Department of Pediatrics

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 Colorado, 2004
• MD, University of Texas - Southwestern Medical Center, 2012
• PhD, University of Texas - Southwestern Medical Center, 2012

Training

• Resident in Pediatrics (ARP), St. Louis Children's Hospital, 2012 - 2014
• Fellow, Pediatric Infectious Diseases, Washington University School of Medicine, 2014 - 2018

Licensure and Board Certification

• 2017American Board of Pediatrics
• 2018 - PresMO, Board of Registration for the Healing Arts
• 2019American Board of Pediatrics, Pediatric Infectious Diseases

Honors and Awards

• Jacob Van Ek Award for Community Service and Academic Excellence, University of Colorado, 2004
• Honorable Mention, Graduate Student Poster Session, UT-Southwestern, 2006
• Keystone Symposium Travel Award, 2006
• 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 Program, 2014
• Outstanding Poster Award, PIDS-St. Jude Pediatric ID Research Conference, 2019
• Finalist, Bridging to Success Award, Society for Pediatric Research, 2019

Recent Publications view all (17)

Publication Co-Authors

Gregory A. Storch, M.D.

Stephanie S Cabler

Cliff J. Luke, Ph.D.

Kevin O'Bryan, M.D.

Kristine Wylie, Ph.D.

Mythili Srinivasan, M.D., Ph.D.

Richard Buller, Ph.D. D(ABMM)

Ahmed, Said, M.D., Ph.D.

Todd N. Wylie

Gary A. Silverman, M.D., Ph.D.

Guoyan Zhao

Melanie Yarbrough

Kevin T. Barton, M.D.

Washington University has a long tradition of collaboration amongst colleagues.The faculty above have co-authored publications with Anthony W. Orvedahl, M.D., Ph.D.

1. Brestoff JR, Wilen CB, Moley JR, Li Y, Zou W, Malvin NP, Rowen MN, Saunders BT, Ma H, Mack MR, Hykes BL Jr, Balce DR, Orvedahl A, Williams JW, Rohatgi N, Wang X, McAllaster MR, Handley SA, Kim BS, Doench JG, Zinselmeyer BH, Diamond MS, Virgin HW, Gelman AE, Teitelbaum SL. Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity. Cell Metab. 2021;33(2):270-282.e8. PMCID:PMC7858234  PMID:33278339 
2. Balce DR, Wang YT, McAllaster MR, Dunlap BF, Orvedahl A, Hykes BL Jr, Droit L, Handley SA, Wilen CB, Doench JG, Orchard RC, Stallings CL, Virgin HW. UFMylation inhibits the proinflammatory capacity of interferon-γ-activated macrophages. Proc Natl Acad Sci U S A. 2021;118(1). PMCID:PMC7817147  PMID:33372156 
3. Cabler SS, French AR, Orvedahl A. A Cytokine Circus with a Viral Ringleader: SARS-CoV-2-Associated Cytokine Storm Syndromes. Trends Mol Med. 2020;26(12):1078-1085. PMCID:PMC7524648  PMID:33051104 
4. Wang YT, Zaitsev K, Lu Q, Li S, Schaiff WT, Kim KW, Droit L, Wilen CB, Desai C, Balce DR, Orchard RC, Orvedahl A, Park S, Kreamalmeyer D, Handley SA, Pfeifer JD, Baldridge MT, Artyomov MN, Stallings CL, Virgin HW. Select autophagy genes maintain quiescence of tissue-resident macrophages and increase susceptibility to Listeria monocytogenes. Nat Microbiol. 2020;5(2):272-281. PMCID:PMC7147835  PMID:31959973 
5. Orvedahl, A, McAllaster, MR, Sansone, A, Dunlap, BF, Desai, C, Wang, YT, Balce, DR, Luke, CJ, Lee, S, Orchard, RC, Artyomov, MN, Handley, SA, Doench, JG, Silverman, GA, Virgin, HW.. 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 
6. Ingle H, Lee S, Ai T, Orvedahl A, Rodgers R, Zhao G, Sullender M, Peterson ST, Locke M, Liu TC, Yokoyama CC, Sharp B, Schultz-Cherry S, Miner JJ, Baldridge MT. Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ. Nat Microbiol. 2019;4(7):1120-1128. PMCID:PMC6588490  PMID:30936486 
7. Amdani SM, Kim HS, Orvedahl A, John AO, Said A, Simpson K. 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 
8. Lee S, Wilen CB, Orvedahl A, McCune BT, Kim KW, Orchard RC, Peterson ST, Nice TJ, Baldridge MT, Virgin HW. 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 
9. Kim YM, Orvedahl A, Morris S, Schmidt R, Mar S. 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 
10. Orvedahl A, Padhye A, Barton K, O'Bryan K, Baty J, Gruchala N, Niesen A, Margoni A, Srinivasan M. 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 
11. Wylie KM, Wylie TN, Orvedahl A, Buller RS, Herter BN, Magrini V, Wilson RK, Storch GA. Genome sequence of enterovirus D68 from St. Louis, Missouri, USA. Emerg Infect Dis. 2015;21(1):184-6. PMCID:PMC4285240  PMID:25532062 
12. Orvedahl A, Sumpter R Jr, Xiao G, Ng A, Zou Z, Tang Y, Narimatsu M, Gilpin C, Sun Q, Roth M, Forst CV, Wrana JL, Zhang YE, Luby-Phelps K, Xavier RJ, Xie Y, Levine B. Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature. 2011;480(7375):113-7. PMCID:PMC3229641  PMID:22020285 
13. Bodemann BO, Orvedahl A, Cheng T, Ram RR, Ou YH, Formstecher E, Maiti M, Hazelett CC, Wauson EM, Balakireva M, Camonis JH, Yeaman C, Levine B, White MA. 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 
14. Orvedahl A, MacPherson S, Sumpter R Jr, Tallóczy Z, Zou Z, Levine B. Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe. 2010;7(2):115-27. PMCID:PMC2860265  PMID:20159618 
15. Burdette DL, Yarbrough ML, Orvedahl A, Gilpin CJ, Orth K. 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 
16. Orvedahl A, Alexander D, Tallóczy Z, Sun Q, Wei Y, Zhang W, Burns D, Leib DA, Levine B. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe. 2007;1(1):23-35. PMID:18005679 
17. Ganaie, SS, Schwarz, MM, McMillen, CM, Price, D, Feng, A, Albe, JR, Wang, W, Miersch, S, Orvedahl, A, Cole, AR, Sentmanat, MF, Mishra, N, Boyles, DA, Koenig, ZT, Kujawa, MR, Demers, MA, Hoehl, RM, Moyle, A, Wagner, N, Stubbs, SH, Cardarelli, L, Teyra, J, McElroy, A, Gross, ML, Whelan, SPJ, Doench, J, Cui, X, Brett, TJ, Sidhu, SS, Virgin, HW, Egawa, T, Leung, DW, Amarasinghe, GK, Hartman, AL. Lrp1 is a host entry factor for Rift Valley Fever Virus. Cell.