David E. Heppner

PhD

David Heppner.

David E. Heppner

PhD

David E. Heppner

PhD

Research Interests

Chemical biology, medicinal chemistry, structure-guided drug design, protein biochemistry, structural biology, cancer biology, protein kinases, allosteric inhibitors, targeted protein degradation, bioinorganic chemistry, redox biology, and biorthogonal chemistry.

Contact Information

515 Natural Sciences Complex

Buffalo NY, 14260

Phone: (716) 645-5133

Fax: (716) 645-6963

davidhep@buffalo.edu

Education

  • Postdoctoral Research Fellow, Dana-Farber Cancer Institute and Havard Medical School, Boston, MA, 2017-2020
  • NIH Postdoctoral Fellow, Larner College of Medicine at the University of Vermont, Burlington, VT, 2014-2017
  • PhD, Stanford University, Stanford, CA, 2014
  • BS Chem., Summa Cum Laude, University of Minnesota, MN, 2007

Awards and Honors

  • Co-chair of Gordon Research Seminar on NADPH Oxidase Enzymes, 2018
  • Young Investigator Award, SFRMB, 2016
  • Ruth L. Kirschstein NRSA Postdoctoral Fellowship (F32), NIH, 2016
  • Beckman Scholar, 2006

Specializations

  • Protein biochemistry, enzymology, and molecular biology
  • Drug discovery, pharmacology, and medicinal chemistry
  • Bioinorganic chemistry and redox biology
  • Biophysical techniques and spectroscopy
  • Targeted protein degradation
  • Structural biology

Research Summary

The Heppner lab studies molecules, proteins, and cells to develop innovative solutions to persistent challenges in human health. We apply an integrative approach through a combination of medicinal chemistry, biochemistry, cellular and molecular biology, biophysics, and structural biology to discover and design novel therapeutics and molecular tools for biological applications. Our research is equally directed to understand protein structural and mechanistic essentials that control biochemical processes important in cancer biology and other diseases. Current areas of interest include:

  • Discovery and design of first-in-class small molecule inhibitors as targeted therapies in cancer and other diseases.
  • Structural and functional understanding of post-translational modifications at protein cysteine residues.
  • Pharmacology and structural biology of metalloproteins and redox enzymes.

Selected Recent Publications

Google Scholar: Link
Publons: Link

  • D.E. Heppner et al., Structural Basis for EGFR Inhibition by Trisubstituted Imidazole Inhibitors. Journal of Medicinal Chemistry. 2020. https://doi.org/10.1021/acs.jmedchem.0c00200
  • D.J.H. De Clercq, D.E. Heppner et al., Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors. ACS Medicinal Chemistry Letters. 2019. https://doi.org/10.1021/acsmedchemlett.9b00381
  • D.E Heppner, C.M. Dustin, C. Liao, et al., Direct Cysteine Sulfenylation Drives Activation of the Src Kinase. Nature Communications. 2018. https://doi.org/10.1038/s41467-018-06790-1
  • D.E. Heppner et al., Cysteine perthiosulfenic acid (Cys-SSOH): A novel intermediate in thiol-based redox signaling. Redox Biology. 2018. https://doi.org/10.1016/j.redox.2017.10.006
  • D.E. Heppner, Y.M.W. Janssen-Heininger, and A. van der Vliet. The role of sulfenic acids in cellular redox siganling: Reconciling chemical kinetics and molecular detection strategies. Archives of Biochemistry and Biophysics. 2017. https://doi.org/10.1016/j.abb.2017.01.008
  • D.E. Heppner et al., The NADPH oxidases DUOX1 and NOX2 play distinct roles in redox regulation of epidermal growth factor receptor signaling. Journal of Biological Chemistry. 2016. https://doi:10.1074/jbc.M116.749028
  • D.E. Heppner and A. van der Vliet. Redox-dependent regulation of epidermal growth factor receptor signaling. Redox Biology. 2016. https://doi.org/10.1016/j.redox.2015.12.002
  • D.E. Heppner et al., Mechanism of the reduction of the native intermediate in the multicopper oxidases: Insights into rapid intramolecular electron transfer in turnover. Journal of the American Chemical Society. 2014. https://doi.org/10.1021/ja509150j
  • D.E. Heppner et al., Molecular origin of rapid versus slow intramolecular electron transfer in the catalytic mechanism of the multicopper oxidases. Journal of the American Chemical Society. 2013. https://doi.org/10.1021/ja4064525