Anthony W. Orvedahl, M.D., Ph.D.  aorvedahl@wustl.edu

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Instructor in Pediatrics, Infectious Diseases
Infectious Diseases

phone: (314) 454-6050

Clinical Interests

Dr. Orvedahl cares for children with infectious diseases and associated complications. He has a particular interest in immunocompromised hosts, inborn errors of immunity, emerging viral infections, and immune dysregulation disorders including sepsis.

Dr. Orvedahl's research interests are in cell-intrinsic immunity and the role of cytosolic quality control pathways in the regulation of inflammatory responses. Current studies aim to identify the basic mechanisms underpinning cell survival during macrophage responses to the cytokines, interferon-gamma and tumor necrosis factor, and the physiological significance of these factors in models of fatal systemic inflammation, such as septic shock. Using genome-wide CRISPR/Cas9 screening approaches, we found that autophagy genes were critical to protect myeloid cells against cytokine induced cell death. Mice with myeloid cell autophagy gene deficiency also succumbed more readily to TNF-induced shock. We are using multi-omics approaches to dissect the mechanisms by which autophagy genes protect against cytokine-induced cell death in vitro and in vivo. Further, we are characterizing additional identified genes that had not been previously linked to cell death or sepsis, which implicate immunometabolism as a central regulator of these processes. Additional studies seek to understand the contributions of cytosolic nucleic acid metabolism and endogenous retroviruses during viral infections and interferon responses.

Education

  • BA, summa cum laude, University of Colorado2004
  • MD, University of Texas - Southwestern Medical Center2012
  • PhD, University of Texas - Southwestern Medical Center2012

Training

  • Resident in Pediatrics (ARP), St. Louis Children's Hospital2012 - 2014
  • Fellow, Pediatric Infectious Diseases, Washington University School of Medicine2014 - 2018

Licensure and Board Certification

  • 2017American Board of Pediatrics
  • 2018 - PresMO, Board of Registration for the Healing Arts

Honors and Awards

  • Jacob Van Ek Award for Community Service and Academic Excellence, University of Colorado2004
  • Honorable Mention, Graduate Student Poster Session, UT-Southwestern2006
  • Keystone Symposium Travel Award2006
  • Keystone Symposium Conference Assistantship, "Autophagy in Health and Disease"2007
  • Keystone Symposium Conference Assistantship, "Cell Biology of Virus Entry, Replication, and Pathogenesis"2008
  • Molecular Microbiology Graduate Program Nominee, Nominata Award (for most outstanding graduate student, UTSW)2010
  • Quality Improvement Showcase selection, St. Louis Children's Hospital Residency Program2014
  • Outstanding Poster Award, PIDS-St. Jude Pediatric ID Research Conference2019
  • Finalist, Bridging to Success Award, Society for Pediatric Research2019

Recent Publications view all (12)


Publication Co-Authors

  1. Autophagy genes in myeloid cells counteract IFNγ-induced TNF-mediated cell death and fatal TNF-induced shock. PNAS. . 2019;116(33):16497-16506. doi:DOI: 10.1073/pnas.1822157116  PMID:31346084 
  2. Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ. Nat Microbiol. 2019;4(7):1120-1128. PMCID:PMC6588490  PMID:30936486 
  3. Successful treatment of fulminant neonatal enteroviral myocarditis in monochorionic diamniotic twins with cardiopulmonary support, intravenous immunoglobulin and pocapavir. BMJ Case Rep. 2018;2018. PMID:29776940 
  4. Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine. Cell Host Microbe. 2017;22(4):449-459.e4. PMCID:PMC5679710  PMID:28966054 
  5. A 12-Year-Old Girl With Encephalopathy and Acute Flaccid Paralysis: A Neuropathological Correlation and Cohort Review. Pediatr Neurol. 2017;66:5-11. PMID:27769728 
  6. Clinical Characterization of Children Presenting to the Hospital with Enterovirus D68 Infection During the 2014 Outbreak in St. Louis. Pediatr Infect Dis J. 2016;35(5):481-7. PMCID:PMC5237429  PMID:26771663 
  7. Genome sequence of enterovirus D68 from St. Louis, Missouri, USA. Emerg Infect Dis. 2015;21(1):184-6. PMCID:PMC4285240  PMID:25532062 
  8. Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature. 2011;480(7375):113-7. PMCID:PMC3229641  PMID:22020285 
  9. RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. Cell. 2011;144(2):253-67. PMCID:PMC3038590  PMID:21241894 
  10. Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe. 2010;7(2):115-27. PMCID:PMC2860265  PMID:20159618 
  11. Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis. Proc Natl Acad Sci U S A. 2008;105(34):12497-502. PMCID:PMC2527940  PMID:18713860 
  12. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe. 2007;1(1):23-35. PMID:18005679 
Last updated: 08/16/2019
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