Dash, Ranjan K., Ph.D. Assistant Professor Specialization: Computational Bioengineering Computational Group CV, Publications Tel:  (414)-955-4497 Fax: (414)-955-6568 Email: rdash@mcw.edu

Area of Specialization and Research Interests:

1. Mathematical modeling and computer simulations of physiological systems
2. Computational algorithms for data analysis and parameter estimation
3. Microcirculatory oxygen and carbon dioxide transport and exchange
4. Analysis of large-scale biochemical systems: regulation of cellular energy metabolism
5. Mitochondrial handling of cations (Ca²⁺, Na⁺, K⁺, H⁺, Mg²⁺) and ROS (O₂^., H₂O₂)
6. Multi-scale modeling of coupled blood-tissue mass transport and cellular energy metabolism in cardiac and skeletal muscles

Research Statement:

Project 1: Roles of Cations and ROS in the Regulation of Mitochondrial Function:

This research project is broadly focused on understanding how functional defects in the kinetics of mitochondrial cation (Ca²⁺, Na⁺, Mg²⁺, K⁺, and H⁺) transport and buffering and mitochondrial generation and scavenging of reactive oxygen species (ROS: O₂^. and H₂O₂) affect the overall mitochondrial bioenergetics and function. Given the fundamental role of mitochondria in cellular energetics and oxidative stress, it is widely believed that dysfunction within these organelles is involved in many aspects of cardiovascular diseases such as hypertension, heart failure, metabolic syndrome, obesity, and diabetes. We have begun to explore and quantify the physiological mechanisms by which mitochondria transport and buffer cations such as Ca²⁺ which is a key regulatory ion and plays a major role in mitochondrial signaling pathways and mitochondrial energy metabolism. Our approach is to use biophysically-based, mathematical modeling in conjunction with experimental observations in isolated cardiac mitochondria to quantitatively understand the roles of cations and reactive oxygen species in the regulation of mitochondrial bioenergetics and function in the working heart.

Project 2: Multi-Scale Computational Modeling of Cellular Metabolism and Energetics:

This research project is broadly focused on developing mathematical models and computational tools to analyze and understand the transport and reaction processes of biochemical species in complex physiological systems. Specifically, we are interested in the quantitative understanding of the mechanisms of metabolic regulation in-vivo in the heart and in skeletal muscle during conditions that challenge ATP homeostasis such as ischemia (decreased blood flow), hypoxia (decreased oxygen supply), and exercise (increased energy demand). For this purpose, we are developing physiologically-based, multi-scale, computational models of mass transport and cellular metabolism and energetics in the heart and in skeletal muscle to predict the integrated subcellular, cellular, and whole-organ responses to increased energy demand and decreased blood flow and oxygen supply. These models are crucial in establishing relationships between energy demand, oxygen supply, substrate transport, and blood flow. These models are also helpful in linking external respiration (at the whole body level) to internal respiration (at the whole cell and mitochondrial levels). Our primary goal is to gain a better understanding of the mechanisms of metabolic regulation in the cells, including the control of mitochondrial oxygen consumption, cellular respiration, and ATP homeostasis during exercise, ischemia and hypoxia.

Group Members: