
Assistant Professor
Primary Thematic Area
M_Microbiology and Immunology
Secondary Thematic Area
Research Summary
NK cells, NK receptors, and NK ligands in viral immunity and tumor immunity.
The Aguilar Lab studies natural killer (NK) cells and are critical for protecting us from viral infections and cancers. They are innate lymphocytes that use cell surface NK receptors to distinguish between self and non-self (or altered-self). If a target cell has been identified as harmful, NK cells release cytotoxic granules that directly kill the target cell. The NK field has greatly advanced our understanding of these cells however, there remain many outstanding questions. Our lab is working to fill in some of these gaps:
- CD16 Fc receptor Biology. In comparing human and mouse NK cell activation through their CD16 Fc receptor, we discovered that these two species behave differently – a difference that is due to the CD3z adaptor molecule. Therefore, we are investigating ways to generate a mouse model with humanized CD16 function to address ways to harness NK cells more effectively through CD16 activation.
- Adaptive NK cells. We now appreciate that NK cells have the ability to generate adaptive-like responses, especially to cytomegalovirus (CMV) infection, however, the signals that generate these specialized cells are not fully discovered. Therefore, we are investigating the signals that drive formation and maintenance of adaptive-like NK cells.
- Recognition and Immune Evasion by cancer and viruses. We are keen on investigating the mechanisms that viruses have evolved to evade NK cell recognition – importantly – investigating how tumor cells may employ similar mechanisms to suppress NK cell activation.
We work with human and mouse models to enhance our understanding of innate immunity as we work towards unlocking their therapeutic potential.
Websites
Publications
Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation.
Nature communications
PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways.
Cancer immunology research
ITAM-based receptors in natural killer cells.
Immunological reviews
MICB Genomic Variant is Associated with NKG2D-mediated Acute Lung Injury and Death.
American journal of respiratory and critical care medicine
The CD16 and CD32b Fc-gamma receptors regulate antibody-mediated responses in mouse natural killer cells.
Journal of leukocyte biology
Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death.
Nature communications
Influence of Self-MHC Class I Recognition on the Dynamics of NK Cell Responses to Cytomegalovirus Infection.
Journal of immunology (Baltimore, Md. : 1950)
The CD3ζ adaptor structure determines functional differences between human and mouse CD16 Fc receptor signaling.
The Journal of experimental medicine
Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients.
Proceedings of the National Academy of Sciences of the United States of America
Natural killer cells activated through NKG2D mediate lung ischemia-reperfusion injury.
The Journal of clinical investigation
Tetramer Immunization and Selection Followed by CELLISA Screening to Generate Monoclonal Antibodies against the Mouse Cytomegalovirus m12 Immunoevasin.
Journal of immunology (Baltimore, Md. : 1950)
Mouse Cytomegalovirus m153 Protein Stabilizes Expression of the Inhibitory NKR-P1B Ligand Clr-b.
Journal of virology
KLF12 Regulates Mouse NK Cell Proliferation.
Journal of immunology (Baltimore, Md. : 1950)
Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12.
Nature immunology
Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition.
Nature communications
NKR-P1B expression in gut-associated innate lymphoid cells is required for the control of gastrointestinal tract infections.
Cellular & molecular immunology
The Inhibitory NKR-P1B:Clr-b Recognition Axis Facilitates Detection of Oncogenic Transformation and Cancer Immunosurveillance.
Cancer research
Transcriptome analysis reveals similarities between human blood CD3- CD56bright cells and mouse CD127+ innate lymphoid cells.
Scientific reports
Freeze-responsive regulation of MEF2 proteins and downstream gene networks in muscles of the wood frog, Rana sylvatica.
Journal of thermal biology
Interferon-Dependent Induction of Clr-b during Mouse Cytomegalovirus Infection Protects Bystander Cells from Natural Killer Cells via NKR-P1B-Mediated Inhibition.
Journal of innate immunity
Expansion and Protection by a Virus-Specific NK Cell Subset Lacking Expression of the Inhibitory NKR-P1B Receptor during Murine Cytomegalovirus Infection.
Journal of immunology (Baltimore, Md. : 1950)
Regulation of SMAD transcription factors during freezing in the freeze tolerant wood frog, Rana sylvatica.
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology
Modulation of Clr Ligand Expression and NKR-P1 Receptor Function during Murine Cytomegalovirus Infection.
Journal of innate immunity
Genetic investigation of MHC-independent missing-self recognition by mouse NK cells using an in vivo bone marrow transplantation model.
Journal of immunology (Baltimore, Md. : 1950)
An in vitro model of innate lymphoid cell function and differentiation.
Mucosal immunology
A truncated human NKG2D splice isoform negatively regulates NKG2D-mediated function.
Journal of immunology (Baltimore, Md. : 1950)
Poxvirus infection-associated downregulation of C-type lectin-related-b prevents NK cell inhibition by NK receptor protein-1B.
Journal of immunology (Baltimore, Md. : 1950)