Coralie Poizat, Ph.D.

Areas of Interest

    Our research focus on understanding molecular genetic and epigenetic mechanisms regulating major cardiovascular disorders, more specifically heart failure and inherited cardiomyopathies. We focus on intracellular signaling pathways, transcriptional regulatory networks and epigenetic events altered in the diseased heart. We use comprehensive novel technologies in cellular systems, genetically modified mice and human heart specimen. The long-term goal is to identify new pathways regulating major cardiac abnormalities to use this information for the development of therapies that will improve patients’ health.

 

Lab focus

  • Identify novel epigenetic regulators implicated in cardiac hypertrophy and heart failure development.
  • How the most abundant nuclear isoform of Calcium/calmodulin-dependent protein kinase II delta (CaMKIId) couples calcium signals to the genome to remodel chromatin and activate transcription.
  • Discover new genetic mutations causing dilated cardiomyopathy in human.
  • Decipher the functional role of the Low Molecular Weight Protein Tyrosine Phosphatase (Lmptp) in the cardiovascular system.

 

Achievements

  • Uncovered a novel function of CaMKII as an epigenetic enzyme by showing that CaMKII directly signals to histone H3 to remodel chromatin and activate cardiac hypertrophy.
  • Identified a novel mutation in PHC1, a member of the Polycomb group of genes, causing Primary Microcephaly by a new mechanism involving defect in cell cycle and DNA repair pathways.
  • Characterized the first mouse model deficient for a protein tyrosine phosphatase named Lmptp which revealed a protective phenotype of the knockout mice against pathological cardiac stress.
  • Discovered FBXO32 as a new cardiomyopathy gene in human. Showed that the mutation impairs the assembly of the SCF (Skp1-Cul1-F box) E3 ubiquitin ligase complex, resulting in abnormal autophagy and heart failure.

 

Research Associate Professor

Other Professional Titles Associate Research Professor Biology Department San Diego State University, San Diego Adjunct Principle Scientist King Faisal Specialist Hospital & Research Centre Riyadh, Saudi Arabia (Part-time)

Email: cpoizat@mmri.edu Phone: (315) 624-7482

 

 

 

 

Research Interest

    Dr Poizat’s research aims at understanding molecular, genetic and epigenetic changes controlling cardiac hypertrophy and heart failure which remain a major cause of death worldwide.

 

Accomplishments

    Prior to joining the Masonic Medical Research Institute, Dr Poizat was the Director of the Cardiovascular Research Program at King Faisal Specialist Hospital & Research Centre in Riyadh, a leading institution in the Middle East. Research from her laboratory contributed to the advancement of cardiovascular human genetics and to epigenetic and signaling mechanisms implicated in heart failure.

 

Training

    A native of France, Dr Poizat obtained her Ph.D. at the University Joseph Fourier in Grenoble, France. She then joined the laboratory of Larry Kedes at the USC Keck School of Medicine in Los Angeles to pursue post-doctoral studies in molecular genetics and transcriptional regulation.

 

Affiliations

  • American Heart Association
  • Editorial Activity for: Nucleic Acid Research, Stem Cell Reports and other cardiovascular journals.

 

Professional Titles

  • Research Associate Professor, Masonic Medical Research Institute, Utica, NY
  • Adjunct Associate Research Professor, Biology Department, San Diego State University
  • Adjunct Principle Scientist, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

 

Education

PhD Universite Joseph Fourier, France

Honors & Awards

  • 1993 Ph.D. with Highest Distinction
  • 1993 Research Fellowship Award, Foundation for Medical Research, France
  • 1995-1996 Research Fellowship, Philippe Foundation Inc., New York
  • 1996 Recipient of the 1996 Clifford & Evelyn Cherry Fellowship Award, American Heart Association, Los Angeles, CA
  • 2002 – 2004 Beginning Grant-in-Aid, American Heart Association, Western States Affiliate
  • 2004-2005 Wright Foundation Research Award, USC Keck School of Medicine,Los Angeles, CA

