Penn Cardiovascular Institute (CVI)
Congrats to Dr. Senthil Selvaraj, recipient of the Measey Fellowship!
Successful candidates will receive a year of support, which will supplement their compensation from the amount paid by their training grant (or other source) to $100,000 per year. The DOM/Measey Fellowship is eligible for yearly renewal up to a total of 3 years, contingent on an annual review by the Oversight Committee, and satisfactory progress towards grant support. DOM/Measey Fellows will be classified as senior research fellows within the DOM, with a specific plan for them to compete for an appointment as Instructor or Assistant Professor. The timing and nature of the application for appointment will be determined by the Fellow’s Division Chief and the Chair of the Department of Medicine.
Congrats to Dr. Senthil Selvaraj, recipient of the Junior Investigator Preliminary/Feasibility Grant Program Award!
The primary goal of the CHPS Junior Investigator Preliminary/Feasibility Grant Program (JIPGP) is to encourage junior investigators to develop clinical research projects that will ultimately lead to competitive extramural funding and a career in Clinical Translational Research Center-focused clinical investigation. The awards are designed to allow junior faculty members and M.D., Ph.D. or D.M.D post-doctoral trainees with appropriate mentors to obtain funds for pilot projects that are investigator-initiated, human-based, CHPS studies that will enable an applicant to obtain preliminary data.
Congratulations to Bonnie Key for her cover story in Cardiology Today!
The cardio-oncology subspecialty has exploded in recent years, with the launch of dedicated cardio-oncology centers, entire conferences focusing on this area and new research, as awareness of cardiotoxicities associated with cancer treatment has increased.
Examining How Commonly Used Blood Pressure Medications Affect Outcomes Among Patients with COVID-19
A trial led by Julio Chirinos, MD, PhD and Jordana B. Cohen, MD, MSCE at the Perelman school of Medicine at the University of Pennsylvania will evaluate whether the use of medications to treat high blood pressure affect outcomes among patients who are prescribed the medication and hospitalized with COVID-19. As part of the multi-center, international trial called REPLACE COVID, investigators will examine whether ACE inhibitors (ACEI) or Angiotensin Receptor Blockers (ARBs)—two classes of medications to treat high blood pressure—help to mitigate complications or lead to more severe symptoms and worse outcomes. The study (NCT04338009) is enrolling patients now.
Ben Prosser and Ken Margulies received an NIH NHLBI award in the amount of $3,432,780 over 5 years entitled: “Mechanical Stress-Dependent Remodeling of the Cardiac Microtubule Network”
Hypertension, which places a mechanical load on the heart, is a common and potent cardiovascular risk factor. Hypertensive heart disease refers to the unfavorable enlargement, stiffening and weakening of the hearts of hypertensive patients that increase the risk of developing heart failure. This research examines how changes in the microtubule cytoskeleton within heart muscle cells contribute to these structural and functional abnormalities in order to develop new treatments to prevent and treat hypertensive heart disease and heart failure.
Zolt Arany received an NIH NHLBI award in the amount of $2,325,257 over 4 years entitled: Branched chain amino acids in heart failure
Branched chain amino acids (BCAAs) are avidly consumed by the normal pancreas, and circulating BCAA levels are elevated in both pancreatic ductal cancer DA and obesity, a strong risk factor for PDA. We propose here that BCAAs contribute to PDA in two keys ways, first by directly promoting tumor initiation, and next by promoting a systemic environment highly supportive of PDA growth, and will test these hypotheses with a range of mouse models and comprehensive studies on the roles of BCAAs in PDA.
Dan Kelly and Ken Margulies, along with collaborators at Temple University, received an NIH NHLBI award in the amount of $3,224,444 over 4 years entitled: Targeting Ketone Metabolism as a Novel Heart Failure Therapy
Current therapies for heart failure are largely directed at maladaptive extra-cardiac circuits rather than towards the heart itself. In this project, this team will build on their recent observations that provision of ketone bodies as an alternate fuel reduced the development of heart failure in small and large animal models. The studies planned will provide new insight into the mechanisms whereby ketone bodies ameliorate heart failure, and will provide rigorous pre-clinical assessment of strategies aimed at increasing delivery of ketone bodies as a novel therapeutic.
A Critical Role for Estrogen-related Receptor Signaling in Cardiac Maturation
ERR Alpha and Gamma are critical regulators of cardiac myocyte maturation, serving as transcriptional activators of adult cardiac metabolic and structural genes, and suppressors of non-cardiac lineages including fibroblast determination.
Tomoya Sakamoto, Ph.D. & Timothy Matsuura, Ph.D.
