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Robert Mettelman, PhD

  • Assistant Professor
  • Department of Pediatrics (Primary)
  • Center for Vaccine Research (Core Faculty)
  • Department of Immunology (Secondary)

Welcome! 

In the Mettelman Lab, we take a collaborative and comprehensive approach to understanding why children experience different disease trajectories following exposure to the same respiratory virus.

Our research employs immunomic, functional, and computational techniques to analyze primary human specimens from large cohort studies, exploring how age influences mucosal and circulating immune responses to common pediatric respiratory viruses such as influenza virus.

A key aspect of our work is identifying immunological correlates of protection, particularly focusing on the role of airway-resident T cells in long-term immunity. From here, we build multivariate models, incorporating immune measures and other host-level factors such as demographics, infection and vaccine histories, and comorbidities (see image below), to predict the risk of severe infection. In parallel studies, our group also models these respiratory viral infections in vertebrate systems to validate mechanisms of protection and susceptibility.

The overarching goals of our group's research is to use the insights from our human and animal studies to improve current immunization strategies for children and help inform next generation vaccine design. Working with our clinical collaborators, we also aim to develop predictive clinical tools guiding best practice care for children hospitalized with respiratory viral infections.

Education & Training

  • Postdoc | St. Jude Children’s Research Hospital | Departments of Immunology and Host-Microbe Interactions (2026)
  • PhD | Loyola University Chicago Stritch School of Medicine | Microbiology and Immunology (2018)
  • BS | University of Wisconsin–Madison | Medical Microbiology and Immunology (2013)

Selected Publications

Richards KA, Mettelman RC, Trombly K, Eismann M, Allen EK, Scott ZB, Joachimiak A, Schultz-Cherry S, Chaves FA, Thomas PG, Sant AJ. A funnel approach to enable analyses of epitope-specific human CD4 T cells specific for influenza and SARS-CoV-2. mBio. 2026 Jun 10;17(6):e0044926. doi: 10.1128/mbio.00449-26.

Jia X, Foo IJ, McQuilten HA, Crawford JC, Cabug AF, Gebregzabher D, Chou J, Mettelman RC, Novak T, Van de Velde LA, Thwaites RS, Randolph AG, Thomas PG, Xu J, Wang Z, Kedzierska K, Kedzierski L, Chua BY. Influenza virus infection drives upregulation of CD84 across a broad range of immune cells. Clin Transl Immunology. 2026;15(3):e70087. doi: 10.1002/cti2.70087.

Cabug AF, Crawford JC, McQuilten HA, Foo IJH, Allen LF, Gebregzabher D, Mettelman RC, Novak T, Chou J, Rowntree LC, Hagen RR, Thomson AJ, Martin GE, Gilbertson B, Souter MN, James F, Goodall E, Rizzetto S, Flerlage T, Jia X, Van de Velde LA, Chang SY, Luciani F, Thwaites RS, Trubiano JA, Kotsimbos TC, Cheng AC, Randolph AG, Thomas PG, Xu J, Wang Z, Nguyen THO, Chua BY, Kedzierski L, Kedzierska K. High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures. Nat Commun. 2025 Nov 24;16(1):10344. doi: 10.1038/s41467-025-65262-5.

Schattgen SA, Turner JS, Ghonim MA, Crawford JC, Schmitz AJ, Kim H, Zhou JQ, Awad W, Mettelman RC, Kim W, McIntire KM, Haile A, Klebert MK, Suessen T, Middleton WD, Teefey SA, Presti RM, Ellebedy AH, Thomas PG. Influenza vaccination stimulates maturation of the human T follicular helper cell response. Nat Immunol. 2024 Sep;25(9):1742-1753. doi: 10.1038/s41590-024-01926-6.

