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Vivek Mittal, PhD

Associate Affiliate Member, Research Institute
Houston Methodist


Biography

Vivek Mittal is the director of the Neuberger Berman Foundation Lung Cancer Laboratory and an associate professor of Cell and Developmental Biology in the cardiothoracic surgery department at Weill Cornell Medical College in New York.

Previously, Dr. Mittal held faculty appointments at Cold Spring Harbor Laboratory and State University of New York, Stony Brook. Dr. Mittal speaks at public engagements to diverse audiences around the world and has produced several patents and authored articles in leading journals including Science, Nature, Cancer Cell, PNAS, and other leading peer-reviewed journals and text books. He contributes to NIH study sections and has chaired sessions at prominent national conferences and symposiums. His research is supported by funds from the National Cancer Institute and private foundations.

As a director of research at the Lung Cancer Center, Dr. Mittal oversees the development of future research themes and educational activities to ensure their concordance with the overall translational mission of the Center. He created a state-of-the art Biobank at Weill Cornell Medical College as a repository for biospecimens from lung cancer, other thoracic malignancies, and benign diseases.

Dr. Mittal is committed to the mentoring of the clinical fellows and faculty in basic research, which is a critical part of the training of the next generation of translational researchers. He is an active teacher and mentor, organizing focus groups and supervising a problem based learning course for medical students. He mentors graduate students, postdoctoral fellows, surgical fellows and junior faculty. He is also dedicated to interviewing candidates for admission to the M.D. and Ph.D. program, and recruitment of junior faculty.

Description of Research

Research in Dr. Mittal’s lab studies de novo lung carcinogenesis, as well as the initiation and progression of metastatic lesions derived from extrapulmonary neoplasms. The program integrates clinical and basic science to foster innovative research for the prevention, detection, and treatment of cancer.

A major aim of his research is to understand cancer cell intrinsic and extrinsic programs that regulate tumor growth and metastasis. Cancer cell intrinsic programs include aberrant signaling pathways, which are investigated at several levels of regulation including transcriptional, epigenetic, and small regulatory RNAs. Cancer cell extrinsic programs include the contribution of the tumor microenvironment. The heterotypic reciprocal signaling between the stromal cells and tumor epithelial compartments that contribute to tumor progression can be unraveled by dissecting the complexity of various stromal cell types that comprise the microenvironment. Dr. Mittal is interested in understanding how these two programs are integrated to regulate key tumorigenic processes including angiogenesis, inflammation, epithelial to mesenchymal transition, therapeutic resistance, metastasis initiation and progression.

Dr. Mittal’s research has produced novel stromal targets for prognosis and drug design. A major goal of this ongoing work is to collaborate with clinicians to rapidly validate additional molecular research findings in preclinical and clinical studies, and determine if they have diagnostic and therapeutic potential for clinical use.

Key contributions include:
-First demonstration that endothelial progenitor cells promote angiogenesis necessary for the formation of lethal macrometastases (Science, 2008).
-First demonstration that myeloid cells induce mesenchymal to epithelial transition that promotes breast cancer metastasis to the lungs (Cancer Research, 2012).
-Discovered microRNA-708, which is epigenetically silenced during metastatic progression in breast cancer (Cancer Cell, 2013 in press). Currently, the potential of miR-708 as a therapeutic against triple negative breast cancer is being evaluated.
-Have identified a novel mechanism, whereby metastasis-incompetent tumors generate metastasis-suppressive niches that inhibit metastasis (in review, Cancer Discovery).
-Analysis of fresh clinical samples have led to the discovery of novel stromal targets of prognostic and therapeutic value in lung cancer.

