Ranjan Dash, Ph.D.

Adjunct Associate Professor
Biomedical Engineering

Professional Preparation:

MS, Applied Mathematics, Utkal University, Bhubaneswar, Orissa, India, 1991
PhD, Computational Biofluid Dynamics, Indian Institute of Technology, Delhi, India, 1998
Postdoc, Computational Biofluid Dynamics, Texas A&M University, College Station, 2000
Postdoc, Computational Systems Biology, University of Washington, Seattle, 2003
Postdoc, Computational Systems Biology, Case Western Reserve University, Cleveland, 2006

Research Interests:
Computational Biology and Bioinformatics
Systems Biology and Bioengineering
Molecular and Cellular Physiology
Cardiac and Skeletal Muscle Metabolism

Research Program:
Research in Dr. Dash’s laboratory is broadly focused on the developments (experimental data-driven) and applications of computational models and tools for predicting and analyzing the behaviors of complex physiological systems ranging over multiple scales of organization from the molecular level to the tissue/organ level. The overall goal of this research program is to work towards a quantitative and integrative understanding of the functioning of complex physiological systems under normal and pathological conditions (health and diseases), and guiding engineering-based manipulations of the systems. Dr. Dash’s major research contributions over the past several years can be classified into the following areas: (1) Microcirculatory O2 and CO2 transport and exchange and acid-base regulation; (2) Physiologically-based pharmacokinetic modeling; (3) Integrated blood-tissue species transport and cellular energy metabolism in cardiac and skeletal muscles; (4) Mitochondrial Ca2+ and ROS (O2.-, H2O2) homeostasis and cellular electrophysiology in cardiac physiology and pathophysiology; and (5) Analysis of biochemical networks, protein-protein interaction networks, and gene regulatory networks.

Over the past several years, Dr. Dash has contributed significantly to the research on the computational modeling and analysis of complex metabolic systems, including cardiac and skeletal muscle microcirculatory O2 and CO2 transport and exchange and cellular energy metabolism, based on extensive in vitro and in vivo published data under diverse experimental conditions. The tissue/organ-level models integrate tissue/organ-specific information over multiple scales ranging from channel/transporter/enzyme to mitochondrial to cellular to tissue/organ levels to simulate the integrated molecular, subcellular, cellular, and tissue/organ responses to physiological and pathophysiological perturbations, e.g. ischemia (decreased blood flow), hypoxia (decreased O2 supply), and exercise (increased energy demand). Such models are helpful for mechanistically establishing relationships between energy demand, O2 supply, substrate availability, and blood flow in tissue/organ systems. Such models are also helpful for mechanistically linking external respiration (at whole-body level) to internal respiration (at whole-cell and mitochondrial levels). Consequently, such models are crucial for quantitative understandings of the mechanisms of metabolic regulation in cells in vivo, including the control of mitochondrial O2 consumption (respiration), substrate and energy metabolism, and ATP homeostasis during ischemia, hypoxia, and exercise. Such models are also crucial for investigating how metabolic remodeling and tissue/organ dysfunction occur in various cardiovascular and metabolic diseases (e.g. heart failure, diabetes).

After joining MCW (June 2006), in collaboration with experimental physiologists, Dr. Dash has developed an integrated research program combining computational modeling of mitochondrial and cellular functions and experimental measurements in isolated cardiac mitochondria, isolated cardiomyocytes, and ex vivo & in vivo hearts from guinea pigs and rats to study the dynamic regulation of mitochondrial and cellular functions (e.g. electrophysiology, bioenergetics, Ca2+ and ROS homeostasis) in the heart under normal and pathological conditions, such as ischemia/reperfusion (IR) or hypoxia/reoxygenation (HR) injury, with and without volatile anesthetics or pharmacological interventions that induce cardioprotection against IR/HR injury. Such an integrative approach is helpful for iteratively formulating and quantitatively testing complex intriguing hypotheses related to the kinetics of mitochondrial respiratory and transport systems, NADH and FAD redox states, O2 consumption, ATP synthesis, proton motive force, Ca2+ transport and buffering, ROS generation and scavenging, and dynamic regulation of mitochondrial and cellular functions in the heart in health and diseases (IR/HR injury). Consequently, such an integrated approach is crucial for quantitative understandings of the biophysical and biochemical mechanisms responsible for IR/HR injury, and how interventions lead to improved mitochondrial and cellular functions in the heart (cardioprotection) after IR/HR injury.

