News/Recent Awards

Cardiovascular Research Center Honors/Awards


Hajjar, Roger:



2016: Chair, Keystone Meeting, RNA Based Approaches in Cardiovascular Diseases

2016: Chair, NHLBI Special Emphasis Panel

2017: Thomas W. Smith Memorial Lecturer, American Heart Association’s Council on Basic Cardiovascular Sciences

2017: George and Angelina Kostas Research Center for Cardiovascular Nanomedicine Annual International Meeting


Fargnoli, Anthony


2016: Outstanding Merit Designation at the 2017 conference for the Cardiovascular and Pulmonary Disease Section.  I was first author and presented earlier in May and won 1st prize for this session/category – Session 3 May 12th.
Fish, Kenneth:


2016: Journal of the American College of Cardiology Simon Dack Award for Outstanding Scholarship


Giannarelli, Chiara:


2016: Junior Faculty Translational Collaborative Research Initiative Award, Department of Medicine, Icahn School of Medicine at Mount Sinai


2016: C1-HT_mRNA-Seq, Single Cell Seq Award, Fluidigm and Icahn School of Medicine at Mount Sinai


Ishikawa, Kiyotake:


2016:   The Richard J. Bing Award for Young Investigators, International Society for Heart Research World Congress

2016    A-CURE Symposium, Research Merit Scholarship


Kovacic, Jason:


2017    Admission into Mount Sinai LEAD Academy (Leadership Emerging in Academic Departments)


Sahoo, Susmita:


2017: The Dr. Harold and Golden Lamport Research Award


Zangi, Lior:


2017: Selected as Cover of the Journal of the American Society of Gene & Cell Therapy: Molecular Therapy, June 7, 2017, Volume 25, Issue 6


2010                Distinguished Alumnus Award, The Johns Hopkins University, Baltimore, MD

2012                Dean’s Award for Excellence in Translational Science, Icahn School of Medicine at Mount Sinai, New York, NY

2012-14          Chairperson of the Cardiac Contractility, Hypertrophy and Failure Study Section – National Heart Lung Blood Institute, Washington, DC

2012                Co-Chair, Basic Cardiovascular Sciences 2012 Scientific Sessions: Frontiers in Cardiovascular Science and Novel Therapy, New Orleans, LA

2013                2013 Best Manuscript Award, Circulation Research, Dallas, TX

2013                2013 AHA BCVS Distinguished Achievement Award, Dallas, TX

2013                Paul Dudley White Lecturer, American College of Cardiology, New York, NY

2014                Member, Association of American Physicians, Chicago, IL

2014                Associate Editor, JACC



Meet the Team

Roger Hajjar MD 2

Dr. Roger J. Hajjar is currently the Director of the Cardiovascular Research Center, and the Arthur & Janet C. Ross Professor of Medicine at Icahn School of Medicine at Mount Sinai, New York, NY. He received a BS in Biomedical Engineering from the Whiting School of the Johns Hopkins University (with University and Departmental honors) in 1986 and his MD (cum laude) from Harvard Medical School and the Harvard-MIT Division of Health Sciences & Technology in 1990. He completed his medical training in internal medicine, cardiology and research fellowships at Massachusetts General Hospital in Boston.

Dr. Hajjar is an internationally renowned scientific leader in the field of cardiac gene therapy for heart failure. His laboratory focuses on molecular mechanisms of heart failure and has validated the cardiac sarcoplasmic reticulum calcium ATPase pump, SERCA2a, as a target in heart failure, developed methodologies for cardiac directed gene transfer that are currently used by investigators throughout the world, and examined the functional consequences of SERCA2a gene transfer in failing hearts. His basic science laboratory remains one of the preeminent laboratories for the investigation of calcium cycling in failing hearts and targeted gene transfer in various animal models. The significance of Dr. Hajjar’s research has been recognized with the initiation and recent successful completion of phase 1 and phase 2 First-in-Man clinical trials of SERCA2a gene transfer in patients with advanced heart failure under his guidance and the start of an international phase 2b/3 trial (August 2012). This product would be the first gene therapy therapeutics for heart failure and would potentially benefit millions of patients.

Since joining Mount Sinai ten years ago, Dr. Hajjar has built an exceptional Cardiovascular Research Center with state-of-the-art equipment and unique resources. The CVRC is currently housed in 25,000 square feet of space in the Hess building and has had impressive and sustained growth in the last 10 years since its inception. The Research Institute has fifteen principal investigators with more than 70 fellows, technicians and students.

The NIH funding within the CVRC has more than tripled from 2007 to 2017 and the number of publications has exponentially increased. There has been substantial growth with both junior and senior investigator targeted recruitment. The development of the Cardiovascular Translational Lab has greatly facilitated movement of potential targets from small animal models to preclinical level and the establishment of the 3-D printing & tissue engineering lab is an added strength. Investigators in the CVRC have been able to travel this trajectory from target to clinical trials.

The purpose of the Center is to provide an interactive environment for scientists and physician-scientists pursuing research elucidating molecular mechanisms of heart failure and ventricular dysfunction. The Center currently comprises 14 principal investigators and 60 postdoctoral fellows, technicians and students. Collectively, their laboratories cover a broad range of research interests such as gene therapy, regenerative medicine, tissue engineering, novel vector design, electropsyiology, exosomes, and translational research. The Center also has multiple core facilities supporting cardiovascular research including: 1) Recombinant adenoviral vectors core, 2) Adeno-associated vectors core, 3) Proteomic/Mass spectroscopy core, 4) Rodent echocardiography and invasive hemodynamics core, 5) a fully equipped large animal cardiac catheterization laboratory for pre-clinical studies, 6) modified RNA, and 7) exosomes. The Center sponsors a seminar series focused on myocardial biology to which national and international scientists are invited. In addition, there is a journal club and biweekly lab meetings where projects and data are discussed. Aside from the formal seminar series, there is a high level of interaction within the Center and within the myocardial biology group, with several collaborative projects already underway. These topics represent the most important themes in current cardiovascular research.

The Center receives approximately $5M in NIH funding through its various investigators led projects. It has grants from American Heart Association and other private foundations. Most notably, the Fondation Leducq in Paris, France, dedicated to improving human health through international efforts to combat cardiovascular disease, awarded a $6 million grant award to a new global research network of cardiovascular scientists which includes three researchers from the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai.

Dr. Hajjar has filed six patents at Mount Sinai through the Business office. One of these patents has already been licensed (SERCA2 therapeutic compositions and methods of use (Pulmonary), two others are currently being licensed (Sumoylation of SERCA and Cardiovacular Diseases and Directed Differentiation of Stem Cells) are currently being negotiated for licensing. Three other intellectual properties are the base of a new company, SUMOCOR, to develop novel therapeutics to treat congestive heart failure using small molecules to target critical pathways. Sumocor’s first therapy is based on the protein SUMO1, which has recently been identified as being pivotal in healthy heart function.

