Jason Bazil, Ph.D.
Ischemic heart disease is the leading cause of mortality in the US and worldwide. And a significant portion of deaths are caused by a myocardial infarction which precipitates a lethal injury that involves mitochondria. According to the AHA, every half minute or so, an American has a myocardial infarction and dies from one every minute and a half. These alarming statistics demonstrate the need for a better understanding of the conditions surrounding the injury. In particular, the critical events during ischemia and the effects caused by the injury are not well defined. In order to develop preventative and mitigative measures, research efforts must characterize these phenomena in greater detail and identify the constitutive elements and their complex interactions. My lab uses an integrative strategy that combines both computational modeling and experimental physiology to study these phenomena.
Mitochondria are known to be involved in many pathologies and injuries. Yet little is known of the precise mechanisms by which mitochondrial processes can lead to disease. My lab is pursuing therapeutic strategies by first characterizing mechanisms of mitochondrial dysfunction in heart disease and then identifying feasible measures to prevent it. Much of our work on this topic is focused on cardiac mitochondria. We use state-of-the-art instrumentation to analyze lethal reperfusion injury by monitoring the response of mitochondria to calcium overload and oxidative stress.
In addition, my lab is developing methods for large-scale data analysis. The availability of tools used to query so-called Big Data in an informative manner lag far behind our ability to produce these data. Unlike standard approaches which rely on statistical inference and association, our contributions in this area couple dynamical modeling with network inference and reverse engineering. My lab applies these tools to analyze large-scale data and generates predictive models that are useful for emerging applications in pharmacogenomics and systems pharmacology.
- Wollenman LC, Vander Ploeg MR, Miller ML, Zhang Y, and JN Bazil. “The effect of respiration buffer composition on mitochondrial metabolism and function.” PLoS One, 2017, 12(11):e0187523. PMC5665555.
- JN Bazil. “Analysis of a Functional Dimer Model of Ubiquinol Cytochrome c Oxidoreductase.” Biophysical Journal, 2017, 113(7):1599-1612. PMC5627346.
- Bazil, JN, KC Vinnakota, and DA Beard. “Catalytic Coupling of Oxidative Phosphorylation, ATP Demand, and Mitochondrial Reactive Oxygen Species Generation.” Biophysical Journal, 2016, 110(4): 962-71. PMID: 26910433.
- Vinnakota, KC, JN Bazil, FA Van den Bergh, RW Wiseman, and DA Beard. “Feedback Regulation and Time Hierarchy of Oxidative Phosphorylation in Cardiac Mitochondria.” Biophysical Journal, 2016, 110(4):972-80. PMID: 26910434.
- Bazil JN, Blomeyer CA, Stowe DF, Dash RK, and AKS Camara. “Mg2+ differentially regulates two modes of mitochondrial Ca2+ uptake in isolated cardiac mitochondria: Implications for mitochondrial Ca2+ sequestration.” Journal of Bioenergetics and Biomembranes, 2016, 48(3): 175-88. PMC5098337.
- Moxley, MA, DA Beard, and JN Bazil. “Global Kinetic Analysis of Mammalian E3 Reveals pH-dependent NAD+/NADH Regulation, Physiological Kinetic Reversibility, and Catalytic Optimum.” Journal of Biological Chemistry, 2016, 291(6):2712-30. PMID: 26644471.
- Moxley, MA, DA Beard, and JN Bazil. “A pH-Dependent Kinetic Model of Dihydrolipoamide Dehydrogenase from Multiple Organisms.” Biophysical Journal, 2014, 107(12): 2993-3007. PMC4269776.
- Bazil JN, VR Pannala, RK Dash, and DA Beard. “Determining the Origins of Superoxide and Hydrogen Peroxide in the Mammalian NADH:Ubiquinone Oxidoreductase.” Free Radical in Biology and Medicine, 2014, 77:121-9. PMC4258523.
- Bazil JN, KD Stamm, X Li, R Thiagarajan, TJ Nelson, A Tomita-Mitchell and DA Beard. “The Inferred Cardiogenic Gene Regulatory Network in the Mammalian Heart,” PLoS ONE, 2014, 9(6): e100842. PMC4074065.
- Pannala VR, JN Bazil, AK Camara and RK Dash, “A Mechanistic Mathematical Model for the Catalytic Action of Glutathione Peroxidase,” Free Radical Research, 2014, 48(4): 487-502. PMC4068149.
- Pannala VR, JN Bazil, AK Camara and RK Dash, “A Biophysically-based Mathematical Model for the Catalytic Mechanism of Glutathione Reductase,” Free Radical in Biology and Medicine, 2013, 65: 1385-97. PMC3870161.
- Bazil JN, KC Vinnakota, F Wu and DA Beard, "Analysis of the kinetics and bistability of ubiquinol:cytochrome c oxidoreductase," Biophysical Journal, 2013, 105(2): 343-355. PMC3714890.
- Bazil, JN, CA Blomeyer, RK Pradhan, AKS Camara, RK Dash, "Modeling the Calcium Sequestration System in Isolated Guinea Pig Cardiac Mitochondria," Journal of Bioenergetics and Biomembranes, 2012, 45(3):177-88. PMC3615037.
- Blomeyer, CA, JN Bazil, DF Stowe, RK Pradhan, RK Dash, AKS Camara, "Dynamic buffering of mitochondrial Ca2+ during Ca2+ uptake and Na+-induced Ca2+ release," Journal of Bioenergetics and Biomembranes, 2012, 45(3):189-202. PMC4065551.
- Tewari, SG, RK Dash, DA Beard and JN Bazil, "A Biophysical Model of the Mitochondrial ATP-Mg/Pi Carrier," Biophysical Journal, 2012, 103(7), 1616-25. PMC3471468.
- Bazil, JN, GT Buzzard and AE Rundell, “A Global Parallel Model Based Design of Experiments Method to Minimize Model Output Uncertainty,” Bulletin of Mathematical Biology, 2012, 74(3), 688-716. PMID: 21989566.
- Bazil, JN, F Qi and DA Beard, "A Parallel Algorithm for Reverse Engineering of Biological Networks," Integrative Biology, 2011, 3(12), 1215-1223. PMC3424073.
- Bazil, JN and RK Dash, “A Minimal Model for the Mitochondrial Rapid Mode of Ca2+ Uptake Mechanism,” PLoS ONE. 2011, 6(6): e21324. PMC3121760.
- Bazil, JN, GT Buzzard and AE Rundell, “A Bioenergetic Model of the Mitochondrial Population Undergoing Permeability Transition,” Journal of Theoretical Biology, 2010, 265. pg. 672-690. PMID: 20538008.
- Bazil, JN, GT Buzzard and AE Rundell, “Modeling Mitochondrial Bioenergetics with Integrated Volume Dynamics,” PLoS Computational Biology, 2010, 6(1):e1000632. PMC2793388.