In the past few years, Dr. Dash has expanded his computational modeling research capabilities and collaborative efforts within MCW and other academic institutions in the Southeast Wisconsin (UWM and MU) to other complimentary areas of research that involve oxidative and nitrosative-stress mediated mitochondrial and cellular dysfunctions and cardiovascular diseases. Examples include: (1) Integrated modeling of NADPH oxidase and mitochondrial crosstalk in mTAL kidney cells to mechanistically investigate the development of oxidative stress, renal dysfunction, and salt-sensitive hypertension; (2) Multi-scale modeling of lung tissue bioenergetics to quantitatively characterize the metabolic basis of acute lung injury and acute respiratory distress syndrome, incorporating the critical role of mitochondria; and (3) Multi-scale modeling of microvessel reactivity and blood flow regulation through endothelial cell and vascular smooth cell communications. In addition, he has recently developed significant interests in the integrated modeling and analysis of large-scale biochemical networks, protein-protein interaction networks, and gene regulatory networks to quantitatively understand the genotype-phenotype relationships in diverse pathologies, such as salt-sensitive hypertension and cell cycle dysregulation.

Current Laboratory Members:

  1. Dr. Neeraj Manhas, Postdoctoral Fellow (Email: nmanhas@mcw.edu)
  2. Dr. Namrata Tomar, Postdoctoral Fellow (Email: ntomar@mcw.edu)

Postdoctoral fellow or predoctoral student positions:

Contact Dr. Dash (rdash@mcw.edu; 414-955-4497) if interested in a postdoctoral fellow or predoctoral student position in his laboratory in the Departments of Biomedical Engineering and Physiology.

Complete List of Published Work in MyBibliography:

http://www.ncbi.nlm.nih.gov/sites/myncbi/ranjan.dash.1/bibliography/40490502/public/?sort=date&direction=descending (68 publications comprising 63 original articles, 3 review articles, and 2 book chapters)

Also see Dr. Dash’s detailed academic profile in MCW Faculty Collaboration Database

 

 

Representative Research Publications:

