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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

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

MS, Jawaharlal Nehru University
PhD, Jawaharlal Nehru University
Publications

Epithelial Mesenchymal Transition in Tumor Metastasis
Mittal, V 2018, Annual Review of Pathology: Mechanisms of Disease, vol 13, pp. 395-412. DOI: 10.1146/annurev-pathol-020117-043854

Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis
Cao, Z, Ye, T, Sun, Y, Ji, G, Shido, K, Chen, Y, Luo, L, Na, F, Li, X, Huang, Z, Ko, JL, Mittal, V, Qiao, L, Chen, C, Martinez, FJ, Rafii, S & Ding, BS 2017, Science Translational Medicine, vol 9, no. 405, aai8710. DOI: 10.1126/scitranslmed.aai8710

Regulation of tumor progression and metastasis by bone marrow-derived microenvironments
El Rayes, T, Gao, D, Altorki, NK, Cox, TR, Erler, JT & Mittal, V 2017, . in Biomarkers of the Tumor Microenvironment: Basic Studies and Practical Applications. Springer International Publishing, pp. 303-328. DOI: 10.1007/978-3-319-39147-2_13

Fischer et al. reply
Fischer, KR, Altorki, NK, Mittal, V & Gao, D 2017, Nature, vol 547, no. 7661, pp. E1-E6. DOI: 10.1038/nature22817

The nuclear transport receptor Importin-11 is a tumor suppressor that maintains PTEN protein
Chen, M, Nowak, DG, Narula, N, Robinson, B, Watrud, K, Ambrico, A, Herzka, TM, Zeeman, ME, Minderer, M, Zheng, W, Ebbesen, SH, Plafker, KS, Stahlhut, C, Wang, VMY, Wills, L, Nasar, A, Castillo-Martin, M, Cordon-Cardo, C, Wilkinson, JE, Powers, S, Sordella, R, Altorki, NK, Mittal, V, Stiles, BM, Plafker, SM & Trotman, LC 2017, The Journal of cell biology, vol 216, no. 3, pp. 641-656. DOI: 10.1083/jcb.201604025

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
Chan, N, Willis, A, Kornhauser, N, Mward, M, 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 2017, Clinical Cancer Research, vol 23, no. 3, pp. 666-676. DOI: 10.1158/1078-0432.CCR-16-1326

Matrix Metalloproteinase 14 promotes lung cancer by cleavage of Heparin-Binding EGF-like Growth Factor
Stawowczyk, M, Wellenstein, MD, Lee, SB, Yomtoubian, S, Durrans, A, Choi, H, Narula, N, Altorki, NK, Gao, D & Mittal, V 2017, Neoplasia (United States), vol 19, no. 2, pp. 55-64. DOI: 10.1016/j.neo.2016.11.005

Epithelial mesenchymal transition in aggressive lung cancers
Mittal, V 2016, . in Advances in Experimental Medicine and Biology. vol. 890, Advances in Experimental Medicine and Biology, vol. 890, Springer New York, pp. 37-56. DOI: 10.1007/978-3-319-24932-2_3

The microenvironment of lung cancer and therapeutic implications
Mittal, V, El Rayes, T, Narula, N, McGraw, TE, Altorki, NK & Barcellos-Hoff, MH 2016, . in Advances in Experimental Medicine and Biology. vol. 890, Advances in Experimental Medicine and Biology, vol. 890, Springer New York, pp. 75-110. DOI: 10.1007/978-3-319-24932-2_5

In Vivo Visualization and Characterization of Epithelial-Mesenchymal Transition in Breast Tumors
Zhao, Z, Zhu, X, Cui, K, Mancuso, J, Federley, R, Fischer, K, Teng, GJ, Mittal, V, Gao, D, Zhao, H & Wong, STC 2016, Cancer Research, vol 76, no. 8, pp. 2094-2104. DOI: 10.1158/0008-5472.CAN-15-2662

Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment
Wang, S, Blois, A, El Rayes, T, Liu, JF, Hirsch, MS, Gravdal, K, Palakurthi, S, Bielenberg, DR, Akslen, LA, Drapkin, R, Mittal, V & Watnick, RS 2016, Science Translational Medicine, vol 8, no. 329, 329ra34. DOI: 10.1126/scitranslmed.aad5653

Expression of the receptor for hyaluronic acid mediated motility (RHAMM) is associated with poor prognosis and metastasis in non-small cell lung carcinoma
Wang, D, Narula, N, Azzopardi, S, Smith, RS, Nasar, A, Altorki, NK, Mittal, V, Somwar, R, Stiles, BM & Nancy Du, YC 2016, Oncotarget, vol 7, no. 26, pp. 39957-39969.

Cancer cell CCL5 mediates bone marrow independent angiogenesis in breast cancer
Sax, MJ, Gasch, C, Athota, VR, Freeman, R, Rasighaemi, P, Westcott, DE, Day, CJ, Nikolic, I, Elsworth, B, Wei, M, Rogers, K, Swarbrick, A, Mittal, V, Pouliot, N & Mellick, AS 2016, Oncotarget, vol 7, no. 51, pp. 85437-85449. DOI: 10.18632/oncotarget.13387

Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1
Rayes, TE, Catena, R, Lee, S, Stawowczyk, M, Joshi, N, Fischbach, C, Powell, CA, Dannenberg, AJ, Altorki, NK, Gao, D & Mittal, V 2015, Proceedings of the National Academy of Sciences of the United States of America, vol 112, no. 52, pp. 16000-16005. DOI: 10.1073/pnas.1507294112

Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance
Fischer, KR, Durrans, A, Lee, S, Sheng, J, Li, F, Wong, STC, Choi, H, El Rayes, T, Ryu, S, Troeger, J, Schwabe, RF, Vahdat, LT, Altorki, NK, Mittal, V & Gao, D 2015, Nature, vol 527, no. 7579, pp. 472-6. DOI: 10.1038/nature15748

Identification of reprogrammed myeloid cell transcriptomes in NSCLC
Durrans, A, Gao, D, Gupta, R, Fischer, KR, Choi, H, El Rayes, T, Ryu, S, Nasar, A, Spinelli, CF, Andrews, W, Elemento, O, Nolan, D, Stiles, B, Rafii, S, Narula, N, Davuluri, R, Altorki, NK & Mittal, V 2015, PLoS ONE, vol 10, no. 6, e0129123. DOI: 10.1371/journal.pone.0129123

Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model
Choi, H, Sheng, J, Gao, D, Li, F, Durrans, A, Ryu, S, Lee, SB, Narula, N, Rafii, S, Elemento, O, Altorki, N, Wong, STC & Mittal, V 2015, Cell Reports, vol 10, no. 7, pp. 1187-1201. DOI: 10.1016/j.celrep.2015.01.040

Signal transduction in tumor angiogenesis
Hla, T, Altorki, N & Mittal, V 2015, . in Molecular Oncology: Causes of Cancer and Targets for Treatment. Cambridge University Press, pp. 861-871. DOI: 10.1017/CBO9781139046947.082

Inflammation and lung cancer: The link to angiogenesis
Ei Rayes, T, Catena, R, Rafii, S, Altorki, N & Mittal, V 2015, . in Inflammation and Lung Cancer. Springer New York, pp. 137-159. DOI: 10.1007/978-1-4939-2724-1_5

EMT process in bone metastasis
Gao, D, Thompson, EW & Mittal, V 2014, . in Bone Cancer: Primary Bone Cancers and Bone Metastases: Second Edition. Elsevier, pp. 451-459. DOI: 10.1016/B978-0-12-416721-6.00038-8