Dr. Montfort has been a member of the University of Arizona Cancer Center for 25 years. His cancer-related research has focused on mechanism in drug binding and on establishing new targets. More recently, they have been developing new methods for drug screening. Targets of past and current interest include thymidylate synthase, thioredoxin, a new transmembrane target called CD47 that regulates nitric oxide signaling and tumor growth, and a variety of kinases. He is pleased now to serve on this grant as Co-Leader of the Therapeutic Development Program.
Dr. Montfort's research broadly concerns the link between protein structure and protein function, including how ligands and drugs bind to their targets and influence activity. One current focus concerns nitric oxide signaling. Their work includes studies on NO binding, transport and signaling regulation, and our approaches span atoms to animals. Among their studies are crystal structures of proteins containing nitrosyl-heme or nitroso-cysteine, transient kinetic measurements, biophysical measurements of transmembrane complexes and functional measurements in live cells, including forward genetics approaches. They seek mechanistic and regulatory details of importance to numerous diseases, including cardiovascular disease, poor wound healing in diabetes, and angiogenesis and tumor growth in cancer.
These studies and the University of Arizona provide an excellent home for cross-disciplinary student training and collaborative studies. Dr. Montfort directs the Biological Chemistry Graduate Program, which brings together chemists, biochemists and medicinal chemists for research at the chemistry/biology interface and is the marquee training program for drug discovery on campus. He has trained over thirty graduate and postdoctoral students from numerous programs, including Biochemistry, Molecular and Cellular Biology, Chemistry, Applied Mathematics and Pharmacology and Toxicology. He has also been intimately involved in establishing collaborative core facilities.
Dr. Montfort established the Macromolecular Crystallography Core facility in 1990 and has continued as faculty director since that time. He is a past member of numerous core facilities and currently serve on the steering committees for the Functional Genomics Facility and the Proteomics Facility.
- Shokhireva, TKh, Weichsel A, Smith KM, Berry RE, Shokhirev NV, Balfour CA, Zhang H, Montfort WR, Walker FA: Assignment of the Ferriheme Resonances of the Low-Spin Complexes of Nitrophorins 1 and 4 by 1H and 13C NMR Spectroscopy: Comparison to Structural Data Obtained from X-ray Crystallography. Inorg. Chem. 46:2041-2056, 2007.
- Cheung LSL, Quick R, Singh SK, Weichsel A., Montfort WR, Zohar Y: Microsystems for UV-visible and X-ray analysis of protein crystals, Proc. 20th International Micro Electro Mechanical Systems Conference, Jan. 21-25, 2007, Kobe, Japan, pp.569-572, 2007.
- Schreiter ER, Rodriguez MM, Weichsel A, Montfort WR, Bonaventura, J: S-Nitrosylation-Induced Conformational Change in Blackfin Tuna Myoglobin. J. Biol. Chem. 282:19773-19780, 2007.
- Kondrashov DA, Montfort WR: Nonequilibrium dynamics simulations of nitric oxide release: comparative study of nitrophorin and myoglobin. J. Phys. Chem. B 111:9244-9252, 2007.
- Amoia AM, Montfort WR: Apo-Nitrophorin 4 at Atomic Resolution. Protein Sci. , 16:2076-2081, 2007.
- Morrison S, Roberts S, Zegeer A, Montfort WR, Bandarian V: A new use for a familiar fold: The x-ray crystal structure of GTP-bound GTP cyclohydrolase III from Methanocaldococcus jannaschii reveals a two metal ion catalytic mechanism. Biochemistry, 47:230-242, 2008.