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Rakesh Kumar, PhD

Distinguished Professor and National Chair in Cancer Research

(O) 471-2781-270

rakeshkumar@rgcb.res.in

rakesh
rakesh

Rakesh Kumar, PhD

Distinguished Professor and National Chair in Cancer Research

(O) 471-2781-270

rakeshkumar@rgcb.res.in

  • Profile

    Experience (Selected)

    • 2014-2017: Visiting Professor of Cancer Medicine, Oxford University, Oxford, UK.
    • 2010-2017: Visiting Distinguished Professor of Biotechnology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
    • 2009-2017: Professor, Department of Biochemistry and Molecular Biology, George Washington University School of Medicine and Health Sciences, Washington DC, USA.
    • 2009-2014: Professor and Chairman, Department of Biochemistry and Molecular Biology, George Washington University School of Medicine and Health Sciences, Washington DC, USA.
    • 2009-2014: Catharine Birch & McCormick Chair, George Washington University School of Medicine and Health Sciences, Washington DC, USA.
    • 2011-2014: Chair of the Chairs of the Basic Sciences Departments, George Washington University School of Medicine and Health Sciences, Washington DC, USA.
    • 2010-2013: Co-Director, W.M. Keck Institute of Proteomics, George Washington University, Washington DC, USA.
    • 2009-2013: Director, Institute of Coregulator Biology, George Washington University, Washington DC, USA.
    • 2006-2009: Research and Academic Operation Leader, Designated Third Institutional Alternate Leader, Institutional Emergency Management Team, University of M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 2003-2009: John G. & Marie Stella Kenedy Memorial Foundation Chair, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 2001-2009: Professor and Vice Chair, Department of Cellular & Molecular Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 1999-2009: Professor of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 1998-2009: Professor, University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.
    • 2005-2007: Chair, Institutional Space Review Committee, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 2002-2003: Edward Rotan Distinguished Professor, University of M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 1998-2000: Professor, Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 1996-1998: Associate Professor, Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 1993-1996: Associate Professor of Medicine and Cellular and Molecular Physiology Penn State University College of Medicine, Hershey, Pennsylvania, USA.
    • 1993-1996: Graduate Faculty, Inter-College Graduate Degree Program in Physiology, Penn State University College of Medicine, Hershey, Pennsylvania, USA.
    • 1991-1992: Associate Lab Member, Molecular Pharmacology & Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, USA.
    • 1989-1991: Assistant Lab Member, Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, USA.
    • 1986-1988: Associate Researcher, Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, USA.

    Honors (Selected)

    • 2013: East Shanghai Cancer Forum Award
    • 2013: Lifetime Achievement Award, American Association of Indian Scientists in Cancer Research
    • 2011: Elaine H. Snyder Cancer Research Award
    • 2008: Ranbaxy Research Award
    • 2007: MDACC Presidential Recognition for a Mentor of Distinction Award
    • 2004-2007: MDACC Exceptional Leadership and Support as a Mentor Award
    • 2002-2007: Annual First Place AMGEN Award in Basic Science to students from Kumar labs
    • 2004: The Norman Brinkler Award for Research Excellence
    • 2004: MDACC Faculty Achievement Award in Basic Science
    • 1995: Hinkle Outstanding Investigator Award, Penn State University, PA
    • 1995: ASIOA Young Scientist Award; A.L. Bortree Lectureship, Penn State University, PA

    Membership (selected)

