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Nineteenth Annual Distinguished Lecturer In Physiology and Biophysics, April 2008

David E. Clapham, M.D., Ph.D.

Department of Neurobiology and Cardiovascular Research
Harvard Medical School Investigator, Howard Hughes Medical Institute
“TRP Channels in Vesicular Trafficking”

Wednesday, April 16, 2008
12:00 P.M.
Sanger Hall, Room 2-020
Virginia Commonwealth University
School of Medicine

Reception Following Lecture

1:00 – 3:00 P.M.
MCV Alumni House
1016 East Clay Street

David Clapham

Dr. David Clapham is an Investigator with the Howard Hughes Medical Institute at Harvard Medical School. He is the Aldo Castañeda Professor and Director of Cardiovascular Research at Children’s Hospital in Boston and a Professor of Neurobiology at Harvard Medical School. He received his electrical engineering degree from Georgia Tech and completed his MD/PhD degree at Emory University with Drs. Louis DeFelice and Robert DeHaan. He pursued his residency training in Internal Medicine and Cardiology at the Brigham & Women’s Hospital in Boston and his postdoctoral training with the Nobel Laureate Erwin Neher at the Max-Planck Institute for Biophysical Chemistry in Goettingen, Germany. He became an Assistant Professor at Harvard Medical School in 1986 before moving to Rochester, MN at the Mayo Foundation in 1987, where he rose through the ranks to Professor of Pharmacology and also Professor of Physiology and Biophysics. After 9 years at Mayo, he returned to Harvard Medical School as Professor of Neurobiology and Professor of Pediatrics.

Dr. Clapham is known internationally for his seminal work in a number of areas. He has been fascinated by the role of intracellular calcium in cellular function, an interest that has guided him to investigate for many years the various ways in which Ca2+ entry into cells is controlled by ion channels. His work on TRP (transient receptor potential) ion channels that are involved in the transmission of and response to sensory stimuli, has yielded multiple important contributions to the field. His laboratory cloned and characterized TRPM7 that not only functions as a channel but also as a protein kinase that binds phospholipase C (PLC). Activation of PLC potently inhibits TRPM7 activity. TRPV3 is another channel in this family, which is activated by changing temperature from 22ºC to 40ºC leading to elevations in intracellular calcium. The Clapham group has carefully characterized this important human channel and has identified novel compounds that activate it. Another contribution in this area has been with the heteromeric TRPC1/TRPC5 that is activated by signals that stimulate PLC. Upon growth factor receptor stimulation TRPC5 channels are rapidly inserted into the plasma membrane and serve to control neurite extension and growth cone motility. A second area where the Clapham laboratory has made important contributions relates to reproductive physiology. They discovered CatSper, a calcium-selective channel that is only found in the tail of mature sperm. Disruption of the CatSper gene results in male sterility by abrogating sperm hyperactivation of motility, required for fertilization. CatSper and its relatives promise to be excellent targets for non-hormonal contraceptives for both men and women. A third area of a long-term interest has been in how G protein-sensitive potassium channels are regulated by GTP binding (G) proteins, heteromeric subunit assembly and post-translational modifications. The Clapham laboratory has made seminal contributions identifying these potassium channels as the first effector target of the βγ subunits of G proteins; showing that the native atrial channels are heteromers of two subunits that when expressed as homomers show little or no activity; and studying knockout mice lacking these channels that exhibit deficits in such diverse functions as pain, learning, and heart rate variability. Another important discovery that the Clapham lab is credited with is the identification of a bacterial Na channel, NaChBac, that like K channels, assemble into tetramers from single subunits, unlike Ca or Na channels that are encoded as tetramers by a single gene. This Na channel has attracted great attention as its simpler architecture and its bacterial origin make it an ideal target for structure-function studies aiming to understand Na selectivity. More than 40 percent of Dr. Clapham’s original work is published in Science, Nature (and sister journals), Cell (and Cell Press journals) and PNAS. The remainder of his original work is published in reputable journals such as EMBO J, JBC, Circ. Research, J. Gen Physiol., Biophys. J, J. Physiol, AJP, Pfluegers Arch., etc. His original work has had a major impact in the scientific community and has exceeded 11,500 citations. Regardless of the area that he has decided to pursue, not only he has made invaluable contributions but has also led scientific inquiry in that area. His research has been continuously funded both by the National Institutes of Health as well as by the Howard Hughes Medical Institute.

Dr. Clapham is the recipient of numerous awards and prizes throughout his career, including the Cole award for contributions to membrane biophysics of the Biophysical Society and the American Heart Association basic science award. He has been elected to the National Academy of Sciences and to the American Academy of Arts and Sciences. He has been involved in teaching numerous courses and has been recognized with the “Excellence in Teaching” award both at Mayo for contributions to graduate education as well as at Harvard Medical School for contributions to medical education. He has trained nearly 100 postdoctoral fellows and graduate students in his laboratory, many of whom hold key positions in academia, industry and government. Dr. Clapham has served in numerous institutional committees and has served in multiple extramural peer review committees, often assuming a leadership role. He serves in the editorial board of many leading biomedical scientific journals, including Cell, Science, and Neuron. He is a popular invited speaker to many scientific meetings and departmental seminars, averaging 16 speaking engagements per year over the past 20 years. Last but not least, Dr. Clapham’s lucid and insightful writing talent makes him a highly sought-after scientific writer. He has authored nearly 100 reviews, book chapters and commentaries ranging from his topics of expertise, opinions on science issues and comments on major scientific findings or major awards given to scientists in his field.