About Dr. Majumder
Dr. Majumder completed his predoctoral schooling at Saha Institute of Nuclear Physics in India and received his Ph.D. from New York University. He subsequently completed his postdoctoral training at Sloan Kettering Cancer Center and at Roche Institute of Molecular Biology. He joined The University of Texas M. D. Anderson Cancer Center in 1995 as an Assistant Professor and was promoted to his current position as Professor in 2006. His current research involves deciphering the mechanisms that control normal brain functions and how aberrations in these mechanisms causes diseased states such as cancer and neurodegenerative disorders. Dr. Majumder has a strong interest in teaching. In addition to leading a lab with undergraduate, graduate, postdoctoral and clinical fellows, he teaches at the Graduate School of Biomedical Sciences and organizes a biennial course at Cold Spring Harbor Laboratories on Brain Tumors. Dr. Majumder has received many awards including M. D. Anderson Fort Worth Living Legend Faculty Achievement Award, National Brain Tumor Society Chaiken Chair of Research Award, and B*CURED Research Award.View a complete list of Dr. Majumder's publications. Visit Dr. Majumder's Lab website!
Professor and Deputy Chair, Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
Professor, Department of Neuro-Oncology, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX
Professor, The University of Texas M.D. Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX
The research in my laboratory is focused on (1) deciphering the mechanisms that control normal development and how aberrations of such mechanisms produce diseases, and (2) investigating how such knowledge can be translated into improved patient care. We begin by studying molecular mechanisms and then build on the lessons learned from those studies using a multi-disciplinary approach that encompasses genomics, bioinformatics, biochemistry, cell biology and mouse genetics. Our work involves close collaboration between basic scientists and clinicians.
One of the first projects in my laboratory focused on advancing understanding of the childhood brain tumor medulloblastoma (MB) as a foundation for patient-specific therapeutic approaches. In the course of our early work, we discovered that the transcriptional repressor REST has a new function in that it maintains self-renewal and blocks differentiation of normal neural stem cells. REST is aberrantly overexpressed in a subclass of MB tumors, and a unique role of REST in these MB tumors is to block differentiation and maintain stemness of the cerebellar stem/progenitor cells. This work was exciting because others and we suggested that REST inhibitors could be utilized to block MB.
Our work then evolved into an investigation of the mechanisms of stemness in neural stem cells, muscle progenitor cells, embryonic stem cells and glioblastoma stem cells. Based on our understanding of these mechanisms, in one line of work, we converted muscle progenitor cells into functional neurons, with a single recombinant molecule we designed based on REST function (REST-VP16), before the iPS system was published. Genome-wide analyses indicated that REST-VP16 shifted global muscle-specific to neuron-specific transcriptome signature in these engineered neurons. Another line of work resolved some of the contradictions in the literature and showed that the REST-mediated regulation of ES cell pluripotency through a microRNA-mediated pathway depends on the cell-type (not all ES lines are the same) as well as the culture conditions, indicating how various factors form part of an interconnected genome-wide network.
In a third line of work, we discovered that REST regulates glioblastoma (GBM) stem cell (GSC) tumorigenicity by maintaining self-renewal and invasion. Importantly, high levels of REST characterize a class of human GBM patient tumors (HR-GBM). Various labs, including ours, by now have suggested that REST is a potential therapeutic target for stratified HR GBM tumors. Our recent genome-wide chromatin and transcriptome filtering analyses followed by biochemical and biological validations indicated that REST performs its functions in GSCs through a microRNA signature pathway (miR-124, a known REST target, and miR-203, a new target). Parallel to this discovery, we used unbiased genome-wide analyses and discovered a new mechanism (miR-21-Sox2 regulatory axis)-based GBM patient classification with implications for precision medicine. We are currently studying specific innovations in chemotherapy suggested by the REST-miR-124/203 mechanism using exosome-mediated delivery of miRs in HR-stratified mouse tumors. Although REST regulates many genes, many of its biological functions still remain undiscovered. Overexpression (OE) of REST is found in many brain tumors, in ischemic insults, and in neurological diseases and behavioral disorders. However, progress in these areas has been hampered by the continuing absence of a conditional REST OE mouse model. We have now created the first conditional REST OE knockin mouse line enabling study of the role of REST OE in vivo. Our published results confirm that REST expression in these mice is physiologically relevant. Genome-wide analyses followed by quantitative ChIP assays and behavioral assays indicated that REST regulates spontaneous locomotion by repressing a new target, Dopamine Receptor 2.