  1. Wade, F, Belhaj, K, Poizat, C. Protein tyrosine phosphatases in cardiac physiology and pathophysiology. Heart Fail Rev. 2018;23 (2):261-272. doi: 10.1007/s10741-018-9676-1. PubMed PMID:29396779 PubMed Central PMC5861171.
  2. Pharaon, LF, El-Orabi, NF, Kunhi, M, Al Yacoub, N, Awad, SM, Poizat, C et al.. Rosiglitazone promotes cardiac hypertrophy and alters chromatin remodeling in isolated cardiomyocytes. Toxicol. Lett. 2017;280 :151-158. doi: 10.1016/j.toxlet.2017.08.011. PubMed PMID:28822817 .
  3. Al-Onazi, AS, Al-Rasheed, NM, Attia, HA, Al-Rasheed, NM, Ahmed, RM, Al-Amin, MA et al.. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways. J. Pharm. Pharmacol. 2016;68 (2):219-32. doi: 10.1111/jphp.12504. PubMed PMID:26817709 .
  4. Al-Yacoub, N, Shaheen, R, Awad, SM, Kunhi, M, Dzimiri, N, Nguyen, HC et al.. FBXO32, encoding a member of the SCF complex, is mutated in dilated cardiomyopathy. Genome Biol. 2016;17 :2. doi: 10.1186/s13059-015-0861-4. PubMed PMID:26753747 PubMed Central PMC4707779.
  5. Alazami, AM, Awad, SM, Coskun, S, Al-Hassan, S, Hijazi, H, Abdulwahab, FM et al.. TLE6 mutation causes the earliest known human embryonic lethality. Genome Biol. 2015;16 :240. doi: 10.1186/s13059-015-0792-0. PubMed PMID:26537248 PubMed Central PMC4634911.
  6. Quijada, P, Hariharan, N, Cubillo, JD, Bala, KM, Emathinger, JM, Wang, BJ et al.. Nuclear Calcium/Calmodulin-dependent Protein Kinase II Signaling Enhances Cardiac Progenitor Cell Survival and Cardiac Lineage Commitment. J. Biol. Chem. 2015;290 (42):25411-26. doi: 10.1074/jbc.M115.657775. PubMed PMID:26324717 PubMed Central PMC4646189.
  7. Wade, F, Quijada, P, Al-Haffar, KM, Awad, SM, Kunhi, M, Toko, H et al.. Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress-induced cardiomyopathy. J. Pathol. 2015;237 (4):482-94. doi: 10.1002/path.4594. PubMed PMID:26213100 PubMed Central PMC5049627.
  8. Shinwari, JM, Khan, A, Awad, S, Shinwari, Z, Alaiya, A, Alanazi, M et al.. Recessive mutations in COL25A1 are a cause of congenital cranial dysinnervation disorder. Am. J. Hum. Genet. 2015;96 (1):147-52. doi: 10.1016/j.ajhg.2014.11.006. PubMed PMID:25500261 PubMed Central PMC4289688.
  9. Awad, S, Al-Haffar, KM, Marashly, Q, Quijada, P, Kunhi, M, Al-Yacoub, N et al.. Control of histone H3 phosphorylation by CaMKIIδ in response to haemodynamic cardiac stress. J. Pathol. 2015;235 (4):606-18. doi: 10.1002/path.4489. PubMed PMID:25421395 PubMed Central PMC4383650.
  10. Shareef, MA, Anwer, LA, Poizat, C. Cardiac SERCA2A/B: therapeutic targets for heart failure. Eur. J. Pharmacol. 2014;724 :1-8. doi: 10.1016/j.ejphar.2013.12.018. PubMed PMID:24361307 .
  11. Shaheen, R, Shamseldin, HE, Loucks, CM, Seidahmed, MZ, Ansari, S, Ibrahim Khalil, M et al.. Mutations in CSPP1, encoding a core centrosomal protein, cause a range of ciliopathy phenotypes in humans. Am. J. Hum. Genet. 2014;94 (1):73-9. doi: 10.1016/j.ajhg.2013.11.010. PubMed PMID:24360803 PubMed Central PMC3882732.
  12. Mahmoud, SA, Poizat, C. Epigenetics and chromatin remodeling in adult cardiomyopathy. J. Pathol. 2013;231 (2):147-57. doi: 10.1002/path.4234. PubMed PMID:23813473 PubMed Central PMC4285861.
  13. Awad, S, Kunhi, M, Little, GH, Bai, Y, An, W, Bers, D et al.. Nuclear CaMKII enhances histone H3 phosphorylation and remodels chromatin during cardiac hypertrophy. Nucleic Acids Res. 2013;41 (16):7656-72. doi: 10.1093/nar/gkt500. PubMed PMID:23804765 PubMed Central PMC3763528.
  14. Awad, S, Al-Dosari, MS, Al-Yacoub, N, Colak, D, Salih, MA, Alkuraya, FS et al.. Mutation in PHC1 implicates chromatin remodeling in primary microcephaly pathogenesis. Hum. Mol. Genet. 2013;22 (11):2200-13. doi: 10.1093/hmg/ddt072. PubMed PMID:23418308 .
  15. Innocenzi, A, Latella, L, Messina, G, Simonatto, M, Marullo, F, Berghella, L et al.. An evolutionarily acquired genotoxic response discriminates MyoD from Myf5, and differentially regulates hypaxial and epaxial myogenesis. EMBO Rep. 2011;12 (2):164-71. doi: 10.1038/embor.2010.195. PubMed PMID:21212806 PubMed Central PMC3049428.
  16. Little, GH, Saw, A, Bai, Y, Dow, J, Marjoram, P, Simkhovich, B et al.. Critical role of nuclear calcium/calmodulin-dependent protein kinase IIdeltaB in cardiomyocyte survival in cardiomyopathy. J. Biol. Chem. 2009;284 (37):24857-68. doi: 10.1074/jbc.M109.003186. PubMed PMID:19602725 PubMed Central PMC2757189.
