• 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

• The Philip S. Portoghese Journal of Medicinal Chemistry/ACS Medicinal Chemistry Letters – Division of Medicinal Chemistry Joint Lectureship Award, 2025
• RSC Medicinal Chemistry Emerging Investigator, 2024
• NIH R35 Maximizing Investigators’ Research Award (MIRA)
  
• Guest Editor “Structural Biology in Drug Discovery and Development” Journal of Medicinal Chemistry & ACS Medicinal Chemistry Letters
• Guest Editor “Kinase themed collection” for RCS Medicinal Chemistry
• Early Career Board Member of The Journal of Medicinal Chemistry, 2023-2025
  
• NIH Early Career Reviewer
  
• CTSI BTC K Scholar, 2022
  
• Co-chair of Gordon Research Seminar on NADPH Oxidase Enzymes, 2018
• Young Investigator Award, SFRBM, 2016
• Ruth L. Kirschstein NRSA Postdoctoral Fellowship (F32), NIH, 2016
• Beckman Scholar, 2006

• 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

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.

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Publications during time at UB (*Corresponding Author)

• B.C. Ogboo, K.B. Patel, M. Massari, S. Marchese, J. Reis, E.J. Joyce, M-C.J. Lin, J.D. Rabb, O.A. Abidakun, Q. Lin, A. van der Vliet, A. Mattevi, D.E. Heppner “Enhancing Selectivity and Potency of SNAr Covalent Inhibitors of NADPH Oxidase Enzymes” Journal of Medicinal Chemistry 2025 https://doi.org/10.1021/acs.jmedchem.5c01272
• D.E. Heppner “Ascertaining a Structural Basis in Drug Discovery and Development” Journal of Medicinal Chemistry 2025 https://doi.org/10.1021/acs.jmedchem.5c00326
• F. Wittlinger, S.P. Chitnis, C.D. Pham, T. Damghani, K.B. Patel, M. Möllers, I.K. Schaeffner, O. Abidakun, M.Q. Deng, B.C. Ogboo, A. Rasch, T.S. Beyett, B. Buckley, F. Feru, T. Shaurova, C. Knappe, M.J. Eck, P.A. Hershberger, D.A. Scott, A.L. Brandt, S.A. Laufer*, D.E. Heppner* “Tilting the scales toward EGFR mutant selectivity: Expanding the scope of bivalent ‘Type V’ kinase inhibitors.” Journal of Medicinal Chemistry 2024 https://doi.org/10.1021/acs.jmedchem.4c02311
• D.E. Heppner,* B.C. Ogboo, D.A. Urul, E.W. May, E.W. Schaefer, A.S. Murkin, A. Gehringer. “Demystifying Functional Parameters for Irreversible Enzyme Inhibitors.” Journal of Medicinal Chemistry 2024 https://doi.org/10.1021/acs.jmedchem.4c01721
• D.E. Heppner, S.V. Bigi-Botterill, A.P. Riley, K. Chibale, C.W. Lindsley. “Structural Biology in Drug Discovery and Development: Call for Papers.” Journal of Medicinal Chemistry & ACS Medicinal Chemistry Letters 2024 https://doi.org/10.1021/acs.jmedchem.4c01492; https://doi.org/10.1021/acsmedchemlett.4c00318
  
• N.P. Damayanti, R.A. Cordova, C. Rupert, I.D. Fontane, L. Shen, S. Orsi, A.J. Klunk, W.M. Linehan, K.A. Staschke, P.C. Hollenhorst, D.E. Heppner, R. Pili. “TFE3-splicing factor fusions represent functional drivers and draggable targets in translational renal cell carcinoma.” Cancer Research 2024 https://doi.org/10.1158/0008-5472.CAN-23-1789
  
