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

Postdoctoral, California Institute of Technology (Chemistry), 2005-2009

PhD, The Pennsylvania State University (Chemistry), 2005

BA, West Virginia University (Biology & Chemistry), 1999

Summary

Harki Lab Group

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.

CURRENT PROJECTS:

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.

Expertise

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 

Research

Publications

Google Scholar Profile

Pubmed Bibliography

Shi K, Carpenter MA, Banerjee S, Shaban NM, Kurahashi K, Salamango DJ, McCann JL, Starrett GJ, Duffy JV, Demir Ö, Amaro RE, Harki DA, Harris RS and Aihara H.  Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B. Nat. Struct. Mol. Biol. 2017,24, 131-139.

Jackson PA, Widen JC, Harki DA and Brummond KM.Covalent modifiers: A chemical perspective on the reactivity of ?,ß-unsaturated carbonyls with thiols via hetero-Michael addition reactions. J. Med. Chem. 2017,60, 839-885.

Widen JC, Kempema, AM, Villalta, PW and Harki DA.Targeting NF-?B p65 with a helenalin inspired bis-electrophile. ACS Chem. Biol. 2017,12, 102-113.

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-?B transcription factors. ACS Chem. Biol. 2016, 11, 1631-1638.