Goldhaber Lab
Research in the Goldhaber Laboratory is directed toward a more complete understanding of the molecular basis of contractile dysfunction of heart muscle associated with acute myocardial infarction and systolic heart failure. The laboratory is also concerned with the consequences of heart failure on other organ systems, particularly the kidney, leading to cardiorenal syndrome and other lethal complications of heart failure.
Over the past two decades, the Goldhaber Laboratory has shown that the fundamental mechanism of heart muscle contraction, known as excitation-contraction (EC) coupling, fails as a result of metabolic and oxidative stress. For example, localized calcium release sites responsible for activating contraction, known as couplons, begin to drop out during metabolic inhibition in a predictable fashion. This is caused by a reduction in the ability of single calcium channels in the cell membrane to open properly because of energy deprivation and abnormal signaling.
The laboratory has a particular interest in the role played by the sodium-calcium exchange (NCX) transporter in the fate of cardiac contractility during metabolic stress. Mice genetically modified to either overexpress or ablate NCX have enabled the laboratory to make paradigm-shifting observations. For example, the lab has shown definitively that NCX ablation allows heart cells to resist ischemia and reperfusion injury, and to maintain normal excitation-contraction coupling. NCX also participates in the activation of calcium release and contraction rather than behaving as a passive participant, removing cellular calcium after each beat. Recent findings in the lab have shown that NCX is a critical component of the heart’s pacemaker system. Mice without NCX have a characteristically abnormal heart rhythm and cellular studies reveal failure of intracellular calcium movements and normal pacemaker activity.
The Goldhaber Laboratory is affiliated with the Cedars-Sinai Smidt Heart Institute and Department of Medicine.
Joshua Goldhaber, MD, leads the National Institutes of Health-supported Goldhaber Laboratory that studies the basic science of heart muscle contraction with a special emphasis on understanding how the strength of heart muscle is regulated at the cellular and molecular levels (excitation-contraction coupling). The overarching goal is to find ways to help diseased heart muscle perform beyond expectations.
- Leica SP5 laser scanning confocal microscope specially outfitted with patch clamp and bridge clamp setups as well as custom-designed perfusion and laser synchronization systems
- Two additional patch clamp setups outfitted with epifluorescence photometry
- One giant patch setup for oocytes
- Broad array of molecular biology and biochemistry equipment
- Incubators for cell and tissue culture
- High-performance computers for image analysis
Learn more about the scientists, faculty members, investigators and other healthcare professionals of the Goldhaber Laboratory, whose dedicated efforts lead to groundbreaking discoveries.
Cho JH, Kilfoil PJ, Zhang R, Solymani RE, Bresee C, Kang EM, Luther K, Rogers RG, de Couto G, Goldhaber JI, et al.
JCI. Insight. 2018 Oct 4;3(19). pii: 121123.
Bögeholz N, Pauls P, Dechering DG, Frommeyer G, Goldhaber JI, Pott C, Eckardt L, Müller FU, Schulte JS.
Front Pharmacol. 2018 Aug 21;9:933.
Cho JH, Zhang R, Aynaszyan S, Holm K, Goldhaber JI, Marbán E, Cingolani E.
Circ Arrhythm Electrophysiol. 2018 Aug;11(8):e006452.
Contact the Goldhaber Lab
8700 Beverly Blvd.
Davis Building, Room 2058
Los Angeles, CA 90048