- Assistant Professor, Departments of Immunology and Medical Microbiology
T. Murooka Lab
- Postdoctoral research fellowship, Massachusetts General Hospital (2009-2014)
- Ph.D. (Immunology), University of Toronto (2002-2008)
- B.Sc. (Microbiology & Immunology), University of British Columbia (1997-2002)
Department of Immunology
College of Medicine
Faculty of Health Sciences
433 Apotex Centre
750 McDermot Avenue
I started my graduate studies in the laboratory of Dr. Eleanor Fish at the University of Toronto, where I was first exposed to the complex interplay between the immune system and viral pathogens. There, I characterized a new signaling pathway triggered by the chemokine ligand, CCL5, on T cells that regulated directional cellular migration. Our findings had broad implications on the optimization of T cell activation and recruitment to sites of infection during microbial insult. This peaked my interest in the dynamics of anti-viral immunity, and I decided to pursue a postdoctoral fellowship in the laboratory of Dr. Thorsten Mempel at Massachusetts General Hospital (MGH) to gain experience with the cutting-edge imaging methodology of intravital multiphoton microscopy (MP-IVM).
We addressed a long-standing question in the virology field of how Human Immunodeficiency Virus-1 (HIV-1) alters the behavior and motility of T cells and whether these changes contributed to viral pathogenesis in vivo. To accomplish this, we infected “humanized” mice with fluorescent HIV-1 reporter strains and visualized the dynamics of infected cells within the lymph node using MP-IVM. We characterized, for the first time, that HIV-1 significantly changes the behavior of infected cells and allows the virus to actively disseminate throughout the body by “hitching a ride” within migratory cells. The application of MP-IVM to characterize the dynamics of an evolving immune response to pathogens will continue to be my main focus as the GSK Research Chair in Immunology and Infectious Disease and Assistant Professor in the Departments of Immunology and Medical Microbiology at the University of Manitoba.
My research interests:
In order to keep us healthy, the immune system must recognize and destroy a wide range of invading pathogens, while limiting damage to healthy tissues. This is accomplished by a complex network of immune cells that continuously survey the body in order to rapidly respond to pathogenic insult. My interests are focused on understanding how cell-to-cell communicative behavior of immune cells is regulated within healthy tissue, and how these behaviors are altered in response to an infection in vivo.
To achieve this, we will use MP-IVM to visualize the migration, dynamic behavior and localization of immune cells within their physiological tissue in live, anaesthetized mice. Situated in a dedicated BSL2+ facility that features a surgical procedure room and an animal holding unit, this state-of-the-art imaging facility allows us to perform mechanistic, in vivo imaging-based studies in animals infected with various pathogens, such as HIV-1. Using a combination of fluorescent-reporter virus strains and a panel of genetic reporter mouse models, we will investigate the spatiotemporal dynamics of how immunity against microbes are generated, with the ultimate goal of providing valuable insights into the development of an effective vaccine strategy.
- Fackler OT, Murooka TT , Imle A and Mempel TR (2014). Adding new dimensions: towards an integrative understanding of HIV-1 spread. Nat Rev Microbiol 12(8): 563-74
- Angin M, Sharma S, King M, Murooka TT , Ghebremichael M, Mempel TR, Walker BD, Bhasin MK, Addo MM (2014). HIV-1 infection impairs regulatory T-cell suppressive capacity on a per-cell basis. J. Infec Dis. 15(210):899-903
- Murooka TT and Mempel TR (2013). Intravital microscopy in BLT humanized mice to study cellular dynamics in HIV infection. J. Infect Dis. 208 Suppl 2:S137-44
- Marangoni F, Murooka TT , Manzo T, Kim EY, Carrizosa E, Elpek NM, Mempel TR (2013). NFAT memory enables signal integration in T cells during serial Interactions with antigen presenting cells. Immunity 38(2): 237-49
- Murooka TT , Deruaz M, Marangoni F, Vrbanac VD, Seung E, von Andrian UH, Tager AM, Luster AD, Mempel TR (2012). HIV-infected T cells are migratory vehicles for viral dissemination. Nature 490(7419):283-7
- Groom JR, Richmond J, Murooka TT , Sorensen EW, Sung JH, Bankert K, von Andrian UH, Moon JJ, Mempel TR, Luster AD (2012). CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity 14;37(6): 1091-103
- Rahbar R, Rogers E, Murooka T , Kislinger T, Fish EN (2012). Glomulin: a permissivity factor for vaccinia virus infection. J Interferon Cytokine Res 32(3): 127-37
- Murooka TT and Mempel T.R. (2012): Multiphoton Intravital Microscopy to Study Lymphocyte Motility in Lymph Nodes. Methods Mol. Biol. 757:247-57.
- Galligan CL, Pennell L, Murooka T , Baig E, Majchrzak-Kita B, Rahbar R, Fish E. (2010). Interferon-beta is a key regulator of proinflammatory events in experimental autoimmune encephalomyelitis. Mult Scler 16(12):1458-73.
- Murooka TT , Rahbar R and Fish EN. (2009). CCL5 promotes proliferation of MCF-7 cells through mTOR-dependent mRNA translation. Biochem Biophys Res Commun 387, 381-386.
- Rahbar R, Murooka TT and Fish EN. (2009). Role for CCR5 in dissemination of vaccinia virus in vivo. J. Virol. 83, 2226-2236.
- Murooka TT , Rahbar R, Platanias LC and Fish EN. (2008). CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1. Blood 111, 4892-4901.
- Rahbar R, Murooka TT , Hinek AA, Galligan CL, Sassano A, Yu C, Srivastava K, Platanias LC and Fish EN. (2006). Vaccinia virus activation of CCR5 invokes tyrosine phosphorylation signaling events that support virus replication. J. Virol. 80, 7245-7259.
- Galligan CL, Murooka TT, Rahbar R, Baig E, Majchrzak-Kita B and Fish EN. (2006). Interferons and viruses: signaling for supremacy. Immunol Res 35, 27-40.
- Murooka TT , Wong MM, Rahbar R, Majchrzak-Kita B, Proudfoot AE and Fish EN. (2006). CCL5-CCR5-mediated Apoptosis in T cells: Requirement for Glycosaminoglycan Binding and CCL5 Aggregation. J Biol Chem 281, 25184 - 25194.
- Murooka TT, Ward SE and Fish EN. (2005). Chemokines and cancer. Cancer Treat Res 126, 15-29