Timothy E O'sullivan

Assistant Professor, MIMG, University of California Los Angeles

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Diabetes and cancer currently represent two of the largest healthcare burdens and leading causes of death in the United States. The O’Sullivan lab seeks to understand the immunoregulatory networks involved in cancer and obesity to develop novel therapeutic strategies that harness the power of the immune system. Our studies have focused on defining the signals that promote innate immune cell activation and survival in the context of both pathogen and non-pathogen induced inflammation. We study clinically relevant mouse models and patient samples to understand the role of circulating and tissue-resident innate lymphocytes during host protection and memory responses. We employ cutting-edge genomic techniques to profile transcriptional and epigenetic circuits that lead to functional cell states in health and during viral infection. Understanding the molecular mechanisms of how the mammalian innate immune system is regulated during inflammation will lead to new therapies for cancer and infectious diseases.

Interests

CRISPR engineering, Immunometabolism, Tumor Immunology, Primary Immunodeficiency, Natural Killer Cells, Systems Immunology, Dendritic Cells, Innate Lymphoid Cells

Education and Training

Memorial Sloan Kettering Cancer Center6/2017Immunology
UCSDPhD9/2012Cancer Immunology
Cornell UniversityBS12/2008Biomedical Engineering

Awards and Honors

  • American Cancer Society Postdoctoral Fellowship, MSKCC, 2015-2017.
  • AAI 2016 Thermo Fisher Trainee Achievement Award, MSKCC, 2016.
  • UCSD-UCLA Diabetes Research Center Junior Faculty Award, UCLA, 2019.
  • Regeneron New Investigator Award for Excellence in Cytokine and Interferon Research, UCLA, 2022.
  • UCLA Life Sciences Excellence in Research Award, UCLA, 2021.