• D.C. Lacy,* D.E. Heppner,* B. Buckley, J. Griffiths, P.S. Gunasekera, J. Patel, Z. Roche-Rivera, K. Coppola, K. Dempsey, S.C. Pillai, B.R. Renzoni. “Twelve CO molecules for the price of one. A simple water-soluble organometallic CORM, [Mn(CO)₃(µ₃-OH)]₄ Polyhedron 2024 https://doi.org/10.1016/j.poly.2024.116859
  
• T.S. Beyett, J.K. Rana, I.K. Schaeffner, D.E. Heppner, M.J. Eck. “Structural analysis of the macrocyclic inhibitor BI-4020 binding to EGFR kinase.” ChemMedChem 2024 https://doi.org/10.1002/cmdc.202300343
  
• F. Wittlinger, B.C. Ogboo, E. Shevchenko, T. Damghani, C.D. Pham, I.K. Schaeffner, B.T. Oligny, S.P. Chitnis, T.S. Beyett, A. Rasch, B. Buckley, D.A. Urul, T. Shaurova, E.W. May, E.M. Schaefer, M.J. Eck, P.A. Hershberger, A. Poso, S.A. Laufer*, D.E. Heppner* “Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.” Communications Chemistry 2024 https://doi.org/10.1038/s42004-024-01108-3
  
• K.W. Hoyt, D.A. Urul, B.C. Ogboo, F. Wittlinger, S.A. Laufer, E.M. Schaefer,* E.W. May,* and D.E. Heppner.* “Pitfalls and considerations in determining the potency and mutant selectivity of covalent epidermal growth factor receptor inhibitors.” Journal of Medicinal Chemistry 2024, 67, 2-16. https://doi.org/10.1021/acs.jmedchem.3c01502
• D. Bhattacharjee, J. Bakar, S.P. Chitnis, E.L. Sausville, K.D. Ashtekar, B.E. Mendelson, K. Long, J.C. Smith, D.E. Heppner,* and J.M. Sheltzer.* “Inhibition of a lower-potency target drives the anti-cancer activity of a clinical p38 inhibitor.” Cell Chemical Biology 2023
  https://doi.org/10.1016/j.chembiol.2023.09.013
• D.E. Heppner* “Design and development of mutant EGFR inhibitors from a structural perspective.” Indian Journal of Biochemistry and Biophysics 2023, 60, 645-650. https://doi.org/10.56042/ijbb.v60i9.3967
• T. Damghani, F. Wittlinger, T.S. Beyett, M.J. Eck, S.A. Laufer, and D.E. Heppner.* “Structural elements that enable specificity for mutant EGFR kinase domains with next-generation small-molecule inhibitors.” Methods in Enzymology 2023, 685, 171-198. https://doi.org/10.1016/bs.mie.2023.03.013
• D.E. Heppner* et al., "Structural Basis for Inhibition of Mutant EGFR with Lazertinib (YH25448)." ACS Medicinal Chemistry Letters 2022 https://pubs.acs.org/doi/full/10.1021/acsmedchemlett.2c00213
  
• B.C. Ogboo, U.V. Grabovyy, A. Maini, S. Scouten, A. van der Vliet, A. Mattevi, and David E. Heppner.* “Architecture of the NADPH Oxidase Family of Enzymes.” Redox Biology 2022 https://doi.org/10.1016/j.redox.2022.102298
• D.E. Heppner* and M.J. Eck.* “A Structural Perspective on Targeting the RTK/Ras/MAP Kinase Pathway in Cancer.” Protein Science 2021. https://doi.org/10.1002/pro.4125
• D.E. Heppner*, “Structural Insights Into Redox-active Cysteine Residues of the Src Family Kinases.” Redox Biology 2021. https://doi.org/10.1016/j.redox.2021.101934

Selected Publications from time prior to UB

• F. Wittlinger, D.E. Heppner et al., Design of a “Two-in-One” Mutant-Selective Epidermal Growth Factor Receptor Inhibitor That Spans the Orthosteric and Allosteric Sites. Journal of Medicinal Chemistry 2022 https://doi.org/10.1021/acs.jmedchem.1c00848
• 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 signaling: 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