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).
Yikes, it’s been a while since the last update. As we begin 2017, this is a good time to reflect on the year that was. A source of pride in 2016 was the publication of the book Manual of Cardiovascular Proteomics, which I co-edited with Dr. Giulio Agnetti Assistant Professor of Medicine and Director of the Center for Research on Cardiac Intermediate Filaments here at Johns Hopkins Cardiology, and Dr. Merry Lindsey, Professor of Physiology/Medicine and Director of the Mississippi Center for Heart Research at the University of Mississippi. It was a delight to work with them as well as the cadre of exceptional contributors that includes both icons of cardiovascular proteomics and emerging stars. Merry, Giulio and I also chipped in a few chapters ;-). The scope of the book is pretty impressive, ranging from the time-honored fundamentals of chromatography and mass spectrometry to the modern tools of statistics, pathway, and network analyses, as they are applied to hotbed fields including ischemia-reperfusion injury, heart failure, vascular dysfunction, stem cell biology and clinical biomarker development. Check it out.
Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death. J Proteome Res. 2016 Sep 2;15(9):3009-28. doi: 10.1021/acs.jproteome.6b00149. PMID: 27399916
in which we examined the transcriptome, proteome and metabolome of heart failure progression in a modified pressure-overload guinea pig model that uniquely recapitulates both the transition from compensated hypertrophy to end-stage heart failure, but also clinically relevant sudden cardiac death. The model was developed by Dr. Ting Liu and Dr. Brian O’Rourke, Professor of Medicine and Vice-Chair for Basic and Translational Research in the Department of Medicine at Johns Hopkins. This paper represents the culmination of a broad collaboration between cardiac physiologists and biochemists, MS specialists, bioinformaticists and statisticians and commercial partners.
The goal was more than to simply extensively phenotype a new model of heart failure. Rather, we used the latest inferential pathway and upstream regulator analyses to garner new insights into likely gene-regulatory programs at work both early in hypertrophy and upon cardiac decompensation. We also wanted to showcase the value of multi-omic integration. The transcriptome provided the greatest depth of coverage particularly for proteomically-recalcitrant proteins like ion channels and other integral membrane proteins. But the proteins are the ultimate executors of cardiac function and for nearly 3000 of them, the correlation between protein and transcript changes in heart failure was fairly weak and were sometimes diametrically opposed, suggesting substantial post-transcriptional regulation. By integrating the proteome and metabolome we were also able to identify putative bottlenecks in metabolism.
Along with Dr. O’Rourke and collaborators, we have laid out the multi-omic landscape of hypertrophy and heart failure and have distilled a few essential take home messages. Moreover, our hope is that this study will serve as a resource for the research community. Along with the article, we have included an expansive online supplement that contains reader-friendly tables of analyses, as well as raw MS2 signal intensities for those who wish mine the data further.
Our most recent paper detailing the sites of lysine acetylation in the heart is now published in the online journal, PLOS One, and is also accessible through PubMed. One of the take home messages of the paper is that lysine acetylation in the heart goes beyond the well documented locations in the mitochondria and nucleus, and extends to calcium-handling proteins of the sarcoplasmic reticulum and the sarcomere. We present novel acetylation sites and outline testable hypotheses by which lysine acetylation might modulate function of key proteins involved in excitation-contraction coupling.