PhD, chemistry (synthetic/medicinal chemistry), University of Montana, Missoula, Montana
Bachelor of Science, chemistry, Central Washington University, Ellensburg, Washington
The focus of the Denton Lab is medicinal chemistry, which means we build new therapies (drugs) using chemistry approaches. Think of a drug as a cool sculpture you or your child has built with Legos, tinker toys or in Minecraft. Each sculpture is made up of the same building blocks, but the number of sculptures one can make is nearly endless. This is what we do. We use a sculpture that already has a purpose (like a drug that can relieve symptoms of Alzheimer’s disease), partially take the sculpture apart and rebuild it a little bit differently. Then we test to see if it is better than the original. If it is better, we make sure to record how we did it and then try again, by using the same size bricks but of a different color, etc. or by modifying a different part of the sculpture, etc.
By being “molecular architects,” there really is no limit to the human diseases we can fight. But there is only so much time in the day, and the true passion of the lab is finding a cure for untreatable cancers, neurodegenerative diseases, nicotine addiction, and understudied metabolic disorders.
As for me personally, I was born in Honolulu, Hawaii (Air Force family), moved from there to Vacaville, California, then to Wenatchee, Washington, Tacoma and finally Moses Lake, Washington, where I spent most of my growing up (from third grade on). I went to Peninsula Elementary followed by Frontier Junior High School and graduated from Moses Lake High School. I then went to College at Central Washington University as a pre-med major. But, once I started doing synthetic medicinal chemistry in the lab of John M. Gerdes in the Department of Chemistry, I was hooked! Dr. Gerdes, Mark Walker and I turned a storage lab into the place where I began my journey by making quinolynoylphenylalkylamines as serotonin transport (SERT) inhibitors. Dr. Gerdes is now a Research Associate Professor of Medicinal Chemistry at the University of Montana. GO GRIZ!!!!!!!
After graduating with a Bachelor of Science in Chemistry I moved to the medicinal chemistry lab of Charles M. Thompson at the University of Montana where I learned about the glutamate neurotransmitter system including the complexities of the excitatory, tripartite synapse, glutamate transporters, receptors, synaptic vesicles and the glutamate-glutamine cycle. This is where we described some of the first pyroglutamate analogues as EAAT2 (GLAST) uptake inhibitors and published Synthesis and Preliminary Evaluation of trans-3,4-Conformationally-Restricted Glutamate and Pyroglutamate Analogues as Novel EAAT2 Inhibitors. Additionally, I was trained in organophosphorus chemistry and became affiliated with Dr. Palmer Taylor of University of California San Diego, Dr. Arthur J. L. Cooper, Gary Gibson, and colleagues at the Weill Cornell College of Medicine where we study phosphonate analogues of the TCA cycle in regard to Alzheimer’s disease and glutaminolysis.
After graduate school I did a post-doc with John R. Cashman at the Human Biomolecular Research Institute in San Diego, California. This is where I began researching cytochrome P-450 2A6 (the main nicotine metabolizing enzyme in humans) inhibitors as nicotine cessation agents.
After my second post-doc I moved back to the beautiful state of Washington and took an Assistant Professor position teaching organic chemistry and the general, organic and biological chemistry series for health science majors and training undergraduates in synthetic medicinal chemistry, chemical biology, carbohydrate and polymer chemistry and molecular biology. While at EWU I had a wonderful group of undergraduate students who presented their research more than 85 times at International, national, regional and local meetings. These students are now practicing nurses, pharmacists, medical doctors, doctors of osteopathic medicine, dentists, dental hygienists, post-doctoral fellows, managers in industry (pharmaceutical companies, computational software, etc.) and more! I am very proud of all the brilliant students I was lucky to mentor while they were undergraduates!
I then upgraded to a Clinical Assistant Professor position in the Department of Pharmaceutical Sciences in the College of Pharmacy and Pharmaceutical Sciences at WSU Health Sciences, Spokane. After receiving my first NIH grant, I was promoted to Assistant Professor (tenure track) and have been in this position since.
I have an active research lab and we are always recruiting new talent. If you are in college nearby (Gonzaga, Whitworth, Spokane Community College, Spokane Falls Community College, EWU, etc. I’d love to teach you some chemistry and how to treat devastating diseases of the human body.
I am the instructor of record (IOR) for the second year Doctor of Pharmacy students for PharDSci 547: Drug Discovery and Development as well as the Doctor of Philosophy in Pharmaceutical Sciences and Molecular Medicine students for PharmSci 576: Biophysical Methods. I also am a co-instructor for Dr. Remsberg in Pharmaceutics.
In my spare time I like to…
My wife, Monica, and I love anything with my family! I have a great time watching my son, Taylor, play soccer (premier level for the Spokane Sounders, High School for Cheney High and alternative club for Cheney Storm) and my daughter, Makenna, ride her horses in either 4-H competitions (performance and gaming), open barrel races, play dates, Northwest Pattern Racing Association (NWPRA) or with her Medical Lake Washington High School Equestrian Team (WAHSET)! I also have a great time with our black lab, Dexter, training, running competitive hunting trials and hunting waterfowl and upland birds!
I grew up in Eastern Washington and always wanted to be a Coug. Now I am!
My Favorite Quote
“Sit down, be humble!” – Kendrick Lamar
- 2012 EWU Distinguished Faculty Award – This award was initiated by nomination by former students and is very special to me. I won’t forget any of you! You know who you are!!!