    • 2016: Chair, Cancer Drug Discovery and Therapeutic Study Section, Special Emphasis Panel, National Institutes of Health, USA.
    • 2016: Co-Chair, Cancer Drug Discovery and Therapeutic Study Section, Special Emphasis Panel, National Institutes of Health, USA.
    • 2013-2014: Chartered Member, Veteran Administration System Study Section, USA
    • 2011-2014: Chartered Member, Cancer Molecular Pathobiology Study Section, National Institutes of Health, USA.
    • 2014: Member, NCI Intramural Peer-review Program Site Visit, National Institutes of Health, USA.
    • 2011-2015: Founding Chair of the "Global Cancer Genomic Consortium" among 6 leading institutions from US, UK, Japan, Portugal and India)
    • 2012 -2014: Member, University Sub-committee on Appointment, Salary and Benefits, George Washington University, Washington DC, USA.
    • 2012: Member, University Strategy Vision Committee on Globalization, George Washington University, Washington DC, USA.
    • 2005-2009: Member, Research Strategy & Advisory Committee, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 2007-2009: Member, Physician-Scientist Program Selection Committee, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 2004-2009: Member, National Institutes of Health Study Section, USA.
    • 2004-2009: Member and Chair, Mike Hogg Award Committee, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. (scope of the committee: select, invite and host a Nobel Laureate each year)
    • 2005-2009: Chartered Member, Drug Discovery & Molecular Pharmacology Study Section, National Institutes of Health, USA.
    • 2007: Member, Selection Committee for the Kirk A. Landon-AACR Prize for Basic Cancer Research, USA.
    • 2008: Co-chair -AACR Conference on "Cytoskeleton Signaling in Cancer" Feb 3-5, San Diego, USA.
    • 2006: AACR Program Committee 2006, Chair -Experimental and Molecular Therapeutics Subcommittee Co-Chair- 2006 Mini-symposium on "Experimental Therapeutic I," USA,
    • 2005: Session Chair/Invited Speaker, Gordon Conference, Hormone Action in Cancer & Development, USA.
    • 2005: Member, 2005 AACR Experimental and Molecular Therapeutics Program Subcommittee, USA.
    • 2002-2005 Member, Institutional Space Review Committee, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
    • 1999-2016: Ad hoc Member - Numerous Peer-review Study Sections, US Department of Defense, USA.
    • 1995-2016: Ad hoc Member - Numerous Peer-review Study Sections, National Institutes of Health, USA.

    Editorial Activities

    • 2016- : Scientific Reports
    • 2015- : Oncogenesis
    • 2014- : Epigenetics
    • 2014- : American Journal of Cancer Research
    • 2013- : Oncogene
    • 2009- : Journal of Cellular Physiology
    • 2009- : Journal of Translational Research
    • 2009- : Genes and Cancer
    • 2002- : Cancer & Metastasis Reviews
    • 2001- : Clinical Cancer Research
    • 2005-2016: Cancer Research (Senior Editor)
    • 2001-2004: Cancer Research (Associate Editor)
    • 2009-2012: Endocrinology
    • 2009-2011: Cancer Letters
    • 2005-2007: Clinical & Experimental Metastasis
    • 2004-2006: Journal of Experimental & Clinical Cancer Research
    • 2003-2007, 2010-13: Journal of Biological Chemistry
    • Students/Postdoctoral Fellows/Fellows Directly Mentored: About 61
    • Current PhD Students - Mentored or Co-Mentored: 3
  • Research

    Research Interests

    Women's Cancer, Cytoskeleton and Chromatin Remodeling, Epigenomic Regulation of Cancer Progression, Cancer Biomarkers, and Therapeutic Targets.

    The laboratory continues to provide novel insights into the significance of cytoskeleton and chromatin remodeling - as two arms of phenotypic signaling - during the progression of women's cancer using physiologically relevant models and tools from molecular biology, genetics, proteogenomics, epigenetics, computational bioinformatics, and emerging platform based technologies. The laboratory contributed to the field of phenotypic signaling by defining how and why breast cancer cells move, with a focus on cytoskeleton signaling and the identification of novel drug targets such as p21-activated kinase (PAK1). The lab was the first to show the hyperactivation of PAK1 in human cancer, discover its numerous physiologic substrates, and establish new functions of PAK1 in cancer cells. The lab also discovered nuclear localization and functions of PAK1, which was previously thought to be a cytoplasmic kinase. Lessons learned from the PAK1 research turned-out to be true for many other PAK family members, and are vigorously pursued by cancer biologists. The second research focus is to reveal new facets of estrogen signaling, and sub-cellular localization of epigenetic modifiers in cancer cells. Specifically, the lab is interested in defining signaling- dependent molecular routers of epigenomic regulation of cancer progression. On-going studies are designed to reveal the significance of signaling-dependent epigenomic regulation of novel molecules which are at the interface of pathways that regulate cell survival, cell death, metabolism, inflammation, and immunomodulation, and thus, could regulate multiple pathways. The laboratory also hopes to continue the tradition of enabling others, particularly younger colleagues and students to live out their dreams in biomedical research, and to become future leaders by closely mentoring.

