About Dr. Rai
I am an Associate Professor of Genomic Medicine at MD Anderson Cancer Center. I also serve as Scientific Director of an epigenetics-focused translation research initiative at MDA, named MDACC Epigenomics Therapy Initiative (METI). My research is focused on understanding contribution of epigenome to cancer progression and identifying new venues for therapy and diagnostic tools. My lab utilizes cutting-edge epigenomic approaches to study chromatin state changes and higher order chromatin structure during evolution of tumor cells. Over last 20 years, I have developed expertise in studying epigenetic processes by identifying factors that perform epigenetic functions, identifying their roles in cellular events that regulate normal organ development and abnormal cell growth during tumorigenesis. The highlights of my current research include comprehensive understanding of chromatin state reprogramming during immunotherapy response (Under revision in Science Translation Medicine ), early stages of melanoma ( Cell Reports 2017 ), colon cancer progression ( Orouji et al, Gut 2021 ) and during metastasis ( Cell Reports 2021 ). We also identified major drivers of pre-malignant to malignant to metastatic transitions ( Cancer Discovery 2015; Nature Communications 2019; Cell Reports 2019 ). In addition, I co-led several studies with other investigators ( Cancer Cell, 2020; Acta Neuropathologica 2021; Nature Communications, 2019 & 2021; Journal of Clinical Investigation 2015; Stem Cell Reports 2017 ). Previously, as a trainee I defined a DNA-repair mediated DNA demethylation process ( Cell 2008 ), and discovered its role in colon cancer initiation ( Cell 2010 ). My PhD work deciphered roles of DNA and histone methyltransferases in early embryonic development ( MCB 2006, G&D 2007 and JBC 2010 ). We have systematically generated chromatin state maps into 9 other tumor types and have generated > 3000 ChIP-Seq datasets (usually undertaken by large consortium efforts) (Under revision in Nature Cell Biology ). These data have led to the discovery of several new concepts including a strategy to stratify patients based on their epigenomic content for specific therapies. We are also heavily invested in the single cell epigenomics ( PNAS, 2021 and Nature Communications 2021 ). Current research focus is on: 1) utilizing machine learning approaches to fully exploit cancer epigenomic data; 2) defining epigenetic aberrations at the single-cell resolution; 3) functionalizing ‘cancer-specific’ epigenetic elements using CRISPR-Cas9 based epigenetic editing approaches and 4) evaluating aberrations in higher-order chromatin structure. My lab is funded by NCI (three RO1s, two R21s, CEPs from 5 SPOREs), CPRIT (two IIRAs), ACS (RSG), private foundations (Melanoma Research Alliance and Melanoma Research Foundation), and MDA Moonshot (Prostate, Colorectal, Pancreatic). In addition, I have lead Epigenetics SPORE for MDA and Prostate Epigenetics PO1 applications.
Assistant Professor, Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Instructor, Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Instructor, Harvard Medical School, Boston, MA
|2006||University of Utah, Salt Lake City, UT, USA, PHD, Cancer Biology|
|2002||Indian Institute of Technology, Kharagpur, IND, B.Tech, Biotechnology and Biochemical Engineering|
|2010-2011||Research Fellowship, Cancer Epigenetics, Dana Farber Cancer Institute, Boston, MA|
|2007-2009||Research Fellowship, Cancer Epigenetics, University of Utah, Salt Lake City, UT|
- Deribe YL, Shi Y, Rai K, Nezi L, Amin SB, Wu CC, Akdemir KC, Mohdavi M, Peng, Chang QE, Harnigold K, Arold ST, Welch HCE, Garraway L, Chin L. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma. Proceedings of National Academy of Sciences 113(9):E1296 - E1305, 2016.
- Keung EZ, Akdemir KC, Al Sannaa GA, Garnett J, Lev D, Torres KE, Lazar AJ, Rai K, Chin L. Increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma. J Clin Invest 10(8):1172, 2015. e-Pub 2015. PMID: 26193637.
- Cheng CS, Rai K, Garber M, Hollinger A, Robbins D, Anderson S, Macbeth A, Tzou A, Carneiro MO, Raychowdhury R, Russ C, Hacohen N, Gershenwald JE, Lennon N, Nusbaum C, Chin L, Regev A, Amit I. Semiconductor-based DNA sequencing of histone modification states. Nat Commun 4:2672, 2013. PMID: 24157732.
