Tamer Mohamed

Assistant Professor of Medicine

Department of Medicine, Division of Cardiovascular Medicine


502-852-8428

Education and Training:

Ph.D.: University of Manchester, Cardiovascular and Molecular Medicine
Postdoctoral Fellowship: Gladstone Institutes (San Francisco)

Research Interests

My main research interest is to identify novel therapies for heart failure focusing on endogenous heart repair and regeneration mechanisms. As a pharmacist by training and the unique combination of academic and industry experience, my major aim is to perform translational research which directly benefits heart failure patients.

During my research endeavors, I have studied novel mechanisms and therapies for cardiac hypertrophy and heart failure in animal models. During my doctoral and first postdoctoral training, I identified the role of the plasma membrane calcium ATPase isoform 4 (PMCA4) in cardiac physiology and pathophysiology.

As a pharmacist, I have a special interest in translating my findings into human drug therapies for heart disease. Thus, I started screening drugs to identify the first specific inhibitor for PMCA4, which could then be used as a novel treatment for cardiac hypertrophy and heart failure. Recently, in collaboration with the Fraunhofer Institute in Germany, the Medical Research Council in the UK, and the drug company Astra Zeneca, we created a program to identify new drugs that treat heart failure by targeting PMCA4.

To expand my expertise in cardiac regeneration, I joined Prof. Deepak Srivastava's laboratory at the Gladstone Institutes in August 2013. In the Srivastava lab I acquired training on cutting-edge technology for direct cardiac reprogramming, and profiling single-cell genomes and epigenomes during the reprogramming process. The skills that I have learned while working with Prof. Srivastava will be invaluable to running my independent laboratory.

I worked on two parallel approaches to induce endogenous heart repair: direct cardiac reprogramming and inducing cardiomyocyte proliferation. Both approaches were highly successful. The direct reprogramming project was highly recognized by our scientific community, as it was awarded a Scientist Development Grant award from the American Heart Association, manuscript was published in Circulationand this work was chosen as finalist at the Louis N. and Arnold M. Katz Basic Science Research Prize for Young Investigators from the AHA in 2016.

In addition, the cardiomyocyte proliferation project was accepted for publication in Cell and awarded the March 22, 2018 issue cover for the journal. In October 2016 Dr. Srivastava has founded a new start up (Tenaya Therapeutics) with $50 million investment from the column group to develop new therapies for heart failure based on my findings. Therefore, I was the first scientist recruited to the company to lead the efforts of direct cardiac reprogramming where I enjoyed the unique industry experience in building a start up from scratch.

In Tenaya I was able to establish novel system for long term culture of human heart slices and efficiently demonstrating direct cardiac reprogramming in such pre-clinical models. In addition, I was able to reduce the number of essential reprogramming factors in human cardiac fibroblasts to 3 essential factors where they are now under pre-clinical testing for in vivo efficiency in large animals (pigs). Due to the quick success in Tenaya, the research and development section ended very soon and now the major focus on scaling up viral manufacturing and filing IND which is away from my interest.

Therefore, I have decided to go back to academia to initiate new discoveries to treat heart failure mainly focusing on understanding the reprogramming process and cell cycle regulation of cardiomyocyte proliferation.

 

