Vashisht G. Yennu-Nanda, Ph.D.
Department of Melanoma Medical Oncology, Division of Cancer Medicine
Present Title & Affiliation
Associate Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Associate Professor, Department of Translational Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
My research encompasses discovering novel molecular drivers of melanoma, and using these discoveries to identify novel melanoma prevention and therapeutic strategies. My contributions in this area broadly include elucidating the role of inflammatory and metabolic signaling in cancer for prevention and therapy resistance. My research employs integrated analysis of high-throughput biological screens and functional genetics assessments. With these approaches, we hope to identify molecular features that promote melanoma and those which could be targeted for its treatment.
Solar ultraviolet radiation (UVR) is the predominant cause of cutaneous melanoma. My basic science research is directed towards identifying molecular mediators of melanoma driver mutagenesis induced by UVR exposure. Multiple events occur between UVR-mediated skin damage and oncogenic transformation of melanocytes. The goal of this research is to understand these events and develop melanoma prevention strategies post-UVR damage to the skin.
Targeted therapies and immunotherapies have meaningfully improved the survival time and quality of life of melanoma patients. However, resistance to these treatments is a significant problem, which eventually leads to disease progression and mortality. My translational research is directed towards identifying molecular and metabolic vulnerabilities in treatment-resistant melanomas, and targeting them to counteract therapy resistance.
Education & Training
|2000||The University of Hyderabad, Hyderabad, IND, PHD, Biochemistry|
|2000-2005||Postdoctoral, Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX|
Experience & Service
Member of The Senate, The University of Texas MD Anderson Cancer Center Faculty Senate, Houston, TX, 2016 - Present
Institutional Committee Activities
Member, Institutional Shared Governance Committee, 2020 - Present
Member, Senate Research Affairs Committee, 2018 - Present
Co-Leader, Melanoma Moonshot Patient-Derived Cell Line Characterization Team, 2015 - 2015
Military or Other Governmental Service
Postdoctoral Fellow, US Army Department of Defense, 2001 - 2005
Honors & Awards
|2007||Developmental Research Award, The University of Texas MD Anderson Cancer Center Melanoma SPORE|
|2006||Developmental Research Award, The University of Texas MD Anderson Cancer Center Melanoma SPORE|
|2005||Developmental Research Award, The University of Texas MD Anderson Cancer Center Melanoma SPORE|
|1999||Servier Young Investigator Award Recipient, International Conference on the Frontier of Pharmacology|
|1994||Pre-Doctoral Research Fellowship Recipient, Council for Scientific and Industrial Research - Government of India|
- Varghese S, Pramanik S, Williams LJ, Hodges HR, Hudgens CW, Fischer GM, Luo CK, Knighton B, Tan L, Lorenzi PL, Mackinnon AL, McQuade JL, Hailemichael Y, Roszik J, Peng W, Vashisht Gopal YN. The Glutaminase Inhibitor CB-839 (Telaglenastat) Enhances the Antimelanoma Activity of T-Cell-Mediated Immunotherapies. Mol Cancer Ther 20(3):500-511, 2021. e-Pub 2020. PMID: 33361272.
- Fischer GM, Guerrieri RA, Hu Q, Joon AY, Kumar S, Haydu LE, McQuade JL, Vashisht Gopal YN, Knighton B, Deng W, Hudgens CW, Lazar AJ, Tetzlaff MT, Davies MA. Clinical, molecular, metabolic, and immune features associated with oxidative phosphorylation in melanoma brain metastases. Neurooncol Adv 3(1):vdaa177, 2021. e-Pub 2021. PMID: 33575655.
- Vashisht Gopal YN, Gammon S, Prasad R, Knighton B, Pisaneschi F, Roszik J, Feng N, Johnson S, Pramanik S, Sudderth J, Sui D, Hudgens C, Fischer GM, Deng W, Reuben A, Peng W, Wang J, McQuade JL, Tetzlaff MT, Di Francesco ME, Marszalek J, Piwnica-Worms D, DeBerardinis RJ, Davies MA. A Novel Mitochondrial Inhibitor Blocks MAPK Pathway and Overcomes MAPK Inhibitor Resistance in Melanoma. Clin Cancer Res 25(21):6429-6442, 2019. e-Pub 2019. PMID: 31439581.
