John K. Walker, Ph.D
Associate Professor
Pharmacology & Physiology
Chemistry
Courses Taught
Course Director for PPY 5110: Introduction to Pharmacology, Course Director PPY 4410/5410: Molecular Pharmacology
Education
B.S. in Chemistry, Southern Illinois University at Edwardsville, 1990
M.S. in Chemistry, Southern Illinois University at Edwardsville, 1992
Ph.D. in Chemistry, Indiana University, 1997
Research Interests
Medicinal Chemistry, Synthetic Organic Chemistry, Pharmacokinetics, Chemical Biology
Research in our lab is focused on the application of medicinal chemistry in the design and synthesis of new bioactive molecules. We incorporate several computational such as molecular modeling and docking techniques, virtual screening, data analysis and physical property descriptors to design new compounds as potential bioactive molecules. We then employ modern state-of-the-art organic synthesis techniques to synthesize these new molecules and test them with our biology collaborators. This is often an iterative process with this design-synthesize-test cycle being repeated several times to arrive at molecules with the desired profile for a given target. We also synthesize tool compounds and probes that can be used by biologists to study various pathways and mechanisms. The overarching theme of research in the Walker Lab is the design and synthesis of new bioactive molecules to address important biology questions.
Currently, a major area of focus in our lab is on the development on new compounds to treat bacterial diseases. Drug-resistant bacteria has emerged as one of the major public health threats of our lifetime and new drugs to combat this are urgently needed. We have identified and developed compounds that act as bacterial efflux pump inhibitors (EPIs). Bacterial efflux is one of the primary mechanisms by which bacteria can develop resistance to current antibiotics, especially in Gram-negative bacteria. These EPI’s have the potential to block this resistance pathway and restore activity to antibiotics that are ineffective. An additional outcome of this research is the potential to develop a better understanding of how these efflux pumps work and how to target them.
Another area of increasing research interest is the development of new modulators or G-coupled protein receptors (GPCRs). Members of this receptor family play important signaling roles in a wide range of inflammatory and pain pathways. We have been working with collaborators to identify and develop both new agonists and antagonists of several different receptors involved in pain signaling.
Publications and Media Placements
Recent Publications:
1) Hampton, C. S.; Situala, S.; Billon, C.; Haynes, K.; Avdagic, A.; Wanninayake, U.; Adeyemi, C. M.; Chatterjee, A.; Griffett, K.; Banerjee, S.; Burris, S. L.; Schoepke, E.; Boehm, T.; Bess, A.; de Vera, I. M.; Burris, T. P.; Walker, J. K.* “Development and pharmacological evaluation of a new chemical series of potent pan-ERR agonists, identification of SLU-PP-915. Euro. J. Med. Chem., 258, 115582 Oct 5th, 2023. PMID 37421886
2) Cao, F.; Kinthada, R.; Boehm, T.; D’ Cunha, N.; Leus, I. V.; Orth, C.; Zgurskaya, H. I.; Walker, J. K.*; Identification and structure-activity relationships for a series of N, N-disubstituted 2-aminobenzothiazoles as potent inhibitors of S. aureus. Bioorg med chem lett., 89, 129301 Apr, 23, 2023. PMID 37094726
3) Billon, C.; Situala, S.; Banerjee, S.; Welch, R.; Elgendy, B.; Hegazy, L.; Oh, T. G.; Kazantris, M.; Chatterjee, A.; Chrivia, J.; Hayes, M. E.; Xu, W.; Hamilton, A.; Huss, J. M.; Walker, J. K.; Downes, M.; Evans, R. M.; Burris, T. P. Synthetic ERRa/b/g Agonist Induces an ERRa-dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chem Biol. 18(4), Apr 21, 2023, 756-771. PMID 36988910
4) Murray, M. H.; Valfort, A. C.; Koelblen, T.; Veerakanellore, G. B.; Elgendy, B.; Walker, J. K.; Hegazy, L.; Burris, T. P. Structural Basis of Synthetic Agonist Activation of the Nuclear Receptor REV-ERB. Nat. Comm., 13(1), 7131, Nov 21, 2022. PMID:36414641
5) Moniruzzaman, M.; Cooper, C. J.; Uddin, M. R.; Walker, J. K.; Parks, J. M. and Zgurskaya, H. I. Analysis of Orthogonal Efflux and Permeation Properties of Cmpounds Leads to the Discovery of New Efflux Pump Inhibitors. ACS Infect. Dis. 8(10), 2149-2160, Oct, 14, 2022. PMID3641464
For a more complete list of publications: https://pubmed.ncbi.nlm.nih.gov/?term=John+K+Walker&filter=years.2023-2023