Faculty Feature Anthony Orvedahl

Anthony Orvedahl, MD, PhD, was born in Denver, CO. He is the product of a professionally eclectic family: his father worked in the aerospace industry; mother was a homemaker and administrative assistant; older brother an accomplished comedian; and younger brother a woodworker. His paternal grandfather designed one of the earliest computers at the Los Alamos National Lab. Prior to embarking on the path to becoming a physician scientist, Anthony spent his Colorado summers skateboarding and his winters snowboarding. While the term “adulting” had not yet been coined, he avoided whatever that entails as long as possible. When this approach proved untenable, he matriculated at the University of Colorado, and subsequently graduated with summa cum laude honors for work on cell death in the round worm C. elegans. He first caught the research bug during a summer undergraduate program studying inflammatory responses mediated by Toll-like receptors (TLRs), which are conserved from humans to fruit flies. After graduating, he descended from these lofty altitudes to the plains of north Texas, where he continued to satisfy an appetite for research studying the role of cellular autophagy (“self-eating”) in antiviral host defenses under the mentorship of Beth Levine, MD. Intriguingly, some of the genes required to rid cells of invading viruses were also important for clearing damaged mitochondria. This helped to spark his interests in how cell intrinsic mechanisms of host defense have evolved to ensure homeostasis both during responses to infection and at steady state.

After receiving his medical and graduate training at UT Southwestern Medical center in Dallas (as well as his “MR” degree, see below), he was drawn to the unparalleled Pediatric Physician Scientist Training Program at St. Louis Children’s Hospital and Washington University in St. Louis. He completed Pediatrics and Infectious Diseases training on the Accelerated Research Pathway. His postdoctoral work is under the mentorship of Skip Virgin, MD, PhD, and Gary Silverman, MD, PhD. Using genome-wide CRISPR/Cas9 screening approaches, they identified a critical cytoprotective role for autophagy genes in macrophages during fatal systemic inflammatory responses in mice. While he has yet to return to the small but mighty C. elegans model, his current research has come full circle by encompassing innate immune responses, including those triggered by TLRs, and the role of autophagy in maintaining cellular homeostasis and counteracting cell death. Ongoing research projects range from studying autophagy and mitochondrial metabolism during cytokine-induced cell death and sepsis to the role of endogenous retroviruses in interferon responses during viral infections. The NIH recently agreed that this was a potentially worthwhile endeavor by awarding him a K08.

Anthony has a long standing interest in understanding the tolerance mechanisms via which his spouse, Melanie Yarbrough, PhD, (Assistant Professor of Pathology and Immunology) does not reject him (Fig 1A, arrow). They are co-PI’s on a self-funded 18 year project (currently in year 5) aimed at evaluating the effects (both positive and negative) of parental professional ambition on human male child development. One subject, named Henry (Fig 1A, arrowhead), has been recruited to date. The Orvedahl-Yarbrough family balances their busy schedules with a love of food and they enjoy cooking and discovering new restaurants in St. Louis and the surrounds. These culinary adventures are intermixed with hiking and biking, visiting the zoo and the many great parks and museums in St. Louis, and photoshopping themselves into scenes of sunsets. Anthony personally enjoys usually losing at chess, occasionally winning at billiards, and is always open to discussing the finer points of the evolution of host pathogen interactions and immunity over a fine beverage.

Figure 1. The Orvedahl-Yarbroughs on location, in Florida (A), Colorado (B), and Texas (C).

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