  • Publications

    Peer Reviewed Publications and Invited Reviews: 294
    Book chapters: 10

    Books/Volumes

    • Protein Kinases in Cancer; Editor: Rakesh Kumar; Cancer Metastasis Reviews 22, Number 4, pages 297-472, 2003; ISSN: 0167-7659
    • Molecular Signaling and Therapeutics; Editor: Rakesh Kumar, Kluwer Press, 2004; Pages 327; ISBN: 1-4020-7822-6
    • NR Coregulators and Human Diseases, Editors: Rakesh Kumar & Bert W. O'Malley World Scientific Publishers 2008; Pages 602; ISBN: 10-9812705368
    • Cytoskeleton Signaling in Cancer; Editors: Rakesh Kumar and Alan Hall; Metastasis Cancer Reviews 28, Number 1-2, pages 1-263, 2009; ISSN: 0167-7659.
    • Nuclear Signaling Pathways and Targeting Transcription in Cancer, Editor: Rakesh Kumar Springer Press 2013; Pages 441; ISBN 978-1-4614-8038-9
    • Functions and Clinical Relevance of MTA Proteins in Human Cancer; Editor: Rakesh Kumar; Cancer Metastasis Reviews 33, Number 4, pages 837-1127, 2014; ISSN: 0167-7659.

    NIH-Gene Wiki Initiative

    • https://en.wikipedia.org/wiki/MTA1
    • https://en.wikipedia.org/wiki/MTA2
    • https://en.wikipedia.org/wiki/MTA3
    • https://en.wikipedia.org/wiki/PAK1
    • https://en.wikipedia.org/wiki/PAK2
    • https://en.wikipedia.org/wiki/PAK3
    • https://en.wikipedia.org/wiki/PAK4
    • https://en.wikipedia.org/wiki/PAK5
    • https://en.wikipedia.org/wiki/PAK6

    Invited Speaker at Academic Institutions, and National and International Conferences: About 252

  • Team


    Prof. Rakesh Kumar
    The laboratory continues to provide novel insights into the significance of cytoskeleton and chromatin remodeling - two arms of phenotypic signaling - during cancer progression using tools from molecular biology, genetics, proteogenomics, epigenetics, computational bioinformatics, and platform technologies, and physiologically relevant model systems. Most of our understanding of kinase-driven oncogenesis is derived from phosphorylation of its substrates and their redistribution in distinct cellular sub-domains upon activation (Fig. 1). However, many of such candidate activated kinases are also commonly found in the nucleus and influences the status of gene expression through currently, poorly understood mechanisms. The laboratory is particularly in understanding the molecular details of signaling and epigenomic regulation of gene expression of molecules which are at the interface of pathways that regulate oncogenesis, cell survival, cell death, metabolism, inflammation, and immunomodulation during cancer progression. Examples of such molecules of interest to the laboratory include, kinases (i.e. EGFR receptors, p21-activated kinases and AKTs) and chromatin remodeling coregulators (i.e. metastasis tumor protein 1 family members and histone modifying components). In addition to making advances in Cancer Biology, these studies are aimed to discover and translate novel therapeutic targets and biomarkers from working pre-clinical models to the bed-side for the benefit of cancer patients. The laboratory hopes to continue the tradition of enabling others, particularly students and fellows and younger colleagues which are co-directed and co-mentored by Prof. Kumar and Prof. Pillai, live out their dreams in biomedical research, and to become future leaders.

    S. Deivendran Pre-postdoctoral Fellow, is addressing the issue of kinase-mediated gene expression at the mechanistic level. Taking advantage of in-house kinase-modulated transcriptomic landscape as derived from our genome-wide ChIP-Seq and RNA-Seq studies and assisted by the computational expertise of Bijesh George, he has begun to validate and translate leads from the genome wide studies into pathways or candidate molecules. For example, via bioinformatic mining of a few dozens of novel candidate molecules and their promoter and regulatory elements, the team has focused on a set of DNA-binding proteins and chromatin remodeling factors that are likely to be involved in the kinase regulation of chromatin remodeling, leading to gene expression (Fig. 2). The goal of these studies is to integrate signal-dependent activation of kinases with genomic functions, leading to biological activities in cancer cells. We envision that these studies will provide new facets of biology of kinases, molecular diagnostics, and therapeutic targeting.

    Bijesh George, a Junior Research Scholar, has undertaken computational bioinformatic approaches, i.e. RNA-sequencing and ChIP-sequencing, to understand the details of the genome wide influence of either activating or depleting or inhibiting the enzymatic activities of a family of signaling kinases in breast cancer cells. Early results suggest that some of these kinases repress the gene expression under basal conditions, and exhibits differential effect on the levels of expression of target genes from distinct functional groups. Based on the functional novelty and expected significance in cancer biology, the team has selected a set of candidate genes and taking forward a highly selected set of validated target genes for functional studies using physiologically relevant experimental models (Fig. 3). Another facet of these studies is to also unearth the role of the candidate family of kinases upon alternative splicing, and thus, have a full appreciation of kinase-regulation of breast cancer transcriptome, allowing providing a catalog of new potential biomarkers and therapeutic targets.

