Zahn, Nicolas

Ph.D.
Chemistry & Biochemistry

Research Lab: Prof. Alexander Arnold

Major Area of Focus: Biochemistry

Minor Area of Focus: Biochemical Assays and Animal Studies

Thesis: Development of New Treatments for Asthma and Neuropathic Pain Based on GABA(A)R Ligands

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Previously Attended

BS Biochemistry, Kinesiology at University of Wisconsin-Milwaukee

Why Biochemistry Interests Me:

The understanding we have today of highly-ordered organisms is due to discoveries and advancements members of the scientific field have made on the cellular and atomic scale. I find this incredibly fascinating and feel fortunate to be able to contribute to expand the frontier of our knowledge. To quote Aaron Ciechanover, the 2004 Nobel Prize winner in Chemistry: “Biochemistry is the science of life. All our life processes – walking, talking, moving, feeding – are essentially chemical reactions. So biochemistry is actually the chemistry of life, and it’s supremely interesting.”

Why I Chose the University of Wisconsin-Milwaukee Chemistry & Biochemistry Graduate Program:

The reason I chose this graduate program was due to the relationships I was able to form with the students and faculty, and most importantly, the encouragement and support I’ve received from my advisor, Dr. Alexander Arnold. The University of Wisconsin-Milwaukee has also attained Research (R1) status by the Carnegie Classification of Institutions of Higher Learning. Having the chance to learn at a top research institution while being surrounded a great support system was an opportunity I couldn’t pass up.

Publications:

  1. Forkuo, G. S., Guthrie, M. L., Yuan, N.Y., Nieman, A.N., Kodali, R., Jahan, R., Stephen, M.R., Yocum, G. T., Treven, M., Poe, M.M., Li, G., Yu, O.B., Hartzler, B.D., Zahn, N.M., et al. (2016). Development of GABAA Receptor Subtype-Selective Imidazobenzodiazepines as Novel Asthma Treatments. Molecular Pharmaceutics. 13, (6): 2026-2038.
  2. Jahan, R., Stephen, M. R., Forkuo, G. S., Kodali, R., Guthrie, M. L., Nieman, A. N., Yuan, N., Zahn, N.M. et al. (2016). Optimization of substituted imidazobenzodiazepines as novel asthma treatments. European Journal of Medicinal Chemistry. (126): 550-560.
  3. Forkuo, G. S., Nieman, A. N., Yuan, N. Y., Kodali, R., Yu, O. B., Zahn, N. M., . . . Arnold, L. A. (2017). Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAA Receptor Modulators. Molecular Pharmaceutics. 14, (6): 2088-2098.
  4. Knutson, D. E., Kodali, R., Divović, B., Treven, M., Stephen, M. R., Zahn, N. M.,et al. (2018). Design and Synthesis of Novel Deuterated Ligands Functionally Selective for the γ-Aminobutyric Acid Type A Receptor (GABAAR) α6 Subtype with Improved Metabolic Stability and Enhanced Bioavailability. Journal of Medicinal Chemistry. 61, (6): 2422-2446.
  5. Forkuo, G. S., Nieman, A. N., Kodali, R., Zahn, N. M., et al. (2018). A Novel Orally Available Asthma Drug Candidate That Reduces Smooth Muscle Constriction and Inflammation by Targeting GABAA Receptors in the Lung. Molecular Pharmaceutics. 15, (5): 1766-1777.
  6. Zahn, N.M., Huber, A.T., Mikulsky, B.N., et al. (2019). MIDD0301 – A first‐in‐class anti‐inflammatory asthma drug targets GABAA receptors without causing systemic immune suppression. Basic & Clinical Pharmacology and Toxicology. 125, (1): 75–84.
  7. Prevot TD, Li G, Vidojevic A, Misquitta, KA, Fee, C., Santrac, A., Knutson, DE., Stephen, MR., Kodali, R., Zahn, N.M., Arnold, LA., et al. (2019). Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles. Mol Neuropsychiatry. 5 (2): 84-97.
  8. Roni MSR, Li G, Mikulsky BN, Knutson, D.E., Mian, Md. Y., Zahn, N.M., et al. (2020). The Effects of pH on the Structure and Bioavailability of Imidazobenzodiazepine-3-Carboxylate MIDD0301. Molecular Pharmacology. 17 (4): 1182-1192.
  9. Li, G.; Nieman, A.N.; Mian, M.Y.; Zahn, N.M.; Mikulsky, B.N.; Poe, M.M.; Methuku, K.R.; Liu, Y.; Cook, J.M.; Stafford, D.C.; Arnold, L.A. (2020). A Structure-Activity Relationship Comparison of Imidazodiazepines Binding at Kappa, Mu, and Delta Opioid Receptors and the GABAA Receptor. Molecules. (25): 3864.
  10. Nieman, A.N.; Li, G.; Zahn, N.M.; Md. Yeunus, Mian; Mikulsky, B.N.; Hoffman, D.A.; Wilcox, T.M.; Kehoe, A.S.; Luecke, I.W.; Poe, M.M.; Alvarez-Carbonell, D.; Cook, J.M.; Stafford, D.C.; Arnold, L.A. (2020). Targeting Nitric Oxide Production in Microglia with Novel Imidazodiazepines for Nonsedative Pain Treatment. ACS Chemical Neuroscience. 11, (13): 2019-2030.
  11. Zahn, N.M.; Mikulsky, B.N.; M.S. Rashid, Roni; Yocum, G.T.; Md Yeunus. Mian; Knutson, D.E.; Cook, J.M.; Emala, C.W.; Stafford, D.C.; Arnold, L.A. (2020). "Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models" ACS Pharmacology & Translational Science. 3, (6): 1381-1390.
  12. Fan, Heli; Zaman, Asad; Chen, Wenbeng; Ali, Taufeeque; Campbell, Anahit; Zhang, Qi; Setu, Nurul; Saxon, Eron; Zahn, Nicolas; Benko, Anna; Arnold, Leggy; Peng, Xiaohua. (2021). Assessment of ROS-Activated Phenylboronic Acid Nitrogen Mustards as Potent and Selective Drug Candidates for Triple Negative Breast Cancer. ACS Pharmacol. Transl. Sci. 4, (2): 687-702.
  13. Roni, M.S.R.; Zahn, N.M.; Mikulsky, B.N.; Webb, .DA.; Mian, Md.Y.; Knutson, D.E.; Guthrie, M.L.; Cook, J.M.; Stafford, D.C.; Arnold, L.A. (2021) Identification and Quantification of MIDD0301 Metabolites. Current Drug Metabolism. 22, (14): 1114-1123.
  14. Zahn, N.M.; Roni, M.S.R.; Yocum, Gene; Meyer, Michelle; Webb, Daniel; Mian, Md Yeunus; Cook, James; Emala, Charles; Stafford, Douglas; Arnold, Leggy. (2021) Development of inhaled GABAA receptor modulators to improve airway function in bronchoconstrictive disorders. ACS Pharmacology & Translational Science. (Submitted, Accepted Jan. 19, 2022).
  15. Roni, M.S.R.; Zahn, N.M.; Yocum, G.T.; Webb, D.A.; Mian ,Md. Yeunus; Meyer, M.J.; Tylek, A.S.; Cook, J.M.; Emala, C.W.; Stafford, D.C.; Arnold, L.A. (2021) Comparative pharmacodynamic and pharmacokinetic study of MIDD0301 and its (S) enantiomer. Drug Development Research. (Submitted, Accepted Jan. 20, 2022).

