Andrew R. Marks, M.D.
Chairman and Professor of Physiology & Cellular Biophysics; Clyde and Helen Wu Professor of Medicine
(Molecular Cardiology); Professor of Biomedical Engineering; Director, Wu Center for Molecular Cardiology
Molecular mechanisms regulating contraction of normal and failing cardiac muscle, molecular triggers for cardiac arrhythmias, and coronary artery restenosis following stent placement.
A major focus of the laboratory is the study of mechanisms that regulate muscle contraction. In particular we use a variety of techniques including molecular biology, biophysics, cell biology, imaging (Live5 Zeiss Confocal), and structural biology to gain better understandings of the regulation of calcium release channels on the sarcoplasmic reticulum that control excitation-contraction (EC) coupling in cardiac and skeletal muscle. There are opportunities for graduate students and postdoctoral fellows to head their own projects using any of the various techniques that we employ to examine the regulation of calcium signaling and muscle function in normal and diseased states. In addition the laboratory has developed numerous genetic mouse models (primarily knock-ins and knock-outs) that are available to address specific questions concerning the regulation of key signaling pathways that control muscle contraction - in both cardiac and skeletal systems.
Much of the work in the laboratory is "translational" in that it leads directly to understanding the molecular basis of human diseases including heart failure and sudden cardiac death. In addition, novel therapeutic approaches are being tested including those that fix the "leak" in the RyR2 calcium release channel that causes heart failure and sudden cardiac death.
In addition, there are projects focusing on gaining better understandings of cardiac muscle growth and excitability, T cell and B cell activation, as well as vascular smooth muscle proliferation. The latter project has lead directly to the development of the drug eluting stents that are currently used for patients with coronary artery disease. - Additional research info
Dridi H, Santulli G, Gambardella J, Jankauskas SS, Yuan Q, Yang J, Reiken S, Wang X, Wronska A, Liu X, Lacampagne A, Marks AR. IP3 receptor orchestrates maladaptive vascular responses in heart failure. J Clin Invest. 2022 Feb 15;132(4):e152859. doi: 10.1172/JCI152859. PMID: 35166236; PMCID: PMC8843748
Melville Z, Kim K, Clarke OB, Marks AR. High-resolution structure of the membrane-embedded skeletal muscle ryanodine receptor. Structure. 2021 Aug 26:S0969-2126(21)00296-3. PMID: 34469755
des Georges A, Clarke OB, Zalk R, Yuan Q, Condon KJ, Grassucci RA, Hendrickson WA, Marks AR, Frank, J Structural Basis for Gating and Activation of RyR1. Cell 2016 Sep 22;167(1):145-157.e17. doi: 10.1016/j.cell.2016.08.075. PMID:27662087
Waning DL, Mohammad KS, Reiken S, Xie W, Andersson DC, John S, Chiechi A, Wright LE, Umanskaya A, Niewolna M, Trivedi T, Charkhzarrin S, Khatiwada P, Wronska A, Haynes A, Benassi MS, Witzmann FA, Zhen G, Wang X, Cao X, Roodman GD, Marks AR, Guise TA
Excess TGF-Beta mediates muscle weakness associated with bone metastases in mice. Nature Medicine, 2015 Oct 12 [Epub ahead of print] PMID:26457758
Ran Zalk, Oliver B. Clarke, Amédée des Georges, Robert A. Grassucci, Steven Reiken, Filippo Mancia, Wayne A. Hendrickson*, Joachim Frank*, Marks, A.R.* (2015) Structure of a mammalian ryanodine receptor Nature 2015; 517(7532):44-9 PMCID: PMC4300236