Eric T. Kool, Ph.D. George and Hilda Daubert Professor of Chemistry: Fellow, ChEM-H Institute, Stanford University

Research description: Dr. Kool’s laboratory is focused on developing molecular probes of nucleic acids and of enzymes that modify and repair them. His group uses the tools of synthetic chemistry, biophysical chemistry and chemical biology to develop practical molecules and methods that are used worldwide in academic labs and in industry. The lab has developed modified nucleotides and oligonucleotides into novel and potentially clinically useful reporters of DNA repair pathways in cells and tissues, some of the first in existence. This work is leading the way to useful biomarker-based cancer diagnostics, and, with groups at Novartis and Stanford, is enabling the development of small molecules that modulate DNA repair in novel anticancer strategies. The Kool lab, in collaboration with clinical labs at Stanford and elsewhere, is currently employing their probes to measure DNA repair activities in pancreatic tumor specimens, and is testing the sensitivity of Ras-mutant pancreatic tumor cells to downregulation of specific DNA repair enzymes.

Dr. Kool’s group has active collaborations with other members of the PCRG, including Drs. Diehn, Ford, and Ji.

List of selected relevant publications (Stanford PCRG members in bold):

  1. T. Ono, S. Wang, C.-K. Koo, L. Engstrom, S. S. David, E. T. Kool, Direct Fluorescence Monitoring of DNA Base Excision Repair, Angew. Chem. Int. Ed. 2012 , 51 , 1689-1693.
  2. S. Karmakar, E. M. Harcourt, D. S. Hewings, F. Schere, A. F. Lovejoy, D. M. Kurtz, T. Ehrenschwender, L. C. Barandun, C. Roost, A. A. Alizadeh, E. T. Kool. Organocatalytic removal of formaldehyde adducts from RNA and DNA bases. Nature Chem. 2015, 7, 752-8.
  3. A. A. Beharry, S. LaCoste, T. O’Connor, E. T. Kool, Real-time Fluorescence Monitoring of the Oxidative Repair of DNA Alkylation Damage by ALKBH3, a Prostate Cancer Marker, J. Am. Chem. Soc. 2016 , 138 , 3647-3650.
  4. D. Ji, A. A. Beharry, J. M. Ford, E. T. Kool, A Chimeric ATP-linked Nucleotide Enables Luminescence Signaling of Damage Repair by MTH1, a Cancer Target, J. Am. Chem. Soc. 2016 , 138 , 9005-9008.
  5. Y. K. Tahara, D. Auld, D. Ji, A. A. Beharry, A. M. Kietrys, D. L. Wilson, M. Jimenez, D. King, Z. Nguyen, E. T. Kool. Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase. J Am Chem Soc. 2018, 140, 2105-2114.