  17. Little, GH, Bai, Y, Williams, T, Poizat, C. Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells. J. Biol. Chem. 2007;282 (10):7219-31. doi: 10.1074/jbc.M604281200. PubMed PMID:17179159 .
  18. Mao, C, Tai, WC, Bai, Y, Poizat, C, Lee, AS. In vivo regulation of Grp78/BiP transcription in the embryonic heart: role of the endoplasmic reticulum stress response element and GATA-4. J. Biol. Chem. 2006;281 (13):8877-87. doi: 10.1074/jbc.M505784200. PubMed PMID:16452489 .
  19. Poizat, C, Puri, PL, Bai, Y, Kedes, L. Phosphorylation-dependent degradation of p300 by doxorubicin-activated p38 mitogen-activated protein kinase in cardiac cells. Mol. Cell. Biol. 2005;25 (7):2673-87. doi: 10.1128/MCB.25.7.2673-2687.2005. PubMed PMID:15767673 PubMed Central PMC1061628.
  20. Kedes, L, Kloner, R, Kong, K, Poizat, C, Simkhovich, B, Iso, T et al.. New cellular and molecular approaches for the treatment of cardiac disease. Semin. Nephrol. 2004;24 (5):437-40. . PubMed PMID:15490406 .
  21. Simkhovich, BZ, Marjoram, P, Poizat, C, Kedes, L, Kloner, RA. Age-related changes of cardiac gene expression following myocardial ischemia/reperfusion. Arch. Biochem. Biophys. 2003;420 (2):268-78. . PubMed PMID:14654066 .
  22. Simkhovich, BZ, Marjoram, P, Poizat, C, Kedes, L, Kloner, RA. Brief episode of ischemia activates protective genetic program in rat heart: a gene chip study. Cardiovasc. Res. 2003;59 (2):450-9. . PubMed PMID:12909328 .
  23. Simkhovich, BZ, Kloner, RA, Poizat, C, Marjoram, P, Kedes, LH. Gene expression profiling--a new approach in the study of myocardial ischemia. Cardiovasc. Pathol. ;12 (4):180-5. . PubMed PMID:12826286 .
  24. Simkhovich, BZ, Abdishoo, S, Poizat, C, Hale, SL, Kedes, LH, Kloner, RA et al.. Gene activity changes in ischemically preconditioned rabbit heart gene: discovery array study. Heart Dis. ;4 (2):63-9. . PubMed PMID:11975836 .
  25. Iso, T, Sartorelli, V, Poizat, C, Iezzi, S, Wu, HY, Chung, G et al.. HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling. Mol. Cell. Biol. 2001;21 (17):6080-9. . PubMed PMID:11486045 PubMed Central PMC87325.
  26. Poizat, C, Sartorelli, V, Chung, G, Kloner, RA, Kedes, L. Proteasome-mediated degradation of the coactivator p300 impairs cardiac transcription. Mol. Cell. Biol. 2000;20 (23):8643-54. . PubMed PMID:11073966 PubMed Central PMC86467.
  27. Jeyaseelan, R, Poizat, C, Baker, RK, Abdishoo, S, Isterabadi, LB, Lyons, GE et al.. A novel cardiac-restricted target for doxorubicin. CARP, a nuclear modulator of gene expression in cardiac progenitor cells and cardiomyocytes. J. Biol. Chem. 1997;272 (36):22800-8. . PubMed PMID:9278441 .
  28. Jeyaseelan, R, Poizat, C, Wu, HY, Kedes, L. Molecular mechanisms of doxorubicin-induced cardiomyopathy. Selective suppression of Reiske iron-sulfur protein, ADP/ATP translocase, and phosphofructokinase genes is associated with ATP depletion in rat cardiomyocytes. J. Biol. Chem. 1997;272 (9):5828-32. . PubMed PMID:9038198 .
  29. Poizat, C, Grably, S, Cuchet, P, Keriel, C. Relationship between heart function and energy production. A study on isolated rat heart. Arch. Physiol. Biochem. 1996;104 (1):71-80. doi: 10.1076/apab.104.1.71.12874 . PubMed PMID:8724883 .
  30. Poizat, C, Keriel, C, Cuchet, P. Is oxygen supply sufficient to induce normoxic conditions in isolated rat heart?. Basic Res. Cardiol. ;89 (6):535-44. . PubMed PMID:7702542 .
  31. Poizat, C, Keriel, C, Garnier, A, Dubois, F, Cand, F, Cuchet, P et al.. An experimental model of hypoxia on isolated rat heart in recirculating system: study of fatty acid metabolism with an iodinated fatty acid. Arch Int Physiol Biochim Biophys. ;101 (6):347-56. . PubMed PMID:7511427 .
  32. Garnier, A, Poizat, C, Keriel, C, Cuchet, P, Vork, MM, de Jong, YF et al.. Modulation of fatty acid-binding protein content of adult rat heart in response to chronic changes in plasma lipid levels. Mol. Cell. Biochem. ;123 (1-2):107-12. . PubMed PMID:8232251 .
  33. Garnier, A, Dubois, F, Keriel, C, Poizat, C, Cand, F, Cuchet, P et al.. Influence of fatty acid backdiffusion on compartmental analysis of external detection curves obtained with 123-iodohexadecenoic acid in isolated rat heart. Nucl. Med. Biol. 1993;20 (3):297-306. . PubMed PMID:8485489 .
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