My laboratory investigates the molecular physiology of ion transport across the plasma membrane. We are particularly interested in the ways cells regulate their cytoplasmic pH and volume, and exploit these mechanisms in polarized epithelia to accomplish reabsorption and secretion of protons and bicarbonate, of salt and water, and of carboxylates such as oxalate. We develop methods and drugs which can regulate or inhibit these functions to modify the course of disease. Our studies are of importance to the understanding of genetic and acquired diseases of acid-base balance, fluid retention and loss, and ectopic calcification. We have worked with or collaborated on human, rodent, frog, fish, worm, yeast, and bacterial experimental systems.
Another theme of the lab is mechanosensitive cellular signaling via Ca entry through nonspecific cation channels.
Tanphaichitr VS, Sumboonnanonda A, Ideguchi H, Shayakul C, Brugnara C, Takao M, Veerakul G, Alper SL. Novel AE1 mutations in recessive distal renal tubular acidosis: rescue of loss-of-function by glycophorin A. J Clin Invest 1998; 102:2173-9
Casula S, Shmukler BE, Wilhelm S, Stuart-Tilley AK, Su W, Chernova MN, Brugnara C, and Alper SL. A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity. J Biol Chem 2001; 276:41870-8
Vandorpe DH, Chernova MN, Jiang L, Sellin L, Wilhelm S, Stuart-Tilley AK, Walz G, Alper SL. The cytoplasmic carboxy- terminal fragment of polycystin-1 (PKD1) regulates a Ca2 -permeable cation channel. J Biol Chem 2001; 276:4093-101
Jiang L, Jha V, Dhanabal M, Sukhatme VP, Alper SL. Intracellular Ca signalling in endothelial cells by the angiogenesis inhibitors endostatin and angiostatin. Am J Physiol 2001; 280:C1140-50.
Alper SL. Genetic diseases of acid-base transporters. Annu. Rev. Physiol 2002 64:899-923
External Recognition:
Interurban Clinical Club 2005
Symposium Organizer and Speaker, 2001 International Union of Physiological Sciences.
Symposium Organizer and Spearer, Experimental Biology 2000
Meeting Organizer, NIH Conference on Advances in Membrane Transport: Lessons from Model Organisms, 1999
Fellow of the AAAS, Section on Medical Sciences (N), 1997
Established Investigator of the American Heart Association 1994-9
Major Collaborative Activities:
Investigator, Boston Sickle Cell Center
Executive Committee and Core Consultant, Harvard DIgestive Diseases Ctr
Member, Harvard Cancer Ctr
