mcelroy lab
Our lab studies some of the world’s most deadly viruses.
Our lab studies some of the world’s most deadly viruses.
We study viruses you might have heard of, such as Ebola or Lassa and others that you may never have heard of such as Rift Valley fever virus (RVFV) and Crimean Congo hemorrhagic fever virus (CCHFV). All of these viruses fall into a group generally called the VHF (Viral hemorrhagic fevers).
The VHF’s get their name because they sometimes (not always) cause disease in people that manifests as bleeding. This can take several forms, it could be oozing from IV sites, vomiting blood, having blood in the stool, or oozing blood from mucous membranes such as the mouth or the nose. While this sounds very scary, it isn’t necessarily the bleeding that makes the disease so severe! When people die, they die from shock (poor blood flow to the organs due to low blood pressure), which leads to organ failure and this leads to death. Our goal is to understand how the VHF’s make people sick so that we can design therapies that will improve patient outcomes.
We use primarily derived human samples to try to understand the pathophysiology of disease. The goal is to use this information to develop hypotheses about why some people get sick and others don’t. We focus our studies on various aspects of human physiology that are clearly clinically disrupted in patients with VHF; this includes aspects of endothelial function, coagulation pathways, inflammation and both innate and adaptive immune function. Only by understanding what is going right (or wrong) in the host can we begin to design therapeutics to augment or abrogate the effect.
While VHF’s can be quite deadly, they are (fortunately) not the most common viruses and special challenges accompany them- they require high biosafety levels and additional regulatory oversight. Since access to primary human samples can be difficult, an alternative is to model the disease in an animal. The added benefit of animal modeling is that hypotheses can be rigorously tested and therapeutic interventions can be evaluated. We have used the mouse model of RVFV to define how host immunity can prevent virally mediated hepatitis and encephalitis, which are known complications of RVFV disease in humans.
Sometimes the quickest way to understand why a virus is pathogenic is to study the virus in cells in the laboratory. This principle certainly applies to RVFV. This virus encodes a protein (NSs) that is known to antagonize the interferon signaling system. Viruses that are missing this protein turn out to be completely non-pathogenic and have become the basis for several RVFV vaccines that are under development.
The figure to the left shows NSs filaments in infected human hepatocytes.
Cartwright HN, Barbeau DJ, Doyle JD, Klein E, Heise MT, Ferris MT, McElroy AK. PLoS Pathog. 2022 Jul 14;18(7):e1010649.PMID: 35834486
Immune correlates of protection following Rift Valley fever virus vaccination.
Doyle JD, Barbeau DJ, Cartwright HN, McElroy AK. NPJ Vaccines. 2022 Oct 28;7(1):129. PMID: 36307416
Barbeau DJ, Cartwright HN, Harmon JR, Spengler JR, Spiropoulou CF, Sidney J, Sette A, McElroy AK. J Virol. 2021 Nov 9;95(23):e0150621. PMID: 34495703
Isotype-Specific Fc Effector Functions Enhance Antibody-Mediated Rift Valley Fever Virus Protection In Vivo.Cartwright HN, Barbeau DJ, McElroy AK .mSphere. 2021 Oct 27;6(5):e0055621. doi: 10.1128/mSphere.00556-21. Epub 2021 Sep 8.
Rift Valley Fever Virus Is Lethal in Different Inbred Mouse Strains Independent of Sex.
Cartwright HN, Barbeau DJ, McElroy AK. Front Microbiol. 2020 Aug 21;11:1962. PMID: 32973712
Immunologic timeline of Ebola virus disease and recovery in humans.
McElroy AK, Akondy RS, Mcllwain DR, Chen H, Bjornson-Hooper Z, Mukherjee N, Mehta AK, Nolan G, Nichol ST, Spiropoulou CF. JCI Insight. 2020 May 21;5(10):e137260.
Rift Valley fever virus vaccination induces long-lived, antigen-specific human T cell responses.
Harmon JR, Barbeau DJ, Nichol ST, Spiropoulou CF, McElroy AK. NPJ Vaccines. 2020 Feb 28;5(1):17. PMID: 32140261
Human Biomarkers of Outcome Following Rift Valley Fever Virus Infection.
McElroy AK, Harmon JR, Flietstra T, Nichol ST, Spiropoulou CF.J Infect Dis. 2018 Oct 20;218(11):1847-1851. PMID: 29955891
McElroy AK, Akondy RS, Harmon JR, Ellebedy AH, Cannon D, Klena JD, Sidney J, Sette A, Mehta AK, Kraft CS, Lyon MG, Varkey JB, Ribner BS, Nichol ST, and Spiropoulou CF. A case of human Lassa virus infection with robust acute T cell activation and long-term virus-specific T cell responses. J Infect Dis 2017, 215 (12): 1862-1872. PMID:28863472
Human Ebola virus infection results in substantial immune activation.
McElroy AK, Akondy RS, Davis CW, Ellebedy AH, Mehta AK, Kraft CS, Lyon GM, Ribner BS, Varkey J, Sidney J, Sette A, Campbell S, Ströher U, Damon I, Nichol ST, Spiropoulou CF, Ahmed R. Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4719-24.PMID: 25775592
Pediatric Infectious Disease Doc
Virologist
Aspiring Immunologist
Military Brat
Ally
Lab manager 2
Microbiologist
Travelholic
Dog Mom
Postdoctoral Associate
Cell Biologist
Aspiring Virologist
Nature lover
Graduate Student/ PhD Candidate
Microbiologist
Spreadsheet lover
Aspiring hockey player
Graduate Student/PhD Candidate
Aspiring physician-scientist
Virologist
Advocate
Graduate Student
Aspiring Virologist
Pedal-powered
Postdoctoral Associate
Passionate Bacteriologist
Aspiring Virologist
Foodie
Research Tech III
Research Dedicated
Star Gazer
Humanitarian
2018-2022
Graduate student
Mellon trainee awardee
Now at Krystal Biotech
2019-2022
Pediatric Infectious Disease Fellow
PIDS/Plotkin Fellowship Awardee
Now at US CDC
2021-2023
Undergraduate
Now at NIH (post-baccalaureate)
K08 AI119448 (completed)
R21 AI145352 (completed)
R01 AI171200
R01 AI183792
U19 AI181984
T32 AI049820 (to Dr. Ling Xu)
T32 AI060525 (to Lindsay Wilson)
Department of Pediatrics
Division of Pediatric Infectious Disease
Pilot and Feasibility Award
COVID-19 Pilot Grant
Stanley and Susan Plotkin and Sanofi Pasteur Fellowship Award (to Dr. Joshua Doyle)
Trainee Award (to Haley Cartwright)
Pilot Award
Clinical Development of ‘DDVAX’, a human vaccine candidate for Rift Valley fever
If you are an enthusiastic graduate student or post doc who would like to join our group email mcelroya@pitt.edu
Follow us on Twitter @fablabpitt