Meet Ronald Wek

Ronald C. Wek, the Showalter professor of biochemistry at Indiana University School of Medicine, joined the ranks of associate editors at the Journal of Biological Chemistry in October 2016. Wek, who earned his Ph.D. from the University of California, Irvine, oversees a research lab that investigates the role that different types of RNA play in stress response pathways and disease states. He recently spoke with John Arnst, ASBMB Today’s science writer. The interview has been edited for clarity and length.

Ronald Wek at the University of California, Irvine, studies mechanisms regulating protein synthesis.

What is your group focused on?

My research is focused on cell stress-response pathways in gene expression and how these contribute to the progression and treatment of diseases such as diabetes and related metabolic disorders. I’m also interested in nutritional deficiencies and in all things that have to do with stress. Specifically, I’m studying the mechanisms that regulate protein synthesis.

There is a translation initiation factor called eIF2 that is phosphorylated upon different cell stresses. It delivers an initiator tRNA to the translational apparatus, and when it becomes phosphorylated it reduces global protein synthesis. Lowered translation serves to conserve energy and resources, allowing cells to reprogram genes expression to stress resistance that helps to alleviate cell damage.

It’s interesting, because you have a global repression of protein synthesis, but coincident to that you have preferential translation of some select mRNAs, and these are the stress responders. These are the gene transcripts that serve to change metabolic strategies and protect against stress damage. I’m interested in how ribosomes determine which of those mRNAs it translates during stress.

What is your background and research training?

I have a Ph.D. from UC Irvine, where I studied nutritional regulation primarily in prokaryotic systems. During my postdoctoral fellowship at the National Institutes of Health, I became interested in eukaryotic systems and translational control in response to nutritional deprivation. Originally, I studied budding yeast as a model system, but it turned out these translational control pathways and these stress response systems were recapitulated in mammalian cells and virtually all eukaryotic cells. So I made the transition not only from yeast to mammalian cells and animal models but also to some pathogenic organisms. I parlayed that foundational knowledge in translational control that I learned as a postdoctoral fellow with Alan Hinnebusch to our studies into stress-response pathways in diverse model systems.

What are some of the pathogens you’ve worked with that way?

I have a long-term collaborative project with Bill Sullivan (Author’s note: Bill Sullivan is a professor in pharmacology at Indiana University School of Medicine) studying Toxoplasma gondii, an obligate intracellular parasite that gained notoriety at the onset of the AIDS epidemic in the early 1980s and continues to be a life-threatening opportunistic infection today. Toxoplasma invades nucleated cells of warm-blooded vertebrates, and it has a tendency to disseminate to the central nervous system and heart tissues, where it converts into a latent tissue cyst. The proliferative stage of Toxoplasma is referred to as the tachyzoite, and the encysted stage is referred to as the bradyzoite. The cysts remain infectious and persist for the remainder of the host’s life. Toxoplasma can be transmitted congenitally, through raw or undercooked meat, or through oocysts expelled by its definitive host, cats, which is the reason pregnant women should avoid cat litter.

Since proliferative tachyzoites rapidly convert to latent bradyzoites in immune-competent individuals, the infection is typically asymptomatic and widely believed to be benign. However, the infection is permanent, as the cysts are impervious to the immune response and current drug treatments. In response to stress, Toxoplasma converts from proliferating tachyzoites into latent bradyzoites, and this conversion is central to pathogenesis and is the primary impediment to a cure for chronic toxoplasmosis. The development of drugs to treat chronic toxoplasmosis has been hindered by our insufficient understanding of stage conversion. We are looking at the molecular mechanisms by which eIF2 phosphorylation and translational control drive Toxoplasma stage conversion, which promises to reveal key insights into the processes governing parasite persistence in infected individuals.

How long have you been involved with JBC?

When I started off as a graduate student, one of the first papers I published as a first author was in JBC. I was also in a pretty independent position where I contributed not only to manuscript writing but also to the cover letter and going through the review process, so I’ve actually had a real fondness for JBC since the beginning of my career.

When I became an independent scientist with Indiana University School of Medicine, I also submitted several manuscripts to JBC, and I really appreciated practicing scientists serving as editors and reviewers. It had a lot of rigor in the process.

I joined the editorial board in 2013, and then I became an associate editor last fall. JBC has had a rich history in the topics of RNA translation, mRNA decay, noncoding mRNAs and stress responses, and I’d like to continue and expand on that.

How’d you react when you were asked to take the position?

I was really excited and honored to be offered this position. I think it is a great time to incorporate RNA biology and translational control into the journal, and I felt it was also an opportunity to pay back in a small way some of the benefits that I have received from the journal.

What do you do outside of the lab? Do you have any hobbies?

I try to balance life. I have a son and daughter who recently have completed college, and my wife and I enjoy spending time with them. I appreciate that there’s more to life than science. We have a family home on Kauai, so we take a lot of trips to Kauai for swimming, snorkeling, hiking, that sort of thing. (Author’s note: Kauai is the fourth-largest of the Hawaiian islands.) One of our favorite hiking trails is called the Sleeping Giant. Alakai Swamp Area near Kokee State Park is another area that’s really got diverse biology. You go to one of the wettest spots on Earth in a swamp area that you can hike through, and you really see the full gamut of fauna change from a tropical to an elevated rainforest-type area.

For any scientists in training or young graduate students, do you have a motto or words of wisdom?

I always say follow your scientific passion. That eureka moment when you discover something, especially for the first time, is worth all of the sacrifices and hard work.

I do a lot of mentoring of students and postdocs, and the one thing I’ve really enjoyed is seeing people come to their full skill sets and learn to be scientists. That is the thing I think I’ve enjoyed the most in my career, the new thinking, the new creativity and enthusiasm that each person brings as they enter the laboratory – it’s almost like a fountain of youth in some respects, because you’re reinvigorated with new people coming into the lab.”