- Gammon ST, Pisaneschi F, Bandi ML, Smith MG, Sun Y, Rao Y, Muller F, Wong F, De Groot J, Ackroyd J, Mawlawi O, Davies MA, Vashisht Gopal YN, Di Francesco ME, Marszalek JR, Dewhirst M, Piwnica-Worms D. Mechanism-Specific Pharmacodynamics of a Novel Complex-I Inhibitor Quantified by Imaging Reversal of Consumptive Hypoxia with [18F]FAZA PET In Vivo. Cells 8(12), 2019. e-Pub 2019. PMID: 31766580.
- Fischer GM, Jalali A, Kircher DA, Lee WC, McQuade JL, Haydu LE, Joon AY, Reuben A, de Macedo MP, Carapeto FCL, Yang C, Srivastava A, Ambati CR, Sreekumar A, Hudgens CW, Knighton B, Deng W, Ferguson SD, Tawbi HA, Glitza IC, Gershenwald JE, Vashisht Gopal YN, Hwu P, Huse JT, Wargo JA, Futreal PA, Putluri N, Lazar AJ, DeBerardinis RJ, Marszalek JR, Zhang J, Holmen SL, Tetzlaff MT, Davies MA. Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases. Cancer Discov 9(5):628-645, 2019. e-Pub 2019. PMID: 30787016.
- Shrestha AK, Bettini ML, Menon RT, Vashisht Gopal YN, Huang S, Edwards DP, Pammi M, Barrios R, Shivanna B. Consequences of early postnatal lipopolysaccharide exposure on developing lungs in mice. Am J Physiol Lung Cell Mol Physiol 316(1):L229-L244, 2019. e-Pub 2018. PMID: 30307313.
- Shrestha AK, Vashisht Gopal YN, Menon RT, Hagan JL, Huang S, Shivanna B. Lung omics signatures in a bronchopulmonary dysplasia and pulmonary hypertension-like murine model. Am J Physiol Lung Cell Mol Physiol 315(5):L734-L741, 2018. e-Pub 2018. PMID: 30047283.
- Cascone T, McKenzie JA, Mbofung RM, Punt S, Wang Z, Xu C, Williams LJ, Wang Z, Bristow CA, Carugo A, Peoples MD, Li L, Karpinets T, Huang L, Malu S, Creasy C, Leahey SE, Chen J, Chen Y, Pelicano H, Bernatchez C, Vashisht Gopal YN, Heffernan TP, Hu J, Wang J, Amaria RN, Garraway LA, Huang P, Yang P, Wistuba II, Woodman SE, Roszik J, Davis RE, Davies MA, Heymach JV, Hwu P, Peng W. Increased Tumor Glycolysis Characterizes Immune Resistance to Adoptive T Cell Therapy. Cell Metab 27(5):977-987.e4, 2018. e-Pub 2018. PMID: 29628419.
- Fischer GM, Vashisht Gopal YN, McQuade JL, Peng W, DeBerardinis RJ, Davies MA. Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications. Pigment Cell Melanoma Res 31(1):11-30, 2018. e-Pub 2017. PMID: 29049843.
- Ndoye A, Budina-Kolomets A, Kugel CH, Webster MR, Kaur A, Behera R, Rebecca VW, Li L, Brafford PA, Liu Q, Vashisht Gopal YN, Davies MA, Mills GB, Xu X, Wu H, Herlyn M, Nicastri MC, Winkler JD, Soengas MS, Amaravadi RK, Murphy ME, Weeraratna AT. ATG5 Mediates a Positive Feedback Loop between Wnt Signaling and Autophagy in Melanoma. Cancer Res 77(21):5873-5885, 2017. e-Pub 2017. PMID: 28887323.
- Li J, Zhao W, Akbani R, Liu W, Ju Z, Ling S, Vellano CP, Roebuck P, Yu Q, Eterovic AK, Byers LA, Davies MA, Deng W, Vashisht Gopal YN, Chen G, von Euw EM, Slamon D, Conklin D, Heymach JV, Gazdar AF, Minna JD, Myers JN, Lu Y, Mills GB, Liang H. Characterization of Human Cancer Cell Lines by Reverse-phase Protein Arrays. Cancer Cell 31(2):225-239, 2017. PMID: 28196595.
- Goedert L, Pereira CG, Roszik J, Plaça JR, Cardoso C, Chen G, Deng W, Vashisht Gopal YN, Silva WA, Davies MA, Espreafico EM. RMEL3, a novel BRAFV600E-associated long noncoding RNA, is required for MAPK and PI3K signaling in melanoma. Oncotarget 7(24):36711-36718, 2016. e-Pub 2016. PMID: 27167340.
