Research
Sudden cardiac death, primarily caused by ventricular arrhythmias, is a major public health problem – it is one of the leading causes of mortality, resulting in more than 350,000 annual deaths in the United States alone. Our group’s efforts are focused on improving our understanding of, and therefore therapies for, cardiac arrhythmias. We primarily investigate biophysical mechanisms of electrophysiological instabilities and arrhythmia onset, from the subcellular to organ level. Because of the complexity of electrophysiological dynamics, we use a multiscale approach that bridges the gap between physics and biology. Our experiments employ manual and multi-cell automated electrophysiological modalities, using induced pluripotent stem-cell derived cardiomyocytes, often via real-time feedback between the experiment and the model (“dynamic clamp”; see Figs. 1 and 2). Such a combination of experimental and computational approaches provides the necessary synergy to impact our understanding of cardiac arrhythmias.
Fig. 1 – schematic of Dynamic Clamp experiment
Fig. 2 – screengrab of Dynamic Clamp experiment
Current Projects:
- Hybrid computational-experimental electrophysiology to illuminate physiology and pathophysiology
- Multiscale cardiac modeling
- Cellular calcium dynamics
Bio
Dr. David Christini serves as the Senior Vice President for Research at SUNY Downstate Health Sciences University, where he is in charge of the University’s research strategy and operations. Dr. Christini, a Professor of Physiology and Pharmacology, leads a research lab that is focused on improving the understanding of, and therapies for, cardiac arrhythmias. He is the author of nearly a hundred peer-reviewed publications, has been continuously funded by the NIH since 2004, and has also received funding from the NSF, the American Heart Association, and various foundations and organizations. He has served as the Program Director on two NIH-funded training grants and has served on multiple NIH and NSF review panels, including as Chair. Prior to joining Downstate in June 2020, Dr. Christini was a tenured Professor at Weill Cornell Medical College. At Weill Cornell, he was Vice Dean of the Weill Cornell Graduate School. Dr. Christini holds a Bachelor of Science in Electrical Engineering from Pennsylvania State University and both his Masters and Doctoral degrees in Biomedical Engineering from Boston University.
Distinctions:
- 2024- : Editorial Board British Journal of Pharmacology
- 2019; 2023: elected co-vice chair (2019) and co-chair (2023) of Gordon Conference on Cardiac Arrhythmia Mechanisms
- 2020- : Associate Editor for Frontiers in Physiology
- 2017-2020: Chair; NIH NIGMS Training and Workforce Development (TWD-B) study section
Selected Publications:
1. Clark AP, Wei S, Christini DJ, Krogh-Madsen T, “Single-cell ionic current phenotyping elucidates non-canonical features and predictive potential of cardiomyocytes during automated drug experiments,” J. Physiol., in press, doi:10.1113/JP285120 (2024).
2. Clark AP, Wei S, Fullerton K, Krogh-Madsen T, Christini DJ, “Single-cell ionic current phenotyping explains stem cell-derived cardiomyocyte action potential morphology,” American Journal of Physiology, 326:H1146– H1154, doi:10.1152/ajpheart.00063.2024 (2024).
3. Fullerton KE, Clark AP, Krogh-Madsen T, Christini DJ, “Optimization of a cardiomyocyte model illuminates role of increased INaL in repolarization reserve,” American Journal of Physiology, 326:H334–H345, doi:10.1152/ajpheart.00553.2023 (2024).
4. Clark AP, Wei S, Kalola D, Krogh-Madsen T, Christini DJ, “An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic proarrhythmia mechanisms,” British Journal of Pharmacology, 179:4829-4843,
doi:10.1111/bph.15915; PMCID: PMC9489646 (2022).
5. Groenendaal W, Ortega FA, Kherlopian AR, Zygmunt AC, Krogh-Madsen T, and Christini DJ, “Cell-specific cardiac electrophysiology models,” PLoS Computational Biology, 11:e1004242; doi:10.1371/journal.pcbi.1004242; PMCID: PMC4415772 (2015).