Daniel A. Harki, PhD

Associate Professor, Department of Medicinal Chemistry

Daniel A. Harki

Contact Info

daharki@umn.edu

Office Phone 612-625-8687

Fax 612-625-4749

Lab Phone 612-625-3701

Office Address:
Medicinal Chemistry Pharmacognosy
2-139 CCRB
2231 6th St SE
Minneapolis, MN 55455

Mailing Address:
College of Pharmacy
1st Floor Mailroom CCRB
2812B
2231 6th St SE
Minneapolis, MN 55455

Lab Address:
University of Minnesota
CCRB 2-139
2231 6th Street S.E.
Minneapolis, MN 55455

PhD, The Pennsylvania State University (Chemistry), 2005

B.A., West Virginia University, 1999

Post Doctorate, California Institute of Technology (Chemistry), 2005-2009

Summary

Awards & Recognition

  • 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 

Research

Research Summary/Interests

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 antiviral and 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.

Current projects in the Harki laboratory include:

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-?B 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.

Publications

Wells SM, Widen JC, Harki DA and Brummond KM. Alkyne ligation handles: Propargylation of hydroxyl, sulfhydryl, amino, and carboxyl groups via the Nicholas reaction. Org. Lett. 2016, 18, 4566-4569.

Perkins AL, Peterson KL, Beito TG, Flatten KS, Kaufmann SH and Harki DA. Synthesis of a peptide-universal nucleotide antigen: Towards next-generation antibodies to detect topoisomerase I-DNA covalent complexes. Org. Biomol. Chem. 2016, 14, 4103-4109.

Struntz NB and Harki DA. Catch & release DNA decoys: Capture and photochemical dissociation of NF-kappaB transcription factors. ACS Chem. Biol. 2016, 11, 1631-1638.

Richards C, Albin JS, Demir Ö, Shaban NM, Luengas EM, Land AM, Anderson BD, Holten JR, Anderson JS, Harki DA, Amaro RE, and Harris RS. The binding interface between human APOBEC3F and HIV-1 Vif elucidated by genetic and computational approaches. Cell Rep. 2015, 13, 1781-1788.

Olson ME, Abate-Pella D, Perkins AL, Li M, Carpenter MA, Rathore A, Harris RS and Harki DA. Oxidative reactivities of 2-furylquinolines: Ubiquitous scaffolds in common high-throughput screening libraries. J. Med. Chem. 2015, 58, 7419-7430.