJ, Matsuyama S. Hdm2 is a ubiquitin ligase of Ku70-Akt promotes cell survival by inhibiting Hdm2-dependent Ku70 destabilization. Cell Death Differ [print-electronic]. 2009 May; 16(5): 758-69. PMID: 19247369, PMCID: PMC2669846, PII: cdd20096, DOI: 10.1038/cdd.2009.6, ISSN: 1476-5403.

Plesca D, Mazumder S, Gama V, Matsuyama S, Almasan A. A C-terminal fragment of Cyclin E, generated by caspase-mediated cleavage, is degraded in the absence of a recognizable phosphodegron. J. Biol. Chem [print-electronic]. 2008 Nov 11/7/2008; 283(45): 30796-803. PMID: 18784078, PMCID: PMC2576529, PII: M804642200, DOI: 10.1074/jbc.M804642200, ISSN: 0021-9258.

Yurchenko V, Xue Z, Gama V, Matsuyama S, Sadofsky MJ. Ku70 is stabilized by increased cellular SUMO. Biochem. Biophys. Res. Commun [print-electronic]. 2008 Feb 2/1/2008; 366(1): 263-8. PMID: 18062920, PMCID: PMC2212819, PII: S0006-291X(07)02572-7, DOI: 10.1016/j.bbrc.2007.11.136, ISSN: 1090-2104.

Li Y, Yokota T, Gama V, Yoshida T, Gomez JA, Ishikawa K, Sasaguri H, Cohen HY, Sinclair DA, Mizusawa H, Matsuyama S. Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Cell Death Differ [print-electronic]. 2007 Dec; 14(12): 2058-67. PMID: 17885668, PII: 4402219, DOI: 10.1038/sj.cdd.4402219, ISSN: 1350-9047.

Gomez JA, Gama V, Yoshida T, Sun W, Hayes P, Leskov K, Boothman D, Matsuyama S. Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides. Biochem. Soc. Trans. 2007 Aug; 35(Pt 4): 797-801. PMID: 17635151, PII: BST0350797, DOI: 10.1042/BST0350797, ISSN: 0300-5127.

Gama V, Yoshida T, Gomez JA, Basile DP, Mayo LD, Haas AL, Matsuyama S. Involvement of the ubiquitin pathway in decreasing Ku70 levels in response to drug-induced apoptosis. Exp. Cell Res. 2006 Feb 2/15/2006; 312(4): 488-99. PMID: 16368436, PII: S0014-4827(05)00546-X, DOI: 10.1016/j.yexcr.2005.11.016, ISSN: 0014-4827.

Yoshida T, Tomioka I, Nagahara T, Holyst T, Sawada M, Hayes P, Gama V, Okuno M, Chen Y, Abe Y, Kanouchi T, Sasada H, Wang D, Yokota T, Sato E, Matsuyama S. Bax-inhibiting peptide derived from mouse and rat Ku70. Biochem. Biophys. Res. Commun. 2004 Sep 9/3/2004; 321(4): 961-6. PMID: 15358121, PII: S0006-291X(04)01528-1, DOI: 10.1016/j.bbrc.2004.07.054, ISSN: 0006-291X.

Martínez JE, Valderrama L, Gama V, Leiby DA, Saravia NG. Clonal diversity in the expression and stability of the metastatic capability of Leishmania guyanensis in the golden hamster. J. Parasitol. 2000 Aug; 86(4): 792-9. PMID: 10958458, DOI: 10.1645/0022-3395(2000)086[0792:CDITEA]2.0.CO;2, ISSN: 0022-3395.

Lucumi A, Robledo S, Gama V, Saravia NG. Sensitivity of Leishmania viannia panamensis to pentavalent antimony is correlated with the formation of cleavable DNA-protein complexes. Antimicrob. Agents Chemother. 1998 Aug; 42(8): 1990-5. PMID: 9687395, PMCID: PMC105721, ISSN: 0066-4804.

Osorio Y, Gonzalez SJ, Gama VL, Travi BL. Reinfection in American cutaneous leishmaniasis: evaluation of clinical outcomes in the hamster model. Mem. Inst. Oswaldo Cruz. 1998 May; 93(3): 353-6. PMID: 9698870, PII: S0074-02761998000300015, ISSN: 0074-0276.