- McQuade JL, Vashisht Gopal YN. Counteracting oxidative phosphorylation-mediated resistance of melanomas to MAPK pathway inhibition. Mol Cell Oncol 2(3):e991610, 2015. e-Pub 2015. PMID: 27308473.
- Vashisht Gopal YN, Rizos H, Chen G, Deng W, Frederick DT, Cooper ZA, Scolyer RA, Pupo G, Komurov K, Sehgal V, Zhang J, Patel L, Pereira CG, Broom BM, Mills GB, Ram P, Smith PD, Wargo JA, Long GV, Davies MA. Inhibition of mTORC1/2 Overcomes Resistance to MAPK Pathway Inhibitors Mediated by PGC1α and Oxidative Phosphorylation in Melanoma. Cancer Res 74(23):7037-47, 2014. e-Pub 2014. PMID: 25297634.
- Chen G, Chakravarti N, Aardalen K, Lazar AJ, Tetzlaff MT, Wubbenhorst B, Kim SB, Kopetz S, Ledoux AA, Vashisht Gopal YN, Pereira CG, Deng W, Lee JS, Nathanson KL, Aldape KD, Prieto VG, Stuart D, Davies MA. Molecular Profiling of Patient-Matched Brain and Extracranial Melanoma Metastases Implicates the PI3K Pathway as a Therapeutic Target. Clin Cancer Res 20(21):5537-46, 2014. e-Pub 2014. PMID: 24803579.
- Mao M, Tian F, Mariadason JM, Tsao CC, Lemos R, Dayyani F, Vashisht Gopal YN, Jiang ZQ, Wistuba II, Tang XM, Bornman WG, Bollag G, Mills GB, Powis G, Desai J, Gallick GE, Davies MA, Kopetz S. Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents. Clin Cancer Res 19(3):657-67, 2013. e-Pub 2012. PMID: 23251002.
- Deng W, Vashisht Gopal YN, Scott A, Chen G, Woodman SE, Davies MA. Role and therapeutic potential of PI3K-mTOR signaling in de novo resistance to BRAF inhibition. Pigment Cell Melanoma Res 25(2):248-58, 2012. e-Pub 2012. PMID: 22171948.
- Vashisht Gopal YN, Deng W, Woodman SE, Komurov K, Ram P, Smith PD, Davies MA. Basal and treatment-induced activation of AKT mediates resistance to cell death by AZD6244 (ARRY-142886) in Braf-mutant human cutaneous melanoma cells. Cancer Res 70(21):8736-47, 2010. e-Pub 2010. PMID: 20959481.
- Altman MK, Vashisht Gopal YN, Jia W, Yu S, Hall H, Mills GB, McGinnis AC, Bartlett MG, Jiang G, Madan D, Prestwich GD, Xu Y, Davies MA, Murph MM. Targeting melanoma growth and viability reveals dualistic functionality of the phosphonothionate analogue of carba cyclic phosphatidic acid. Mol Cancer 9:140, 2010. e-Pub 2010. PMID: 20529378.
- Davies MA, Stemke-Hale K, Lin E, Tellez C, Deng W, Vashisht Gopal YN, Woodman SE, Calderone TC, Ju Z, Lazar AJ, Prieto VG, Aldape K, Mills GB, Gershenwald JE. Integrated Molecular and Clinical Analysis of AKT Activation in Metastatic Melanoma. Clin Cancer Res 15(24):7538-7546, 2009. e-Pub 2009. PMID: 19996208.
- Woodman SE, Trent JC, Stemke-Hale K, Lazar AJ, Pricl S, Pavan GM, Fermeglia M, Vashisht Gopal YN, Yang D, Podoloff DA, Ivan D, Kim KB, Papadopoulos N, Hwu P, Mills GB, Davies MA. Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates. Mol Cancer Ther 8(8):2079-85, 2009. e-Pub 2009. PMID: 19671763.
- Vashisht Gopal YN, Chanchorn E, Van Dyke MW. Parthenolide promotes the ubiquitination of MDM2 and activates p53 cellular functions. Mol Cancer Ther 8(3):552-62, 2009. e-Pub 2009. PMID: 19276167.
- Baby J, Pickering BF, Vashisht Gopal YN, Van Dyke MW. Constitutive and inducible nuclear factor-kappaB in immortalized normal human bronchial epithelial and non-small cell lung cancer cell lines. Cancer Lett 255(1):85-94, 2007. e-Pub 2007. PMID: 17493745.