- 2017-2018 Department of Pharmaceutical Sciences Service Award
- 2019 – Inducted into the Steve Gleason Institute of Neuroscience as an inaugural fellow.
Neurochemistry, neuroscience and the neurobiology of diseases, especially the role of Autophagy in neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis, Lou Gehrig’s disease), Alzheimer’s disease, Parkinson’s diseases and Multiple Sclerosis.
- Multiple-step, one-pot synthesis of 2-substituted-3-phosphono-1-thia-4-aza-2-cyclohexene-5-carboxylates and their corresponding ethyl esters. Shen D, Hensley K, Denton TT. Bioorg Med Chem Lett. 2018 Feb 15;28(4):562-565. doi: 10.1016/j.bmcl.2018.01.052. PMID: 29398540
- A standardized method for incorporation of drugs into food for use with Drosophila melanogaster. Kruger L, Denton TT. Anal Biochem. 2020 Jun 15;599:113740. doi: 10.1016/j.ab.2020.113740. PMID: 32320689
- An overview of sulfur-containing compounds originating from natural metabolites: Lanthionine ketimine and its analogues. Shen D, Hensley K, Denton TT. Anal Biochem. 2020 Feb 15;591:113543. doi: 10.1016/j.ab.2019.113543. PMID: 31862405
- Alternative functions of the brain transsulfuration pathway represent an underappreciated aspect of brain redox biochemistry with significant potential for therapeutic engagement. Hensley K, Denton TT. Free Radic Biol Med. 2015 Jan;78:123-34. doi: 10.1016/j.freeradbiomed.2014.10.581. PMID: 25463282
The glutaminase II pathway in cancer prevention: ω-Amidase and the understudied metabolites α-ketoglutaramate and α-ketosuccinamate in relation to glutamine metabolism and anaplerosis.
- Synthesis of α-Ketoglutaramic acid. Shen D, Kruger L, Deatherage T, Denton TT. Anal Biochem. 2020 Oct 15;607:113862. doi: 10.1016/j.ab.2020.113862. PMID: 32771374
- The metabolic importance of the overlooked asparaginase II pathway. Cooper AJL, Dorai T, Pinto JT, Denton TT. Anal Biochem. 2020 Dec 22:114084. doi: 10.1016/j.ab.2020.114084. PMID: 33347861
- The Metabolic Importance of the Glutaminase II Pathway in Normal and Cancerous Cells. Dorai T, Pinto JT, Denton TT, Krasnikov BF, Cooper AJL. Anal Biochem. 2020 Dec 19:114083. doi: 10.1016/j.ab.2020.114083. PMID: 33352190
Metabolism and metabolic perturbations related to neurodegenerative diseases.
- Rewiring of Glutamine Metabolism Is a Bioenergetic Adaptation of Human Cells with Mitochondrial DNA Mutations. Chen Q, Kirk K, Shurubor YI, Zhao D, Arreguin AJ, Shahi I, Valsecchi F, Primiano G, Calder EL, Carelli V, Denton TT, Beal MF, Gross SS, Manfredi G, D’Aurelio M. Cell Metab. 2018 May 1;27(5):1007-1025.e5. doi: 10.1016/j.cmet.2018.03.002. PMID: 29657030
- Mild metabolic perturbations alter succinylation of mitochondrial proteins. Chen H, Xu H, Potash S, Starkov A, Belousov VV, Bilan DS, Denton TT, Gibson GE. J Neurosci Res. 2017 Nov;95(11):2244-2252. doi: 10.1002/jnr.24103. PMID: 28631845
- The Novel CYP2A6 Inhibitor, DLCI-1, Decreases Nicotine Self-Administration in Mice. Chen YC, Fowler JP, Wang J, Watson CJW, Sherafat Y, Staben A, Lazarus P, Denton TT, Fowler CD. J Pharmacol Exp Ther. 2020 Jan;372(1):21-29. doi: 10.1124/jpet.119.260653. PMID: 31628204
- Identification of the 4-Position of 3-Alkynyl and 3-Heteroaromatic Substituted Pyridine Methanamines as a Key Modification Site Eliciting Increased Potency and Enhanced Selectivity for Cytochrome P-450 2A6 Inhibition. Denton TT, Srivastava P, Xia Z, Chen G, Watson CJW, Wynd A, Lazarus P. J Med Chem. 2018 Aug 23;61(16):7065-7086. doi: 10.1021/acs.jmedchem.8b00084. PMID: 29995408
Intranasal formulation science using nanoliposomes:
- Liposomal Encapsulated FSC231, a PICK1 Inhibitor, Prevents the Ischemia/Reperfusion-Induced Degradation of GluA2-Containing AMPA Receptors. Achzet LM, Astruc-Diaz F, Beske PH, Natale NR, Denton TT, Jackson DA. Pharmaceutics. 2021 Apr 30;13(5):636. doi: 10.3390/pharmaceutics13050636. PMID: 33946313
Teaching and learning pedagogy utilizing active learning in pharmacy education.
- Drug development and the process of transitioning to team-based learning in a qualitative way. Bertsch TG, Denton TT, Perea NM, Ahmed A, McKeirnan KC. Curr Pharm Teach Learn. 2021 Jun;13(6):723-728. doi: 10.1016/j.cptl.2021.01.025. Epub 2021 Feb 10. PMID: 33867071