|Address:||Science & Engineering Hall
800 22nd Street, NW
Professor Entcheva is recognized for pioneering cardiac optogenetics - the genetically mediated light sensitization of heart cells and tissue to allow optical stimulation, imaging and control of their electrical activity. The goal of Prof. Entcheva’s laboratory (the Cardiac Optogenetics & Optical Imaging Laboratory) is to work out the biophysical limits of and develop the technological innovations needed for a fundamentally new highly-parallel framework for all-optical cardiac electrophysiology in vitro and in vivo. Guided by our own theoretical/computational work in the area of bioelectricity, we experimentally integrate, test and validate new optical modalities for actuation (stimulation), including optogenetics, and sensing (fluorescent and dye-free optical mapping) of the electromechanical function in cardiac cells and tissues. Our tools are particularly useful for mechanistic dissection of cardiac cell excitation, cell-cell communication and spatiotemporal phenomena like cardiac arrhythmias, in response to pharmacological, genetic or other manipulations, in lab-on-a-chip platforms, using single primary or stem-cell-derived cardiomyocytes and engineered tissues, as well as in vivo animal models. This is done in a high-throughput fashion not affordable by other methods.
Our group leads efforts in the concept and development of new fully automated high-throughput all-optical electrophysiology platforms to improve drug testing, human stem cell research and gene therapies for the treatment of cardiac arrhythmias. We collaborate with companies or other researchers to characterize the electromechanical function of disease-specific patient-derived iPS-CMs in a massively parallel fashion. In addition to contributions to the field of computational optogenetics (in collaboration with Dr. Trayanova and Boyle at JHU), we have recently demonstrated the first application of optogenetics for dynamic “wave control” by light in living tissue using patterned light (collaboration with Dr. Bub, Oxford). Our goal is to stimulate and engage others in the cardiac community in adopting these newly available all-optical tools for dissection and control of normal and abnormal heart function.
- Wednesday: 3:00 – 5:00 pm
- B.S./M.S. Electrical Engineering, Technical University – Sofia, Bulgaria
- Ph.D. Biomedical Engineering, The University of Memphis, 1998
- Postdoctoral, Biomedical Engineering, Johns Hopkins University, 2000
From the last five years
- Entcheva E and Bub G, All-optical control of cardiac excitation: Combined high-resolution optogenetic actuation and optical mapping. Journal of Physiology, 2016 (invited perspective), in press.
- Klimas A, Ambrosi CM, Yu Y, Williams JC, Bien H, Entcheva E. OptoDyCE: Automated System for High-Throughput All-Optical Dynamic Cardiac Electrophysiology. Preprint BioRxiv. 2015. doi: 10.1101/023572
- Ambrosi CM, Boyle PM, Chen K, Trayanova NA and Entcheva E, Optogenetics-enabled assessment of viral gene and cell therapy for restoration of cardiac excitability. Scientific Reports, doi:10.1038/srep17350, 2015.
- Yu J, Chen K, Lucero RV, Ambrosi CM and Entcheva E, Cardiac optogenetics: Enhancement by all-trans-retinal. Scientific Reports, doi:10.1038/srep16542, 2015.
- Burton RAB, Klimas A, Ambrosi CM, Tomek J, Corbett A, Entcheva E and Bub G, Optical control of excitation waves in cardiac tissue. Nature Photonics, 9(12), 813-816, 2015 (* media coverage).
- Yu J and Entcheva E, Inscribing optical excitability to non-excitable cardiac cells: viral delivery of optogenetic tools in primary cardiac fibroblasts. Methods in Molecular Biology, (invited article), in press.
- Entcheva E. A step closer to cardiac optogenetics in vivo. (invited editorial), Cardiovascular Research, 106(2):180-1. doi: 10.1093/cvr/cvv116, 2015.
- Boyle PM, Karathanos TV, Entcheva E and Trayanova NA. Computational modeling of cardiac optogenetics: Methodology overview and review of findings from simulations. Computers in Biology and Medicine, doi: 10.1016/j.compbiomed.2015.04.036, 2015.
