Areas of Interest
More than 5 million adults have heart failure in the United States today. With an economic cost estimated at 30 billion per year, heart failure is on the rise. Heart failure can be managed by treatment with drugs but unfortunately has no cure. Our research focuses on understanding genetic and epigenetic mechanisms controlling heart failure. We use comprehensive technologies including in vitro transcription from chromatin templates, iPSC-cardiomyocytes, primary cardiomyocytes and genetically modified mice to understand intracellular signaling pathways, transcriptional regulatory networks and epigenetic events altered in the failing heart. Our long-term goal is to identify new pathways regulating this major cardiac disease to use this information for the development of therapies that will improve patients’ health.
- Epigenetic mechanisms regulating heart failure
Heart failure occurs when the heart can no longer pump blood efficiently to distribute it to the different organs of the body. One exciting ongoing area of research is on heart failure mechanisms at the “epigenetic level”. Genetic information is stored in our DNA, wrapped around histones, which form chromatin. The role of chromatin is to condense DNA in the confined space of the cell nucleus. We now know that chromatin is “fluid” and undergoes dynamic changes from an “open” to a “close” status which can turn genes “on” or “off” in specific parts of the genome. We are discovering protein complexes that are critical for the maintenance of chromatin conformation. Under stress condition, chromatin regulators can be altered, which can cause chromatin to adopt the wrong conformation and activate the wrong set of genes. This abnormal epigenetic process can lead to major cardiac pathologies such as heart failure. Our goal is to identify cardiac epigenetic factors critical for heart homeostasis and understand how their dysregulation leads to heart failure.
- Genetic mutations causing various forms of cardiomyopathy
Heart failure can be caused by genetic mutations. We have discovered the first missense homozygous mutation in FBXO32 (also known as Atrogin-1) that causes dilated cardiomyopathy in humans by disrupting the integrity of a large protein complex named Skp1/Cul1/Fbox (SCF). Patients carrying this mutation develop advanced heart failure at a very young age. We are using CRISPR/Cas9 gene editing technology to reconstitute the mutation in human induced pluripotent stem cells (hiPSCs). hiPSCs can be re-programmed into embryonic-stem-cell like cells and then differentiated into different cell types for example cardiomyocytes. This “disease in a dish” model system allows us to compare the morphology, function and biochemical properties of the “normal” and “mutant” iPSC-cardiomyocytes, to ultimately understand how the FBXO32 mutation causes cardiomyopathy. Using this system, we can test novel or existing drugs, for their ability to prevent or reverse the cardiac defects due to the FBXO32 mutation. This is one step closer to precision medicine, an approach to patient care that is revolutionizing medicine.
- Cardiac epigenetics
- Genetic mutations causing dilated cardiomyopathy
- Transcriptional assays
- “Omics” technology
- iPSC-cardiomyocytes to model disease
- 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.
PhD Ph.D. with Highest Distinction
Université Joseph Fourier, Grenoble, France
Awards & Fundings
Dr Poizat is the recipient of several awards and grants from the Philippe Foundation Inc., New York;
the American Heart Association; the Wright Foundation Research of the USC Keck School of Medicine, Los Angeles, NIH/NHLBI and King Abdulaziz City for Science and Technology (KACST), Riyadh.
Coralie Poizat, Ph.D.
Associate Professor of Biomedical Research
and Translational Medicine
Other Professional Titles
Associate Research Professor (Adjunct)
Biology Department, San Diego State University, San Diego, CA
Dr. Poizat’s research aims at understanding molecular genetic and epigenetic changes of heart failure which remains a major cause of death worldwide.
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.
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.
- Associate Professor, Masonic Medical Research Institute, Utica, NY
- Adjunct Associate Research Professor, Biology Department, San Diego State University, San Diego, CA
- Maya Hammonds