F A C U L T Y P R O F I L E
MARX, STEVEN O., M.D.
Molecular biology/macromolecular complex formation of ion channels.
Office: Presbyterian Hospital | Room 3 Center
The Marx laboratory studies the regulation of ion channels by macromolecular complexes. We have demonstrated that specific sequences within the ion channel (leucine zippers) recruit regulatory proteins, which modulate the ion channel function in normal and pathologic conditions. The laboratory is now focused on understanding the molecular components and functional implications of macromolecular complex formation of the large conductance calcium-activated potassium channel (BKCa, maxi-K) and the L-type voltage gated calcium channel. The laboratory utilizes both molecular biologic and electrophysiologic (planar lipid bilayer, patch clamp) techniques to elucidate these fundamental processes and emphasizes the links between these fundamental molecular processes and systems function. To date our work has had significant impact in understanding the triggers of fatal cardiac arrhythmias and mechanical dysfunction in heart failure. Present experiments are very likely to impact our understanding of control of peripheral blood pressure by the sympathetic nervous system.
Ion channel regulation by macromolecular complexes
The objectives of this project are to examine the mechanisms that underlie the recruitment of adaptor proteins and kinases/phosphatases to cardiac ion channels. Since several cardiac ion channels (RyR2, a1c subunit of L-type Ca2+ channel, KvLQT1) have leucine zipper motifs and are regulated by phosphorylation, understanding the mechanism(s) of specific modulator targeting via leucine zippers may lead to a new paradigm for the study of ion channel regulation. Three specific aims are proposed to elucidate the targeting and functional role of RyR2-associated phosphatases: (1) Characterization of the mechanism by which PP1/spinophilin interacts with RyR2; (2) Characterization of the leucine zipper motif and identification of the targeting adaptor protein responsible for PP2A/RyR2 interaction; and (3) Functional characterization of the role of the anchoring of phosphatases to RyR2 using expression of constructs that specifically disrupt local signaling. National Heart, Lung, and Blood Institute (9/2001-6/2005).
1. Lehnart SE, Huang F, Marx SO, Marks AR.Immunophilins and coupled gating of ryanodine receptors. [Review.] Curr Top Med Chem.
2. Marx S. (2003) Ion channel macromolecular complexes in the heart. [Review.] J Mol Cell Cardiol. 3(12):1383-91.
3. Kass RS, Kurokawa J, Marx SO, Marks AR. (2003) Leucine/isoleucine zipper coordination of ion channel macromolecular signaling complexes in the heart. Roles in inherited arrhythmias. [Review.] Trends Cardiovasc Med. 35(1):37-44.
4. Marx SO, Marks AR. (2003) Regulation of the ryanodine receptor in heart failure. [Review.] Basic Res Cardiol. 13(2):I49-51.
5. Marks AR, Marx SO, Reiken S. (2002) Regulation of ryanodine receptors via macromolecular complexes: a novel role for leucine/isoleucine zippers. [Review.] Trends Cardiovasc Med. 12(4):166-70.
6. Marks AR, Reiken S, Marx SO. (2002) Progression of heart failure: is protein kinase a hyperphosphorylation of the ryanodine receptor a contributing factor? Circulation. 105(3):272-5.
Honors and Awards
1982 Westinghouse Science Talent Search Semi-Finalist
1986 Magna Cum Laude, Biology/Sociology
1988 Alpha Omega Alpha (AOA)
1994-1995 American College of Cardiology/Merck Fellow
1995 American College of Cardiology, NYS Chapter Young Investigator Award
1995 Astra-Merck Young Investigator's Forum Second Prize in Basic Research
1994-1995 John C. Sable Memorial Heart Fund Research Award
1995 The Denber Prize for Research, Mount Sinai Cardiovascular Institute
1996 Katz Award Finalist, American Heart Association
1996-1997 Glorney-Raisbeck Fellowship of the NY Academy of Medicine
1996-2001 Clinician-Scientist Award, American Heart Association