Prior to joining Mount Sinai, Dr. Hajjar served as Director of the Cardiovascular Laboratory of Integrative Physiology and Imaging at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. Dr. Hajjar has also been a staff cardiologist in the Heart Failure & Cardiac Transplantation Center at Massachusetts General Hospital.

Dr. Hajjar has also also created an international alliance between the Cardiovascular Research Center and the Universite de Paris covering more than 100 scientists.

Research Assistant Professors:

Jiqiu Chen, MD

Jiqiu received his medical degree at Guilin Medical College located in Guilin, Guangxi, China, and then completed his residency at Liujiang Hospital, Liuzhou, China. He received an MSc degree from Kunming Medical College and then joined the Department of Pathophysiology, Guilin Medical College (1988-2000). He moved to Boston, MA, in 2000, and joined Dr. Paul Huang’s Lab at the Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School. There, he conducted research on atherosclerosis and molecular imaging. In 2007, Dr. Roger J. Hajjar recruited him to the Cardiovascular Research Institute at Icahn School of Medicine at Mount Sinai in New York, NY. His area of research focuses on stem cell therapy for cardiac ischemic injury, heart failure and atherosclerosis in rodent animals. He discovered a new model of congestive heart failure in rats and has published more than 30 articles. He is currently exploring the role of fibrosis, coronary arterial neointima, left atrial thrombus and capillary dysfunction in congestive heart failure.

Instructors of Medicine, Cardiology:

Dongtak Jeong, PhD

Dongtak received his PhD degree at Gwangju Institute of Science and Technology (GIST) in South Korea. He was recruited to Dr. Hajjar’s lab in 2008. He has an extensive background in molecular cardiology, with specific training and expertise in hypertrophic signaling pathway and various surgery-induced heart failure animal models. Dr. Jeong’s research focuses on two different projects. The first project aims to determine the molecular and cellular mechanism of miR-25 in terms of cardiac function. Recently, our group has shown that the inhibition of miR-25 enhances cardiac function through restoration of SERCA2a expression in both in vitro and in vivo systems. Based on this finding, Dr. Jeong is exploring the beneficial effect of antagonization of miR-25 in different animal models. In addition, we have generated the most efficient sequence to eliminate endogenous miR-25, called “decoy”, and applied it to the AAV system to attain long-term and efficient delivery. The second project aims to understand the mechanism of cardiac fibrosis and its therapeutic application in animal models. We have recently identified “CCN5” as an anti-fibrotic molecule and proved its activity in HF animal model. Additionally, Dr. Jeong has recently identified a profibrotic molecule “Cytl1”. He hypothesizes that antagonism of Cytl1 may ameliorate cardiac fibrosis since Cytl1 expression is dramatically elevated in HF patients and animal models. He is currently investigating the molecular and cellular mechanisms underlying the induction of cardiac fibrosis by Cytl1.

Francesca Stillitano, PhD

Francesca has a broad background in cardiovascular biology focusing on the molecular basis of cardiac arrhythmias and pathological cardiac remodeling. As a graduate student, she acquired knowledge and skills in molecular and cellular biology while studying molecular mechanisms of cardiac electrical remodeling in heart failure using both in vitro and in vivo models.
During her postdoctoral training, she used the methodologies gained from her experience as a graduate student to study cardiac remodeling during development. She worked with a team of collaborators to develop protocols that allow production of cardiomyocytes from both mouse and human embryonic stem cells (ESCs) and used them as a suitable model for studying the developmental changes of the electrophysiological properties of cardiac cells.
In 2011, she joined Dr. Roger Hajjar’s laboratory as a postdoctoral fellow and has recently been promoted to Instructor of Medicine, Cardiology. Her research is focused on the generation of patient-specific induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes (iPSC-CMs). She uses iPSC-CMs as a platform for modeling cardiac diseases and for cardiotoxicity screening.
As part of these projects, she characterized iPSC-derived cardiomyocyte from patients with inherited Dilated Cardiomyopathy (DCM) induced by a mutation (R14del) in the coding region of the phospholamban (PLN) gene. PLN is a critical regulator of calcium cycling in cardiac myocytes but there was no model to recapitulate its function as observed in human hearts. Using this human cell assay, she determined the role of this mutation in calcium handling abnormalities and arrhythmias typical of DCM. In addition, she used a combination of genome editing and gene transfer techniques, to reverse the diseased phenotype, thus offering novel strategies for targeting pathogenic mutations associated with cardiomyopathies. In continuation to this project, I will work on a mouse model of PLN-R14del-induced DCM and use gene therapy (by Adeno-Associated Viruses) and gene editing (by CRISPR-Cas9) approaches, to correct the mutation in vivo.
Francesca is also working on a second project where she developed a platform based on a genetically diverse panel of iPSCs that reproduces susceptibility to develop cardiotoxic drug response. She generated iPSC-CMs from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with Sotalol. In vitro, the responses to Sotalol were highly variable but largely correlated to the inter-individual differences observed in vivo. These findings offer novel insights for the development of iPSC-based screening assays for toxic drug reactions.

Postdoctoral Fellows:

Delaine Ceholski, PhD

Delaine is a postdoctoral fellow at the Icahn School of Medicine at Mount Sinai (ISMMS) in New York. She obtained her PhD in Biochemistry from the University of Alberta (Canada), where the focus of her thesis was on in vitro characterization of hereditary mutations in phospholamban linked to dilated cardiomyopathy. During her PhD, Dr. Ceholski was funded by the Canadian Institutes of Health Research, Alberta Innovates, and the University of Alberta. Dr. Ceholski was recruited to the Cardiovascular Research Center at the ISMMS in 2013, where the focus of her research is on the elucidation of the mechanisms of inherited dilated cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes. She is funded by an American Heart Association Fellowship.

Jaegyun Oh, PhD

Jaegyun graduated from Gwangju Institute of Science and Technology, Korea, with a Ph.D. degree in 2013. In the course of his Ph.D., he studied molecular pathways during heart failure. He specifically focused on the role of PKC-interacting cousin of thioredoxin (PICOT) in the heart. He first identified PICOT as a cardiac hypertrophy related molecule. Then he determined the mechanisms underlying the calcium regulatory effects of PICOT. During his PhD, Dr. Oh collaborated with Dr. Roger J. Hajjar evaluating the effects of small ubiquitin-like modifier type 1 (SUMO1) overexpression in isolated cardiomyocytes. As a result of this collaboration, the team determined SUMO1 as a critical SERCA2a modifier and Dr. Oh was a co-author on Dr. Hajjar’s Nature 2011 paper. This collaboration led to Dr. Oh’s being offered a postdoctoral position in Dr. Hajjar’s laboratory. Dr. Oh has interests at molecular pathophysiology and physiology in heart failure and specialized skills for in vitro calcium transient assessments and molecular analysis.

