Manjeet K. Rao, Ph.D.
Director (Interim), Greehey Children’s Cancer Research Institute
Department of Cell Systems and Anatomy
Co-Leader, Experimental and Development Therapeutics, Mays Cancer Center
Discipline Director, Cancer Biology, IBMS
Cancer– We are actively engaged in translational research to discover new, more effective and safe regimens for treating cancers. Towards that goal, we recently discovered that an anti-depressant and its derivative can block cancer cell’s ability to repair DNA. Our study became the basis for the clinical trial, which is currently underway.
Another focus of my laboratory is to use microRNAs as novel biomarkers and therapeutics for the diagnosis/prognosis and treatment of pediatric brain tumors and adult cancers. Our recent research achievements of safe and efficacious delivery of microRNA using lipid and FDA-approved nanoparticle-based systemic delivery approaches to treat cancers in mouse tumor model paves the way for a clinical trial in the near future.
In addition to miRNA, using unbiased genomewide synthetic lethal screens, we have identified novel proteins that play a causal role in tumorigenesis and render cancer cell resistant to cancer treatment drugs. With our expertise in medicinal chemistry, structural biology, in silicomodeling and small molecule screening, we have rationally designed and synthesized several lead small molecules that can interfere with the key residues that are critical for the activity of those proteins.
RNA epigenetics- We were the first group to design novel algorithms that can identify transcriptome wide methylation as well as differential RNA methylation in normal and disease condition. Recently, in a groundbreaking study, we showed that writers, erasers and readers of RNA methylation cross-talk with each other to maintain a level of RNA methylation that is critical for the stability of key progrowth/proliferation-specific genes and any pro-tumorigenic stimulus that perturbs that cross-talk leads to uncontrolled activity of those genes, resulting in tumor growth and progression. We are currently investigating the role of specific RNA epigenetic modifiers in children’s and adult cancers.
MicroRNA and Development – In addition to cancer, my group has made some seminal discoveries in the field of miRNA and development. We were the first group to develop an in vivoRNA interference (RNAi) approach that that mimics the principle by which “microRNAs” are processed (Rao et al., Genes & Dev, 2006). Furthermore, we were first to show that miRNA plays a critical role in chromatin condensation during germ cell development (Chang et al., PNAS, 2012). Recently, in a groundbreaking work, we showed that LC3-associated phagocytosis is not only confined to macrophages but it is actively used by Sertoli cells to engulf and clear germ cell during germ cell differentiation (Panneerdoss et al., Nature Communications, 2018).
Field of study: Adult and Children’s Cancer; MicroRNA; Small Molecule Inhibitors
Sub field of study: Drug development, Translational Research
Research areas: Cancer, Epigenetics, Development
Relevant diseases: Medulloblastoma; Osteosarcoma; Breast Cancer; Glioblastoma
Research Techniques: Mouse tumor models; Ex-vivo explants from cancer patients; Nanoparticle-based drug delivery; RNA-seq; Me-RIP-Seq; PAR-CLIP; Fiber analysis; IHC; Routine Molecular biology techniques
- 2004 - Postdoctoral Fellowship - Cancer Biology - U. T. M. D. Anderson Cancer Center
- 1999 - Postdoctoral Fellowship - Physiology - University of Western Ontario
- 1998 - PhD - Molecular Endocrinology - University of Delhi
- 1991 - MS - Zoology - University of Delhi
- 1989 - BS - Zoology - University of Delhi