  1. Pannala VR, Camara AKS, and Dash RK. Modeling the detailed kinetics of mitochondrial cytochrome c oxidase: Catalytic mechanism and nitric oxide inhibition. J Appl Physiol, 2016.
  2. Ranji M, Salehpour F, Motlagh MM, Sepehr R, Heisner JS, Dash RK, and Camara AKS. Optical cryoimaging reveals a heterogeneous distribution of mitochondrial redox states in the ex vivo guinea pig heart and its alteration during ischemia and reperfusion. J Trans Eng Health Med 4:1800210, 2016.
  3. Blomeyer CA, Bazil JN, Stowe DF, Dash RK, and Camara AKS. Mg2+ differentially regulates two modes of mitochondrial Ca2+ uptake in isolated cardiac mitochondria: Implications for mitochondria Ca2+ J Bioenerg Biomemb 48(3):175-178, 2016.
  4. Dash RK, Korman B, and Bassingthwaighte JB. Simple accurate mathematical models of blood HbO2 and HbCO2 dissociation curves at varied physiological conditions – Evaluation and comparison with other mathematical models. Eur J Appl Physiol, 116(1): 97-113, 2016.
  5. Tewari SG, Zhou Y, Otto BJ, Dash RK, Kwok WM, and Beard DA. Markov chain Monte Carlo based analysis of post-translationally modified VDAC gating kinetics. Front Physiol 5:513, 2015.
  6. Pannala VR and Dash RK. Mechanistic characterization of the thioredoxin system in the removal of hydrogen peroxide. Free Radic Biol Med 78:42-55, 2015.
  7. Bazil JN, Pannala VR, Dash RK, and Beard DA. Determining the origins of superoxide and hydrogen peroxide in the mammalian NADH:ubiquinone oxidoreductase. Free Radic Biol Med 77: 121-129, 2014.
  8. Tewari SG, Camara AKS, Stowe DF, and Dash RK. Computational analysis of Ca2+ dynamics in isolated cardiac mitochondria predicts two distinct modes of Ca2+ uptake. J Physiol 592(9): 1917-1930, 2014.
  9. Pannala VR, Bazil JN, Camara AKS, and Dash RK. A mechanistic mathematical model for the catalytic action of glutathione peroxidase. Free Radic Res 48(4): 487-502, 2014.
  10. Agarwal B, Dash RK, Stowe DF, Bosnjak ZJ, and Camara AKS. Isoflurane modulates cardiac mitochondrial bioenergetics by selectively attenuating respiratory complexes. Biochim Biophys Acta Bioenerg 1837(3): 354-365, 2014.
  11. Pannala VR, Bazil JN, Camara AKS, and Dash RK. A Biophysically-based mathematical model for the catalytic mechanism of glutathione reductase. Free Radic Biol Med 65: 1385-1397, 2013.
  12. Bazil JN, Blomeyer CA, Pradhan RK, Camara AKS, and Dash RK. Modeling the calcium sequestration system in isolated guinea pig cardiac mitochondria. J Bioenerg Biomembr 45(3): 177-188, 2013.
  13. Aldakkak M, Stowe DF, Dash RK, and Camara AKS. Mitochondrial handling of excess Ca2+ is substrate-dependent with implications for reactive oxygen species generation. Free Radic Biol Med 56: 193-202, 2013.
  14. Agarwal B, Camara AKS, Stowe DF, Bosnjak ZJ, and Dash RK. Enhanced charge-independent mitochondrial free Ca2+ and attenuated ADP-induced NADH oxidation by isoflurane: Implications for cardioprotection. Biochim Biophys Acta Bioenergetics 1817(3): 453-465, 2012.
  15. Pradhan RK, Qi F, Beard DA, and Dash RK. Characterization of Mg2+ inhibition of mitochondrial Ca2+ uptake by a mechanistic model of mitochondrial Ca2+ Biophys J 101(9): 2071-2081, 2011.
  16. Vinnakota KC, Dash RK, and Beard DA. Stimulatory effects of calcium on respiration and NAD(P)H synthesis in intact rat heart mitochondria utilizing physiological substrates cannot explain respiratory control in vivo. J Biol Chem 286(35): 30816-30822, 2011.
  17. Pradhan RK, Beard DA, and Dash RK. A biophysically-based mathematical model for the kinetics of mitochondrial Na+-Ca2+ Biophys J 98(2): 218-230, 2010.
  18. Li Y#, Dash RK#, Kim J, Saidel GM, and Cabrera ME. Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise - In silico studies. Am J Physiol Cell Physiol 296(1): C25-46, 2009. [# Equal contributions]
  19. Dash RK, Li Y, Kim J, Beard DA, Saidel GM, and Cabrera ME. Metabolic dynamics in skeletal muscle during acute reduction in blood flow and oxygen supply to mitochondria – In silico studies using a multi-scale, top-down integrated model. PLoS One 3(9): e3168, 2008.
  20. Dash RK and Beard DA. Analysis of cardiac mitochondrial Na+/Ca2+ exchanger kinetics with a biophysical model of mitochondrial Ca2+ handling suggests a 3:1 stoichiometry. J Physiol 586(13): 3267-3285, 2008.