Areas Of Expertise

Breast cancer Tumor microenvironment microRNA Lung cancer Genomics Epigenome Mouse models
Education & Training

MS, Jawaharlal Nehru University
PhD, Jawaharlal Nehru University
Publications

Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I–III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial
Altorki, NK, Walsh, ZH, Melms, JC, Port, JL, Lee, BE, Nasar, A, Spinelli, C, Caprio, L, Rogava, M, Ho, P, Christos, PJ, Saxena, A, Elemento, O, Bhinder, B, Ager, C, Amin, AD, Sanfilippo, NJ, Mittal, V, Borczuk, AC, Formenti, SC, Izar, B & McGraw, TE 2023, , Nature Communications, vol. 14, no. 1, 8435. https://doi.org/10.1038/s41467-023-44195-x

A vertebral skeletal stem cell lineage driving metastasis
Sun, J, Hu, L, Bok, S, Yallowitz, AR, Cung, M, McCormick, J, Zheng, LJ, Debnath, S, Niu, Y, Tan, AY, Lalani, S, Morse, KW, Shinn, D, Pajak, A, Hammad, M, Suhardi, VJ, Li, Z, Li, N, Wang, L, Zou, W, Mittal, V, Bostrom, MPG, Xu, R, Iyer, S & Greenblatt, MB 2023, , Nature, vol. 621, no. 7979, pp. 602-609. https://doi.org/10.1038/s41586-023-06519-1

Epigenetic dysregulation from chromosomal transit in micronuclei
Agustinus, AS, Al-Rawi, D, Dameracharla, B, Raviram, R, Jones, BSCL, Stransky, S, Scipioni, L, Luebeck, J, Di Bona, M, Norkunaite, D, Myers, RM, Duran, M, Choi, S, Weigelt, B, Yomtoubian, S, McPherson, A, Toufektchan, E, Keuper, K, Mischel, PS, Mittal, V, Shah, SP, Maciejowski, J, Storchova, Z, Gratton, E, Ly, P, Landau, D, Bakhoum, MF, Koche, RP, Sidoli, S, Bafna, V, David, Y & Bakhoum, SF 2023, , Nature, vol. 619, no. 7968, pp. 176-183. https://doi.org/10.1038/s41586-023-06084-7

Tumor-intrinsic IRE1a signaling controls protective immunity in lung cancer
Crowley, MJP, Bhinder, B, Markowitz, GJ, Martin, M, Verma, A, Sandoval, TA, Chae, CS, Yomtoubian, S, Hu, Y, Chopra, S, Tavarez, DA, Giovanelli, P, Gao, D, McGraw, TE, Altorki, NK, Elemento, O, Cubillos-Ruiz, JR & Mittal, V 2023, , Nature Communications, vol. 14, no. 1, 120, pp. 120. https://doi.org/10.1038/s41467-022-35584-9

Simultaneous quantitative imaging of two PET radiotracers via the detection of positron–electron annihilation and prompt gamma emissions
Pratt, EC, Lopez-Montes, A, Volpe, A, Crowley, MJ, Carter, LM, Mittal, V, Pillarsetty, N, Ponomarev, V, Udías, JM, Grimm, J & Herraiz, JL 2023, , Nature Biomedical Engineering, vol. 7, no. 8, pp. 1028-1039. https://doi.org/10.1038/s41551-023-01060-y

Tumor-Targeted Nonablative Radiation Promotes Solid Tumor CAR T-cell Therapy Efficacy
Quach, HT, Skovgard, MS, Villena-Vargas, J, Bellis, RY, Chintala, NK, Amador-Molina, A, Bai, Y, Banerjee, S, Saini, J, Xiong, Y, Vista, WR, Byun, AJ, De Biasi, A, Zeltsman, M, Mayor, M, Morello, A, Mittal, V, Gomez, DR, Rimner, A, Jones, DR & Adusumilli, PS 2023, , Cancer immunology research, vol. 11, no. 10, pp. 1314-1331. https://doi.org/10.1158/2326-6066.CIR-22-0840