Featured Publications

  • Mohamed TMA, Ang YS, Radzinsky E, Zhou P, Huang Y, Elfenbein A, Foley A, Magnitsky S, Srivastava D. Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration. Cell. 2018 Mar 22;173(1):104-116.e12. doi: 10.1016/j.cell.2018.02.014. Epub 2018 Mar 1. PubMed PMID: 29502971; PubMed Central PMCID: PMC5973786.
  • Hegab Z, Mohamed TMA, Stafford N, Mamas M, Cartwright EJ, Oceandy D. Advanced glycation end products reduce the calcium transient in cardiomyocytes by increasing production of reactive oxygen species and nitric oxide. FEBS Open Bio. 2017 Sep 26;7(11):1672-1685. doi: 10.1002/2211-5463.12284. eCollection 2017 Nov. PubMed PMID: 29123976; PubMed Central PMCID: PMC5666397.
  • Robertson A, Mohamed TM, El Maadawi Z, Stafford N, Bui T, Lim DS, Cartwright EJ, Oceandy D. Genetic ablation of the mammalian sterile-20 like kinase 1 (Mst1) improves cell reprogramming efficiency and increases induced pluripotent stem cell proliferation and survival. Stem Cell Res. 2017 Apr;20:42-49. doi: 10.1016/j.scr.2017.02.011. Epub 2017 Feb 27. PubMed PMID: 28257933; PubMed Central PMCID: PMC5376382.
  • Mohamed TM, Stone NR, Berry EC, Radzinsky E, Huang Y, Pratt K, Ang YS, Yu P, Wang H, Tang S, Magnitsky S, Ding S, Ivey KN, Srivastava D. Chemical Enhancement of In Vitro and In Vivo Direct Cardiac Reprogramming. Circulation. 2017 Mar 7;135(10):978-995. doi: 10.1161/CIRCULATIONAHA.116.024692. Epub 2016 Nov 10. PubMed PMID: 27834668; PubMed Central PMCID: PMC5340593.
  • Ang YS, Rivas RN, Ribeiro AJS, Srivas R, Rivera J, Stone NR, Pratt K, Mohamed TMA, Fu JD, Spencer CI, Tippens ND, Li M, Narasimha A, Radzinsky E, Moon-Grady AJ, Yu H, Pruitt BL, Snyder MP, Srivastava D. Disease Model of GATA4 Mutation Reveals Transcription Factor Cooperativity in Human Cardiogenesis. Cell. 2016 Dec 15;167(7):1734-1749.e22. doi: 10.1016/j.cell.2016.11.033. PubMed PMID: 27984724; PubMed Central PMCID: PMC5180611.
  • Huebsch N, Loskill P, Deveshwar N, Spencer CI, Judge LM, Mandegar MA, Fox CB, Mohamed TM, Ma Z, Mathur A, Sheehan AM, Truong A, Saxton M, Yoo J, Srivastava D, Desai TA, So PL, Healy KE, Conklin BR. Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses. Sci Rep. 2016 Apr 20;6:24726. doi: 10.1038/srep24726. PubMed PMID: 27095412; PubMed Central PMCID: PMC4837370.
  • Mohamed TM, Abou-Leisa R, Stafford N, Maqsood A, Zi M, Prehar S, Baudoin-Stanley F, Wang X, Neyses L, Cartwright EJ, Oceandy D. The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy. Nat Commun. 2016 Mar 29;7:11074. doi: 10.1038/ncomms11074. PubMed PMID: 27020607; PubMed Central PMCID: PMC4820544.
  • Ribeiro AJ, Ang YS, Fu JD, Rivas RN, Mohamed TM, Higgs GC, Srivastava D, Pruitt BL. Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness. Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):12705-10. doi: 10.1073/pnas.1508073112. Epub 2015 Sep 28. PubMed PMID: 26417073; PubMed Central PMCID: PMC4611612.
  • Baggott RR, Alfranca A, López-Maderuelo D, Mohamed TM, Escolano A, Oller J, Ornes BC, Kurusamy S, Rowther FB, Brown JE, Oceandy D, Cartwright EJ, Wang W, Gómez-del Arco P, Martínez-Martínez S, Neyses L, Redondo JM, Armesilla AL. Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin. Arterioscler Thromb Vasc Biol. 2014 Oct;34(10):2310-20. doi: 10.1161/ATVBAHA.114.304363. Epub 2014 Aug 21. PubMed PMID: 25147342.
  • Zi M, Maqsood A, Prehar S, Mohamed TM, Abou-Leisa R, Robertson A, Cartwright EJ, Ray SG, Oh S, Lim DS, Neyses L, Oceandy D. The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy. J Biol Chem. 2014 Aug 29;289(35):24275-88. doi: 10.1074/jbc.M114.562405. Epub 2014 Jul 17. PubMed PMID: 25035424; PubMed Central PMCID: PMC4148857.
  • Mohamed TM, Zi M, Prehar S, Maqsood A, Abou-Leisa R, Nguyen L, Pfeifer GP, Cartwright EJ, Neyses L, Oceandy D. The tumour suppressor Ras-association domain family protein 1A (RASSF1A) regulates TNF-α signalling in cardiomyocytes. Cardiovasc Res. 2014 Jul 1;103(1):47-59. doi: 10.1093/cvr/cvu111. Epub 2014 Apr 28. PubMed PMID: 24776599; PubMed Central PMCID: PMC4207857.
  • Mohamed TM, Abou-Leisa R, Baudoin F, Stafford N, Neyses L, Cartwright EJ, Oceandy D. Development and characterization of a novel fluorescent indicator protein PMCA4-GCaMP2 in cardiomyocytes. J Mol Cell Cardiol. 2013 Oct;63:57-68. doi: 10.1016/j.yjmcc.2013.07.007. Epub 2013 Jul 21. PubMed PMID: 23880607.
