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Paula M. Oliver, PhD
Paula M. Oliver
Co-Chief, Division of Protective Immunity

Dr. Oliver investigates the mechanisms governing T cell activation and protective immunity. Her goal is to define mechanisms that, when dysregulated, result in autoimmunity or allergic disorders like asthma.

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Bio

Dr. Oliver's research centers on identifying ubiquitin ligases and then using genetic, cellular, and biochemical approaches to define how those enzymes regulate immune cell function.

Some of her recent efforts have focused on catalytic ubiquitin ligases of the Nedd4-family. Along with colleagues in her lab, she identified a small family of membrane tethered adaptors, Ndfip1 and Ndfip2, that activate Nedd4-family ligases, and determined that these adaptors regulate T cell activation, CD4 differentiation and effector function, and Treg cell metabolism, and lineage stability. Dr. Oliver and her team combined this information on biologic function with biochemical data in which it defined precisely how these adaptors activate the enzymatic activity of Nedd4-family ligases. Dr. Oliver is now using this information in the rational design of therapeutics. Based on the data, such therapeutics will be particularly useful in the treatment of autoimmune and/or allergic disease.

In addition, Dr. Oliver's recent work has employed systems biology approaches in which it has integrated transcriptome, proteome, and ubiquitome information to identify Cullin E3 ubiquitin ligases that are particularly active as T cells transition from resting to activated states. She has now generated genetic models in which to test the biologic relevance of these ligases in protective immune responses, and she and her lab team are now poised to define how cullin ligases form distinct ubiquitin complexes in T cells or other immune cells, and the unique set of substrates targeted by these complexes. Answering these questions will position investigators to translate this information into new therapies for patients.

Education and Training

BS, North Carolina State University (Zoology), 1989

PhD, University of North Carolina at Chapel Hill (Pathology), 1998

Fellowship, National Jewish Health (Immunology), 2007

Titles and Academic Titles

Co-Chief, Division of Protective Immunity

Co-Leader, Protective Immunity and Immunopathology Research Affinity Group

Associate Professor of Pathology and Laboratory Medicine

Professional Memberships

Abramson Cancer Center, 2008-

Institute for Immunology, University of Pennsylvania, 2010-

Professional Awards

Leukemia and Lymphoma Society Fellow, 1999-2002

Christopher and Peter Gitzen Fellowship, 2000-2001

Howard Hughes Medical Institute, 2002-2005

Foerderer Award, 2008-2009

American Asthma Foundation Scholar, 2013-2016

Publication Highlights

Dybas JM, O’Leary CE, Ding H, Spruce LA, Seeholzer SH, Oliver PM. Integrative proteomics reveals that CD4+ T cell activation promotes predominantly non-degradative ubiquitylation. Nat Immunol. 2019 Jan; In press
Moser EK, Field NS, Oliver PM. Aberrant Th2 inflammation drives dysfunction of alveolar macrophages and susceptibility to bacterial pneumonia. Cell Mol Immunol. 2018 May; 15(5):480-492. PMID: 28260794
Layman AAK, Deng G, O'Leary CE, Tadros S, Thomas RM, Dybas JM, Moser EK, Wells AD, Doliba NM, Oliver PM. Ndfip1 restricts mTORC1 signalling and glycolysis in regulatory T cells to prevent autoinflammatory disease. Nat Commun. 2017 May; 8:15677. PMID: 28580955
O'Leary CE, Riling CR, Spruce LA, Ding H, Kumar S, Deng G, Liu Y, Seeholzer SH, Oliver PM. Ndfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4+ effector T cells. Nat Commun. 2016 Apr; 7:11226. PMID: 27088444
Riling C, Kamadurai H, Kumar S, O'Leary CE, Wu KP, Manion EE, Ying M, Schulman BA, Oliver PM. Itch WW Domains Inhibit Its E3 Ubiquitin Ligase Activity by Blocking E2-E3 Ligase Trans-thiolation. J Biol Chem. 2015 Sep; 290(39):23875-87. PMID: 26245901