Daniel A. Harki, PhD
Research in the Harki laboratory focuses on the design, synthesis and biological characterization of novel small molecules, peptides, and oligonucleotides that influence cellular function. Applications for these molecules range from anticancer drug discovery to new tools for modern biotechnology research. Our core science is organic chemistry. However, we use techniques of modern biochemistry, biophysics, and cellular/molecular biology to evaluate the biological activities of the compounds we synthesize.
Development of APOBEC3 Chemical Probes
In collaboration with multiple groups at the University of Minnesota and external, we are developing the first-in-class chemical probes of the APOBEC3 family of DNA cytosine-to-uracil deaminases. Our approach to chemical probe discovery relies on high-throughput small molecule and fragment screening, as well as computation- and structure-based designs, to inform our iterative cycles of rational compound design, synthesis, and biochemical/cellular evaluation.
Chemical Modulation of Transcription Factor Signaling
Aberrant transcription factor (TF) signaling drives the progression of numerous diseases and represents a formidable challenge for the development of chemical probes. We are developing small molecule and nucleic acid-based chemical probes of multiple TFs, including NF-kB and androgen receptor. We are particularly focused on covalent inhibitors of TF signaling networks with a strong interest in natural product-based analogues. Additionally, our group has extensive experience synthesizing non-natural nucleosides and oligonucleotides, which are useful for developing TF-targeted probes.
Medicinal chemistry, chemical biology, nucleic acids, mutation
Awards & Recognition
- 2016 - Inductee, Rho Chi Pharmacy Honor Society, Mu Chapter
- Professor of the Semester, University of Minnesota, College of Pharmacy, Class of 2013 - Duluth, Fall 2013
- V Foundation V Scholar, V Foundation for Cancer Research, 2012
- California Tobacco-Related Disease Research Program, Postdoctoral Fellowship, 2007-09
- Friedreich's Ataxia Research Alliance, Postdoctoral Fellowship, 2006-07
- American Heart Association, Predoctoral Fellowship, 2002-05
- Phi Beta Kappa, Alpha of West Virginia, West Virginia University, 1999
Associate Professor and Director of Graduate Studies, Department of Medicinal Chemistry
Co-Leader, Cellular Mechanisms Program, Masonic Cancer Center (MCC)
Institute for Molecular Virology
Faculty, PhD Program in Biochemistry, Molecular Biology and Biophysics
Faculty, Masters Program in Stem Cell Biology
Postdoctoral, California Institute of Technology (Chemistry), 2005-2009
PhD, The Pennsylvania State University (Chemistry), 2005
BA, West Virginia University (Biology & Chemistry), 1999
Kvach MV, Barzak FM, Harjes S, Schares HAM, Jameson GB, Ayoub AM, Moorthy R, Aihara H, Harris RS, Filichev V, Harki DA and Harjes E. Inhibiting APOBEC3 activity with single-stranded DNA containing 2'-deoxyzebularine analogs. Biochemistry2019, 58, 391-400.
Passow KT and Harki DA. 4-Cyanoindole-2'-deoxyribonucleoside (4CIN): A universal fluorescent nucleoside analogue. Org. Lett. 2018, 20, 4310-4313.
Widen JC, Kempema AM, Baur JW, Skopec HM, Edwards JT, Brown TJ, Brown DA, Meece FA and Harki DA. Helenalin analogues targeting NF-kappaB p65: Thiol reactivity and cellular potency studies of varied electrophilies.ChemMedChem 2018, 13, 303-311.
Olson ME, Harris RS and Harki DA. APOBEC enzymes as targets for virus and cancer therapy.Cell Chem. Biol. 2018, 25, 36-49.
Jackson PA, Widen JC, Harki DA and Brummond KM. Covalent modifiers: A chemical perspective on the reactivity of alpha,beta-unsaturated carbonyls with thiols via hetero-Michael addition reactions. J. Med. Chem. 2017, 60, 839-885.