2016 Stetten Lecture -- Elements of Health and Disease: Inorganic Fluxes and Metal Receptors That Control Cell Fate Decisions

Masur Auditorium
Clinical Center (Building 10)
National Institutes of Health
Bethesda, Maryland

Start Date: 10/19/2016 3:00 PM

End Date: 10/19/2016 4:00 PM

2016 Stetten Lecture poster - Elements of Health and Disease

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Speaker: Thomas V. O’Halloran, Ph.D.
Department of Chemistry, Department of Molecular Biosciences
Northwestern University

Biographical Sketch

For the past three decades, Thomas V. O’Halloran has investigated how fluctuations in the amount of metal ions inside cells influence key cellular decisions. Using genetic, chemical, structural and mechanistic approaches, he has uncovered new types of metal receptors and tied their function to a number of disease-related physiological processes. O’Halloran identified early examples of metal ion receptors called metalloregulatory proteins that regulate gene expression. He and his collaborators also discovered a second class of metal receptors called metallochaperone proteins that govern the flow of metals within the cell. The O’Halloran lab currently focuses on how intracellular fluxes of iron, copper, zinc and other metals regulate pathways needed for cell growth and proliferation.

O’Halloran and his team have recently demonstrated essential roles for intracellular zinc fluctuations in mammalian oocyte maturation and fertilization. Using novel small-molecule probes as well as single-cell X-ray fluorescence microscopy, the research group established that the uptake of billions of zinc atoms regulates meiotic cell cycle progression. In contrast, the researchers found rapid zinc exocytosis events, triggered by fertilization and collectively known as “zinc sparks,” must occur before embryonic development can proceed. These findings may one day be useful in improving in vitro fertilization methods.

Changes in metal ion concentrations also control fundamental developmental decisions in bacteria and disease-causing parasites, as reported by O’Halloran and his colleagues. For example, the invasion of pathogens that cause fungal brain disease and malaria depends on spikes in copper and zinc, respectively.

These insights into the inorganic chemistry of the cell have led O’Halloran’s team to develop new therapeutic agents that selectively target metalloenzymes or harness the biological chemistry of nonessential metals such as molybdenum, arsenic and platinum.

O’Halloran earned a B.S. and an M.A. in chemistry from the University of Missouri in 1980 and a Ph.D. in chemistry from Columbia University in 1985. He studied the role of metals in regulating biological processes as a Ruth L. Kirschstein National Research Service Award postdoctoral fellow at the Massachusetts Institute of Technology. Since 1986, O’Halloran has been on the faculty of Northwestern University, where he is the Charles E. and Emma H. Morrison Professor in the departments of chemistry and molecular biosciences as well as the founding director of the Chemistry of Life Processes Institute. He is also the director of the Northwestern University Physical Sciences-Oncology Center.

O’Halloran’s honors include a Sloan research fellowship, a Guggenheim fellowship, a Searle scholar award, an NIH MERIT award and a Presidential Young Investigator Award. He is a fellow of the American Association for the Advancement of Science, the Japan Society for the Promotion of Science and the Royal Society of Chemistry. He holds 10 patents and is the co-founder of three pharmaceutical companies.

NIGMS has supported O’Halloran’s work since 1987 under grants R01GM038784, R01GM045972, R01GM054111 and R01GM115848.