Principal Research 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 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
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. Find more information on our publications page.
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-κB 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. Find more information on our publications page.