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Department of Chemistry

Walter J. Chazin

Professor of Biochemistry & Chemistry
Chancellor's Chair in Medicine

Dr. Chazin is currently accepting graduate students for Fall 2024 - APPLY TODAY

The Chazin group uses a structural and chemical perspective to investigate the molecular basis for the function and dysfunction of proteins and protein complexes important for human health and disease. Three key factors govern our approach: (1) a deep commitment to pursuing the research question using whatever tool is needed to obtain the answer; (2) fascination with the mechanics of multi-protein machinery; (3) firm belief in the power of collaboration and multi-disciplinary team science. We use a wide range of tools and approaches spanning basic biochemistry, biophysics, chemical biology and structural biology.

A primary research focus is genome maintenance and cancer. One project is directed to using AI to predict how defects in specific DNA repair genes alter the response to standard cancer chemotherapeutics and to developing an inhibitor of DNA repair that will reduce the development of resistance to the drug. A second project involves determining how the leading and lagging strands are primed to enable the synthesis of complementary strands during DNA replication. A second research focus is the ligands and receptors mediating innate immunity, which can cause chronic inflammation. Projects include elucidating the molecular basis for activation of specific receptors by their cognate ligands and developing inhibitors to test the potential therapeutic value of targeting receptor activation to suppress chronic inflammatory disorders.

Specializations

Biochemistry, Physical

Representative Publications

https://orcid.org/0000-0002-2180-0790
https://scholar.google.com/citations?user=RrcYL0AAAAAJ&hl=en

 

A.M. Blee, B. Li, T. Pecen, J. Meiler, Z.D. Nagel, J.A. Capra and W.J. Chazin. “An active learning framework improves tumor variant interpretation.”  Cancer Research 82, 2704-2715 (2022).

E.A. Mullins, L.E. Salay, C.L. Durie, J.E. Jackman, M.D. Ohi, W.J. Chazin* and B.F. Eichman. “A mechanistic model of primer synthesis from catalytic structures of DNA polymerase α-primase.” bioRxiv:2023.03.16.533013 (2023).

M.B. Adolph, T.M. Mohamed, S. Balakrishnan, C. Xue, F. Morati, M. Modesti, E.C. Greene, W.J. Chazin* and D. Cortez*. “RADX controls RAD51 filament dynamics to regulate replication fork stability.”  Mol. Cell 81, 1074-1083 (2021).

A. Bera, R. Wu, S. Harrison, C. Cornelissen, W.J. Chazin and N. Noinaj.  “TdfH selectively binds metal-loaded tetrameric calprotectin for zinc import.”  Commun. Biol. 5, e103 (2022).

N. Kozlyuk, B.A. Gilston, L.E. Salay, R.D. Gogliotti, P.P. Christov, K. Kim, M. Ovee, A.G. Waterson and W.J. Chazin.  “A Fragment-Based Approach to Discovery of RAGE Inhibitors.”  Proteins: Structure, Function, and Bioinformatics 89, 1399-1412 (2021).