Circulation Research, March 2020, in press
A Balance Between Intermediate Filaments and Microtubules Maintains Nuclear Architecture in the Cardiomyocyte
Disrupting the tethering of desmin to the nucleus results in a loss of nuclear homeostasis and rapid alterations to cardiomyocyte function. Our data suggest that a balance of forces imposed by intermediate filaments and microtubules is required to maintain nuclear structure and genome organization in the cardiomyocyte.
Benjamin Prosser, Ph.D. & Rajan Jain, M.D.
Circulation Research. 2020;126:e10–e26
Microtubules Increase Diastolic Stiffness in Failing Human Cardiomyocytes and Myocardium
This study provides the first evidence that targeting microtubules reduces viscous forces during diastolic stretch of failing human myocardium, improving myocardial compliance. This work motivates the development of therapies to target microtubule detyrosination specifically, or cardiac viscoelasticity more broadly.
Benjamin Prosser, Ph.D. & Kenneth Margulies, M.D.
Circulation, Volume 141, Issue 11, 17 March 2020; Pages 902-915
Congratulations to Marielle Scherrer-Crosbie on her feature in Penn Medicine News!
Patients with acute lymphoblastic leukemia or acute myeloid leukemia who 
are treated with anthracyclines are at a heightened risk of heart failure — often within one year of exposure to the chemotherapy treatment, according to a new study led by Marielle Scherrer-Crosbie, MD, PhD, director of the Cardiac Ultrasound Laboratory and a professor of Cardiovascular Medicine. To identify a patient’s risk for heart failure following the treatment, researchers developed a risk score based on clinical and echographic variables.
See also Cardiology Today, AJMC Newsroom, and News-Medical.net
Stanford-Penn Symposium 2019 Photos
View some images from the Stanford-Penn Symposium in November 2019
Congratulations to Winners at the Northwestern Cardiovascular Young Investigators' Forum!
Junior Faculty (Clinical) Winner of the Jeremiah Stamler Award:
Payman Zamani, MD, MTR
"Impaired Skeletal Muscle Oxidative Capacity in HFpEF"
Fellows (Basic Science) 2nd Place:
Eliot Graham Peyster, MD, MSc
"In-situ Immune Profiling of Heart Transplant Biopsies to Improve Diagnostic Accuracy and Rejection Risk Stratification"
Junior Faculty (Basic Science) 1st Place:
Marie Guerraty, MD, PhD
"Friend of GATA 2 (FOG2/ZFPM2) is Associated with Coronary Microvascular Disease and Mediates Hypoxia-inducible Factor (HIF) Angiogenic Gene Expression"
Stanford-Penn Cardiovascular Symposium
Featuring: Daniel Kelly, MD; Saman Nazarian, MD, PhD; Thomas Cappola, MD, ScM; Bonnie Ky, MD, MSCE; Daniel Rader, MD; Rajan Jain, MD; Kiran Musunuru, MD, PhD, MPH; Zoltan Arany MD, PhD; Scott Damrauer, MD.
November 4-5, 2019 – Stanford, California
The ADP/ATP translocase drives mitophagy independent of nucleotide exchange.
Mitochondrial homeostasis vitally depends on mitophagy, the programmed degradation of mitochondria. In this paper we devised a multidimensional genome-wide CRISPR/Cas9 screen to uncover numerous new components of Parkin-dependent mitophagy. In particular, and quite unexpectedly, we identify the adenine nucleotide translocator (ANT) complex as required for mitophagy, independently of its nucleotide translocase catalytic activity. We work out the mechanism by which ANT does so, and link the findings to disease-causing mutations in human ANT1, thus suggesting that these diseases may in fact partly be due to defects mitophagy
Zoltan Arany, M.D., Ph.D.
Nature. 2019 Nov;575(7782):375-379. doi: 10.1038/s41586-019-1667-4. Epub 2019 Oct 16.
"Targeting cardiac fibrosis with engineered T cells"
Jonathan Epstein, Ph.D., Rajan Jain, M.D., and Kenneth Margulies, M.D.
Congratulations to Drs. Rajan Jain and Arjun Raj!
Recipients of the 2019 NIH Director's Transformative Research Award!
Genomics-First Evaluation of Heart Disease Associated With Titin-Truncating Variants.
Zoltan Arany, M.D., Ph.D.