- Genovese G, Ergun A, Shukla SA, Campos B, Hanna J, Ghosh P, Quayle SN, Rai K, Colla S, Ying H, Wu CJ, Sarkar S, Xiao Y, Zhang J, Zhang H, Kwong L, Dunn K, Wiedemeyer WR, Brennan C, Zheng H, Rimm DL, Collins JJ, Chin L. microRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma. Cancer Discov 2(8):736-749, 2012. e-Pub 2012. PMID: 22750848.
- Rai K, Sarkar S, Broadbent TJ, Voas M, Grossmann KF, Nadauld LD, Dehghanizadeh S, Hagos FT, Li Y, Toth RK, Chidester S, Bahr TM, Johnson WE, Sklow B, Burt R, Cairns BR, Jones DA. DNA demethylase activity maintains intestinal cells in an undifferentiated state following loss of APC. Cell 142(6):930-42, 2010. PMID: 20850014.
- Rai K, Jafri IF, Chidester S, James SR, Karpf AR, Cairns BR, Jones DA. Dnmt3 and G9a cooperate for tissue-specific development in zebrafish. J Biol Chem 285(6):4110-21, 2010. e-Pub 2009. PMID: 19946145.
- Phelps RA, Chidester S, Dehghanizadeh S, Phelps J, Sandoval IT, Rai K, Broadbent T, Sarkar S, Burt RW, Jones DA. A two-step model for colon adenoma initiation and progression caused by APC loss. Cell 137(4):623-34, 2009. PMID: 19450512.
- Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 135(7):1201-12, 2008. PMID: 19109892.
- Rai K, Chidester S, Zavala CV, Manos EJ, James SR, Karpf AR, Jones DA, Cairns BR. Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish. Genes Dev 21(3):261-6, 2007. PMID: 17289917.
- Rai K, Nadauld LD, Chidester S, Manos EJ, James SR, Karpf AR, Cairns BR, Jones DA. Zebra fish Dnmt1 and Suv39h1 regulate organ-specific terminal differentiation during development. Mol Cell Biol 26(19):7077-85, 2006. PMID: 16980612.
- Nadauld LD, Chidester S, Shelton DN, Rai K, Broadbent T, Sandoval IT, Peterson PW, Manos EJ, Ireland CM, Yost HJ, Jones DA. Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development. Proc Natl Acad Sci U S A 103(36):13409-14, 2006. e-Pub 2006. PMID: 16938888.
- Rai K*. Genomic Classification of Cutaneous Melanoma. Cell 7(161):1681-96. e-Pub 2015. PMID: 26091043.
- Keung EZ, Rai K. H3K9me3 Mediated Repression of KLF6: Discovering a Novel Tumor Suppressor in Liposarcoma Using a Systematic Epigenomic Approach. Mol Cell Oncol 3(3):e1093691, 2016. e-Pub 2015. PMID: 27314083.
|Title:||Investigating the Mechanism of Action of Epigenetic Modifications and Factors during Metastatic Progression of Melanoma|
|Funding Source:||Charles A King Trust Post-doctoral Fellowship|
|Title:||Epigenetic regulators of metastasis in bladder cancer|
|Funding Source:||MDACC BLADDER CANCER SPORE|
|Title:||Defining metastasis-specific higher-order chromatin structure in melanoma|
|Funding Source:||UTMDACC Center for Cancer Epigenetics|
|Title:||Epigenome changes during melanoma progression|
|Funding Source:||Center for Cancer Epigenetics|
|Title:||Epigenetic of Melanoma Metastasis|
|Title:||Characterization of epigenome in cancer cell lines|
|Title:||UT MD Anderson Cancer Center Melanoma SPORE- Project 4|
|Title:||UTMDACC Brain SPORE - Career Enhancement Project|
|Title:||Epigenetic of Melanoma Metastasis|
|Title:||CRC Moonshot project #9|
|Title:||UTMDACC Lung SPORE: Career Enhancement Program Award|
|Title:||Melanoma Research Foundation|
|Funding Source:||Melanoma Research Foundation|