Current Research

Arrhythmogenic role of SAC's in the Border Zone

Dr. Keener and I are exploring the role of stretch-activated channels in myocardial tissue. The following is a formal description of the project:

A defibrillator generates a large electrical shock that causes the heart to contract in an effort to restore a normal heartbeat. Similarly, contraction and other mechanical stimuli, such as blunt impact to the chest, generate excitable currents in myocardium. These mechanically induced currents can explain normal phenomena such as the Frank-Starling law (increased diastolic volume leads to increased systolic contraction), but are also suspected of having an arrhythmogenic role during regional ischemia. Ischemic myocardium contracts slower and generates less force than normal myocardium. Consequently, strain becomes localized in the region between normal and ischemic myocardium (the border zone), which then increases the open probability of channels sensitive to or activated by strain. The protein subunits of the human stretch-activated channel have been identified recently and can be activated by strain in the plasma membrane alone. I am in the process of creating a Hidden Markov Model of these stretch-activated channels, which will then be incorporated into a single cell and later into a 2-D sheet of myocardial tissue. This model will be used to explore the arrhythmogenic role of stretch-activated channels in the border zone during regional ischemia in human myocardium.

This thesis employs the following tools

• Hidden Markov Models: To create a model of a single stretch-activated channel
• Gillespie Algorithm: Making numerically accurate simulations of the stretch-activated channels
• Maximum Likelihood Optimization: To find ``best fit" parameters and and ideal topology for the Markov model
• Oxford Heart Model: To simulate strain in a single cell and multiple cells (i.e. a 1-D chain and a 2-sheet)

The following is an informal timeline of the status of my thesis work:

• Update #1: Background reading on ischemia and some preliminary comments on BZ's.
• Update #1b: I contributed to an NSF grant on Prof Keener's request an described my current SAC modelling project. A complete description of this problem will appear in the written component of my oral defence.
• (Dec 12, 2006) Defined a Thesis Problem: What is the arrhythmogenic role of stretch-activated channels in the border zone during the first 15 minutes of acute regional ischemia in human myocardium? (right on schedule!)
• April - July 2007: Delay in thesis research due to back injury :..(
• Sept 11, 2007: Received multiple channel data from Dr. Owen Hamill (!!!)
• Sept 28-30, 2007: Invited to UBC to give a talk on my current research.
• Oct - Dec 2007: Lab work at the CVRTI with Dr. Frank Sachse.

Quorum Sensing in Vibrio fischeri

As for "sideline interests", Dr. Keener and I are working on a project involving quorum sensing in V.fischeri. This project arose as a result of a project in his Math Physiology course that I took in the Fall 2005 term. At this point I've "completed" the background research and formulated a model. Currently I'm finding the mechanism by which quorum sensing is turned on (i.e. by a soft or a hard switch).

Research Groups

The following are some discussion groups that I (try to) attend on a regular basis.

• Physiology Group
• Biofluids Group
• Math Biology Seminar
• CVRTI (cool group for those interested in electrophysiology!)