Dr. Oh’s projects include the identification of an effective microRNA (miR) which will stabilize Ca2+ cycling. He identified miR-146a as a Ca2+ regulatory miR which attenuates Ca2+ transient and cardiac function. Blocking miR-146a restored cardiac contractility in vitro. Interestingly, miR-146a showed inhibitory activity on SUMO1 expression. The relationship between miR-146a and SUMO1 has not been elucidated yet. He has shown correlative expression of miR-146a with SUMO1. Currently, he is focusing on the detailed mechanisms underlying the relationship between miR-146a and SUMO1. Because we have shown that intracellular calcium normalization by gene transfer of SUMO1 restored cardiac function in heart failure, this miR-146a research may lay the foundation for a new strategy to treat HF.

Yassine Sassi, PhD

Yassine received his PhD in cardiac physiology from the Pierre et Marie Curie University (Paris VI), Paris, France. His undergraduate research focused on exploring the mechanisms of cyclic nucleotides transport in the cardiovascular system. His PhD work demonstrated that cAMP extrusion via a transporter, called Abcc4, acts together with phosphodiesterases to control cAMP levels in vascular smooth muscle cells and cardiac myocytes. For his first postdoctoral fellow, he joined Dr. Stefan Engelhardt team (Munich, Germany). Besides his interest in characterizing the role of different microRNAs in cardiac remodeling, Dr. Sassi has also been applying his basic knowledge of cAMP metabolism and signal transduction to study the molecular pathways underlying cardiac hypertrophy and fibrosis. His work revealed the presence of a protective extracellular cAMP pathway in the heart and a paracrine role for secreted cAMP in intercellular signaling in the myocardium. In Dr. Hajjar’s lab, Dr. Sassi is currently interested in characterizing the pathophysiological role of different microRNAs in pulmonary arterial hypertension (PAH). Dr. Sassi is also investigating novel strategies for targeting the pathogenic mutations associated with cardiomyopathies using patient-specific-induced pluripotent stem cells. In addition, Dr. Sassi is also continuing his efforts to investigate the key role of extracellular cAMP, this time in pulmonary arterial vessel remodeling. The goal of one of his present projects is to investigate the presence of the extracellular cAMP pathway in pulmonary vascular cells and to investigate whether extracellular cAMP infusion may prevent and/or reverse pathological vascular remodeling in PAH using human pulmonary artery cells in vitro and animal models of PAH in vivo. A major objective of Dr. Sassi’s future plans is initiating new directions in cardiovascular therapy research.

Maria Giovanna Trivieri, MD, PhD

Maria’s career has a strong academic foundation based on broad-based multidisciplinary and international training. She received her Medical Degree and PhD from the University of Pisa. She subsequently completed her residency in Internal Medicine and fellowship in Cardiology at the University of Toronto and became Board Certified from the Royal College of Physician and Surgeon of Canada as well as the American Board of Internal Medicine. Dr. Trivieri currently hold unrestricted and independents medical licenses for the USA (New York), Canada (Ontario, CPSO) and Italy.
In 2014, Dr. Trivieri moved to New York to receive advanced training in Heart Failure and Cardiac Transplantation with the team of Dr. Pinney and was involved in landmark studies on the use of PET/MR for the assessment Sarcoid and Amyloid Cardiomyopathies.
After completing her clinical training, she joined the laboratory of Dr. Hajjar to characterize a Phospholamban (PLN) mutation responsible for a lethal form of cardiomyopathy. Her current research focuses on the development of a multidisciplinary program whose goal is to investigate the central biology of PLN in humans utilizing state of the art techniques of genetic engineering and stem cell biology, with a view toward clinical translation. With her work, Dr. Trivieri aims at fostering a renewed appreciation of the fundamental role of PLN in relation to homeostasis of calcium and intracellular signaling in cardiac pathophysiology, enabling the identification of new pathways and molecular targets involved in the onset and progression of Heart Failure.
Throughout the course of her career, Dr. Trivieri has received numerous awards and fellowship from the Italian Ministry of Education, the Scuola Superiore Sant’Anna/Italian “Grand Ecoles”, the Heart and Stroke foundation of Canada, the Department of Medicine of the University of Toronto, the Richard Lear Center of Canada, the Thalassemia Foundation of Canada and the NIH (T32 training grants). She has authored several original high-impact papers, abstracts, book chapter and reviews in basic and clinical cardiovascular medicine.

Shin Watanabe, MD, PhD

Shin is a postdoctoral research fellow in the Cardiovascular Research Center of Icahn School of Medicine at Mount Sinai. He received his MD in Medical Science from Toyama Medical and Pharmaceutical University of Medicine (Japan) in 2001 and his Ph.D. in Medical Science from Kyoto University (Japan) in 2011.
After 10 years of clinical practice as an interventional cardiologist in Japan, Dr. Watanabe joined Dr. Roger J. Hajjar’s laboratory in 2015 as a postdoctoral research fellow.
His work involves researching translational gene based therapies in large animal models of heart failure. He is instrumental in creating heart failure models including aortic constriction, acute myocardial infarction, chronic coronary occlusion and mitral valve regurgitation. He then tests therapies such as AAV, micro RNA and modified RNA. Dr. Watanabe aims to bridge novel useful tools for basic biological research to clinical applications.


Okkil Kim, BS, MS

Okkil acquired a dual Bachelor’s degree in “Biochemistry and Molecular Biology” and a Master’s degree of Science at Hanyang University in Korea. She possesses a diverse set of skills in molecular and cellular biology.  Additionally, she has a broad experience with specialized software and data sets used in the field. Her main focus is on AAV mass production for translational research purposes in in vivo models.

Erik Kohlbrenner, BS

Erik’s primary objective in the lab is to collaborate with researchers to generate recombinant Adeno-Associated Virus (rAAV) vectors containing the genes under investigation in their projects.  He attended the University of Florida and gained a Bachelors degree in Microbiology.  After graduation he began working at the UF Vector Core, where he learned multiple aspects of vector production, including cloning recombinant AAV plasmids, large scale production, various purification techniques, and quality control.  Prior to joining Dr. Hajjar’s team, he joined a colleague’s lab at the Icahn School and further studied the biology of AAV, the infectivity differences between wild type and recombinant virus, and the nature of AAV integration into the host genome.   Since joining Dr. Hajjar’s lab, interest in using rAAV as a tool for cardiovascular research has greatly increased, and as a result Erik has been responsible for training new lab members, rotating students, visiting colleagues, and international collaborators in the methods of AAV production.   His additional projects have included designing new assays to determine viral titer by capsid protein content, enhancing rAAV prep infectivity by using a modified purification strategy, scaling up production using an insect cell producer line, and designing strategies to more accurately determine the level of AAV transduction achieved in animal studies.

Lifan Liang, MD

Lifan is a senior associate researcher in Dr. Hajjar’s laboratory. As such, her role is multifaceted. She manages lab operations, amplifies and purifies adenovirus, isolates myocytes from neonate and adult rats and assists with animal surgeries. She is an integral part of projects examining the mechanisms of SERCA2 regulation by post-translational modifications (PTMs) and studying cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes.

Small Animal Surgeon:

Vadim Chepurko, PhD

Vadim received his M. Sc. degree in Physics and Math from Saint Petersburg State University, Russia. In the course of his Ph.D., he studied molecular and radiation biophysics in The Petersburg Nuclear Physics Institute and veterinary technology in The Veterinary Institute of Poultry Technology, Saint Petersburg, Russia. He has been graduated as Ph.D. in Biological Sciences at All-Russian Research Institute of Agricultural Radiology and Agroecology. He has working background in computer aided biochemical engineering. His primary research interests include but are not limited to: animal model development and computational tools for imaging analysis. He is involved in the ECHO examination of mice hearts in normal and pathological conditions, as well as he performs mouse TAC surgical model of heart hypertrophy. He implements PV Loop investigation for different groups of experimental mice.

Jimeen Yoo, BA

Jimeen Yoo has received a bachelor of arts for English and Chemistry at Williams College and is currently a Master’s of Biomedical Sciences student at Icahn School of Medicine at Mount Sinai. She has a diverse set of skills in cellular biology and experience with specialized software and analyzing datasets. Her current research focus is on evaluating promoter designs for atrial specificity gene therapy viral vectors.

Roger Hajjar's Lab 2






  1. Stillitano F, Karakikes I, Hajjar RJ. Gene Transfer in Cardiomyocytes Derived from ES and iPS Cells. Methods Mol Biol. 2017;1521:183-93. doi: 10.1007/978-1-4939-6588-5_12. PubMed PMID: 27910049.
  2. Stillitano F, Hansen J, Kong CW, Karakikes I, Funck-Brentano C, Geng L, Scott S, Reynier S, Wu M, Valogne Y, Desseaux C, Salem JE, Jeziorowska D, Zahr N, Li R, Iyengar R, Hajjar RJ, Hulot JS. Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells. Elife. 2017;6. doi: 10.7554/eLife.19406. PubMed PMID: 28134617; PMCID: PMC5279943.
  3. Sahoo S, Mathiyalagan P, Hajjar RJ. Pericardial Fluid Exosomes: A New Material to Treat Cardiovascular Disease. Mol Ther. 2017. doi: 10.1016/j.ymthe.2017.02.002. PubMed PMID: 28215995.
  4. Ishikawa K, Hajjar RJ. Current Methods in Cardiac Gene Therapy: Overview. Methods Mol Biol. 2017;1521:3-14. doi: 10.1007/978-1-4939-6588-5_1. PubMed PMID: 27910038.
  5. Hajjar RJ, Ishikawa K. Introducing Genes to the Heart: All About Delivery. Circ Res. 2017;120(1):33-5. doi: 10.1161/CIRCRESAHA.116.310039. PubMed PMID: 28057788; PMCID: PMC5221570.
  6. Del Monte F, Ishikawa K, Hajjar RJ. Gene Transfer to Rodent Hearts In Vivo. Methods Mol Biol. 2017;1521:195-204. doi: 10.1007/978-1-4939-6588-5_13. PubMed PMID: 27910050.
  7. Aguero J, Hadri L, Hammoudi N, Leonardson L, Hajjar RJ, Ishikawa K. Inhaled Gene Transfer for Pulmonary Circulation. Methods Mol Biol. 2017;1521:339-49. doi: 10.1007/978-1-4939-6588-5_24. PubMed PMID: 27910061.


  8. Stillitano F, Turnbull IC, Karakikes I, Nonnenmacher M, Backeris P, Hulot JS, Kranias EG, Hajjar RJ, Costa KD. Genomic correction of familial cardiomyopathy in human engineered cardiac tissues. Eur Heart J. 2016;37(43):3282-4. doi: 10.1093/eurheartj/ehw307. PubMed PMID: 27450564.
  9. Santos-Gallego CG, Vahl TP, Goliasch G, Picatoste B, Arias T, Ishikawa K, Njerve IU, Sanz J, Narula J, Sengupta PP, Hajjar RJ, Fuster V, Badimon JJ. Sphingosine-1-Phosphate Receptor Agonist Fingolimod Increases Myocardial Salvage and Decreases Adverse Postinfarction Left Ventricular Remodeling in a Porcine Model of Ischemia/Reperfusion. Circulation. 2016;133(10):954-66. doi: 10.1161/CIRCULATIONAHA.115.012427. PubMed PMID: 26826180.
  10. Jeong D, Lee MA, Li Y, Yang DK, Kho C, Oh JG, Hong G, Lee A, Song MH, LaRocca TJ, Chen J, Liang L, Mitsuyama S, D’Escamard V, Kovacic JC, Kwak TH, Hajjar RJ, Park WJ. Matricellular Protein CCN5 Reverses Established Cardiac Fibrosis. J Am Coll Cardiol. 2016;67(13):1556-68. doi: 10.1016/j.jacc.2016.01.030. PubMed PMID: 27150688.
  11. Jang SP, Oh JG, Kang DH, Kang JY, Kang SW, Hajjar RJ, Park WJ. A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells. PLoS One. 2016;11(10):e0165569. doi: 10.1371/journal.pone.0165569. PubMed PMID: 27792751; PMCID: PMC5085086.
  12. Hulot JS, Ishikawa K, Hajjar RJ. Gene therapy for the treatment of heart failure: promise postponed. Eur Heart J. 2016;37(21):1651-8. doi: 10.1093/eurheartj/ehw019. PubMed PMID: 26922809; PMCID: PMC4887702.
  13. Greenberg B, Butler J, Felker GM, Ponikowski P, Voors AA, Pogoda JM, Provost R, Guerrero J, Hajjar RJ, Zsebo KM. Prevalence of AAV1 neutralizing antibodies and consequences for a clinical trial of gene transfer for advanced heart failure. Gene Ther. 2016;23(3):313-9. doi: 10.1038/gt.2015.109. PubMed PMID: 26699914.
  14. Fargnoli AS, Katz MG, Bridges CR, Hajjar RJ. Gene Therapy in Heart Failure. Handb Exp Pharmacol. 2016. doi: 10.1007/164_2016_81. PubMed PMID: 27796512.
  15. Chaanine AH, Kohlbrenner E, Gamb SI, Guenzel AJ, Klaus K, Fayyaz AU, Nair KS, Hajjar RJ, Redfield MM. FOXO3a regulates BNIP3 and modulates mitochondrial calcium, dynamics, and function in cardiac stress. Am J Physiol Heart Circ Physiol. 2016;311(6):H1540-H59. doi: 10.1152/ajpheart.00549.2016. PubMed PMID: 27694219; PMCID: PMC5206339.
  16. Benard L, Oh JG, Cacheux M, Lee A, Nonnenmacher M, Matasic DS, Kohlbrenner E, Kho C, Pavoine C, Hajjar RJ, Hulot JS. Cardiac Stim1 Silencing Impairs Adaptive Hypertrophy and Promotes Heart Failure Through Inactivation of mTORC2/Akt Signaling. Circulation. 2016;133(15):1458-71; discussion 71. doi: 10.1161/CIRCULATIONAHA.115.020678. PubMed PMID: 26936863; PMCID: PMC4829441.
  17. Bartunek J, Terzic A, Davison BA, Filippatos GS, Radovanovic S, Beleslin B, Merkely B, Musialek P, Wojakowski W, Andreka P, Horvath IG, Katz A, Dolatabadi D, El Nakadi B, Arandjelovic A, Edes I, Seferovic PM, Obradovic S, Vanderheyden M, Jagic N, Petrov I, Atar S, Halabi M, Gelev VL, Shochat MK, Kasprzak JD, Sanz-Ruiz R, Heyndrickx GR, Nyolczas N, Legrand V, Guedes A, Heyse A, Moccetti T, Fernandez-Aviles F, Jimenez-Quevedo P, Bayes-Genis A, Hernandez-Garcia JM, Ribichini F, Gruchala M, Waldman SA, Teerlink JR, Gersh BJ, Povsic TJ, Henry TD, Metra M, Hajjar RJ, Tendera M, Behfar A, Alexandre B, Seron A, Stough WG, Sherman W, Cotter G, Wijns W, Program C. Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial. Eur Heart J. 2016. doi: 10.1093/eurheartj/ehw543. PubMed PMID: 28025189.
  18. Bartunek J, Davison B, Sherman W, Povsic T, Henry TD, Gersh B, Metra M, Filippatos G, Hajjar R, Behfar A, Homsy C, Cotter G, Wijns W, Tendera M, Terzic A. Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design. Eur J Heart Fail. 2016;18(2):160-8. doi: 10.1002/ejhf.434. PubMed PMID: 26662998; PMCID: PMC5064644.
  19. Aguero J, Ishikawa K, Hadri L, Santos-Gallego CG, Fish KM, Kohlbrenner E, Hammoudi N, Kho C, Lee A, Ibanez B, Garcia-Alvarez A, Zsebo K, Maron BA, Plataki M, Fuster V, Leopold JA, Hajjar RJ. Intratracheal Gene Delivery of SERCA2a Ameliorates Chronic Post-Capillary Pulmonary Hypertension: A Large Animal Model. J Am Coll Cardiol. 2016;67(17):2032-46. doi: 10.1016/j.jacc.2016.02.049. PubMed PMID: 27126531.


