Donald Hilgemann, Ph.D.

Professor

Endowed Title: Floyd C. Rector, Jr., M.D. Professorship in Acid-Base Regulation; Robert W. Lackey Professorship in Physiology; Roy and Christine Sturgis Chair in Biomedical Research
School: Medical School
Department: Physiology | Charles and Jane Pak Center for Mineral Metabolism and Clinical Research | Internal Medicine
Graduate Programs: Neuroscience

Biography

We study physiological processes that modify and regulate the plasma membrane of cells. Initially we studied the function and regulation of Na transporters that regulate cardiac myocyte function and determine cardiac fate in metabolic stress. We developed new electrical methods to do so, and we achieved microsecond resolution of partial reactions of transporters. We went on to study how lipids regulate ion channels and transporters, and we discovered that the negatively charged lipid, PIP₂, directly regulates and is essential for activity of many transport processes. We refined electrical methods to monitor electroneutral ion fluxes in cells and isolated membrane patches. We are now concentrated on turnover of the surface membrane. We have identified new mechanisms that can remove surface membrane more rapidly and more extensively than conventional endocytosis, which relies on membrane adapter proteins, such as clathrin and dynamin. These non-conventional mechanisms rely on domain formation within membranes. They can be active constitutively, and the become highly activated in metabolic stress. They are involved in multiple cell processes that require membrane turnover, including cell migration and particle uptake. In addition, we discovered a new mechanism of plasma membrane expansion that does not appear to involve exocytosis. In many cells, large fractions of the surface membrane are locked into closed invaginations that are not ‘excised’ from the surface. This large membrane reserve can be opened when needed to expand the surface during cell swelling or spreading, as well as other processes that require more membrane area. In summary, I have strived throughout my career to bring new approaches and difficult experimentation to bear on outstanding open questions related to membrane biology and ion transport. In recognition for these contributions, I was elected to the National Academy of Sciences in 2021.

Education

Graduate School: University of Tuebingen , Biology
Medical School: University of Tuebingen (1980), Medicine

Research Interest

Calcium Signaling
Electrophysiology
Lipid Signaling
Membrane transport mechanisms
Nonconventional endocytic mechanisms

Publications

Featured Publications

Author Correction: TMEM16F activation by Ca²⁺ triggers plasma membrane expansion and directs PD-1 trafficking.: Bricogne C, Fine M, Pereira PM, Sung J, Tijani M, Wang Y, Henriques R, Collins MK, Hilgemann DW, Sci Rep 2019 May 9 1 7705
TMEM16F activation by Ca²⁺ triggers plasma membrane expansion and directs PD-1 trafficking.: Bricogne C, Fine M, Pereira PM, Sung J, Tijani M, Wang Y, Henriques R, Collins MK, Hilgemann DW, Sci Rep 2019 Jan 9 1 619
Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis.: Hilgemann DW, Dai G, Collins A, Lariccia V, Magi S, Deisl C, Fine M J. Gen. Physiol. 2018 Jan
Na/K pump inactivation, subsarcolemmal Na measurements, and cytoplasmic ion turnover kinetics contradict restricted Na spaces in murine cardiac myocytes.: Lu FM, Hilgemann DW J. Gen. Physiol. 2017 Jun
Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes.: Lu FM, Deisl C, Hilgemann DW Elife 2016 Sep 5
Palmitoylation of the Na/Ca exchanger cytoplasmic loop controls its inactivation and internalization during stress signaling.: Reilly L, Howie J, Wypijewski K, Ashford ML, Hilgemann DW, Fuller W FASEB J. 2015 Jul
Human-induced pluripotent stem cell-derived cardiomyocytes for studies of cardiac ion transporters.: Fine M, Lu FM, Lin MJ, Moe OW, Wang HR, Hilgemann DW Am. J. Physiol., Cell Physiol. 2013 Jun
Massive palmitoylation-dependent endocytosis during reoxygenation of anoxic cardiac muscle.: Lin MJ, Fine M, Lu JY, Hofmann SL, Frazier G, Hilgemann DW Elife 2013 2 0
Massive endocytosis triggered by surface membrane palmitoylation under mitochondrial control in BHK fibroblasts.: Hilgemann DW, Fine M, Linder ME, Jennings BC, Lin MJ Elife 2013 2 0
Massive endocytosis driven by lipidic forces originating in the outer plasmalemmal monolayer: a new approach to membrane recycling and lipid domains.: Fine M, Llaguno MC, Lariccia V, Lin MJ, Yaradanakul A, Hilgemann DW J. Gen. Physiol. 2011 Feb 137 2 137-54

Honors & Awards

National Academy of Science
Election to the Physiology/Pharmacology Section of the NAS (2121)
1983
Lievre Research Award for best cardiovascular research, Greater Los Angeles (0)
1989-1992
Established Investigatorship, American Heart Association (0)
1993
Fellow, Japan Society for the Promotion of Science (University of Kyoto) (0)
1997
Young Investigator Award: International Biophysical Society (0)

Professional Associations/Affiliations

Biophysical Society