Donald W. Hilgemann

The University of Texas Southwestern Medical Center


Primary Section: 23, Physiology and Pharmacology
Membership Type:
Member (elected 2021)

Biosketch

Donald Hilgemann is a physiologist recognized for his work on Na transporters and regulation of membrane transport by signaling lipids.  He is known for his development of giant patch methods which he used to analyze the function of Na/K pumps, Na/Ca exchangers, Na/Cl/GABA cotransporters, and Na/H exchangers.  Experiments with giant patches also led to his discovery that the phospholipid, PIP2, is a major direct regulator of numerous ion channels and transporters.  He now uses electrical methods extensively to study plasma membrane turnover.  Hilgemann was born in Postville, Iowa and started undergraduate studies at the University of Iowa in Iowa City. He continued his studies at the University of Tuebingen in Germany in Biology and Preclinical Medicine, completing a Ph.D. in Physiology and Pharmacology in 1980.  He subsequently worked at the Merrell-Dow Research Institute in Strasbourg, followed by post-doctoral work at UCLA and the University of Oxford. He joined the faculty of the University of Texas Southwestern Medical School in 1988.  He takes an active role in medical school education, teaching basic principles of physiology with his own simulations and animations.  He became a member of the National Academy of Sciences in 2021.

Research Interests

Donald Hilgemann's laboratory is interested in membrane transport and its regulation by lipid signaling. Connected to these interests, the lab studies unconventional membrane trafficking mechanisms. These include the formation of membrane domains that are avidly internalized without involvement of conventional endocytic proteins and plasma membrane expansion via the opening of invaginations held shut (but not excised) by adapter proteins such as dynamins. The lab has developed and improved multiple patch clamp methods to study these processes. The giant excised patch method fundamentally improved our ability to analyze the function of Na transporters with analysis of partial reactions in the microsecond range. This method also revealed profound regulation of ion transporters and channels via direct binding of signaling lipids known as phosphoinositides. Our most recent work concerns endocytosis which relies on lipidation (palmitoylations) of membrane-associated proteins, thereby promoting the formation of ordered membrane domains. A major working hypothesis of the lab is that this form of endocytosis plays a key role in cell migration by internalizing membrane at the backward end of cells, thereby allowing cells to move membrane to the front end and to move further forward. A second hypothesis is that these powerful endocytic processes are the major mechanism by which macophages internalize LDL particles and become foam cells that cause atherosclerosis.

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