 Poster Presentations:

  1. Metabolic Analysis of Benzodiazepines in Human and Mouse Liver Microsomes. (2017). Zahn, NM, Kodali, R., Guthrie, M.L., Jahan, R., Stephen, MR., Poe, MM., Cook, J., Stafford, D., Arnold, L.A.
  2. Characterization of a Novel Orally Available α₅β₃γ₂ Subtype-Selective GABAₐ Receptor Agonist for the Treatment of Asthma. (2019). Zahn, NM, Kodali, R., Guthrie, M.L., Li, G., Huber, A., Trepanski, M., Jahan, R., Stephen, MR., Poe, MM., Cook, J., Stafford, D., Arnold, L.A.
  3. Development of new treatments for asthma and neuropathic pain. (2021). Zahn, NM; Mikulsky, B.N.; M.S. Rashid, Roni; Md. Yeunus, Mian; Knutson, Daniel; Cook, J.; Emala, C.; Stafford, D.; Arnold, L.A.
  4. Nebulized MIDD0301 Recues Airway Hyperresponsiveness and Bronchoconstriction in Murine Models. (2021). Zahn, N.M.; Mikulsky, B.N.; M.S. Rashid, Roni; Md. Yeunus, Mian; Knutson, D.E.; Cook, J.; Emala, C.W.; Stafford, D.C.; Arnold, L.A.

 

Awards:

  • 2015 University of Wisconsin-Milwaukee Undergraduate Symposium Poster Award
  • 2019 – 2020 University of Wisconsin-Milwaukee Distinguished Graduate Student Fellowship
  • Spring 2021 Pantherics Inc. Fellowship
  • Fall 2021 – Spring 2022 University of Wisconsin-Milwaukee Distinguished Dissertator Fellowship