Alexey V. Glukhov, PhD

Pubmed

More information:

• Dr. Glukhov’s Lab Website

Focus Groups: 

Developmental Biology & Regenerative Medicine; Membrane Biology and Protein Trafficking; Physiology

 Research Description:

Our laboratory is a part of the Cellular and Molecular Arrhythmia Research Program (CMARP) involving multiple investigators working on a wide range of research projects exploring the molecular function of ion channels in human physiology, pharmacology, and disease. Our research interests are focused on studying cellular and molecular mechanisms of cardiac excitability and contractility, neurohormonal regulation of cardiac physiology, and mechanisms of abnormal heart rhythms (arrhythmias). We use electrophysiology, cell biology, molecular biology techniques, and various state-of-the art imaging modalities to identify triggers and treatments of cardiac disease. The primary goal of our research is to improve the health of people with cardiac arrhythmias, including the most common abnormal heart rhythm, atrial fibrillation, affecting about 2% to 3% of the Western population. To accomplish this, we aim to identify novel diagnostic tools and therapeutic targets through investigation of mechanisms of cardiac remodeling and arrhythmogenesis.

Our group has a multidisciplinary background that includes expertise in physiology, cell biology, biomedical engineering, biophysics, and confocal microscopy. We employ several state-of-the-art techniques, including high-resolution fluorescent optical mapping and scanning ion conductance microscopy (SICM) equipped with “smart” patch-clamp. This unique set of skills and experimental techniques allow us to investigate mechanisms of arrhythmias across multiple scales from protein expression, localization and function, to electrical and mechanical activity of an intact heart. Our research is specifically focused on elucidating the functionality of subcellular nanodomains and their role in regulation of proteins responsible for normal and pathophysiological electro-mechanical activity of the heart. We pursue two main directions: (1) determining the cellular and molecular mechanisms underlying normal electrical activity and dysfunction of the sinoatrial node, the heart’s natural pacemaker, and (2) discovering novel strategies for atrial fibrillation treatment and risk stratification.

Our group has several collaborative projects with SCRMC PIs, including Drs. Timothy Kamp, Lee Eckhardt, Carter Ralphe, Wendy Crone, Timothy Hacker and others. One of the collaborative projects aims to study cellular and molecular mechanisms of stretch-induced arrhythmogenesis and involves the use of human engineered cardiac tissue (ECTs) constructs which are generated from atrial- or ventricular-like cardiomyocytes derived from human induced pluripotent stem cells mixed with human fibrin and cast into cylindrical constructs to form highly organized tissue strips. ECTs represent a highly-controlled three-dimensional construct that leads to high-precision, high-throughput, repeatable platforms to investigate cardiac electrophysiology and rapid assessment of disease-specific manifestations of arrhythmias and response to therapies.

Also a trainer in the following programs:

Molecular and Cellular Pharmacology (MCP), Cellular and Molecular Biology (CMB), Cardiovascular Training Program

Selected References:

• Alexanian R, Lalit P, Lang D, Lea M, Vaidyanathan R, Markandeya Y, Zhai A, Schmuck E, Eckhardt L, Glukhov A, Kamp TJ. Reporterless Reprogrammed Cardiac Progenitor Cells Attach, Migrate, and Repopulate Decellularized Whole Mouse Hearts. American Heart Association Scientific Sessions, November 12 – 15, 2016. New Orleans, LA, USA. Circulation. 2016; 134: A20576.
• Miragoli M, Glukhov AV. Atrial fibrillation and fibrosis: Beyond the cardiomyocyte centric view. BioMed Research International. 2015: 798768.
• Efimov IR, Fedorov VV, Glukhov A, Lou Q, Ambrosi C, Janks D, Hucker WJ, Kurian T, Schuessler RB, Moazami N. Multiscale imaging of the human heart: Building the foundation for human systems physiology and translational medicine. Conf Proc IEEE Eng Med Biol Soc. 2010; 1:5177-80.
• Glukhov AV, Fedorov VV, Lou Q, Ravikumar VK, Kalish PW, Schuessler RB, Moazami N, Efimov IR. Transmural dispersion of repolarization in failing and non-failing human ventricle. Circ Res. 2010; 106(5):981-91.
• Glukhov AV, Fedorov VV, Kalish PW, Ravikumar VK, Lou Q, Janks D, Schuessler RB, Moazami N, Efimov IR. Conduction remodeling in human end-stage nonischemic left ventricular cardiomyopathy. Circulation. 2012; 125:1835-184.