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College of Pharmacy

College of Pharmacy

Faculty Profile

singh-ravi.jpgRavi K. Singh, Ph.D.

Assistant Professor of Pharmacology
Department of Pharmacological and Pharmaceutical Sciences

Office: 
University of Houston College of Pharmacy
Health 2, Room 5023
4349 Martin Luther King Boulevard
Houston, TX 77204-5017

Contact: rksingh4@central.uh.edu - 713-743-9770

Research Overview:

Our research aims to identify molecular mechanisms that promote postnatal cardiac and skeletal muscle growth, contractile function, and metabolic adaptations. We focus on alternative splicing, the process of selecting a different set of exons from a pre-mRNA to generate several unique mRNAs, resulting in multiple protein isoforms from a single gene. The human genome encodes fewer than 20,000 protein-coding genes, and alternative splicing greatly expands the proteomic capacity of the human genome. Notably, up to 1/3 of disease-causing mutations disrupt splicing or its regulation, including muscular dystrophies, cancers, and neurological diseases.

Over 90% of protein-coding genes are alternatively spliced, and the majority are spliced in a tissue-specific manner, i.e., brain, heart, skeletal muscle, etc. Many of these alternative exons are highly conserved and alternatively spliced during the postnatal period, suggesting a role for these alternate protein isoforms. However, the regulation and functional consequences of alternative splicing are still not fully understood. We hypothesize that alternative splicing plays a role in postnatal growth, contractile function, and metabolic adaptations in response to diet, exercise, and aging. The broad goals of our research are:

  • To identify mechanisms that regulate alternative splicing in heart and skeletal muscle. 
  • To determine the role of protein isoforms produced by alternative splicing in the context of development, disease, and aging.

Our research employs state-of-the-art techniques, including mouse genetics (classical and CRISPR-based), cell/molecular biology methods, transcriptome- and proteome-wide experimental and bioinformatic approaches. Our research aims to gain new insights that could be translated into novel therapeutics to treat diseases affected by splicing, prevent the decline of cardiac and skeletal muscle function with age, and improve the health span and overall quality of life.

  • Ph.D. in Molecular, Cellular and Developmental Biology, The Ohio State University, Columbus, Ohio
  • M.S. in Biotechnology, Madurai Kamaraj University, Madurai, TN, India
  • B.S. in Botany, Kirorimal College, University of Delhi, New Delhi, India