In a fourth line of work using REST OE mice, we collaborated with Dr. Hui-Lin Pan’s lab to study the role of REST in chronic pain. We are currently studying the central hypothesis that REST in DRG neurons is involved in regulating opioid analgesia in chronic neuropathic pain and in opioid-induced hyperalgesia /analgesic tolerance by governing the opioid receptor expression through epigenomic regulation of these genes. Thus, manipulation of REST in DRG neurons could be utilized to increase opioid analgesic efficacy and reduce opioid consumption.
|1985||New York University, New York, NY, USA, PHD, Microbiology|
|1988-1992||Research Associate, Enhancer Function in Mice, Roche Institute of Molecular Biology, Nutley, NJ|
|1985-1988||Exxon Postdoctoral Fellow, Protein Kinases, Memorial Sloan-Kettering Cancer Center, New York, NY|
|2010||Elected Fellow of the Indian Society of Agricultural Biochemists|
|2008||MDACC Fort Worth Living Legend Faculty Achievement Award in Basic Research, The University of Texas M.D. Anderson Cancer Center|
|2000||Pediatric Brain Tumor Foundation of the United States Award|
- Marisetty A, Lu L, Veo B, Liu B, Coarfa C, Kamal M, Kassem D, Irshad K, Lu Y, Gumin J, Henry V, Paulucci-Holthauzen A, Rao G, Lang F, Fuller F, Majumder S. REST-DRD2 mechanism impacts glioblastoma stem cell-mediated tumorigenesis. Neuro-Oncology 21(16):775-785, 2019. PMID: 30953587.
- Lu L, Marisetty A, Liu B, Kamal MM, Gumin J, Veo B, Cai Y, Kassem D, Weng C, Maynard M, Hood K, Fuller G, Pan Z, Cykowski MD, Dash P, Majumder S. REST overexpression in mice causes deficits in spontaneous locomotion. Sci Rep 8(1):12083, 2018. PMID: 30108242.
- Marisetty AL, Singh SK, Nguyen TN, Coarfa C, Liu B, Majumder S. REST represses miR-124 and miR-203 to regulate distinct oncogenic properties of glioblastoma stem cells. Neuro Oncol 19(4):514-523, 2017. PMID: 28040710.
- Sathyan P, Zinn PO, Marisetty AL, Liu B, Kamal MM, Singh SK, Bady P, Lu L, Wani KM, Veo BL, Gumin J, Kassem DH, Robinson F, Weng C, Baladandayuthapani V, Suki D, Colman H, Bhat KP, Sulman EP, Aldape K, Colen RR, Verhaak RG, Lu Z, Fuller GN, Huang S, Lang FF, Sawaya R, Hegi M, Majumder S. Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact. J Neurosci 35(45):15097-112, 2015. PMID: 26558781.
- Kamal MM, Sathyan P, Singh SK, Zinn PO, Marisetty AL, Liang S, Gumin J, El-Mesallamy HO, Suki D, Colman H, Fuller GN, Lang FF, Majumder S. REST regulates oncogenic properties of glioblastoma stem cells. Stem Cells 30(3):405-14. doi:10.1002/stem.1020, 2012. PMID: 22228704.
- Singh SK, Veo BL, Kagalwala MN, Shi W, Liang S, Majumder S. Dynamic status of REST in the mouse ESC pluripotency network. PLoS One 7(8):e43659. doi:10.1371/journal.pone.0043659, 2012. e-Pub 2012. PMID: 22952733.
- Gopalakrishnan V, Sinnappah-Kang N, Adams H, Fuller G, Pan ZZ, and Majumder S. Myoblast-derived neuronal cells form glutamatergic neurons in the mouse cerebellum. Stem Cells 28:1839-1847, 2010. PMID: 20799335.
- Kagalwala M, Singh S, Majumder S. Stemness is only a state of the cell. Cold Spring Harbor Laboratories Symposium on Quantitative Biology (on Stem Cells), 2009. e-Pub 2009.
- Singh S, Kagalwala M, Zhao Z, Majumder S. REST maintains self-renewal and pluripotency of embroyonic stem cells. Nature 453(7192):223-237, 2008. e-Pub 2008. PMID: 18362916.
- Su X, Gopalakrishnan V, Stearns D, Aldape K, Lang FF, Fuller G, Snyder E, Eberhart CG, Majumder S. Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation. Mol Cell Biol 26:1666-78, 2006. PMID: 16478988.
- Su X, Kameoka S, Lentz S, Majumder S. Activation of REST/NRSF target genes in neural stem cells is sufficient to cause neuronal differentiation. Mol Cell Biol 24(18):8018-25, 2004. PMID: 15340064.
- Watanabe Y, Kameoka S, Gopalakrishnan V, Aldape KD, Pan ZZ, Lang FF, Majumder S. Conversion of myoblasts to physiologically active neuronal phenotype. Genes and Development 18(8):889-900, 2004. PMID: 15078815.
- Rastelli L, Robinson K, Xu Y, Majumder S. Reconstitution of enhancer function in paternal pronuclei of one-cell mouse embryos. Mol Cell Biol 21(16):5531-40, 2001. PMID: 11463835.
- Lawinger P, Venugopal R, Guo ZS, Immaneni A, Sengupta D, Lu W, Rastelli L, Marin Dias Carneiro A, Levin V, Fuller GN, Echelard Y, Majumder S. The neuronal repressor REST/NRSF is an essential regulator in medulloblastoma cells. Nature Medicine 6(7):826-31, 2000. PMID: 10888935.
- Singh SK, Marisetty A, Sathyan P, Kagalwala M, Zhao Z, Majumder S. REST-miR-21-SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells. Stem Cell Res 15(2):305-311. e-Pub 2015. PMID: 26209818.