The following is a short questionnaire about my research, prepared for the American Heart Association. This is intended to provide you an understanding of what I do.


1. What is the major problem being addressed by this study?

We address an important question about the function of “chloride channel” proteins. Chloride channels are embedded in the cell membrane and play diverse roles that are essential for cell survival. The cell membrane is the outer layer of the cell that functions as a barrier, which prevents salts and molecules from entering and leaving the cell. Chloride channels form pores that selectively allow chloride ions to move across the cell membrane. Disruption of chloride channel function leads to several human diseases including muscle, kidney and bone disorders. Our goal is to understand how the structure of a chloride channel allows it to transport chloride across the cell membrane.

2. What specific questions are you asking and how will you attempt to answer them?

Disease causing mutations in chloride channels change their structure. This structure change in turn disrupts the ability of the channel to transport chloride ions. The central question our work addresses is how mutations change chloride channel structure and how those structure changes disrupt channel function.

Although the overall structure of chloride channels is known, we need to use computer simulations to predict finer details of the structure the particular chloride channel we study. Based on our computer predictions, we will engineer mutations that are expected to alter the structure of specific regions of the chloride channel. We will choose regions of the channel that are believed to be important for function. We will then asses the affect of our engineered mutations on the channels ability to transport chloride ions.


3. What is the long-term biomedical significance of your work, particularly as it pertains to the cardiovascular area? What major therapeutic advance(s) do you anticipate that it will lead to? For instance, new drug(s), a surgical technique/procedure, a diagnostic tool/test, a previously undetected risk factor, etc.

Our work addresses a basic biomedical question that is relevant to many diseases. For example, in humans it has been observed that mutations in chloride channels lead to a muscle disorder referred to as myotonia, a bone-hardening disorder, and disorders of kidney function. Disruption of kidney function can lead to high blood pressure. Chloride channels are important for a variety of cardiac functions such as maintaining regular heart beats and controlling the thickness of heart walls. Changes in heart wall thickness are a long term response to high demands on cardiac function, such as regular exercise. Our research will provide new insights into a variety of biological processes and diseases including those of cardiac, muscular, bone, and brain function. Understanding how the structure of chloride channels alters their function could lead to the development of new drugs to treat chloride channel and related diseases.


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