Office: ISA 5108
Lab: ISA 5025B/5027B
Ph.D. Biophysics, 2006, Ohio University
Markov chain models
Cell signaling pathways
Application of control theory to biology
Neurological diseases such as epilepsy and Alzheimer’s inflect a heavy toll on human population, both in terms of health and economic impact. So far effective disease-modifying therapies remain elusive for most of these diseases. The lack of understanding of the disease pathogeneses hinders the efforts to develop efficient therapeutics. We use computational techniques to gain deep insight into the pathogeneses of neuronal disorders. The following projects are currently underway in the Computational Biophysics Laboratory.
(1) In epileptic seizures and other brain states the excitability of neuronal networks not only depends on the nonlinear interaction between excitatory and inhibitory neuronal subtypes but also a variety of metabolic processes such as potassium concentration gradients and local oxygen availability. Our motivation is to develop next generation biophysical models that will account for the metabolic variables, such as potassium, sodium, chloride, calcium and oxygen concentrations, glucose supply, and pH levels along with the electrical component. An essential component of these models are the glial network and vasculature surrounding the neurons. These models will not only enable us to study the role of neuronal microenvironment in epileptic seizures but will also set the foundation for the mathematical description of cerebral hypoxia and hypoxia-induced seizures.
Figure: Neuronal microenvironment.
(2) Overwhelming evidence suggests a key role of calcium signaling dysfunction in Alzheimer's and other age-related diseases. Calcium signaling dysfunction accounts for the early cognitive and memory impairments as well as the progressive cell death during neurodegenerative diseases. However, the molecular pathways leading to the observed calcium dysfunction are not well understood. We develop computational models to pinpoint the signaling pathways that are upstream in the calcium cascade and to understand their role in cell bioenergetics and apoptosis.
Figure: Calcium signaling pathways in Alzheimer’s disease.
(3) Existing experimental techniques can measure only a few of the many variables controlling the dynamics of biological systems. However, recent advances in nonlinear control theory offer a paradigm shifting improvement in our ability to estimate, predict, and control spatiotemporal biological systems. We use cutting edge state reconstruction techniques such as Kalman filter to estimate the experimentally inaccessible biological variables from as few as one experimentally observed variable.
Figure: Kalman filter tracking of neuronal dynamics during epileptic seizures.