  20. Sultana N, Zhang L, Yan J, Chen J, Cai W, Razzaque S, Jeong D, Sheng W, Bu L, Xu M, Huang GY, Hajjar RJ, Zhou B, Moon A, Cai CL. Resident c-kit(+) cells in the heart are not cardiac stem cells. Nat Commun. 2015;6:8701. doi: 10.1038/ncomms9701. PubMed PMID: 26515110; PMCID: PMC4846318.
  21. Rapti K, Stillitano F, Karakikes I, Nonnenmacher M, Weber T, Hulot JS, Hajjar RJ. Effectiveness of gene delivery systems for pluripotent and differentiated cells. Mol Ther Methods Clin Dev. 2015;2:14067. doi: 10.1038/mtm.2014.67. PubMed PMID: 26052535; PMCID: PMC4449028.
  22. Lara-Pezzi E, Menasche P, Trouvin JH, Badimon L, Ioannidis JP, Wu JC, Hill JA, Koch WJ, De Felice AF, de Waele P, Steenwinckel V, Hajjar RJ, Zeiher AM. Guidelines for translational research in heart failure. J Cardiovasc Transl Res. 2015;8(1):3-22. doi: 10.1007/s12265-015-9606-8. PubMed PMID: 25604959.
  23. Kho C, Lee A, Jeong D, Oh JG, Gorski PA, Fish K, Sanchez R, DeVita RJ, Christensen G, Dahl R, Hajjar RJ. Small-molecule activation of SERCA2a SUMOylation for the treatment of heart failure. Nat Commun. 2015;6:7229. doi: 10.1038/ncomms8229. PubMed PMID: 26068603; PMCID: PMC4467461.
  24. Karakikes I, Stillitano F, Nonnenmacher M, Tzimas C, Sanoudou D, Termglinchan V, Kong CW, Rushing S, Hansen J, Ceholski D, Kolokathis F, Kremastinos D, Katoulis A, Ren L, Cohen N, Gho JM, Tsiapras D, Vink A, Wu JC, Asselbergs FW, Li RA, Hulot JS, Kranias EG, Hajjar RJ. Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy. Nat Commun. 2015;6:6955. doi: 10.1038/ncomms7955. PubMed PMID: 25923014; PMCID: PMC4421839.
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  92. Cutler MJ, Wan X, Plummer BN, Liu H, Deschenes I, Laurita KR, Hajjar RJ, Rosenbaum DS. Targeted sarcoplasmic reticulum Ca2+ ATPase 2a gene delivery to restore electrical stability in the failing heart. Circulation. 2012;126(17):2095-104. doi: 10.1161/CIRCULATIONAHA.111.071480. PubMed PMID: 23019291; PMCID: PMC3538142.
  93. Chemaly ER, Chaanine AH, Sakata S, Hajjar RJ. Stroke volume-to-wall stress ratio as a load-adjusted and stiffness-adjusted indicator of ventricular systolic performance in chronic loading. J Appl Physiol (1985). 2012;113(8):1267-84. doi: 10.1152/japplphysiol.00785.2012. PubMed PMID: 22923502; PMCID: PMC3472487.
  94. Chaanine AH, Jeong D, Liang L, Chemaly ER, Fish K, Gordon RE, Hajjar RJ. JNK modulates FOXO3a for the expression of the mitochondrial death and mitophagy marker BNIP3 in pathological hypertrophy and in heart failure. Cell Death Dis. 2012;3:265. doi: 10.1038/cddis.2012.5. PubMed PMID: 22297293; PMCID: PMC3288347.


