Tim O’Sullivan, PH.D.
615 Charles E. Young Drive South Los Angeles, CA 90095 BSRB 245F
Affiliations
Research Interests
Our research is dedicated to understanding the molecular mechanisms responsible for protective or pathologic immune responses during cancer, viral infection, and obesity. We will exploit this knowledge to design effective therapeutic strategies with potential clinical applications for type II diabetes and cancer. Our research program is composed of three major directions:
1. Mechanisms of immune surveillance and immune escape in cancer
Our research goal is to dissect the cellular and molecular mechanisms that control tissue-resident and circulating innate immunosurveillance and tumor escape. Our previous work demonstrated that the innate immune system could protect mice from tumor development (O’Sullivan et al., J Exp Med 2012).
We are interested in the following questions:
-How are tissue-resident immune cells activated by developing cancer?
-How are circulating Natural Killer (NK) cells recruited into the tumor microenvironment?
-What are the molecular and cellular mechanisms that lead to NK cell dysfunction in the tumor microenvironment?
2. Mechanisms of adipose tissue inflammation and insulin resistance during diet-induced obesity
Our research was the first to identify protective and pathologic roles for tissue-resident type 1 innate lymphoid cells (ILC1) during viral infection, liver injury, and obesity (O’Sullivan et al., Immunity 2016; Weizman et al., Cell 2017; Nabekura et al., Immunity 2019).
We are interested in the following questions:
-What is the complete cellular composition of mammalian adipose tissue?
-How do cells interact in the adipose tissue micronevironment during homeostasis and obesity?
-What causes adipose tissue inflammation during obesity?
3. ILC responses to viral infection and generation of immunological memory
The innate immune system was previously considered to be composed of short-lived cells that perform effector functions during infection and then rapidly die once their task is accomplished. However, our studies and others suggest that ILCs posses characteristics of the adaptive immune system, such as clonal expansion, longevity, and immunological memory (O’Sullivan et al., Immunity 2015; Weizman et al., Nature Immunology 2019)
We are interested in the following questions:
-What are the transcriptional and epigenetic mechanisms that control memory cell formation?
-How do effector lymphocytes survive to form memory cells?
Biography:
Dr. O’Sullivan is an Associate Professor of Microbiology, Immunology, and Molecular Genetics. He received his Bachelors of Science Degree (B.S.) from Cornell University and his Doctor of Philosophy Degree (Ph.D.) in Biomedical Science from the University of California San Diego. Dr. O’Sullivan’s thesis work focused on the interactions between the innate immune system and cancer. Dr. O’Sullivan subsequently completed his American Cancer Society postdoctoral fellowship at Memorial Sloan Kettering Cancer Center where he studied the role of circulating and tissue-resident innate lymphoid cells (ILC) during viral infection and diet-induced obesity. Dr. O’Sullivan established his own laboratory at UCLA in 2017.
Publications
A selected list of publications:
Hildreth, A.D., Riggan, L., and O’Sullivan T.E. CRISPR Cas9 ribonucleoprotein-mediated genomic editing in primary innate immune cells. STAR Protocols (2020).
Riggan, L., Hildreth, A.D., Rolot, M., Wong Y.Y., Satyadi, W., Sun, R., Huerta, C., and O’Sullivan, T.E. CRISPR Cas9 ribonucleoprotein-mediated genomic editing in primary mature innate immune cells. Cell Reports (2020).
Rolot, M., & O’Sullivan, T.E. Living with Yourself: Innate Lymphoid Cell Immunometabolism. Cells. (2020).
O’Sullivan Timothy E, Sun Joseph C 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; 1799: 109-119.
Nabekura Tsukasa, Riggan Luke, Hildreth Andrew D, O’Sullivan Timothy E, Shibuya Akira Type 1 Innate Lymphoid Cells Protect Mice from Acute Liver Injury via Interferon-γ Secretion for Upregulating Bcl-xL Expression in Hepatocytes Immunity, 2019; 10(10): 2235.
O’Sullivan Timothy E Dazed and Confused: NK Cells Frontiers in immunology, 2019; 10(10): 2235.
Riggan Luke, Freud Aharon G, O’Sullivan Timothy E True Detective: Unraveling Group 1 Innate Lymphocyte Heterogeneity Trends in immunology, 2019; 40(10): 909-921.