- Williams JC and Entcheva E, Optogenetic vs. electrical stimulation of human cardiomyocytes: Modeling insights. Biophysical Journal 108(8):1934-45. doi: 10.1016/j.bpj.2015.03.032, 2015.
- Klimas A and Entcheva E, Toward microendoscopy-inspired cardiac optogenetics in vivo: technical overview and perspective. Journal of Biomedical Optics, 19(8):080701. doi: 10.1117/1.JBO.19.8.080701, 2014.
- Entcheva E and Williams JC, Channelrhodopsin2 current during the action potential: “Optical AP clamp” and approximation. Scientific Reports, 4:5838, doi:10.1038/srep05838, 2014.
- Ambrosi CM, Klimas A, Yu JZ and Entcheva E, Cardiac applications of optogenetics. Progress in Biophysics & Molecular Biology, doi: 10.1016/j.pbiomolbio.2014.07.001, 2014.
- Ambrosi CM and Entcheva E, Optogenetic control of cardiomyocytes via viral delivery. Methods in Molecular Biology, 1181:215-28, doi: 10.1007/978-1-4939-1047-2_19, 2014.
- Wu CY, Chen B, Jiang YP, Jia Z, Martin DW, Liu S, Entcheva E, Song LS, Lin RZ. Calpain-dependent cleavage of junctophilin-2 and T-tubule remodeling in a mouse model of reversible heart failure, Journal of the American Heart Association, PMID: 24958777, 3(3):e000527, 2014.
- Entcheva E. Fiat lux in understanding cardiac pacing, resynchronization and signaling by way of optogenetics. (invited editorial), Cardiovascular Research, PMID: 24760549, 102(3):342-3, 2014.
- Ambrosi CM, and Entcheva E. Optogenetics' promise: Pacing and cardioversion by light? (invited editorial), Future Cardiology 10(1):1-4, 2014.
- Boyle PM, Entcheva E, and Trayanova N. See the light: Can optogenetics restore healthy heartbeats? And if it can, is it really worth the effort? (invited editorial) Expert Review of Cardiovascular Therapy, PMID 24308809. 2014.
- Williams JC, Xu J, Lu Z, Klimas A, Chen X, Ambrosi CM, Cohen IS, and Entcheva E. Computational Optogenetics: Empirically-Derived Voltage- and Light-Sensitive Channelrhodopsin-2 Model. PLoS Computational Biology 9:e1003220, 2013.
- Boyle PM Williams JC, Ambrosi CM, Entcheva E, and Trayanova NA. A comprehensive multiscale framework for simulating optogenetics in the heart. Nature communications 4:2370, 2013. (* media coverage)
- Entcheva E, Cardiac Optogenetics, (invited review/perspective), American Journal of Physiology - Heart & Circ Physiol, 304(9):H1179-91, 2013.
- Entcheva E, Integration of optical stimulation with high-resolution optical imaging of cardiac tissue, Microscopy & Analysis, 27(1): D4, 2013.
- Boink GJJ, Lu J, Driessen HE, Duan L, Sosunov EA, Anyukhovsky EP, Shlapakova IN, Lau DH, Rosen TS, Danilo P, Jia Z, Guo Y, Brink PR, Kryukova Y, Robinson RB, Entcheva E, Cohen IS, and Rosen MR, Effect of SkM1 sodium channels delivered via a cell platform on cardiac conduction and arrhythmia induction , Circulation: Arrhythmia & Electrophysiology, 5(4):831-840, 2012.
- Lu, J, Wang HZ, Jia Z, Zuckerman J, Lu Z, Guo Y, Brink PR, Robinson RB, Rosen MR, Entcheva E, and Cohen IS, Improving cardiac conduction with a skeletal muscle sodium channel by gene and cell therapy, Journal of Cardiovascular Pharmacology, 60(1):88-99, 2012.
- Jia Z, Bien H, Shiferaw Y and Entcheva E, Cardiac cellular coupling and the spread of early instabilities in intracellular Ca2+, Biophysical Journal, 102(6): 1294-1302, 2012.
- Wu, CY, Jia Z, Wang W, Ballou LM, Jiang YP, Chen B, Mathias RT, Cohen IS, Song LS, Entcheva E, and Lin RZ, PI3Ks maintain the structural integrity of T-tubules in cardiac myocytes, PLoS One, 6(9):e24404, 2011.