  95. Shin JH, Bostick B, Yue Y, Hajjar R, Duan D. SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice. J Transl Med. 2011;9:132. doi: 10.1186/1479-5876-9-132. PubMed PMID: 21834967; PMCID: PMC3162513.
  96. Rapti K, Chaanine AH, Hajjar RJ. Targeted gene therapy for the treatment of heart failure. Can J Cardiol. 2011;27(3):265-83. doi: 10.1016/j.cjca.2011.02.005. PubMed PMID: 21601767.
  97. Lyon AR, Bannister ML, Collins T, Pearce E, Sepehripour AH, Dubb SS, Garcia E, O’Gara P, Liang L, Kohlbrenner E, Hajjar RJ, Peters NS, Poole-Wilson PA, Macleod KT, Harding SE. SERCA2a gene transfer decreases sarcoplasmic reticulum calcium leak and reduces ventricular arrhythmias in a model of chronic heart failure. Circ Arrhythm Electrophysiol. 2011;4(3):362-72. doi: 10.1161/CIRCEP.110.961615. PubMed PMID: 21406682; PMCID: PMC3119354.
  98. Ladage D, Turnbull IC, Ishikawa K, Takewa Y, Rapti K, Morel C, Karakikes I, Hadri L, Muller-Ehmsen J, Costa KD, Hajjar RJ, Kawase Y. Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine model. Gene Ther. 2011;18(10):979-85. doi: 10.1038/gt.2011.52. PubMed PMID: 21512506; PMCID: PMC3651891.
  99. Ladage D, Tilemann L, Ishikawa K, Correll RN, Kawase Y, Houser SR, Molkentin JD, Hajjar RJ. Inhibition of PKCalpha/beta with ruboxistaurin antagonizes heart failure in pigs after myocardial infarction injury. Circ Res. 2011;109(12):1396-400. doi: 10.1161/CIRCRESAHA.111.255687. PubMed PMID: 21998327; PMCID: PMC3237728.
  100. Kho C, Lee A, Jeong D, Oh JG, Chaanine AH, Kizana E, Park WJ, Hajjar RJ. SUMO1-dependent modulation of SERCA2a in heart failure. Nature. 2011;477(7366):601-5. doi: 10.1038/nature10407. PubMed PMID: 21900893; PMCID: PMC3443490.
  101. Kawase Y, Ladage D, Hajjar RJ. Method of gene delivery in large animal models of cardiovascular diseases. Methods Mol Biol. 2011;709:355-67. doi: 10.1007/978-1-61737-982-6_23. PubMed PMID: 21194040.
  102. Kawase Y, Ladage D, Hajjar RJ. Rescuing the failing heart by targeted gene transfer. J Am Coll Cardiol. 2011;57(10):1169-80. doi: 10.1016/j.jacc.2010.11.023. PubMed PMID: 21371634; PMCID: PMC3070185.
  103. Kang S, Chemaly ER, Hajjar RJ, Lebeche D. Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathways. J Biol Chem. 2011;286(21):18465-73. doi: 10.1074/jbc.M110.200022. PubMed PMID: 21478152; PMCID: PMC3099663.
  104. Jessup M, Greenberg B, Mancini D, Cappola T, Pauly DF, Jaski B, Yaroshinsky A, Zsebo KM, Dittrich H, Hajjar RJ, Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease I. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation. 2011;124(3):304-13. doi: 10.1161/CIRCULATIONAHA.111.022889. PubMed PMID: 21709064.
  105. Ishikawa K, Tilemann L, Fish K, Hajjar RJ. Gene delivery methods in cardiac gene therapy. J Gene Med. 2011;13(10):566-72. doi: 10.1002/jgm.1609. PubMed PMID: 21954037.
  106. Ishikawa K, Ladage D, Tilemann L, Fish K, Kawase Y, Hajjar RJ. Gene transfer for ischemic heart failure in a preclinical model. J Vis Exp. 2011(51). doi: 10.3791/2778. PubMed PMID: 21633324; PMCID: PMC3197127.
  107. Ishikawa K, Ladage D, Takewa Y, Yaniz E, Chen J, Tilemann L, Sakata S, Badimon JJ, Hajjar RJ, Kawase Y. Development of a preclinical model of ischemic cardiomyopathy in swine. Am J Physiol Heart Circ Physiol. 2011;301(2):H530-7. doi: 10.1152/ajpheart.01103.2010. PubMed PMID: 21551276; PMCID: PMC3154674.
  108. Hulot JS, Fauconnier J, Ramanujam D, Chaanine A, Aubart F, Sassi Y, Merkle S, Cazorla O, Ouille A, Dupuis M, Hadri L, Jeong D, Muhlstedt S, Schmitt J, Braun A, Benard L, Saliba Y, Laggerbauer B, Nieswandt B, Lacampagne A, Hajjar RJ, Lompre AM, Engelhardt S. Critical role for stromal interaction molecule 1 in cardiac hypertrophy. Circulation. 2011;124(7):796-805. doi: 10.1161/CIRCULATIONAHA.111.031229. PubMed PMID: 21810664; PMCID: PMC3428713.
  109. Goonasekera SA, Lam CK, Millay DP, Sargent MA, Hajjar RJ, Kranias EG, Molkentin JD. Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle. J Clin Invest. 2011;121(3):1044-52. doi: 10.1172/JCI43844. PubMed PMID: 21285509; PMCID: PMC3049367.
  110. Cimmino G, Giannarelli C, Chen W, Alique M, Santos-Gallego CG, Fuster V, Hajjar RJ, Walsh CE, Badimon JJ. Adeno-associated virus serotype 8 ApoA-I gene transfer reduces progression of atherosclerosis in ApoE-KO mice: comparison of intramuscular and intravenous administration. J Cardiovasc Pharmacol. 2011;57(3):325-33. doi: 10.1097/FJC.0b013e3182092841. PubMed PMID: 21164355.
  111. Chen J, Lee SK, Abd-Elgaliel WR, Liang L, Galende EY, Hajjar RJ, Tung CH. Assessment of cardiovascular fibrosis using novel fluorescent probes. PLoS One. 2011;6(4):e19097. doi: 10.1371/journal.pone.0019097. PubMed PMID: 21533060; PMCID: PMC3080412.
  112. Chen J, Chemaly ER, Liang LF, LaRocca TJ, Yaniz-Galende E, Hajjar RJ. A new model of congestive heart failure in rats. Am J Physiol Heart Circ Physiol. 2011;301(3):H994-1003. doi: 10.1152/ajpheart.00245.2011. PubMed PMID: 21685270; PMCID: PMC3191108.
  113. Chaanine AH, Hajjar RJ. AKT signalling in the failing heart. Eur J Heart Fail. 2011;13(8):825-9. doi: 10.1093/eurjhf/hfr080. PubMed PMID: 21724622; PMCID: PMC3143831.
  114. Bobe R, Hadri L, Lopez JJ, Sassi Y, Atassi F, Karakikes I, Liang L, Limon I, Lompre AM, Hatem SN, Hajjar RJ, Lipskaia L. SERCA2a controls the mode of agonist-induced intracellular Ca2+ signal, transcription factor NFAT and proliferation in human vascular smooth muscle cells. J Mol Cell Cardiol. 2011;50(4):621-33. doi: 10.1016/j.yjmcc.2010.12.016. PubMed PMID: 21195084; PMCID: PMC3062203.


