January 21, 2020

Dustyn Barnette Student Highlight

Dustyn is a Ph.D. Student in his 5th year in the Biochemistry and Molecular Biology Department. He joined the laboratory of Dr. Grover P. Miller for his research studies.

He has a B.S. in Biology from Ouachita Baptist University with minors in chemistry and art.

Research Interest Statement

A major obstacle in drug development is the occurrence of drug-induced liver injury (DILI).  DILI can cause drugs to be rejected for market approval, or it can be idiosyncratic, meaning that it may not be discovered until after market approval.

The focus of my graduate research is to study metabolic activation of drugs to form toxic metabolites, which is one of the possible causes of idiosyncratic DILI.  I am interested in the development and use of in vitro systems and computational models to serve as alternatives to in vivo trials for predicting and investigating mechanisms of drug induced hepatotoxicity.  I have conducted thorough analyses of metabolic pathways of three marketed drugs (warfarin, terbinafine, and meloxicam) with special focus on pathways that contribute to bioactivation or detoxification.  Through these efforts, I am working to establish the mechanisms that explain the idiosyncratic DILI observed for some drugs.  The clinical application of this mechanistic knowledge is to be able to predict which patients will be vulnerable to DILI based on factors that affect metabolism such as genetics, environmental exposures, and drug-drug interactions.

Something Notable about Time as a Graduate Student

Last spring, I got to go to Baltimore to present my research at the annual Society of Toxicology meeting.  Of course, the very first thing I did when I got there is take the metro train from the airport to the convention center.  When the train got to my final stop, I walked over to the door ready to get off.  I had no idea that this station was closed for construction, and the train was only stopping there because it had to wait on a crossing.  No worries though, I found this all out very quickly after the train suddenly lurched ahead again, sending my unsuspecting self toppling like a flailing rag doll straight onto the lap of some random guy sitting next to the door.  Sometimes, to only way to learn things is the hard way.

Career Goals

Once I get my Ph.D. I want to enroll in a post-doctoral position in a government research lab.  Long term, I want my career to facilitate the development, improvement, and use of in vitro systems and computational models as alternatives to in vivo for predicting and investigating mechanisms of drug induced hepatotoxicity.

Experiment or Technique You Would Most Like to Do

I always enjoy when I get to use fluorescent compounds to chemically label the metabolites that I’m studying.  There is something very fulfilling about working with brightly colored samples.

Fun fact

I like to hike.  One of my favorite trails in Arkansas is the Lost Valley Trail near Ponca.  At the hike’s end there’s a big cave with a waterfall in it, but my favorite part is actually around the halfway point.  There’s a little cave located a couple hundred feet off the main trail that my cousins and I just stumbled upon by chance one time.  You have to crawl to get into it, but once you’re in, you get to see dozens of little aquatic invertebrate fossils all over the walls and ceiling.  It looks very cool!

Publications

Comprehensive kinetic and modeling analyses revealed CYP2C9 and 3A4 determine terbinafine metabolic clearance and bioactivation.  Dustyn A. Barnette, Mary A. Davis, Noah Flynn, Anirudh S. Pidugu, S. Joshua Swamidass, and Grover P. Miller.  Biochemical Pharmacology.  October 9, 2019.  doi: 10.1016/j.bcp.2019.113661, PMID: 31605674.

CYP2C19 and 3A4 dominate metabolic clearance and bioactivation of terbinafine based on computational and experimental approaches.  Mary A. Davis, Dustyn A. Barnette, Noah R. Flynn, Anirudh S. Pidugu, S. Joshua Swamidass, Gunnar Boysen, Grover P. Miller.  Chemical Research in Toxicolgoy.  2019 Apr 10. doi: 10.1021/acs.chemrestox.9b00006, PMID: 30925039.

Lamisil (terbinafine) toxicity: Determining pathways to bioactivation through computational and experimental approaches. Dustyn A. Barnette, Mary A. Davis, Na L. Dang, Anirudh S. Pidugu, Tyler Hughes, S. Joshua Swamidass, Gunnar Boysen, Grover P. Miller.  Biochemical Pharmacology.  August 2018, 156, 10-21.  doi:  https://doi.org/10.1016/j.bcp.2018.07.043, PMID: 30076845.

Stereospecific Metabolism of R- and S-Warfarin by Human Hepatic Cytosolic Reductases.  Dustyn A. Barnette, Bryce P. Johnson, Dakota L. Pouncey, Robert Nshimiyimana, Linda Desrochers, Thomas E. Goodwin, Grover P. Miller.  Drug Metabolism and Disposition.  September 2017, 45 (9) 1000-1007.  doi: https://doi.org/10.1124/dmd.117.075929, PMID: 28646078.

Exposure cessation during adulthood did not prevent immunotoxicity caused by developmental exposure to low-level trichloroethylene in drinking water.  Kathleen M. Gilbert, Shasha Bai, Dustyn Barnette, and Sarah J. Blossom.  Toxicological Sciences.  March 2017, 157 (2): 429-437.  doi:10.1093/toxsci/kfx061, PMID: 28369519.

Evaluation of virulence and antimicrobial resistance in Salmonella enterica serovar Enteritidis isolates from humans and chicken- and egg-associated sources. Jing Han, Kuppan Gokulan, Dustyn Barnette, Sangeeta Khare, Anthony W. Rooney, Joanna Deck, Rajesh Nayak, Rossina Stefanova, Mark E. Hart, and Steven L. Foley. Foodborne Pathogens and Disease. December 2013, 10 (12): 1008-1015. doi:10.1089/fpd.2013.1518, PMID: 24102082.

Awards

UAMS Graduate Student Association Research Symposium – Third Place for Poster Presentations (Fall 2019)

Arkansas Academy of Sciences Conference – Third Place for Biochemistry/Chemistry Oral Presentation (Spring 2016)