09/20/18 - 9:45 AM to 10:45 AM
Kolthoff Lectureship #3: Professor John T. Groves
Izaak M. Kolthoff Lectureship in Chemistry
Bioinorganic Chemistry, the Immune Response and Cancer
Indoleamine 2,3-dioxygenase (IDO1) is a heme protein that oxidizes the essential amino acid tryptophan to produce N-formylkynurenine. This enzyme is present in many tissues and is significantly upregulated in response to inflammation, specifically the presence of cytokines such as IFNγ and bacterial lipopolysaccharides. Cells expressing IDO1 are able to deplete the inflamed environment of the metabolically expensive substrate, tryptophan, inhibiting the proliferation of immune targets. IDO1 also serves as an immunosuppressive enzyme. Cells expressing IDO1 inactivate surrounding immune cells through the combined effects of low tryptophan and high concentrations of kynurenine. T-cells are especially sensitive to low tryptophan concentrations, causing them to cease proliferation and to differentiate into immunosuppressive regulatory states. The importance of IDO1 in precise immune regulation is highlighted by its effects in a variety of processes and disease states including autoimmune disorders, response to infection, tolerance in transplantation, HIV infection, blood pressure regulation and the ability of cancer cells to avoid immune detection. In this lecture, we will discuss mechanisms by which human IDO1 affects the immune response in the context of the field of bioinorganic chemistry.
- Micah T. Nelp, Patrick A. Kates, John T. Hunt, John A. Newitt, Aaron Balog, Derrick Maley, Xiao Zhu, Lynn Abell, Alban Allentoff, Robert Borzilleri, Hal A. Lewis, Zeyu Lin, Steven P. Seitz, Chunhong Yan, John T. Groves, The immune modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form, Proc. Nat. Acad. Sci. USA, 2018, 115, 3249-3254.
- Xiongyi Huang and John T. Groves, Oxygen activation and radical transformations in heme proteins and metalloporphyrins, Chem. Rev. 2018, 118, 2491−2553
Professor Groves' research program is at the interface of organic, inorganic, and biological chemistry. Current efforts focus on the design of new, biomimetic catalysts and the molecular mechanisms of these processes, the design and assembly of large scale membrane-protein-small molecule constructs, studies of host-pathogen interactions related to iron acquisition by small molecule siderophores, and molecular probes of the role of peroxynitrite in biological systems.
Professor Groves received an undergraduate degree in chemistry at the Massachusetts Institute of Technology, where he worked with Frederick Greene. In 1965, he began his doctoral studies under the direction of Professor Ronald Breslow at Columbia University. Upon receiving his doctorate, Groves began his independent research career at the University of Michigan, in 1969. In 1985, he moved to Princeton University where he is Hugh Stott Taylor Chair of Chemistry. Groves is an award-winning inorganic chemist, receiving numerous accolades, including the American Chemical Society National Award in Inorganic Chemistry and the Sigma-Aldrich Award in Inorganic Chemistry. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and a Fellow of the Royal Society of Chemistry.
Kolthoff Lectureship in Chemistry
Izaak Maurits Kolthoff was born on February 11, 1894, in Almelo, Holland. He died on March 4, 1993, in St. Paul, Minnesota. In 1911, he entered the University of Utrecht, Holland. He published his first paper on acid titrations in 1915. On the basis of his world-renowned reputation, he was invited to join the faculty of the University of Minnesota’s Department of Chemistry in 1927. By the time of his retirement from the University in 1962, he had published approximately 800 papers. He continued to publish approximately 150 more papers until his health failed. His research, covering approximately a dozen areas of chemistry, was recognized by many medals and memberships in learned societies throughout the world, including the National Academy of Sciences and the Nichols Medal of the American Chemical Society. Best known to the general public is his work on synthetic rubber. During World War II, the government established a comprehensive research program at major industrial companies and several universities, including Minnesota. Kolthoff quickly assembled a large research group and made major contributions to the program. Many of Kolthoff’s graduate students went on to successful careers in industry and academic life and, in turn, trained many more. In 1982, it was estimated that approximately 1,100 Ph.D. holders could trace their scientific roots to Kolthoff. When the American Chemical Society inaugurated an award for excellence in 1983, he was the first recipient.