  115. Yoon PO, Lee MA, Cha H, Jeong MH, Kim J, Jang SP, Choi BY, Jeong D, Yang DK, Hajjar RJ, Park WJ. The opposing effects of CCN2 and CCN5 on the development of cardiac hypertrophy and fibrosis. J Mol Cell Cardiol. 2010;49(2):294-303. doi: 10.1016/j.yjmcc.2010.04.010. PubMed PMID: 20430035.
  116. Poller W, Hajjar R, Schultheiss HP, Fechner H. Cardiac-targeted delivery of regulatory RNA molecules and genes for the treatment of heart failure. Cardiovasc Res. 2010;86(3):353-64. doi: 10.1093/cvr/cvq056. PubMed PMID: 20176815; PMCID: PMC2868179.
  117. Lompre AM, Hajjar RJ, Harding SE, Kranias EG, Lohse MJ, Marks AR. Ca2+ cycling and new therapeutic approaches for heart failure. Circulation. 2010;121(6):822-30. doi: 10.1161/CIRCULATIONAHA.109.890954. PubMed PMID: 20124124; PMCID: PMC2834781.
  118. Lipskaia L, Chemaly ER, Hadri L, Lompre AM, Hajjar RJ. Sarcoplasmic reticulum Ca(2+) ATPase as a therapeutic target for heart failure. Expert Opin Biol Ther. 2010;10(1):29-41. doi: 10.1517/14712590903321462. PubMed PMID: 20078230; PMCID: PMC3001226.
  119. LaRocca TJ, Schwarzkopf M, Altman P, Zhang S, Gupta A, Gomes I, Alvin Z, Champion HC, Haddad G, Hajjar RJ, Devi LA, Schecter AD, Tarzami ST. beta2-Adrenergic receptor signaling in the cardiac myocyte is modulated by interactions with CXCR4. J Cardiovasc Pharmacol. 2010;56(5):548-59. doi: 10.1097/FJC.0b013e3181f713fe. PubMed PMID: 20729750; PMCID: PMC2978286.
  120. Kho C, Lee A, Jeong D, Hajjar RJ. Refilling Intracellular Calcium Stores. Drug Discov Today Dis Mech. 2010;7(2):e145-e50. doi: 10.1016/j.ddmec.2010.08.004. PubMed PMID: 21170146; PMCID: PMC3001621.
  121. Ishikawa K, Ladage D, Rapti K, Fernandez-Friera L, Maria Garcia-Lopez A, Sanz J, Hajjar RJ, Kawase Y, Garcia MJ. Multimodality imaging of chronic ischemia. Cardiol Res Pract. 2010;2011:739702. doi: 10.4061/2011/739702. PubMed PMID: 20981290; PMCID: PMC2963130.
  122. Hajjar RJ, Akar FG. Regression of cardiac hypertrophy by cyclic guanosine monophosphate-dependent protein kinase signaling are myocytes active sources or mere beneficiaries? J Am Coll Cardiol. 2010;56(24):2031-2. doi: 10.1016/j.jacc.2010.09.005. PubMed PMID: 20970281.
  123. Hadri L, Bobe R, Kawase Y, Ladage D, Ishikawa K, Atassi F, Lebeche D, Kranias EG, Leopold JA, Lompre AM, Lipskaia L, Hajjar RJ. SERCA2a gene transfer enhances eNOS expression and activity in endothelial cells. Mol Ther. 2010;18(7):1284-92. doi: 10.1038/mt.2010.77. PubMed PMID: 20461063; PMCID: PMC2911258.
  124. Chen J, Chemaly E, Liang L, Kho C, Lee A, Park J, Altman P, Schecter AD, Hajjar RJ, Tarzami ST. Effects of CXCR4 gene transfer on cardiac function after ischemia-reperfusion injury. Am J Pathol. 2010;176(4):1705-15. doi: 10.2353/ajpath.2010.090451. PubMed PMID: 20133817; PMCID: PMC2843462.
  125. Chen G, Zhou X, Florea S, Qian J, Cai W, Zhang Z, Fan GC, Lorenz J, Hajjar RJ, Kranias EG. Expression of active protein phosphatase 1 inhibitor-1 attenuates chronic beta-agonist-induced cardiac apoptosis. Basic Res Cardiol. 2010;105(5):573-81. doi: 10.1007/s00395-010-0106-3. PubMed PMID: 20512582; PMCID: PMC3095219.
  126. Beeri R, Chaput M, Guerrero JL, Kawase Y, Yosefy C, Abedat S, Karakikes I, Morel C, Tisosky A, Sullivan S, Handschumacher MD, Gilon D, Vlahakes GJ, Hajjar RJ, Levine RA. Gene delivery of sarcoplasmic reticulum calcium ATPase inhibits ventricular remodeling in ischemic mitral regurgitation. Circ Heart Fail. 2010;3(5):627-34. doi: 10.1161/CIRCHEARTFAILURE.109.891184. PubMed PMID: 20634484; PMCID: PMC2939951.

Grant Funding


1R01 HL117505 (Hajjar)
SUMO1 and SERCA2a Function

This project will examine the role of SUMO1 in the setting of heart failure.

T32 HL007824 (Gelb/Hajjar)
Training Program in Molecular and Cellular Cardiology

This training program seeks to train physician-scientists and post-doctoral fellows in molecular and cellular cardiology.  Cellular and Molecular Targets to Promote Therapeutic Cardiac Regeneration.

Source: Fondation Leducq (Sassoon/Finkel)
Role: Core Member

This project brings together both established and younger scientists who study cardiac stem cell biology, cardiac de–‐differentiation, cardiac gene transfer and clinical heart disease to jointly address cellular and molecular processes contributing to cardiac repair.

R01 HL119046 (Hajjar/Akar)
Targeting Abnormal Calcium Cycling Using Novel Gene Therapy Vectors

This goal of this project is to examine the role of altering calcium cycling proteins by gene transfer in pre-clinical models of heart failure.

NCRP Winter 2014 Center Strategically Focused Prevention Research Network
American Heart Association (Fuster)
Children Heart Research Study Program

This project takes a multi-disciplinary approach of lifestyle interventions in children and their parents in Harlem, New York.
Role: Training Director, Center

R01HL129814 (Thomas/Hajjar)
Calcium Pump Activators for Heart Failure Therapy

In this proposal, we will test small molecules generated at the University of Minnesota in single isolated cardiac myocytes and in murine and porcine models of myocardial infarction induced heart failure.

1R01HL128072 (Hajjar/Mercola)
Role of miR25 in Heart Failure

In this proposal, we will investigate the role of a non-coding microRNA (miR25) in failing hearts. Modulating miR25 expression may be a promising therapeutic approach to enhance cardiac function in heart failure.

1R01HL128099 (Levine/Hajjar)
Treating Ventricle and Valve: New Synergies for Ischemic LV Remodeling with MR

In this proposal, we will be involved in developing the viral vectors necessary for the completion of the application. Specifically, AAV vectors encoding for CCN5 and SERCA2a will be developed.

1R01HL130423-01 (Kovacic)
Toward Therapeutic Manipulation of Endothelial to Mesenchymal Transition
Role: Co-Investigator

This proposal seeks to leverage several novel discoveries made by our team to define the core biologic mechanisms of EndMT in atherosclerosis and cardiovascular disease, to understand how we can manipulate EndMT to promote healing after vascular grafting procedures, and ultimately to develop novel therapeutic strategies for cardiovascular disease.

HL105826 (Sadayappan)
Cardiac myosin binding protein-C: Structure and Function
Role: Co-Investigator

In this proposal, we will work with Dr. Sadayappan and his lab members, Dr. Govindan and Mr. Lin, in assisting with vector design, injection protocol and systematic delivery of AAV9 particles, as well as the validation of the results.