PRSS2 remodels the tumor microenvironment via repression of Tsp1 to stimulate tumor growth and progression
Sui, L, Wang, S, Ganguly, D, El Rayes, TP, Askeland, C, Børretzen, A, Sim, D, Halvorsen, OJ, Knutsvik, G, Arnes, J, Aziz, S, Haukaas, S, Foulkes, WD, Bielenberg, DR, Ziemys, A, Mittal, V, Brekken, RA, Akslen, LA & Watnick, RS 2022, , Nature Communications, vol. 13, no. 1, 7959. https://doi.org/10.1038/s41467-022-35649-9

Neutrophil phenotypes and functions in cancer: A consensus statement
Quail, DF, Amulic, B, Aziz, M, Barnes, BJ, Eruslanov, E, Fridlender, ZG, Goodridge, HS, Granot, Z, Hidalgo, A, Huttenlocher, A, Kaplan, MJ, Malanchi, I, Merghoub, T, Meylan, E, Mittal, V, Pittet, MJ, Rubio-Ponce, A, Udalova, IA, van den Berg, TK, Wagner, DD, Wang, P, Zychlinsky, A, de Visser, KE, Egeblad, M & Kubes, P 2022, , Journal of Experimental Medicine, vol. 219, no. 6, e20220011. https://doi.org/10.1084/jem.20220011

Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma
Altorki, NK, Borczuk, AC, Harrison, S, Groner, LK, Bhinder, B, Mittal, V, Elemento, O & McGraw, TE 2022, , Cell Reports, vol. 39, no. 1, 110639, pp. 110639. https://doi.org/10.1016/j.celrep.2022.110639

Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer
Wennerberg, E, Mukherjee, S, Spada, S, Hung, C, Agrusa, CJ, Chen, C, Valeta-Magara, A, Rudqvist, NP, Van Nest, SJ, Kamel, MK, Nasar, A, Narula, N, Mittal, V, Markowitz, GJ, Zhou, XK, Adusumilli, PS, Borczuk, AC, White, TE, Khan, AG, Balderes, PJ, Lorenz, IC, Altorki, N, Demaria, S, McGraw, TE & Stiles, BM 2022, , Science translational medicine, vol. 14, no. 636, abe8195, pp. eabe8195. https://doi.org/10.1126/scitranslmed.abe8195

Author Correction: Radiation-activated secretory proteins of Scgb1a1 + club cells increase the efficacy of immune checkpoint blockade in lung cancer. Radiation-activated secretory proteins of Scgb1a1 + club cells increase the efficacy of immune checkpoint blockade in lung cancer (Nature Cancer, (2021), 2, 9, (919-931), 10.1038/s43018-021-00245-1)
Ban, Y, Markowitz, GJ, Zou, Y, Ramchandani, D, Kraynak, J, Sheng, J, Lee, SB, Wong, STC, Altorki, NK, Gao, D & Mittal, V 2022, , Nature Cancer, vol. 3, no. 2, pp. 262. https://doi.org/10.1038/s43018-022-00330-z

Regulation of Tumor Progression and Metastasis by Bone Marrow-Derived Microenvironments
Ramchandani, D, El Rayes, TP, Gao, D, Altorki, NK, Cox, TR, Erler, JT & Mittal, V 2022, . in Biomarkers of the Tumor Microenvironment, Second Edition. Springer International Publishing, pp. 245-266. https://doi.org/10.1007/978-3-030-98950-7_14

Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis
Ramchandani, D, Berisa, M, Tavarez, DA, Li, Z, Miele, M, Bai, Y, Lee, SB, Ban, Y, Dephoure, N, Hendrickson, RC, Cloonan, SM, Gao, D, Cross, JR, Vahdat, LT & Mittal, V 2021, , Nature Communications, vol. 12, no. 1, 7311, pp. 7311. https://doi.org/10.1038/s41467-021-27559-z

Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
Liu, YL, Bager, CL, Willumsen, N, Ramchandani, D, Kornhauser, N, Ling, L, Cobham, M, Andreopoulou, E, Cigler, T, Moore, A, LaPolla, D, Fitzpatrick, V, Ward, M, Warren, JD, Fischbach, C, Mittal, V & Vahdat, LT 2021, , npj Breast Cancer, vol. 7, no. 1, 108. https://doi.org/10.1038/s41523-021-00313-w