Weizman Orr-El, Song Eric, Adams Nicholas M, Hildreth Andrew D, Riggan Luke, Krishna Chirag, Aguilar Oscar A, Leslie Christina S, Carlyle James R, Sun Joseph C, O’Sullivan Timothy E Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12 Nature immunology, 2019; 20(8): 1004-1011.
Hildreth Andrew D, O’Sullivan Timothy E Tissue-Resident Innate and Innate-Like Lymphocyte Responses to Viral Infection Viruses, 2019; 11(3): .
Rapp Moritz, Lau Colleen M, Adams Nicholas M, Weizman Orr-El, O’Sullivan Timothy E, Geary Clair D, Sun Joseph C Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses Science immunology, 2017; 2(18): .
Weizman Orr-El, Adams Nicholas M, Schuster Iona, Krishna Chirag, Pritykin Yuri, Lau Colleen, Degli-Esposti Mariapia A, Leslie Christina S, Sun Joseph C, O’Sullivan Timothy E ILC1 Confer Early Host Protection at Initial Sites of Viral Infection Cell, 2017; .
O’Sullivan Timothy E, Sun Joseph C Innate Lymphoid Cell Immunometabolism Journal of molecular biology, 2017; .
O’Sullivan Timothy E, Rapp Moritz, Fan Xiying, Weizman Orr-El, Bhardwaj Priya, Adams Nicholas M, Walzer Thierry, Dannenberg Andrew J, Sun Joseph C Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance Immunity, 2016; 45(2): 428-41.
Saddawi-Konefka Robert, Seelige Ruth, Gross Emilie T E, Levy Eric, Searles Stephen C, Washington Allen, Santosa Endi K, Liu Beichen, O’Sullivan Timothy E, Harismendy Olivier, Bui Jack D Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance Cell reports, 2016; 16(9): 2348-58.
O’Sullivan Timothy E, Geary Clair D, Weizman Orr-El, Geiger Theresa L, Rapp Moritz, Dorn Gerald W, Overholtzer Michael, Sun Joseph C Atg5 Is Essential for the Development and Survival of Innate Lymphocytes Cell reports, 2016; 15(9): 1910-9.
O’Sullivan Timothy E, Sun Joseph C, Lanier Lewis L Natural Killer Cell Memory Immunity, 2015; 43(4): 634-45.
O’Sullivan Timothy E, Johnson Lexus R, Kang Helen H, Sun Joseph C BNIP3- and BNIP3L-Mediated Mitophagy Promotes the Generation of Natural Killer Cell Memory Immunity, 2015; 43(2): 331-42.
O’Sullivan Timothy E, Sun Joseph C Generation of Natural Killer Cell Memory during Viral Infection Journal of innate immunity, 2015; 7(6): 557-62.
Geiger Theresa L, Abt Michael C, Gasteiger Georg, Firth Matthew A, O’Connor Margaret H, Geary Clair D, O’Sullivan Timothy E, van den Brink Marcel R, Pamer Eric G, Hanash Alan M, Sun Joseph C Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens The Journal of experimental medicine, 2014; 211(9): 1723-31.
O’Sullivan Timothy, Saddawi-Konefka Robert, Gross Emilie, Tran Miller, Mayfield Stephen P, Ikeda Hiroaki, Bui Jack D Interleukin-17D mediates tumor rejection through recruitment of natural killer cells Cell reports, 2014; 7(4): 989-98.
O’Sullivan Timothy, Saddawi-Konefka Robert, Vermi William, Koebel Catherine M, Arthur Cora, White J Michael, Uppaluri Ravi, Andrews Daniel M, Ngiow Shin Foong, Teng Michele W L, Smyth Mark J, Schreiber Robert D, Bui Jack D Cancer immunoediting by the innate immune system in the absence of adaptive immunity The Journal of experimental medicine, 2012; 209(10): 1869-82.
O’Sullivan Timothy, Dunn Gavin P, Lacoursiere Daphne Y, Schreiber Robert D, Bui Jack D Cancer immunoediting of the NK group 2D ligand H60a Journal of immunology (Baltimore, Md. : 1950), 2011; 187(7): 3538-45.