R01HL131404 (Hajjar/Weber)
Anti-AAV Antibodies as an Obstacle to Cardiac AAV Gene Therapy

The goals of this project are 1) to determine the effect of neutralizing antibodies on the treatment of heart failure with AAV1.SERCA2a, 2) to determine the major epitopes of the cardiotropic AAVs, AAV1, AAV6 and AAV6 and to isolate cardiotropic AAVs with increased resistance to pre-existing neutralizing antibodies and 3) to develop plasmapheresis with AAV-columns to deplete neutralizing antibodies from the blood of patients. This proposal will evaluate the role of STIM1 in cardiac hypertrophy and heart failure.

1R01HL133554 (Hadri)
Interactions of SERCA2a and BMPRII in Vascular Disease
Role: Co-Investigator

Our goal is to attenuate pulmonary vascular remodeling by using SERCA2a gene therapy as a therapeutic approach to restore BMPR2 and reverse the pathological changes in PAH.

1R01HL135093 (Hajjar/Fish)
Therapeutic Mechanisms of Cardiac Progenitors in Ischemic Cardiomyopathy

The goal of this project is to evaluate the mechanisms by which endogenous cKit+ cardiac progenitor cells in the infarcted heart improve cardiac function and outcomes in large animal models of heart failure.

Research Projects

Our laboratory focuses on understanding the molecular mechanisms of heart failure and developing novel therapies for the treatment of heart failure. Our work is based on the examination of calcium cycling abnormalities in various models of heart failure and we have developed new strategies to improve intracellular dynamics within the cell and the function of the whole heart.

Gene Therapy for Heart Failure

We have developed the world’s first clinically tested platform for gene therapy vector for the treatment of heart failure known as AAV1.SERCA2a. This vector based therapy enables the precise delivery of therapeutics to damaged heart tissue, and introduces a new realm of treatment modalities for advanced heart failure patients. Additionally, we are also exploring the use of novel gene therapy vectors to target various forms of heart failure, ventricular arrhythmias, pulmonary hypertension, and myocardial infarction.

The laboratory has continued to target calcium cycling proteins in the heart. Recently they have been successful in delivering the constitutively active form of protein phosphatase 1 inhibitor (I-1) protein directly into damaged heart cells and targets type 1 protein phosphatase (PP1), a critical negative regulator of calcium cycling and contractility. They used newly developed recombinant adeno-associated viruses which are non-pathogenic viruses naturally existing in the human body and are pathogenically safe while having a very low immune response profile. Carfostin is a one-time treatment and will be delivered via the femoral artery into the coronary arteries.

Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) is a rare, rapidly progressing disease that occurs when blood pressure is too high in vessels leading from the heart to the lungs. There is currently no cure for PAH, and about 50 percent of people who are diagnosed will die from the disease within five years. The high pressure is caused by abnormal remodeling of the lung blood vessels that sometimes leads to failure of the right ventricle and premature death. Thickening and narrowing of pulmonary vessels is seen with all types of pulmonary hypertension and is triggered by abnormal calcium levels within the vascular cells. The sarcoplasmic reticulum calcium ATPase pump (SERCA2a) regulates intracellular calcium in vascular cells and prevents them from proliferating in the vessel wall. We have delivered a therapeutic gene called SERCA2a in aerosol form to damaged blood vessels of the lung using an engineered adeno-associated virus. Two months after the gene delivery in a pig model of severe pulmonary hypertension, scientists performed tests to see if the new therapeutic genes were present and functioning in the vessels of the animals’ lungs, and whether the transfer was producing the desired effects. When they examined the animals, they found that that heart and lung function had improved and abnormal cellular changes causing PH were reduced.

Targeting Cardiac Fibrosis

CCN5, a matricellular protein, has been found to reverse established cardiac fibrosis in heart failure models. Cardiac fibrosis occurs when healthy cardiac cells are replaced with fibrous connective tissue, causing scarring and a stiffer and less compliant cardiac muscle. It is found to be an independent predictor for the progression of heart failure, which accounts for approximately 450,000 deaths per year in the United States. While there currently are no effective cardiac fibrosis therapies available, it is considered a valid target for treatment. Our team, having already established that CCN5 is significantly lower in the myocardium of patients with severe heart failure, examined whether CCN5 can reverse cardiac fibrosis in experimental models. They induced extensive cardiac fibrosis in models of heart failure, and then proceeded to transfer CCN5 to the hearts. Eight weeks later, the team examined the cellular and molecular effects. The results revealed that CCN5 reversed cardiac fibrosis in the models. Researchers used trichrome staining and analysis of myofibroblast contents before and after CCN5 gene transfer to clearly show the reversal. The therapeutic efficacy of CCN5 continues to be investigated in pre-clinical models of heart failure with extensive fibrosis.

Gene Editing in Inherited Cardiomyopathies

Gene therapy can clip out genetic material linked to heart failure and replace it with the normal gene in human cardiac cells. Genetic mutations, the small random, changes in the genetic code making up genes, are major culprits in the weakening heart muscle seen in patients with heart failure  Cardiomyopathies are diseases of weakened heart muscle, which can lead to heart enlargement and heart failure. The conditions are often genetically inherited. A number of inherited gene mutations have been associated with cardiomyopathies, including mutations in the phospholamban (PLN) gene, which is a critical regulator of healthy cardiac cell function and its calcium cycling. Calcium is a critical mineral for heart muscle cells to properly contract and pump blood from the heart to the rest of the body. The R14del mutation within the PLN gene has been identified in a number of families with genetic heart failure. The mutation is linked to dilated heart muscle, dysfunctional heart muscle contraction, dangerous arrhythmias, and the development of heart failure by middle age. In a recent study, Our team collected skin cell samples from a heart failure patient who has the R14del mutation. The skin cells from the patient were then transformed in the laboratory to become induced pluripotent stem cells (iPSCs). These stem cells, which carry the genetics of the heart failure patient, were then differentiated from the skin cells into specialized heart muscle cells called cardiomyocytes (iPSC-CMs), which also carry the patient’s genetic history. To correct the gene mutation in cardiomyocytes researchers successfully used two novel methods. First, they used a specifically designed transcription activator-like effector nucleases called TALENs to target and eliminate the presence of R14del-associated disease in cardiac cells. This genome engineering technique cut out the diseased gene and replaced it with a normal PLN gene resulting in normally functioning cardiomyocytes. Our  team used an adeno-associated viral-vector (AAV) gene therapy approach with the harmful part of a virus removed to safely target the inside of cardiac cells and knock-down the abnormal PLN gene in cardiac cells and simultaneously express normal PLN gene successfully reversing disease. This method works within the diseased cardiac cells to suppress the expression of the diseased gene and express normal PLN proteins. This gene therapy approach also corrected the functional abnormalities of the cardiac cells. These offer potentially new strategies to target and interrupt the disease causing path of the mutation associated with cardiomyopathies and heart failure. Similar methods are being used for cardiomyopathies caused by Duchenne Dystrophy, Friedreich’s Ataxia and Amyloidosis.