Publications

  1. Mandy I Cheng, Joey H Li, Luke Riggan, Bryan Chen, Rana Yakhshi Tafti, Scott Chin, Feiyang Ma, Matteo Pellegrini, Haley Hrncir, Arthur P Arnold, Timothy E O'Sullivan, Maureen A Su . The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences. Nature Immunology, 2023.
  2. Hildreth AD, Padilla ET, Tafti RY, Legala AR, O'Sullivan TE. Sterile liver injury induces a protective tissue-resident cDC1-ILC1 circuit through cDC1-intrinsic cGAS-STING-dependent IL-12 production.. Cell reports, 2023.
  3. Schuster IS, Sng XYX, Lau CM, Powell DR, Weizman OE, Fleming P, Neate GEG, Voigt V, Sheppard S, Maraskovsky AI, Daly S, Koyama M, Hill GR, Turner SJ, O'Sullivan TE, Sun JC, Andoniou CE, Degli-Esposti MA. Infection induces tissue-resident memory NK cells that safeguard tissue health.. Immunity, 2023.
  4. Krämer B, Nalin AP, Ma F, Eickhoff S, Lutz P, Leonardelli S, Goeser F, Finnemann C, Hack G, Raabe J, ToVinh M, Ahmad S, Hoffmeister C, Kaiser KM, Manekeller S, Branchi V, Bald T, Hölzel M, Hüneburg R, Nischalke HD, Semaan A, Langhans B, Kaczmarek DJ, Benner B, Lordo MR, Kowalski J, Gerhardt A, Timm J, Toma M, Mohr R, Türler A, Charpentier A, van Bremen T, Feldmann G, Sattler A, Kotsch K, Abdallah AT, Strassburg CP, Spengler U, Carson WE, Mundy-Bosse BL, Pellegrini M, O'Sullivan TE, Freud AG, Nattermann J. Single-cell RNA sequencing identifies a population of human liver-type ILC1s.. Cell reports, 2023.
  5. Wang J, Chang CY, Yang X, Zhou F, Liu J, Zhu S, Yu XZ, Liu C, O'Sullivan TE, Xie P, Feng Z, Hu W. Leukemia inhibitory factor protects against graft-versus-host disease while preserving graft-versus-leukemia activity.. Blood, 2022.
  6. Riggan L, Ma F, Li JH, Fernandez E, Nathanson DA, Pellegrini M, O'Sullivan TE. The transcription factor Fli1 restricts the formation of memory precursor NK cells during viral infection.. Nature immunology, 2022.
  7. Li JH, O'Sullivan TE. Back to the Future: Spatiotemporal Determinants of NK Cell Antitumor Function.. Frontiers in immunology, 2022.
  8. Hildreth AD, Ma F, Wong YY, Sun R, Pellegrini M, O'Sullivan TE. Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity.. Nature immunology, 2021.
  9. Riggan L, Shah S, O'Sullivan TE. Arrested development: suppression of NK cell function in the tumor microenvironment.. Clinical & translational immunology, 2021.
  10. Hildreth AD, Riggan L, O'Sullivan TE. CRISPR-Cas9 Ribonucleoprotein-Mediated Genomic Editing in Primary Innate Immune Cells.. STAR protocols, 2020.
  11. Riggan L, Hildreth AD, Rolot M, Wong YY, Satyadi W, Sun R, Huerta C, O'Sullivan TE. CRISPR-Cas9 Ribonucleoprotein-Mediated Genomic Editing in Mature Primary Innate Immune Cells.. Cell reports, 2020.
  12. Nabekura T, Riggan L, Hildreth AD, O'Sullivan TE, Shibuya A. Type 1 Innate Lymphoid Cells Protect Mice from Acute Liver Injury via Interferon-γ Secretion for Upregulating Bcl-xL Expression in Hepatocytes.. Immunity, 2019.
  13. O'Sullivan TE. Dazed and Confused: NK Cells.. Frontiers in immunology, 2019.
  14. Riggan L, Freud AG, O'Sullivan TE. True Detective: Unraveling Group 1 Innate Lymphocyte Heterogeneity.. Trends in immunology, 2019.
  15. Weizman OE, Song E, Adams NM, Hildreth AD, Riggan L, Krishna C, Aguilar OA, Leslie CS, Carlyle JR, Sun JC, O'Sullivan TE. Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12.. Nature immunology, 2019.
  16. Hildreth AD, O'Sullivan TE. Tissue-Resident Innate and Innate-Like Lymphocyte Responses to Viral Infection.. Viruses, 2019.
  17. O'Sullivan TE, Sun JC. Determination of the Fate and Function of Innate Lymphoid Cells Following Adoptive Transfer of Innate Lymphoid Cell Precursors.. Methods in molecular biology (Clifton, N.J.), 2018.
  18. Rapp M, Lau CM, Adams NM, Weizman OE, O'Sullivan TE, Geary CD, Sun JC. Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses.. Science immunology, 2017.
  19. Weizman OE, Adams NM, Schuster IS, Krishna C, Pritykin Y, Lau C, Degli-Esposti MA, Leslie CS, Sun JC, O'Sullivan TE. ILC1 Confer Early Host Protection at Initial Sites of Viral Infection.. Cell, 2017.
  20. O'Sullivan TE, Sun JC. Innate Lymphoid Cell Immunometabolism.. Journal of molecular biology, 2017.
  21. Adams NM, O'Sullivan TE, Geary CD, Karo JM, Amezquita RA, Joshi NS, Kaech SM, Sun JC. NK Cell Responses Redefine Immunological Memory.. Journal of immunology (Baltimore, Md. : 1950), 2016.
  22. Saddawi-Konefka R, Seelige R, Gross ET, Levy E, Searles SC, Washington A, Santosa EK, Liu B, O'Sullivan TE, Harismendy O, Bui JD. Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance.. Cell reports, 2016.
  23. O'Sullivan TE, Rapp M, Fan X, Weizman OE, Bhardwaj P, Adams NM, Walzer T, Dannenberg AJ, Sun JC. Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance.. Immunity, 2016.
  24. O'Sullivan TE, Geary CD, Weizman OE, Geiger TL, Rapp M, Dorn GW, Overholtzer M, Sun JC. Atg5 Is Essential for the Development and Survival of Innate Lymphocytes.. Cell reports, 2016.
  25. O'Sullivan TE, Sun JC, Lanier LL. Natural Killer Cell Memory.. Immunity, 2015.
  26. O'Sullivan TE, Johnson LR, Kang HH, Sun JC. BNIP3- and BNIP3L-Mediated Mitophagy Promotes the Generation of Natural Killer Cell Memory.. Immunity, 2015.
  27. O'Sullivan TE, Sun JC. Generation of Natural Killer Cell Memory during Viral Infection.. Journal of innate immunity, 2015.
  28. Geiger TL, Abt MC, Gasteiger G, Firth MA, O'Connor MH, Geary CD, O'Sullivan TE, van den Brink MR, Pamer EG, Hanash AM, Sun JC. Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens.. The Journal of experimental medicine, 2014.