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Calcium and Cell Death

What We Study

When most people think of calcium, they think of the building blocks of bone. However, all of the cells in your body use calcium as a way to transmit signals from the outside of the cell to the inside. Sometimes this can result in the death of the cell. This is a normal process which is happening all of the time in your body to remove old cells and those which are no longer needed. Sometimes, this process goes awry leading to cancer (not enough cell death) or neurodegeneration (too much cell death). We try to understand how this happens and what we can do to prevent diseases associated with altered cell death.

Our Work In Scientific Terms

Our lab is interested in apoptotic cell death, and how this process is altered in cancer and neurodegeneration.  One area of investigation concerns calcium channel activation during apoptosis. The inositol 1,4,5-trisphosphate receptor (IP3R) is a ligand-gated ion channel which releases calcium from ER stores. We and others have shown that the IP3R plays a critical role in apoptotic calcium release. Our current efforts are focused several related projects. One project investigates the molecular mechanisms leading to calcium release from the IP3R in response to activation of the Fas death receptor with relevance to lymphoma and autoimmunity.  Another project is investigating a role for BRCA1, which is mutated in hereditary breast and ovarian cancer, as a pro-apoptotic protein and modulator of IP3R activity.

 

Cardio.jpgCardiovascular Disease

What We Study

Heart disease is responsible for 25% of all deaths in the United States. When the heart is overworked there are often changes in how the heart functions. For example, in people with high blood pressure the cells of the heart get bigger to try to help it pump with greater force. However, these changes also increase the risk of heart failure. We try to understand how pathological changes in the heart occur at the molecular level, and whether these processes can be reversed in people with heart disease.

Our Work In Scientific Terms

Our lab is interested in how the IP3R calcium channel regulates cardiovascular physiology. Our recent work has focused on how this channel contributes to ventricular cardiomyocyte contractility and the hypertrophic stress response. We are currently evaluating the role of IP3R channels in signaling downstream of endothelin-1 stimulation, and how these channels regulate the complex spatio-temporal aspects of calcium signaling in ventricular cardiomyocytes. Finally, we are interested in how post-translation modifications of proteins with lipids such as palmitic acid regulates cardiomyocyte function, with a focus on G protein-coupled receptor signaling.

 

Neurodegenerative Diseases

What We Study

Neurodegenerative diseases such as Alzheimer's disease and Lou Gehrig's disease (also known as ALS) are devastating and fatal diseases with few treatment options. A common theme in many neurodegenerative diseases is that proteins in the neurons clump up and become toxic causing them to die. We study a protein called ubiquilin which may help to stop other proteins from clumping up and thus prevent neurons from dying. We are currently studying how these proteins are associated with Alzheimer's disease and ALS, and whether increasing the activity of ubiquilin can slow or prevent disease.

Our Work In Scientific Terms

A major focus of our lab is apoptotic signaling in neurodegeneration. We are investigating how the ubiquilin family of proteins contribute to the pathogenesis of Alzheimer’s disease and amyotrophic lateral sclerosis.  Specifically, we have evidence that the ubiquilin proteins function as molecular chaperones in neurons preventing the aggregation of disease-relevant proteins. We are investigating how the activity of these proteins is altered during disease progression to affect neuronal proteostasis.