- 9/2014 - Associate Professor and Associate Professor of Medicine - The U. T. Health Science Center at San Antonio, Cellular & Structural Biology, San Antonio
Instruction & Training
- 2/2013 - Present, INTD 6007: Advanced Molecular Biology
- 10/2012 - Present, CSBL 6074: Molecular aspects of epigenetics
- 9/2012 - Present, Post-Doctoral Student Supervision, UTHSCSA
- 5/2011 - Present, Post-Doctoral Student Supervision, Greehey Children's Cancer Research Institute (UTHSCSA)
- 6/2010 - Present, Core Course IV: Meth in Cell Bio, The University of Texas Health Science Center
- 6/2009 - Present, Membership on Supervising Committee, Dept. of Cellular Structural Biology (UTHSCSA)
- 8/2008 - Present, Summer Internship Program, Greehey Children's Cancer Research Institute
- 4/2008 - Present, Stem Cell Biology, The University of Texas Health Science Center
- 7/2007 - Present, Post-Doctoral Student Supervision, Greehey Children's Cancer Research Institute
Research & Grants
microRNA, Leukemia, Genetics of Cancer
Cancer Development and Progression Program
Funding Agency NCI Title 1R01CA179120-01: miRNAs as safe and effective therapeutic adjuvants to treat triple negative breast cancers Status Active Period 2/2015 - 1/2020 Role Principal Investigator Grant Detail The major goals of this grant are to (1) evaluate miRNAs as potential biomarkers for drug response in chemo-resistant triple negative breast cancers; (2) elucidate the mechanisms by which candidate miRNAs regulate sensitivity/resistance of triple negative breast cancer cells; (3) investigate the potential of candidate miRNAs as therapeutic adjuvants for the treatment of triple negative breast cancer. Funding Agency NIH (NIGMS) Title 1 R01 GM113245-0: Graphic models for global RNA methylation Status Active Period 9/2014 - 8/2017 Role Co-Principal Investigator Grant Detail
Funding Agency GCCRI Title GCCRI Tobacco Fund: Role of miRNA in pediatric cancer growth and metastasis. Status Active Period 9/2012 - Present Role Principal Investigator Grant Detail Funding Agency CPRIT Title 1RP140594: microRNAs as novel therapeutic adjuvants for treating drug resistant breast cancers Status Active Period 9/2014 - 8/2017 Role Principal Investigator Grant Detail
Zoghi B, Ravdin P, Imam JS, Plyler JR, Bansal H, Prajapati S, Bansal S, Panneerdoss S, Chang YG, Chen Y and Rao MK.
Press coverage: This presentation was one of the four presentations that were selected for panel discussion on the last day of the meeting. Data presented in this meeting received extensive media and press coverage.
http://www.uthscsa.edu/hscnews/singleformat2.asp?newID=4276; http://www.sciencedaily.com/releases/2012/10/121002092843.htm http://forum.tnbcfoundation.org/new-hope-for-taming tnbc_topic10350_post106473.html http://entertainmenttonighthosts.sims2dl.com/1441/new-hope-for-taming-triple-negative breast-cancer/ . Improving the efficacy of chemotherapy drug in triple negative breast; 2012 Aug. (J Clin Oncol; vol. 30, no. 27).
Chang YF, Zoghi B, Panneerdoss S, Pertsemlidis A, and Rao MK. MicroRNAs as novel therapeutic targets to treat drug-resistant breast cancers; 2012 Apr. (Cancer Research; vol. 72, no. 8 (1)). Roy S Saha, Rao MK, Sun L, Tekmal RR, and Vadlamudi RK. Proto-Oncogene PELP1 Promotes metastasis through miR-200 Dependent Pathway; 2012 Feb. (Cancer Research; vol. 71, no. P2010). Hima Bansal, Theresea Siefert, Divya Chakravarthy, Manjeet Rao, Gail E Tomlinson, Swaminathan Padmanabhan, and Sanjay Bansal . Wilm`s Tumor 1 Protein Confers TRAIL Resistance in Myeloid Leukemia Cells Through Bcl-Xl; 2011 Nov. (Blood (ASH Annual Meeting Abstracts); vol. 118, no. 2557). J. Saadi Imam, Kalyan Buddavarapu, Jennifer S. Lee-Chang, Peter Hornsby, Yidong Chen, Kihoon Yoon, and Rao, Manjeet. Deregulation of tumor suppressor miRNAs results in Six1 oncogene overexpression in pediatric