The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases
Marullo, R, Castro, M, Yomtoubian, S, Nieves Calvo-Vidal, M, Revuelta, MV, Krumsiek, J, Cho, A, Morgado, PC, Yang, SN, Medina, V, Roth, BM, Bonomi, M, Keshari, KR, Mittal, V, Navigante, A & Cerchietti, L 2021, , Science Advances, vol. 7, no. 45, eabg1964. https://doi.org/10.1126/sciadv.abg1964

Radiation-activated secretory proteins of Scgb1a1 + club cells increase the efficacy of immune checkpoint blockade in lung cancer
Ban, Y, Markowitz, GJ, Zou, Y, Ramchandani, D, Kraynak, J, Sheng, J, Lee, SB, Wong, STC, Altorki, NK, Gao, D & Mittal, V 2021, , Nature Cancer, vol. 2, no. 9, pp. 919-931. https://doi.org/10.1038/s43018-021-00245-1

Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity
Chow, A, Schad, S, Green, MD, Hellmann, MD, Allaj, V, Ceglia, N, Zago, G, Shah, NS, Sharma, SK, Mattar, M, Chan, J, Rizvi, H, Zhong, H, Liu, C, Bykov, Y, Zamarin, D, Shi, H, Budhu, S, Wohlhieter, C, Uddin, F, Gupta, A, Khodos, I, Waninger, JJ, Qin, A, Markowitz, GJ, Mittal, V, Balachandran, V, Durham, JN, Le, DT, Zou, W, Shah, SP, McPherson, A, Panageas, K, Lewis, JS, Perry, JSA, de Stanchina, E, Sen, T, Poirier, JT, Wolchok, JD, Rudin, CM & Merghoub, T 2021, , Cancer Cell, vol. 39, no. 7, pp. 973-988.e9. https://doi.org/10.1016/j.ccell.2021.05.006

Connecting copper and cancer: from transition metal signalling to metalloplasia
Ge, EJ, Bush, AI, Casini, A, Cobine, PA, Cross, JR, DeNicola, GM, Dou, QP, Franz, KJ, Gohil, VM, Gupta, S, Kaler, SG, Lutsenko, S, Mittal, V, Petris, MJ, Polishchuk, R, Ralle, M, Schilsky, ML, Tonks, NK, Vahdat, LT, Van Aelst, L, Xi, D, Yuan, P, Brady, DC & Chang, CJ 2022, , Nature Reviews Cancer, vol. 22, no. 2, pp. 102-113. https://doi.org/10.1038/s41568-021-00417-2

EMT process in bone metastasis
Gao, D, Zhang, XHF, Thompson, EW & Mittal, V 2021, . in Bone Cancer: Bone Sarcomas and Bone Metastases - From Bench to Bedside. Elsevier, pp. 359-370. https://doi.org/10.1016/B978-0-12-821666-8.00009-8

Erratum: Influencing the tumor microenvironment: A phase II study of copper depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence and in preclinical models of lung metastases (Clinical Cancer Research (2017) 23 (666-676) DOI: 10.1158/1078-0432.CCR-16-1326)
Chan, N, Willis, A, Kornhauser, N, Ward, MM, Lee, SB, Nackos, E, Seo, BR, Chuang, E, Cigler, T, Moore, A, Donovan, D, Cobham, MV, Fitzpatrick, V, Schneider, S, Wiener, A, Guillaume-Abraham, J, Aljom, E, Zelkowitz, R, Warren, JD, Lane, ME, Fischbach, C, Mittal, V & Vahdat, L 2020, , Clinical Cancer Research, vol. 26, no. 18, pp. 5051. https://doi.org/10.1158/1078-0432.CCR-20-3177

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