    Ananda Mukherjee, Ph.D. - a Senior Research Associate, is advancing the laboratory findings to evolve a unified model of gene regulation by extracellular milieu during cancer progression. Interestingly, many of cancer-relevant kinases are also oncogenic in nature and hyper-activated and/or mutated in human cancer, and activated kinases translocate to the nucleus to manifest their genomic functions. In addition to kinases, the biology of human cancer is profoundly regulated by the chromatin remodeling and DNA-binding factors. To fully appreciate the basic of genomic functions of cancer-relevant kinases, the team is defining it would be important to explore the principles of coordinated regulation of gene expression by chromatin remodeling and DNA-binding factors by kinases. To identify the common molecules/pathways that are coordinately regulated by kinases, chromatin remodeling factors, or DNA-binding factors, the team has utilized the genome-wide RNA-seq approaches (Fig. 4). This approach was very efficient in identifying a subset of novel shared targets with roles in cancer progression. To fully appreciate the basis of genomic functions of kinases, the team is defining the principles of coordinated regulation of gene expression by chromatin remodeling and DNA-binding factors by kinases. These studies will not only identify the basis of gene expression by two apparently distinct routes but provide new surrogate endpoints to predict the co-activation of pathways which could be co-targeted in tumor cells.
    Aswathy Mary Paul, a Junior Research Scholar, has taken advantage of computational biology approaches to better understand transcriptomicalterations in cervical cancer with focus on signaling kinases and the genome wide epigenomic alterations that could confer another regulatory layer onto transcriptomic landscape by upstream signals, including, chromatin remodeling factors, in cervical cancer. The goal of these studies is to reveal the nature of epigenomic landscape of cervical cancer and map out shared and selective elements among gynaecological cancers, and to study the impact of human papillomavirus 16 (HPV 16) E6 oncogene on the expression of epigenetic regulators and in-turn, on transcriptome in a cell based model system (Fig. 5).



    Rajesh Raju, Ph.D., DST Young Scientist, has taken a proteomic and system biology approach to better understand the details of signaling-dependent phenotypic changes in cancer cells. Steady-state levels of regulatory proteins and their post-translational modifications (PTMs) are integral part of both signaling-dependent epigenomic regulation of gene expression as well as end-points of gene expression to manifest and maintenance of cancerous phenotypes. Towards this, he is investigating the temporal cell surface initiated signaling cascades and phosphorylation of novel target substrates as well as the proteome and phosphoproteome events from the cancer cells in the regulation of expression of a co-regulated panel of genes, and finally, connecting with phenotypic readouts (Fig. 6). This approach is being also used to delineate the cross-talks in signaling networks and predict the sequentially of activation of multiple receptor-mediated signaling systems.




    Rahul Sanawar, a Senior Research Fellow: Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that does not respond to most of the current targeted therapies. As a part of a doctoral degree dissertation project, Rahul has identified the FAM171A1 as a potential candidate gene overexpressed in TNBC cell lines and breast tumors. Our studies show that estrogen receptor-alpha (ERα) negative breast cancer cells express a high expression of FAM171A1 as compared to ER positive breast cancer cell lines. Interestingly, we found an inverse correlation between the levels of FAM171A1 and ERα in breast cancer and that ectopic overexpression of FAM171A1 in breast cancer cells may be accompanied by an increased mammosphere-forming ability and epithelial-to-mesenchymal transition. Conversely, FAM171A1 depletion in breast cancer cells was accompanied by a decreased ability of cancer cells to form mammospheres and undergo through epithelial-to-mesenchymal transition. Unexpectedly, ectopic expression of ERα in ER-negative breast cells was associated with a reduced FAM171A1 expression, raising a possibility of a feedback regulation of FAM171A1 by ERα. On-going studies are exploring the mechanism of ERα regulation of FAM171A1 with a focus on microRNAs. We expect that a greater understanding of bi-directional regulation of FAM171A1 and ERα in breast cancer cells, and could possibly serve a functional readout of a sub-set of breast cancer.

  • Alumni