and adult human cancers; 2011 Jan. (Cancer Research; vol. 70, no. 2107). Yao-Fu Chang, Jennifer S. Lee-Chang, J. Saadi Imam, Amiya P. Sinha Hikim, and Rao. MK. Regulation of Translational Suppression in Post-Meiotic Germ Cells: Crosstalk Between MicroRNAs and Actin-Associated Proteins; 2010 Jan. (Biol. Reprod; vol. 83, no. Sup.1). Sanjay Bansal, Hima Bansal, Manjeet Rao, Ronan Swords, Kevin Kelly, Jennifer Carew, Kelvin Lee, Frank Giles, and Swaminathan Padmanabhan. . WT1 interacts with the chaperone protein HSP90 and this regulates its expression; 2009 Apr. (Proceedings of the 100th Annual Meeting of the American Society for Cancer Research (AACR); vol. 2009, no. 1498). Hima Bansal, Sanjay Bansal, Kamalesh Sankhala, Manjeet Rao, Ronan Swords, Devalingam Mahalingam, Kevin Kelly, Jennifer Carew, Frank Giles, and Swaminathan Padmanabhan. . Interferons downregulate WT1 through the JAK/STAT pathway; 2009 Apr. (Proceedings of the 100th Annual Meeting of the American Society for Cancer Research (AACR); vol. 2009, no. 1541). Yao-Fu Chang and Rao, MK. MicroRNAs and Male Germ Cell Differentiation; 2009 Mar. (Biol. Reprod; vol. 78, no. Sup.1). Rao, MK, Sreenath Shanker, Yuiko Matsumoto, Anjana Bharadwaj, and Miles Wilkinson. Hormone- and stress-induced relief of a tissue-specific transcriptional elongation block; 2008 Sep. (Biol. Reprod; vol. 77, no. Sup.1). Rao MK, Wayne CM, Meistrich M, and Wilkinson MF. A promoter that directs transcription in a Sertoli cell-specific, stage-specific, and androgen dependent manner in vivo; 2002 Jan. (Biol. Reprod; vol. 66, no. Sup.1). Wilkinson, MF., Rao, MK., Maiti, S. & MacLean, JA. Transcriptional Regulation of the Pem Homeobox Gene by Ets and Sp-1 Family Members in Primary Granulosa Cells and Diverse Tumor Cell Types; 2001 Jan. (Biol. Reprod; vol. 64, no. sup.1). Rao, MK., Sutton, K., Pagani, R.L., Lamb, D.J. & Wilkinson, M.F. Identification of Pem Homeobox Gene Promoter Sequences Sufficient to Drive High Transcription Levels in Sertoli Cells and Principal Cells of Caput Epididymis In Vivo; 2001 Jan. (Biol. Reprod; vol. 64, no. sup 1). Rao, M.K., Maiti, S. & Wilkinson, M.F. Transcriptional Regulation of the Androgen-Dependent Homeobox Gene Pem by Ets and Sp1 Family Members in Reproductive Tissues; 2000 Jan. (Biol. Reprod; vol. 62, no. sup1).
Panneerdoss S, Eedunuri VK, Yadav P, Timilsina S, Rajamanickam S, Viswanadhapalli S, Abdelfattah N, Onyeagucha BC, Cui X, Lai Z, Mohammad TA, Gupta YK, Huang TH, Huang Y, Chen Y, Rao MK. Cross-talk among writers, readers, and erasers of m6A regulates cancer growth and progression Sci Adv 2018 Oct;. Abdelfattah N, Rajamanickam S, Panneerdoss S, Timilsina S, Yadav P, Onyeagucha BC, Garcia M, Vadlamudi R, Chen Y, Brenner A, Houghton P, Rao MK. MiR-584-5p potentiates vincristine and radiation response by inducing spindle defects and DNA damage in medulloblastoma Nat Commun 2018 Oct;. Wei Z, Panneerdoss S, Timilsina S, Zhu J, Mohammad TA, Lu ZL, de Magalh?es JP, Chen Y, Rong R, Huang Y, Rao MK, Meng J. Topological Characterization of Human and Mouse m5C Epitranscriptome Revealed by Bisulfite Sequencing Int J Genomics 2018 Jun;. Cui X, Zhang L, Meng J, Rao MK, Chen Y, Huang Y. MeTDiff: A Novel Differential RNA Methylation Analysis for MeRIP-Seq Data IEEE/ACM Trans Comput Biol Bioinform 2018 Mar;. Onyeagucha B, Subbarayalu P, Abdelfattah N, Rajamanickam S, Timilsina S, Guzman R, Zeballos C, Eedunuri V, Bansal S, Mohammad T, Chen Y, Vadlamudi RK, Rao MK. Novel post-transcriptional and post-translational regulation of pro-apoptotic protein BOK and anti-apoptotic protein Mcl-1 determine the fate of breast cancer cells to survive or die Oncotarget 2017 Oct;. Panneerdoss S, Viswanadhapalli S, Abdelfattah N, Onyeagucha BC, Timilsina S, Mohammad TA, Chen Y, Drake M, Vuori K, Kumar TR, Rao MK. Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells Nat Commun 2017 Sep;. Cui X, Meng J, Zhang S, Rao MK, Chen Y, Huang Y. A hierarchical model for clustering m(6)A methylation peaks in MeRIP-seq data BMC Genomics 2016 Aug;. Welborn JP, Davis MG, Ebers SD, Stodden GR, Hayashi K, Cheatwood JL, Rao MK, MacLean JA 2nd. Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results in Impaired Male Fertility in Mice Biol Reprod 2015 Jul;. Cui X, Meng J, Rao MK, Chen Y, Huang Y. HEPeak: an HMM-based exome peak-finding package for RNA epigenome sequencing data BMC Genomics 2015 Apr;16 Su:2-2. Liu H, Flores MA, Meng J, Zhang L, Zhao X, Rao MK, Chen Y, Huang Y. MeT-DB: a database of transcriptome methylation in mammalian cells Nucleic Acids Res. (co-correponding author) 2015 Jan;. Rao MK. Hormone- and DNA Demethylation-Induced Relief of Tissue-Specific and Developmentally Regulated Promoter Proximal Pausing Journal of Biological Chemistry 2014 Dec;289(51). Meng J, Lu Z, Liu H, Zhang L, Zhang S, Chen Y, Rao MK, Huang Y. A protocol for RNA methylation differential analysis with MeRIP-Seq data and exomePeak R/Bioconductor package Methods 2014 Oct;69(3). Roy SS, Kumar GV, Bandyopadhyay A, Rao MK, Goodall G, Sun L, Tekmal RR, and Vadlamudi RK. Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast Cancer Oncogene 2014 Jul;33(28):3707-3716. Bansal H, Yihua Q, Ganapathy S, Penalva LO, Proia D, Tomlinson GE, Rao MK, Kornblau SM, Bansal S. Novel Oncogenic role for WTAP in acute myeloid leukemia Leukemia 2014 Jun;28(5):1171-1174. Mishra S, Deng JJ, Gowda PS, Rao MK, Chun-Lin Lin, Chun-Liang Chen, Huang T and Sun LZ. Androgen Receptor and MicroRNA-21 axis down-regulates transforming growth factor beta receptor II (TGFBR2) expression in Prostate Cancer Oncogene 2013 Jul;33(31):4097-4106. Yao-Fu Chang, Jennifer S. Lee-Chang, J. Saadi Imam, Kalyan Buddavarapu, Sarah S. Subaran, Amiya P. Sinha Hikim, Myriam Gorospe and Rao Manjeet K. . Interaction between miRNAs and actin associated protein Arpc5 regulate translation suppression in male germ cells Proc. Natl. Acad. Sci. USA 2012 Apr;109(15):5750-5755. Bansal H, Bansal S, Rao M, Foley KP, Sang J, Proia DA, Blackman RK, Ying W, Barsoum J, Baer MR, Kelly K, Swords R, Tomlinson GE, Battiwalla M, Giles FJ, Lee KP, Padmanabhan S. Heat shock protein 90 regulates the expression of Wilms tumor 1 protein in myeloid leukemias Blood 2010 Nov;116(22):4591-4599. Imam JS, Buddavarapu K, Lee-Chang JS, Ganapathy S, Camosy C, Chen Y, Rao MK. MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers Oncogene 2010 Sep;29(35):4971-4979. Bhardwaj A, Rao MK, Kaur R, Buttigieg MR, Wilkinson MF. GATA factors and androgen receptor collaborate to transcriptionally activate the Rhox5 homeobox gene in Sertoli cells Mol Cell Biol 2008 Apr;28(7):2138-2153. Rao MK, Pham J, Imam JS, MacLean JA, Murali D, Furuta Y, Sinha-Hikim AP, Wilkinson MF. Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis Genes Dev 2006 Jan;20(2):147-152. Maclean JA, Chen MA, Wayne CM, Bruce SR, Rao M, Meistrich ML, Macleod C, Wilkinson MF, Rao MK. Rhox: a new homeobox gene cluster Cell 2005 Feb;120(3):369-382. Rao MK, Wayne CM, Wilkinson MF. Pem homeobox gene regulatory sequences that direct androgen-dependent developmentally regulated gene expression in different subregions of the epididymis J Biol Chem 2002 Dec;277(50):48771-48778. Rao MK, Xu A, Narayanan N. Glucocorticoid modulation of protein phosphorylation and sarcoplasmic reticulum function in rat myocardium Am J Physiol Heart Circ Physiol 2001 Jul;281(1):325-333. Manjeet K R, Ghosh B, Rao MK. Quercetin inhibits LPS-induced nitric oxide and tumor necrosis factor-alpha production in murine macrophages Int J Immunopharmacol 1999 Jul;21(7):435-443.