Truncating variants in the Titin gene (TTNtvs) are common in individuals with idiopathic dilated cardiomyopathy (DCM). Here, we reviewed whole exome sequence data for >71,000 individuals and used detailed linked electronic health records (EHR) to evaluate associations of TTNtvs with diagnoses and quantitative echocardiographic measures. We identify a number of key findings: 1) >90% of individuals with TTNtvs in a general population are without symptoms or cardiac diagnosis, highlighting the low penetrance of TTNtvs for causing disease; 2) these same individuals, however, do have detectable mildly reduced ejection fraction on echocardiography, indicating that TTNtvs do impact their cardiac function; 3) individuals with TTNtvs are also more prone to arrhythmias, in particular atrial fibrillation; and 4) the risk for DCM conferred by TTNtvs is less pronounced in individuals of African ancestry. Given these findings, clinical identification of TTNtv carriers may alter clinical management strategies.
Circulation. 2019 Jul 2;140(1):42-54.
Congratulations to Dr. Zoltan Arany for his election to Association of American Physicians (AAP)!
Zoltan Arany, M.D., Ph.D.
Professor of Medicine
Director, Cardiovascular Metabolism Program
Penn Cardiovascular Institute, Perelman School of Medicine
Posted: April 5, 2019
Congratulations to Bonnie Ky for her Editorship with JACC CardioOncology!
The American College of Cardiology (ACC) will expand the JACC family of journals with the launch of JACC: CardioOncology in September 2019. Bonnie Ky, MD, MSCE, FACC, will serve as Editor-in-Chief.
~ JACC: CardioOncology – Launching in September 2019
Congratulations to Rajat Deo and Kenneth Margulies on their published Op-Ed!
Coronary artery disease is the most common risk factor linked to sudden cardiac death. Yet, questions exist about why some people are more likely to die suddenly than others who have the same medical condition.
~ Understanding Who's at Risk for Sudden Cardiac Death Published in The Inquirer
Congratulations to Dr. Kiran Musunuru for Receiving the AFMR 2019 Outstanding Investigator Award!
An Outstanding Investigator Award is presented annually to an AFMR member in recognition of excellence in biomedical research.
~AFMR
New Heart Valve Modeling Technique Enables Customized Medical Care for Patients
Robert Gorman, M.D.
Professor of Surgery
Perelman School of Medicine
“Cardiac surgeons must decide upon the best possible treatment for heart valve repair without knowing all the facts,” said Dr. Robert Gorman, professor of surgery in the Perelman School of Medicine at the University of Pennsylvania and a key collaborator on the study. “Most rely on their own experiences or how they were taught to perform valve repair surgery in medical school.”
~ University of Texas at Austin News
Congratulations to Drs. Rajan Jain, Mark Kahn, and Zoltan Arany for receiving the AHA-Allen Award!
Rajan Jain, M.D.
Assistant Professor of Medicine
Perelman School of Medicine
Mark Kahn, M.D.
Cooper-McLure Professor of Medicine
Director, Center for Vascular Biology
Penn Cardiovascular Institute, Perelman School of Medicine
Zoltan Arany, M.D., Ph.D.
Professor of Medicine
Director, Cardiovascular Metabolism Program
Penn Cardiovascular Institute, Perelman School of Medicine
~ The American Heart Association
Posted: November 13, 2018
Congratulations to Dr. Zoltan Arany for his election to a Fellow of ISHR!
Zoltan Arany, M.D., Ph.D.
Professor of Medicine
Director, Cardiovascular Metabolism Program
Penn Cardiovascular Institute, Perelman School of Medicine
See: ISHR World Newsletter pg. 13
Posted: November 13, 2018
Congratulations to Dr. Kiran Musunuru for Receiving the 2018 Judson Daland Prize!
Kiran Musunuru, M.D. Ph,D., M.P.H.
Associate Professor; Director
Genetic and Epigenetic Origins of
Disease Program, Cardiovascular
Institute, Perelman School of Medicine
"The prize was presented to Kiran Musunuru at the American Philosophical Society 2018 November Meeting, in recognition of his work discovering and therapeutically targeting cardiovascular disease genes."
~The American Philosophical Society
Posted: June 5, 2018
Congratulations to Dr. Rajan Jain for Receiving a New Innovator NIH Director's Award!
Rajan Jain, M.D.
Assistant Professor of Medicine
Perelman School of Medicine
"Rajan Jain, MD, an assistant professor of Medicine and Cell and Developmental Biology and member of the Cardiovascular Institute (CVI) and Institute for Regenerative Medicine (IRM), will be provided $2.4 million to advance understanding how cell identity is established and maintained. This generous support will help his group decode the rules that instruct genome organization and cellular identity, ultimately revealing implications for human disease."
~Penn Medicine News
Dr. Kiran Musunuru Testifying in the US Senate:
Dr. Musunuru briefing staff members of the U.S. Senate Committee on Health, Education, Labor and Pensions about genomic medicine and gene editing on September 28, 2018, in Washington, DC, as a representative of the American Society of Human Genetics.
Photo credits: Ann Klinck.