Jia X, Crawford JC, Gebregzabher D, Monson EA, Mettelman RC, Wan Y, Ren Y, Chou J, Novak T, McQuilten HA, Clarke M, Bachem A, Foo IJ, Fritzlar S, Carrera Montoya J, Trenerry AM, Nie S, Leeming MG, Nguyen THO, Kedzierski L, Littler DR, Kueh A, Cardamone T, Wong CY, Hensen L, Cabug A, Laguna JG, Agrawal M, Flerlage T, Boyd DF, Van de Velde LA, Habel JR, Loh L, Koay HF, van de Sandt CE, Konstantinov IE, Berzins SP, Flanagan KL, Wakim LM, Herold MJ, Green AM, Smallwood HS, Rossjohn J, Thwaites RS, Chiu C, Scott NE, Mackenzie JM, Bedoui S, Reading PC, Londrigan SL, Helbig KJ, Randolph AG, Thomas PG, Xu J, Wang Z, Chua BY, Kedzierska K. High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases. Cell. 2024 Aug 22;187(17):4586-4604.e20. doi: 10.1016/j.cell.2024.07.026.

Bodansky A*, Mettelman RC*, Sabatino JJ Jr, Vazquez SE, Chou J, Novak T, Moffitt KL, Miller HS, Kung AF, Rackaityte E, Zamecnik CR, Rajan JV, Kortbawi H, Mandel-Brehm C, Mitchell A, Wang CY, Saxena A, Zorn K, Yu DJL, Pogorelyy MV, Awad W, Kirk AM, Asaki J, Pluvinage JV, Wilson MR, Zambrano LD, Campbell AP, Overcoming COVID-19 Network Investigators, Thomas PG, Randolph AG, Anderson MS, DeRisi JL. Molecular mimicry in multisystem inflammatory syndrome in children. Nature. 2024 Aug;632(8025):622-629. doi: 10.1038/s41586-024-07722-4. (*Equal contribution)

Mettelman RC*, Souquette A*, Van de Velde LA, Vegesana K, Allen EK, Kackos CM, Trifkovic S, DeBeauchamp J, Wilson TL, St James DG, Menon SS, Wood T, Jelley L, Webby RJ, Huang QS, Thomas PG, SHIVERS-II Investigation Team. Baseline innate and T cell populations are correlates of protection against symptomatic influenza virus infection independent of serology. Nat Immunol. 2023 Sep;24(9):1511-1526. doi: 10.1038/s41590-023-01590-2. (*Equal contribution)

Pogorelyy MV, Rosati E, Minervina AA, Mettelman RC, Scheffold A, Franke A, Bacher P, Thomas PG. Resolving SARS-CoV-2 CD4(+) T cell specificity via reverse epitope discovery. Cell Rep Med. 2022 Aug 16;3(8):100697. doi: 10.1016/j.xcrm.2022.100697.
Minervina AA, Pogorelyy MV, Kirk AM, Crawford JC, Allen EK, Chou CH, Mettelman RC, Allison KJ, Lin CY, Brice DC, Zhu X, Vegesana K, Wu G, Trivedi S, Kottapalli P, Darnell D, McNeely S, Olsen SR, Schultz-Cherry S, Estepp JH, SJTRC Study Team, McGargill MA, Wolf J, Thomas PG. SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8(+) T cells. Nat Immunol. 2022 May;23(5):781-790. doi: 10.1038/s41590-022-01184-4.

Mudd PA, Minervina AA, Pogorelyy MV, Turner JS, Kim W, Kalaidina E, Petersen J, Schmitz AJ, Lei T, Haile A, Kirk AM, Mettelman RC, Crawford JC, Nguyen THO, Rowntree LC, Rosati E, Richards KA, Sant AJ, Klebert MK, Suessen T, Middleton WD, SJTRC Study Team, Wolf J, Teefey SA, O'Halloran JA, Presti RM, Kedzierska K, Rossjohn J, Thomas PG, Ellebedy AH. SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans. Cell. 2022 Feb 17;185(4):603-613.e15. doi: 10.1016/j.cell.2021.12.026.

