Milan G. Chheda, M.D.

Assistant Professor
Internal Medicine

Molecular Genetics and Genomics Program
Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program

Research Abstract:

The Chheda lab opened in the summer 2015. We are interested in identifying and characterizing the genetic and epigenetic events that induce cancer and maintain tumors. Often, in other contexts, these same molecules enable normal human development.

Our initial work has focused on glioma as a model to study the tumor initiating cell state (sometimes known as the cancer stem cell state). Glioblastoma, the highest-grade glioma, is the most common and aggressive brain tumor. Tumor initiating cells exist in many types of cancer and are often more resistant to treatment than other parts of any given patient’s tumor.

Genetic aberrations found in patient tumors guide our experiments. We use these clues to discover fundamental biological mechanisms that impel tumors. We identified transcription factors and chromatin remodeling factors that are required to maintain the glioma tumor initiating cell state. This work provided a proof of principle that differentiation therapy might be feasible in solid tumors. We want to unearth new ways to kill tumor cells and uncover the signals and pathways that tumor cells use to resist our treatments. To advance our mission, we employ patient-derived tumor cells, functional genomics (loss-of-function and gain-of-function screens), biochemistry, in vivo imaging, and computational techniques.

Post-doctoral and graduate student rotation positions are available. We are extremely excited to mentor and train those who are fearless and driven.

Selected Publications:

1: Chheda MG, Wen PY, Hochberg FH, Chi AS, Drappatz J, Eichler AF, Yang D,Beroukhim R, Norden AD, Gerstner ER, Betensky RA, Batchelor TT. Vandetanib plus sirolimus in adults with recurrent glioblastoma: results of a phase I and dose expansion cohort study. J Neurooncol. 2015 Feb;121(3):627-34. doi: 10.1007/s11060-014-1680-2. Epub 2014 Dec 13. PubMed PMID: 25503302; PubMed Central PMCID: PMC4324090.

2: Chudnovsky Y, Kim D, Zheng S, Whyte WA, Bansal M, Bray MA, Gopal S, Theisen MA, Bilodeau S, Thiru P, Muffat J, Yilmaz OH, Mitalipova M, Woolard K, Lee J, Nishimura R, Sakata N, Fine HA, Carpenter AE, Silver SJ, Verhaak RG, Califano A, Young RA, Ligon KL, Mellinghoff IK, Root DE, Sabatini DM, Hahn WC, Chheda MG. ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state. Cell Rep. 2014 Jan 30;6(2):313-24. doi: 10.1016/j.celrep.2013.12.032. Epub 2014 Jan 16. PubMed PMID: 24440720; PubMed Central PMCID: PMC4041390.

3: Quayle SN, Chheda MG, Shukla SA, Wiedemeyer R, Tamayo P, Dewan RW, Zhuang L, Huang-Hobbs E, Haidar S, Xiao Y, Ligon KL, Hahn WC, Chin L. Integrative functional genomics identifies RINT1 as a novel GBM oncogene. Neuro Oncol. 2012 Nov;14(11):1325-31. doi: 10.1093/neuonc/nos246. Epub 2012 Oct 16. PubMed PMID: 23074196; PubMed Central PMCID: PMC3480269.

4: Dunn GP, Rinne ML, Wykosky J, Genovese G, Quayle SN, Dunn IF, Agarwalla PK, Chheda MG, Campos B, Wang A, Brennan C, Ligon KL, Furnari F, Cavenee WK, Depinho RA, Chin L, Hahn WC. Emerging insights into the molecular and cellular basis of glioblastoma. Genes Dev. 2012 Apr 15;26(8):756-84. doi: 10.1101/gad.187922.112. Review. PubMed PMID: 22508724; PubMed Central PMCID: PMC3337451.

5: Zheng S, Chheda MG, Verhaak RG. Studying a complex tumor: potential and pitfalls. Cancer J. 2012 Jan-Feb;18(1):107-14. doi:10.1097/PPO.0b013e3182431c57. Review. PubMed PMID: 22290264; PubMed Central PMCID: PMC3342695.

6: Wiedemeyer WR, Dunn IF, Quayle SN, Zhang J, Chheda MG, Dunn GP, Zhuang L, Rosenbluh J, Chen S, Xiao Y, Shapiro GI, Hahn WC, Chin L. Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11501-6. doi: 10.1073/pnas.1001613107. Epub 2010 Jun 7. PubMed PMID: 20534551; PubMed Central PMCID: PMC2895056.

7: Zheng H, Ying H, Wiedemeyer R, Yan H, Quayle SN, Ivanova EV, Paik JH, Zhang H,Xiao Y, Perry SR, Hu J, Vinjamoori A, Gan B, Sahin E, Chheda MG, Brennan C, Wang YA, Hahn WC, Chin L, DePinho RA. PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas. Cancer Cell. 2010 May 18;17(5):497-509. doi: 10.1016/j.ccr.2010.03.020. PubMed PMID: 20478531; PubMed Central PMCID: PMC2900858.

8: Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino S, Chheda MG, Tamayo P, Finn S, Shrestha Y, Boehm JS, Jain S, Bojarski E, Mermel C, Barretina J, Chan JA, Baselga J, Tabernero J, Root DE,Fuchs CS, Loda M, Shivdasani RA, Meyerson M, Hahn WC. CDK8 is a colorectal canceroncogene that regulates beta-catenin activity. Nature. 2008 Sep 25;455(7212):547-51. doi: 10.1038/nature07179. Epub 2008 Sep 14. PubMed PMID: 18794900; PubMed Central PMCID: PMC2587138.

9: Chheda MG, Drappatz J, Greenberger NJ, Kesari S, Weiss SE, Gigas DC, Doherty LM, Wen PY. Hepatitis B reactivation during glioblastoma treatment with temozolomide: a cautionary note. Neurology. 2007 Mar 20;68(12):955-6. PubMed PMID: 17372135.

Last Updated: 2/26/2016 9:18:26 AM

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