Publications

Google Scholar

Research and Review Articles

  • Comiskey DF, Montes M, Khurshid S, Singh RK, Chandler DS. SRSF2 regulation of MDM2 reveals splicing as a therapeutic vulnerability of the p53 pathway. Mol Cancer Res. 2019 Oct 29. pii: molcanres.0541.2019. doi: 10.1158/1541-7786.MCR-19-0541.
  • Singh RK*, Kolonin AM, Fiorotto ML, and Cooper TA*. Rbfox splicing factors maintain skeletal muscle mass by regulating calpain3 and proteostasis. Cell Reports. 2018 July 03; 24 (1): 197-208. Doi:10.1016/j.celrep.2018.06.017
  • Palacios G, Shaw T, Li Y, Singh RK, Valentine M, Sandlund JT, Lim MS, Mullighan CG, and Leventaki V. A new variant of Anaplastic Lymphoma Kinase (ALK) fusion in a case of Anaplastic Large Cell Lymphoma involving EEF1G, a subunit of the elongation factor-1 complex. Leukemia. 2017 Mar;31(3):743-747. doi: 10.1038/leu.2016.331.
  • Comiskey DF Jr, Jacob AG, Singh RK, Tapia-Santos AS, Chandler DS. Splicing factor SRSF1 negatively regulates alternative splicing of MDM2. Nucleic Acids Research 2015 Apr 30; 43(8):4202-18. doi: 10.1093/nar/gkv223.
  • Gennarino VA, Singh RK, White JJ, De Maio A, Han K, Kim JY, Jafar-Nejad P, di Ronza A, Kang H, Sayegh LS, Cooper TA, Orr HT, Sillitoe RV and Zoghbi HY. Pumilio1 haploinsufficiency leads to SCA1-like neurodegeneration by increasing wild-type ataxin1 levels. Cell, Mar 12;160(6):1087-98. doi: 10.1016/j.cell.2015.02.012.
  • Pedrotti S, Giudice J, Dagnino-Acosta A, Knoblauch M, Singh RK, Hanna A, Mo Q, Hicks J, Hamilton S, Cooper TA. The RNA-binding protein Rbfox1 regulates splicing required for skeletal muscle structure and function. Hum Mol Genet. 2015 Apr 15;24(8):2360-74. doi: 10.1093/hmg/ddv003.
  • Singh RK, Xia Z, Bland CS, Kalsotra A, Scavuzzo MA, Curk T, Ule J, Li W and Cooper TA. Rbfox2- coordinated alternative splicing of Mef2d and Rock2 controls myoblast fusion during myogenesis. Molecular Cell. 2014 Aug 21; 55(4): 592-603. doi:10.1016/j.molcel.2014.06.035.
  • Jacob AG§, Singh RK§, Comiskey DF Jr., Rouhier MF, Mohammad F, Bebee TW, Chandler DS. Stress induced alternative splice forms of MDM2 and MDMX modulate the p53-pathway in distinct ways. PLoS One, 2014 Aug 8;9(8):e104444. doi: 10.1371/journal.pone.0104444. eCollection 2014. (§- Co-first author).
  • Jacob AG, Singh RK, Mohammad F, Bebee TW, Chandler DS. The splicing factor FUBP1 is required for the efficient splicing of oncogene MDM2 premRNA. J Biol Chem. 2014 Jun 20; 289(25): 17350-17364. doi: 10.1074/jbc.M114.554717.5
  • Kalsotra A, Singh RK, Gurha P, Ward AJ, Creighton C and Cooper TA. Loss of Mef2 expression in myotonic dystrophy type 1 leads to altered miRNA and mRNA expression in heart. Cell Reports, 09 January 2014, doi: 10.1016/j.celrep.2013.12.025.
  • Jacob AG, O'Brien D, Singh RK, Comiskey DF Jr, Littleton RM, Mohammad F, Gladman JT, Widmann MC, Jeyaraj SC, Bolinger C, Anderson JR, Barkauskas DA, Boris-Lawrie K, Chandler DS. Stress-induced Isoforms of MDM2 and MDM4 Correlate with High-Grade Disease and an Altered Splicing Network in Pediatric Rhabdomyosarcoma. Neoplasia. 2013 Sep; 15(9): 1049-63. doi: 10.1593/neo.13286.
  • Singh RK, Cooper TA. Pre-mRNA splicing in disease and therapeutics. Trends Mol Med. 2012 Aug; 18(8): 472-82. doi: 10.1016/j.molmed.2012.06.006. 
  • Singh RK, Tapia-Santos A, Bebee TW, and Chandler DS. Conserved sequences in the final intron of MDM2 are essential for the regulation of alternative splicing of MDM2 in response to stress. Exp Cell Res. 2009; 315(19): 3419-32. doi: http://dx.doi.org/10.1016/j.yexcr.2009.07.017.
  • Wang H, Garzon R, Sun H, Ladner KJ, Singh RK, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC. NF-kappaB-YY1- miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell. 2008 Nov 4; 14(5): 369-81. doi: 10.1016/j.ccr.2008.10.006.
  • Chandler DS, Singh RK, Caldwell LC, Bitler JL, and Lozano G. Genotoxic stress induces coordinately regulated alternative splicing of the p53 modulators MDM2 and MDM4. Cancer Research, 2006, 66:9502-9508. doi: 10.1158/0008- 5472.CAN-05-4271.
  • Ray P, Malik J, Singh RK, Bhatnagar S, Bahl R, Kumar R, Bhan MK (2003) Rotavirus nonstructural protein NSP4 induces heterotypic antibody responses during natural infection in children. J Infectious Disease 187 (11): 1786-93. doi: 10.1086/375243.

Awards & Honors

  • 2023 Awarded R21 grant from NIH
  • 2022 Teaching pin awarded for facilitating the Molecular and Cellular Research (MCR) Pathway discussions for medical students at Medical College of Wisconsin
  • 2020 Pilot grant from Research Affairs Committee, Medical College of Wisconsin
  • 2019 Pilot Innovative Research award, Children’s Research Institute, Wisconsin
  • 2015-19 Scientist Development Award from the American Heart Association
  • 2012-14 Postdoctoral Fellowship from the American Heart Association