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Overview: The goal of my research program is to understand the role of bicarbonate transport in human disease.  Bicarbonate (HCO3-) is a waste product of energy production, the end-point of respiratory oxidation.  HCO3-/ CO2 forms the major pH buffering system of our bodies.  HCO3- is impermeable to biological membranes.  Specialized plasma membrane bicarbonate transport proteins (bicarbonate transporter) are therefore required to facilitate HCO3- movement into and out of cells.  Because HCO3- is a base, bicarbonate transporter-mediated influx induces cellular alkalinization, while efflux causes acidification.  Physiologically bicarbonate transporter serves to:

  1. regulate cellular pH,
  2. regulate whole body pH,
  3. regulate cell volume and fluid secretion,
  4. dispose of the body’s major metabolic waste product (CO2/HCO3-). 

Given the fundamental nature of these processes, it is not surprising that bicarbonate transporter action has established involvement in many disease states, including cystic fibrosis, renal tubular acidosis, retinitis pigmentosa (RP) and cardiac ischemia and hypertrophy.  In addition to diseases with established links to HCO3- transport, many other diseases are likely to have a component of HCO3- transport in their pathology.  My laboratory has taken a comprehensive approach to the study of HCO3- transport.  We are studying the structure and transport mechanism of Anion Exchanger 1 (AE1), because AE1 structure is likely representative of all members of the bicarbonate transporter family and because a high-resolution structure will explain at molecular level the basis for diseases of bicarbonate transport.  We are also studying the role of bicarbonate transporter in specific diseases.

Below are some research questions that our lab strives to answer:

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