Mettelman RC, O'Brien A, Whittaker GR, Baker SC. Generating and evaluating type I interferon receptor-deficient and feline TMPRSS2-expressing cells for propagating serotype I feline infectious peritonitis virus. Virology. 2019 Nov;537:226-236. doi: 10.1016/j.virol.2019.08.030

O'Brien A*, Mettelman RC*, Volk A, André NM, Whittaker GR, Baker SC. Characterizing replication kinetics and plaque production of type I feline infectious peritonitis virus in three feline cell lines. Virology. 2018 Dec;525:1-9. doi: 10.1016/j.virol.2018.08.022. (*Equal contribution)

Deng X, Hackbart M, Mettelman RC, O'Brien A, Mielech AM, Yi G, Kao CC, Baker SC. Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages. Proc Natl Acad Sci U S A. 2017 May 23;114(21):E4251-E4260. doi: 10.1073/pnas.1618310114

Research Interest Summary

Investigating how age and tissue site shape immune response trajectories during pediatric respiratory viral infection

Academic and Research Interests

In the Mettelman Lab, we take a collaborative and comprehensive approach to understanding why children experience different disease trajectories during a respiratory viral infection (RVI).

Using functional and immunomic approaches, we measure and profile the innate and adaptive antiviral immunity captured in primary human subjects sampled across mucosal and systemic compartments. To contextualize these responses, we then apply computational approaches, which integrate large immune datasets with patient-level demographic and clinical information, to identify drivers of susceptibility and protection. In parallel, we use vertebrate models to validate the immune drivers identified in our human studies and to define the mechanisms underlying differing clinical outcomes.

Working with our clinical collaborators across the University of Pittsburgh and UPMC Children’s Hospital of Pittsburgh, our team is developing the Immunity Mediating Pediatric Respiratory Outcomes of Viral Exposures (IMPROVE) study, a collaborative effort to obtain respiratory and peripheral specimens from children with common RVIs across a range of severities. The long-term goals of IMPROVE are to define age- and tissue-specific correlates of protection, improve risk prediction, and establish a scalable pediatric biorepository.

By understanding what distinguishes protection from severe disease, my group aims to improve vaccine strategies, support clinical decision-making, and develop approaches to better predict illness outcomes.

Our current research efforts comprise three main areas of interest:

1. Defining immune correlates of protection against respiratory viral infection. A central focus of our research is identifying innate, cellular, and humoral immune responses that determine or correlate with susceptibility to and protection from severe respiratory viral infections. Building on our prior work demonstrating that innate and T cell immune signatures are stronger predictors of symptomatic influenza than traditional serologic measures, our current studies examine how these protective immune profiles may vary by age (comparing pediatric and adult responses) and tissue site (comparing lung and peripheral immunity). By sampling multiple tissues sites in adults and children prior to and following natural viral exposures, we are working to define mucosal response scores - metrics by which respiratory immune responses can be predicted through peripheral immune measures alone. Defining mucosal response scores, which likely differ by age and virus species, involves multivariate modeling to integrate immune site-specific features with host-level covariates including demographics, infection and vaccination history, and comorbidities.

2. Exploring early-life T cell immunity and immune memory development after viral exposures. Efforts to investigate how virus-specific T cell responses are generated, maintained, and shaped by early-life exposures to viral antigens are also underway in my lab. Prior studies have examined how first influenza infection or vaccination in children influences of T cell memory development and the composition of antiviral responses. Ongoing and future work in my lab focuses on defining the diversity, specificity, and functional properties of virus-specific T cells, with particular emphasis on TCR repertoire dynamics of tissue-resident T cell populations in the respiratory tract. These studies aim to define how immune memory is established during childhood and how early-life exposures shape (imprint) protection later in life.

3. Investigating viral triggers of chronic or autoimmune inflammation in children. In addition to protective immunity, my group also studies immune drivers of severe disease and autoimmune inflammatory complications following viral infection. Building on our prior work implicating molecular mimicry in multisystem inflammatory syndrome in children (MIS-C), a post-COVID-19 sequelae, our group seeks to define the mechanisms behind this severe immune-mediated pathology and identify and characterize additional viral triggers of autoimmunity. Together, we aim to improve understanding of pediatric viral disease, autoimmune triggers, and identify immune pathways that can be leveraged for improved diagnostics or therapeutic intervention.