- Jia Z, Valiunas V, Lu Z, Bien H, Wang HZ, Liu H, Rosati B, Brink, PR, Cohen IS and Entcheva E, Stimulating cardiac muscle by light: cardiac optogenetics by cell delivery, Circulation: Arrhythmia & Electrophysiology, 4(5):753-60, 2011. (* media coverage)
- Quinn TA, Entcheva E, Kohl P, Minimum information about a cardiac electrophysiology experiment (MICEE): Standardised reporting for model reproducibility, interoperability, and data sharing, Progress in Biophysics and Molecular Biology, 107(1):4-10, 2011.
- Leigh S, Tattu A, Mitchell JSB and Entcheva E, M3: Microscope-based Maskless Micropatterning with Dry-Film Photoresist, Biomedical Microdevices, 13(2):375-81, 2011.
- Chung CY, Bien H, Sobie EA, Dasari V, McKinnon D, Rosati B and Entcheva E, Hypetrophic phenotype in cardiac cell assemblies solely by structural cues and ensuing self-organization, FASEB Journal, 25(3):851-62, 2011.
Ongoing Extramural Grant Support
- National Institutes of Health (NIH-NHLBI): R01: Cardiac Optogenetics: A Cell Delivery Approach”, PI: E. Entcheva
- National Science Foundation (NSF-Biophotonics): All-Optical Interrogation System for Cardiac Dynamics, PI: Entcheva
Editorial Board Service
Reviewer for over 20 scientific journals
- Editorial Board Member for Scientific Reports (Nature family of journals)
- Editor for Frontiers in Computational Physiology & Medicine
- Ad hoc Associate Editor for PLoS Computational Biology
- Bub G, Entcheva E et. al. “Optical interrogation and control of dynamic biological functions”, (2014).
- Bub G, Entcheva E et. al. “Optical interrogation and control of dynamic biological functions”, (2014).
- Elected AIMBE Fellow for “pioneering work in cardiac optogenetics & spearheading the development and biophysical characterization of new bioengineering tools towards all-optical electrophysiology”, 2016
- Member of the NIH ESTA (Electrical Signaling, Ion Transport and Arrhythmias) grant review study section
- Ad hoc member of the MABS (Modeling & Analysis of Biological Systems) grant review study section and for Special Emphasis panels at NIH
- Ad hoc grant reviewer for multiple study sections at the National Science Foundation (NSF), the American Heart Association (AHA)
- Ad hoc reviewer for the Welcome Trust Fund (UK), NC3Rs (UK), ZonMW (Netherlands), HFSP, GIF etc.
- Organizer (1 of 5) of a 4-week International Workshop “Integrative Cardiac Dynamics” at the Kavli Institute for Theoretical Physics (KITP), University of California, Santa Barbara, CA, (www.kitp.ucsb.edu/), pending proposal for Summer 2018.
- Session Chair at the Heart Rhythm Society (HRS) Annual Meeting, New Technologies, Boston, MA, 05/13-05/16/2015.
- Plenary Speaker at the IEEE International Conference on "System Cell Engineering" in Nagoya, Japan, 11/06-11/09/2008.
- Founding Faculty Member for the Systems Biology Center in New York State, funded by an NIH-NIGM grant, 2007
- Invited Core Lecturer for International Workshop “Dynamic aspects of biological networks”, Pohang, Korea, organized by APCTP (Asia-Pacific Center for Theoretical Physics and the Center for Cell Dynamics, Seoul University, 11/04 – 11/15/2007.
- Organizer (1 of 5) of a 4-week International Workshop “Cardiac Dynamics: From Cell to Organ” at the Kavli Institute for Theoretical Physics (KITP), University of California, Santa Barbara, CA, 07/15-08/04/2006.
- Theme Chair “Cellular and Functional Tissue Engineering”, 28th Annual International Conference of the IEEE - Engineering in Medicine and Biology Society (EMBS), New York, NY
- Over 25 invited talks over the last 5 years in the US, UK, Canada, France, Germany, Netherlands, Finland.