We have three major research areas: (1) the regulation of intracellular pH (pHi), including the broader field of acid-base homeostasis, (2) Sensors for extracellular CO2 and HCO3-- and (3) gas channels
The regulation of pHi is critically important because virtually every biological process—cell division, metabolism, motility, signal transduction, and the actions of channels and transporters—depends on pHi. My work as a graduate student (with Paul De Weer) demonstrated for the first time that cells actively regulate their pH. That is, if we suddenly lower pHi, the cell responds by actively returning pHi toward its initial value. Since that time, my colleagues and I have been trying to understand the molecular mechanisms of pHi regulation and the factors that control it. As a postdoc (with Emile Boulpaep) we discovered sodium/bicarbonate cotransport. Later, Michael Romero in my lab expression cloned the cDNA encoding the electrogenic Na/HCO3 cotransporter NBCe1, the first Na+-coupled HCO3− transporter to be cloned. As summarized under "Projects," we are now using a variety of approaches to understand how Na+-coupled HCO3− transporters work, the role they play in pHi regulation, and in the importance of HCO3– transport in organs such as the kidney and brain, both in health and disease.
Although we all had thought that gases such as carbon dioxide cross all biological membrane simply by dissolving in and diffusion through the lipid phase of the membrane, this dogma turns out not to be true. Steve Waisbren in my lab discovered the first gas-impermeable membranes (the apical membranes of gastric-gland cells). Nazih Nakhoul and Gordon Cooper then showed that the water channel aquaporin 1 (AQP1) can conduct CO2—the first demonstration of a gas channel. We now know that AQP1 can also conduct ammonia, and that the Rh proteins can also conduct CO2 and NH3. Raif Musa-Aziz then demonstrated that the AQPs and Rh proteins can exhibit selectivity for CO2 vs NH3. As summarized under "Projects," we are now trying to understand the molecular mechanism by which gases move through channels, and the physiological and pathophysiological importance of these processes.
None at this time