Assistant Professor, Medical Science
Office: Myers 200A
Phone: 812/ 856-1207
M.S., Devi Ahilya University, India, 1998.
Ph.D., University of Mumbai, India, 2007.
Postdoctoral Fellow, University of Chicago, 2007-2013.
The role of microenvironment regulated microRNAs in promoting ovarian cancer metastasis.
My laboratory seeks to understand the paracrine and juxtacrine interactions between cancer cells and their microenvironment that regulate metastatic colonization in ovarian cancer. Most ovarian cancer patients present with extensive metastasis when they are first diagnosed leading to a poor prognosis. This makes ovarian cancer the most lethal of all gynecologic malignancies with no significant improvement in survival rates over the last three decades. During the process of abdominal dissemination, the cancer cells floating in the peritoneal fluid have to attach to the mesothelial cells lining the peritoneal organs and interact with the microenvironment at the site of metastasis to successfully establish metastatic colonies. The cross talk between the cancer cells with the microenvironment of the metastasis site and the regulation of the initial steps of colonization is crucial and largely unknown.
We are using in vitro organotypic 3D culture models, live 3D time lapse microscopy and mouse xenograft models of metastasis along with cell and molecular biological approaches to study the reciprocal interactions between the metastasizing cancer cells with their microenvironment at the site of metastasis. We are specifically interested in the regulation of key microRNAs and transcription factors by these paracrine/juxtacrine interactions and the mechanism by which they drive metastatic colonization in ovarian cancer.
Mitra AK*, Davis DA, Tomar S, Roy L, Gurler H, Xie J, Lantvit DD, Cardenas H, Fang F, Liu Y, Loughran E, Yang J, Sharon S*, Emerson RE, Cowden Dahl KD*, Barbolina M*, Nephew KP*, Matei D* and Burdette J*. In vivo tumor growth of high-grade serous ovarian cancer cell lines. Gynecologic Oncology 2015 (Epublished ahead of print; PMID: 26050922).
* Corresponding Authors.
Kohlhapp FJ, Mitra AK, Lengyel E, Peter ME. MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment. Oncogene. 2015 (Epublished ahead of print; Review. PubMed PMID:25867073).
Mitra AK*, Chiang CY, Tiwari P, Tomar S, Watters KM, Peter ME, and Lengyel E*. Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis. Oncogene (In Press).
* Corresponding Authors.
Kenny HA, Lal-Nag M, White EA, Shen M, Chiang CY, Mitra AK, Zhang Y, Curtis M, Schryver E, Bettis S, Jadhav A, Boxer MB, Li Z, Ferrer M, and Lengyel E. High throughput screening using a physiologically-relevant primary human three-dimensional organotypic culture predicts in vivo efficacy. Nat Commun 2015, 6:6220.
Lengyel E, Litchfield LM, Mitra AK, Nieman KM, Mukherjee A, Zhang Y, Johnson A, Bradaric M, Lee WS, and Romero IL. Metformin inhibits ovarian cancer growth and increases sensitivity to paclitaxel in mouse models. Am J Obstet Gynecol. 2014, pii: S0002-9378(14)01081-3.
Zhang Y, Kenny HA, Swindell EP, Mitra AK, Hankins PL, Ahn RW, Gwin K, Mazar AP, O’Halloran TV, and Lengyel E. Urokinase Plasminogen Activator System Targeted Delivery of Nanobins as a Novel Ovarian Cancer Therapeutics. Mol Cancer Ther. 2013, 12:2628-39.
Mitra AK, Zillhardt M, Hua YJ, Tiwari P, Peter ME, and Lengyel E. microRNAs mediate cancer cell-induced reprogramming of normal fibroblasts into cancer associated fibroblasts. Cancer Discovery. 2012, 2:1100-8.
Commentary on this article by Chou and Werb: Cancer Discovery 2012, 2:1078-80
Mitra AK, Sawada K, Tiwari P, Mui K, Gwin K, and Lengyel E. Ligand-independent activation of c-Met by fibronectin and α5β1-integrin regulates ovarian cancer invasion and metastasis. Oncogene. 2011, 30:1566-76.
Romero IL, Lee WS, Mitra AK, Gordon IO, Zhao Y, Leonhardt P, Penicka P, Mui KL, Krausz TN, Greene GL, and Lengyel E. The effects of 17β-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis. Gynecologic Oncology. 2012, 124:134-41.
Kenny HA, Nieman KM, Mitra AK, and Lengyel E. The First Line of Intra-abdominal Metastatic Attack: Breaching the Mesothelial Cell Layer. Cancer Discovery. 2011, 1:100-102.
Kaur S, Kenny HA, Jagadeeswaran S, Zillhardt MR, Montag AG, Kistner E, Yamada SD, Mitra AK, and Lengyel E. b3-integrin expression on tumor cells inhibits tumor progression, reduces metastasis, and is associated with a favorable prognosis in patients with ovarian cancer. American Journal of Pathology. 2009, 175:2184-96.
Sawada K, Mitra AK, Radjabi AR, Bhaskar V, Kistner EO, Tretiakova M, Jagadeeswaran S, Montag A, Becker A, Kenny HA, Peter ME, Ramakrishnan V, Yamada SD, Lengyel E. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Research. 2008, 68:2329-39.
Mitra AK, Krishna M. Fractionated and acute irradiation induced signaling in a murine tumor. Journal of Cellular Biochemistry. 2007, 101:745-52.
Mitra AK, Singh RK, Krishna M. MAP kinases: differential activation following in vivo and ex vivo irradiation. Molecular and Cellular Biochemistry. 2007, 294:65-72.
Mitra AK, Krishna M. Radiation-induced bystander effect: activation of signaling molecules in K562 erythroleukemia cells. Journal of Cellular Biochemistry. 2007, 100:991-7.
Mitra AK, Bhat N, Sarma A, Krishna M. Alteration in the expression of signaling parameters following carbon ion irradiation. Molecular and Cellular Biochemistry. 2005, 276:169-73.
Mitra AK, Sarma A, Krishna M, Verma NC. Expression of NF-kappaB and ERK following heavy ion irradiation. Journal of Environmental Pathology, Toxicology and Oncology. 2004, 23:53-9.
Mitra AK, Krishna M. In vivo modulation of signaling factors involved in cell survival. Journal of Radiation Research (Tokyo). 2004, 45:491-5.
Mitra AK, Singh RK, Narang H, Maurya SK, Krishna M. Differential activation of signaling factors following low and high doses of gamma irradiation in vivo. International Journal of Low Radiation. 2004, 1:358-367.
Hebbar SA*, Mitra AK*, George KC, Verma NC. Caffeine ameliorates radiation-induced skin reactions in mice but does not influence tumour radiation response. Journal of Radiological Protection. 2002, 22:63-9. ( *Both authors have contributed equally)