- Vashisht Gopal YN, Arora TS, Van Dyke MW. Parthenolide Specifically Depletes Histone Deacetylase 1 Protein and Induces Cell Death through Ataxia Telangiectasia Mutated. Chem Biol 14(7):813-23, 2007.
- Vashisht Gopal YN, Van Dyke MW. Depletion of histone deacetylase protein: a common consequence of inflammatory cytokine signaling?. Cell Cycle 5(23):2738-43, 2006. e-Pub 2006. PMID: 17172847.
- Vashisht Gopal YN, Arora TS, Van Dyke MW. Tumour necrosis factor-alpha depletes histone deacetylase 1 protein through IKK2. EMBO Rep 7(3):291-6, 2006. e-Pub 2005. PMID: 16374504.
- Vashisht Gopal YN, Van Dyke MW. Combinatorial determination of sequence specificity for nanomolar DNA-binding hairpin polyamides. Biochemistry 42(22):6891-903, 2003. PMID: 12779344.
- Vashisht Gopal YN, Konuru N, Kondapi AK. Topoisomerase II antagonism and anticancer activity of coordinated derivatives of [RuCl(2)(C(6)H(6))(dmso)]. Arch Biochem Biophys 401(1):53-62, 2002. PMID: 12054487.
- Vashisht Gopal YN, Kondapi AK. Topoisomerase II poisoning by indazole and imidazole complexes of ruthenium. J Biosci 26(2):271-6, 2001. PMID: 11426063.
- Vashisht Gopal YN, Jayaraju D, Kondapi AK. Topoisomerase II poisoning and antineoplastic action by DNA-nonbinding diacetyl and dicarboxaldoxime derivatives of ferrocene. Arch Biochem Biophys 376(1):229-35, 2000. PMID: 10729210.
- Jayaraju D, Vashisht Gopal YN, Kondapi AK. Topoisomerase II is a cellular target for antiproliferative cobalt salicylaldoxime complex. Arch Biochem Biophys 369(1):68-77, 1999. PMID: 10462441.
- Vashisht Gopal YN, Jayaraju D, Kondapi AK. Inhibition of topoisomerase II catalytic activity by two ruthenium compounds: a ligand-dependent mode of action. Biochemistry 38(14):4382-8, 1999. PMID: 10194357.
Grant & Contract Support
|Title:||Molecular recognition of DNA-binding Antibiotics|
|Funding Source:||American Cancer Society|
|Title:||Regulation of Breast Cancer gene expression by small molecule drugs|
|Funding Source:||Department of Defense (DOD)|
|Title:||Therapeutic potential of Dominant-Negative NF- kB in Pancreatic Cancer|
|Funding Source:||The Topper Fund for Pancreatic Cancer Research|
|Title:||Inhibition of RelA in Pancreatic Cancer cells by short, interfering RNAs,|
|Funding Source:||Goodwin Funds Target Discovery Grant|
|Title:||Abolition of histone deacetylases by activated NF-kappa B in Breast Cancer|
|Funding Source:||DOD Concept Grant|
|Title:||Target Discovery in Breast Cancer Cells with Dominant-Repressive Transcription Factor Chimeras,|
|Funding Source:||Goodwin Funds|
|Title:||Molecular Mechanism of Action of a Novel Anti-melanoma Drug|
|Title:||Targeting the MDM2-p53-HDAC1 nexus in melanoma with a small molecule drug|
|Title:||Pre-clinical activity of a small molecule with anti-melanoma activity|
|Title:||Role of melanin in Oncogenesis|
|Title:||A Novel Mitochondrial Complex I Inhibitor to Sensitizes MAPK inhibition-resistant melanomas|
|Funding Source:||Melanoma Research Alliance|
|Title:||Exploiting Molecular and Metabolic Dependencies to Optimize Personalized Therapeutic Approaches for Melanomas|
|Funding Source:||Cancer Prevention & Research Institute of Texas (CPRIT)|
|Title:||Rational approaches to melanoma therapy|
|Title:||Characterization and Optimization of the Glutaminase Inhibitor CB-839 for Melanoma|
|Funding Source:||Calithera Biosciences|
|Title:||Overcoming metastasis and therapeutic resistance in melanoma|
|Funding Source:||Adelson Medical Research Foundation|
|Title:||Role of AMPK in Melanoma Brain Metastasis|