  • Mohamed TM, Zakeri SA, Baudoin F, Wolf M, Oceandy D, Cartwright EJ, Gul S, Neyses L. Optimisation and validation of a high throughput screening compatible assay to identify inhibitors of the plasma membrane calcium ATPase pump--a novel therapeutic target for contraception and malaria. J Pharm Pharm Sci. 2013;16(2):217-30. PubMed PMID: 23958191.
  • Baggott RR, Mohamed TM, Oceandy D, Holton M, Blanc MC, Roux-Soro SC, Brown S, Brown JE, Cartwright EJ, Wang W, Neyses L, Armesilla AL. Disruption of the interaction between PMCA2 and calcineurin triggers apoptosis and enhances paclitaxel-induced cytotoxicity in breast cancer cells. Carcinogenesis. 2012 Dec;33(12):2362-8. doi: 10.1093/carcin/bgs282. Epub 2012 Sep 7. PubMed PMID: 22962307.
  • Mohamed TM, Oceandy D, Zi M, Prehar S, Alatwi N, Wang Y, Shaheen MA, Abou-Leisa R, Schelcher C, Hegab Z, Baudoin F, Emerson M, Mamas M, Di Benedetto G, Zaccolo M, Lei M, Cartwright EJ, Neyses L. Plasma membrane calcium pump (PMCA4)-neuronal nitric-oxide synthase complex regulates cardiac contractility through modulation of a compartmentalized cyclic nucleotide microdomain. J Biol Chem. 2011 Dec 2;286(48):41520-9. doi: 10.1074/jbc.M111.290411. Epub 2011 Sep 29. PubMed PMID: 21965681; PubMed Central PMCID: PMC3308863.
  • Egom EE, Mohamed TM, Mamas MA, Shi Y, Liu W, Chirico D, Stringer SE, Ke Y, Shaheen M, Wang T, Chacko S, Wang X, Solaro RJ, Fath-Ordoubadi F, Cartwright EJ, Lei M. Activation of Pak1/Akt/eNOS signaling following sphingosine-1-phosphate release as part of a mechanism protecting cardiomyocytes against ischemic cell injury. Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1487-95. doi: 10.1152/ajpheart.01003.2010. Epub 2011 Jun 24. PubMed PMID: 21705677; PubMed Central PMCID: PMC3197364.
  • Oceandy D, Mohamed TM, Cartwright EJ, Neyses L. Local signals with global impacts and clinical implications: lessons from the plasma membrane calcium pump (PMCA4). Biochim Biophys Acta. 2011 May;1813(5):974-8. doi: 10.1016/j.bbamcr.2010.12.007. Epub 2010 Dec 15. Review. PubMed PMID: 21167220.
  • Cartwright EJ, Mohamed T, Oceandy D, Neyses L. Calcium signaling dysfunction in heart disease. Biofactors. 2011 May-Jun;37(3):175-81. doi: 10.1002/biof.149. Epub 2011 Jun 14. Review. PubMed PMID: 21674639.
  • Holton M, Mohamed TM, Oceandy D, Wang W, Lamas S, Emerson M, Neyses L, Armesilla AL. Endothelial nitric oxide synthase activity is inhibited by the plasma membrane calcium ATPase in human endothelial cells. Cardiovasc Res. 2010 Aug 1;87(3):440-8. doi: 10.1093/cvr/cvq077. Epub 2010 Mar 7. PubMed PMID: 20211863; PubMed Central PMCID: PMC2904661.
  • Egom EE, Ke Y, Musa H, Mohamed TM, Wang T, Cartwright E, Solaro RJ, Lei M. FTY720 prevents ischemia/reperfusion injury-associated arrhythmias in an ex vivo rat heart model via activation of Pak1/Akt signaling. J Mol Cell Cardiol. 2010 Feb;48(2):406-14. doi: 10.1016/j.yjmcc.2009.10.009. Epub 2009 Oct 21. PubMed PMID: 19852968; PubMed Central PMCID: PMC3102016.
  • Mohamed TM, Baudoin-Stanley FM, Abou-Leisa R, Cartwright E, Neyses L, Oceandy D. Measurement of plasma membrane calcium-calmodulin-dependent ATPase (PMCA) activity. Methods Mol Biol. 2010;637:333-42. doi: 10.1007/978-1-60761-700-6_18. PubMed PMID: 20419444.
  • Oceandy D, Pickard A, Prehar S, Zi M, Mohamed TM, Stanley PJ, Baudoin-Stanley F, Nadif R, Tommasi S, Pfeifer GP, Armesilla AL, Cartwright EJ, Neyses L. Tumor suppressor Ras-association domain family 1 isoform A is a novel regulator of cardiac hypertrophy. Circulation. 2009 Aug 18;120(7):607-16. doi: 10.1161/CIRCULATIONAHA.109.868554. Epub 2009 Aug 3. PubMed PMID: 19652091.
  • Mohamed TM, Oceandy D, Prehar S, Alatwi N, Hegab Z, Baudoin FM, Pickard A, Zaki AO, Nadif R, Cartwright EJ, Neyses L. Specific role of neuronal nitric-oxide synthase when tethered to the plasma membrane calcium pump in regulating the beta-adrenergic signal in the myocardium. J Biol Chem. 2009 May 1;284(18):12091-8. doi: 10.1074/jbc.M809112200. Epub 2009 Mar 10. PubMed PMID: 19278978; PubMed Central PMCID: PMC2673278.
  • Holton M, Yang D, Wang W, Mohamed TM, Neyses L, Armesilla AL. The interaction between endogenous calcineurin and the plasma membrane calcium-dependent ATPase is isoform specific in breast cancer cells. FEBS Lett. 2007 Aug 21;581(21):4115-9. Epub 2007 Jul 31. PubMed PMID: 17689535.
  • Williams JC, Armesilla AL, Mohamed TM, Hagarty CL, McIntyre FH, Schomburg S, Zaki AO, Oceandy D, Cartwright EJ, Buch MH, Emerson M, Neyses L. The sarcolemmal calcium pump, alpha-1 syntrophin, and neuronal nitric-oxide synthase are parts of a macromolecular protein complex. J Biol Chem. 2006 Aug 18;281(33):23341-8. Epub 2006 May 30. PubMed PMID: 1673550.