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With the award of an R01 grant from the National Institutes of Health we are excited to begin a deep dive into understanding precisely how Vitamin A (retinol) is converted to all-trans retinoic acid (ATRA) in the adult mammalian heart and how retinoid metabolism becomes discombobulated in the setting of heart failure (see Research tab). These studies extend our longstanding collaboration with Dr. Maureen Kane (co-PI), of the University of Maryland School of Pharmacy.
Congrats to Kyriakos, whose study on the impact of O-GlcNacylation on the MAP kinases, p38 and Erk1/2 in cardiac myocytes was accepted for publication in the Journal of Biological Chemistry. This work was carried out in collaboration with Dr. Brian O’Rourke (Division of Cardiology) and Dr. Natasha Zachara (Dept of Biological Chemistry). Kyriakos’ studies were aided by our talented undergraduate students Jessica, Cecelia, Amir and Eddie.
It was tough work, but someone had to do it. Brian was invited to present at the 8th International Caparica Conference on Analytical Proteomics in Caparica, Portugal (across the bay from Lisbon), July 18-21, 2022. Specifically, he talked about how the lab has used integrated proteomics (whole proteome and targeted MS quantification) and metabolomics to reveal a role for cardiac ATRA insufficiency in the pathogenesis of HF in both preclinical models and patients. The conference, organized by the indefatigable Jose Luis Capelo (NOVA University of Lisboa), featured an excellent keynote presentation from Christopher Overall (University of British Columbia) and American Journal of Physiology editor, Dr. Merry Lindsey (Meharry College). The program was strong and the venue afforded a beautiful vista of the Atlantic Ocean, two reasons Brian will definitely put the meeting on his calendar for 2024.
It was a pleasure to present face-to-face at the 6th International Conference of Retinoids held June 5-10, at Ohio University in Athens, Ohio. The info-packed conference was chaired by Dr. Maureen Kane (U Maryland) and Alex Moise (Northern Ontario School of Medicine). We presented our latest work on the role of cardiac ATRA insufficiency in heart failure. Indeed, Hopkins was well represented, with Laszlo Nagy, Ph.D. who spoke on the role of RXRs in the epigenetic control of macrophage polarization and Keith West, DrPH, who gave a keynote address chronicling his work on the impact of Vitamin A supplementation in Asia…which was interrupted halfway through by an emergency tornado warning! Memorable on many levels.
Congrats to Kyriakos for earning a career development award from the American Heart Association to study the role of O-GlcNacylation in the context of cardioprotection. Kyriakos is a highly talented researcher with a broad skill set in molecular cardiology. He will be in the market for an Assistant Professor position soon. Interested parties should contact firstname.lastname@example.org.
We are honored to have been awarded a 1-year grant from the Saving Tiny Hearts Society to initiate studies of the enzymes that underlie the metabolism in the human heart. The premise of the work is that notwithstanding advances in pediatric cardiac surgery, children born with CHD remain at risk of developing HF throughout their development to adulthood and beyond. We submit that proper retinoid metabolism and signaling is key to both human heart development and post-natal heart health, yet the enzymes responsible for the metabolism of retinol to retinoic acid in the human heart are largely unknown. This represents a fundamental knowledge gap in cardiac biology. We believe that identifying these enzymes represents a crucial first step toward the design of therapies to preserve cardiac ATRA homeostasis.
The labors of the past few years came to fruition with the publication of Cardiac retinoic acid levels decline in heart failure in JCI Insight.Brian would like to extend tremendous thanks to all of the co-authors, but particularly our tireless visiting postdoc, Ni Yang (1st author), our super-talented undergraduate trainee, Lauren Parker, and our team of collaborators at the University of Maryland School of Pharmacy led by Dr. Maureen Kane. The project showcases the power of systems biology in action, with molecular and physiological experiments informed by multi-omic analysis and network inference.
Brian and Lauren hit the Basic Cardiovascular Sciences 2018 Scientific Sessions in San Antonio, July 31-Aug2, last week. Brian presented his invited seminar entitled Altered Retinostasis in Heart Failure in the Tuesday session on Transcriptional Regulation and Epigenetics. Stunning talks by all the speakers, including Enzo Porello from Murdoch Children’s Research Institute, Tom Vondriska from UCLA and Sam Bhattacharyya from UTSW.
Lauren presented her first poster at a national meeting entitled Characterization of the Mechanisms of Retinoic Acid-Mediated Suppression of Cardiac Hypertrophy, in the Wednesday afternoon poster session. She nailed it! Lots of traffic, interest and feedback.
Brian and Lauren would like to thank the organizers of the BCVS 2018 meeting for the opportunity to present their data.
A few weeks ago we were thrilled to learn that the AHA has chosen to fund our work on altered retinoic acid homeostasis in heart failure progression with a Transformational Project Award. I wish to extend my thanks to the AHA, past and present members of the research team (Ni, Lauren & Kyriakos), as well as colleagues for their critical advice and support (you know who you are).
D. Brian Foster Ph.D.
Assistant Professor of Medicine
Division of Cardiology
Director, Laboratory of Cardiovascular Biochemistry
The Johns Hopkins University School of Medicine
Ross Research Building, Room 847
720 Rutland Avenue
Baltimore, MD 21205
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