Olaf Wiest // People // Department of Chemistry & Biochemistry // University of Notre Dame

Olaf Wiest

Organic & Bioorganic reaction mechanisms

Biography

2005-present: Professor, University of Notre Dame
2001-2005: Associate Professor, University of Notre Dame
1996-2001: Assistant Professor, University of Notre Dame
1993-1995: Postdoctoral Fellow, University of California, Los Angeles
1993: Dr. rer. nat. University of Bonn, Germany
1991: Diplom, University of Bonn, Germany

Selected Awards

2012: Fellow of the American Association for the Advancement of Science
2004: John Kaneb Award for undergraduate teaching
2001: Camille Dreyfus Teacher-Scholar Award
1997: NSF CAREER Award
1997: NIH First Award

Research Interests

The central topic of the research in the Wiest group is how molecules interact and react. The structure and energetics of non-covalent complexes and transition states is probed theoretically and experimentally. The detailed understanding of intermolecular interactions can then be exploited for the design of assays for biophysical studies and for drug design. Four distinct areas of research are currently under investigation: (1) development of epigenetic modulators targeting histone deacetylases and bromodomains as chemical tools and drug leads, (2) rare and neglected diseases, specifically Niemann Pick Type C disease, (3) mechanistic studies of transition metal and enzyme catalyzed reactions, and (4) development of Q2MM methods for the virtual screening of chiral ligands for asymmetric catalysis.

The research in the Wiest group uses a wide range of experimental and computational methods that are applied to fundamental and applied problems in organic and biophysical chemistry. In this work, we collaborate with a number of other researchers in synthetic chemistry, biology, physics, and at medical schools at Notre Dame and around the world.

Recent Publications

Durbin, A. D.; Wang, T. J.; Wimalasena, V. K.; Zimmerman, M. W.; Li, D. Y.; Dharia, N. V.; Mariani, L.; Shendy, N.; Nance, S.; Patel, A. G.; Shao, Y.; Mundada, M.; Maxham, L.; Park, P.; Sigua, L. H.; Morita, K.; Conway, A. S.; Robichaud, A. L.; Perez-Atayde, A. R.; Bikowitz, M. J.; Quinn, T. R.; Wiest, O.; Easton, J.; Schonbrunn, E.; Bulyk, M. L.; Abraham, B. J.; Stegmaier, K.; Look, A. T. and Qi, J. "EP300 Selectively Controls the Enhancer Landscape of MYCN-Amplified Neuroblastoma" 2022 Cancer Discovery, 12 (3), pp.730-751. DOI: 10.1158/2159-8290.CD-21-0385.
Huizar, F. J.; Hill, H. M.; Bacher, E. P.; Eckert, K. E.; Gulotty, E. M.; Rodriguez, K. X.; Tucker, Z. D.; Banerjee, M.; Liu, H. N.; Wiest, O.; Zartman, J. and Ashfeld, B. L. "Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic in Vivo Drosophila Model System**" 2022 ChemMedChem, 17 (4), e202100512. DOI: 10.1002/cmdc.202100512.
Wahlers, J.; Margalef, J.; Hansen, E.; Bayesteh, A.; Helquist, P.; Dieguez, M.; Pamies, O.; Wiest, O. and Norrby, P. O. "Proofreading Experimentally Assigned Stereochemistry through Q2MM Predictions in Pd-Catalyzed Allylic Aminations" 2021 Nature Communications, 12 (1), 6719. DOI: 10.1038/s41467-021-27065-2.
Pipalia, N. H.; Saad, S. Z.; Subramanian, K.; Cross, A.; Al-Motawa, A.; Garg, K.; Blagg, B.; Neckers, L.; Helquist, P.; Wiest, O.; Ory, D. S. and Maxfield, F. R. "HSP90 Inhibitors Reduce Cholesterol Storage in Niemann-Pick Type C1 Mutant Fibroblasts" 2021 Journal of Lipid Research, 62, 100114. DOI: 10.1016/j.jlr.2021.100114.
Kim, C.; Mahasenan, K. V.; Bhardwaj, A.; Wiest, O.; Chang, M. and Mobashery, S. "Production of Proteins of the SARS-CoV-2 Proteome for Drug Discovery" 2021 ACS Omega, 6 (30), pp.19983-19994. DOI: 10.1021/acsomega.1c02984.
Cruz, D. L.; Pipalia, N.; Mao, S.; Gadi, D.; Liu, G.; Grigalunas, M.; O'Neill, M.; Quinn, T. R.; Kipper, A.; Ekebergh, A.; Dimmling, A.; Gartner, C.; Melancon, B. J.; Wagner, F. F.; Holson, E.; Helquist, P.; Wiest, O. and Maxfield, F. R. "Inhibition of Histone Deacetylases 1, 2, and 3 Enhances Clearance of Cholesterol Accumulation in Niemann-Pick C1 Fibroblasts" 2021 ACS Pharmacology & Translational Science, 4 (3), pp.1136-1148. DOI: 10.1021/acsptsci.1c00033.