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Photo of Jonathan Heusel

Jonathan Heusel

This person no longer has an active appointment with the University of Iowa.

Education

BS, Biology, University of Nebraska
MD, Washington University School of Medicine
PhD, Immunology, Washington University
Residency, Laboratory Medicine, Washington University School of Medicine and Barnes-Jewish Hospital
Fellowship, Research, Howard Hughes Medical Institute, Washington University School of Medicine
Post-Doc, Rheumatology, Washington University School of Medicine

Research Interests

molecular pathology, natural killer (NK) cell, viral immunity

MeSH Terms from Publications



Research Summary

Natural killer (NK) cells are a heterogeneous population of lymphocytes that performs diverse biological functions, including defense against a wide variety of infectious microbes.  NK cell responses include direct cytotoxicity toward infected or antibody-coated 'target' cells and the secretion of multiple cytokines (e.g., IFN-γ, TNF-α), chemokines (e.g., CCL3-5) and growth factors (e.g. IL-3, GM-CSF).  Through these 'effector functions' NK cells are able to control the microbial load during the earliest phase of infection, and also coordinate the subsequent adaptive immune response through recruitment and activation of other important immune cell subsets, such as dendritic cells (DC). Although NK cells are not activated by antigen-specific receptors per se, NK cells are capable of mounting specific responses during viral infection.  The long-term goal of our research program is to understand how NK cells function in the integrated immune responses to viral pathogens and in the contexts of hematopoietic stem cell transplantation and neoplastic transformation.

The laboratory exploits two mouse models of viral infection to study both detailed molecular parameters of NK cell activation and the cellular interactions involving NK cells that lead to successful immune responses.  The first project utilizes a robust in vitro reporter cell system to dissect the structural aspects of Ly49 receptor-ligand interactions, both in trans (opposing cells) and in cis (receptor-ligand binding on the same cell).  Using this system, we have identified a potent ligand for the activating Ly49H receptor of NK cells—a GPI-linked glycoprotein (m157) encoded by murine cytomegalovirus (MCMV) and expressed on infected cells.  In addition to Ly49H (C57BL/6 strain), m157 also specifically binds the inhibitory Ly49I receptor of 129 mice (in trans).  We are interested in the functional consequences of cis-ligand interactions, including those involving m157, on NK cell activation during MCMV infection.  The second project is focused on NK cell responses in the lung and draining lymph nodes during influenza A virus (IAV) infection.  Using a variety of gene-targeted and recombinant-congenic mouse strains, we have developed a unique NK cell depletion and reconstitution system that allows us to evaluate the contributions from specific NK cell-associated molecules (e.g., IFN-γ, granzyme B, perforin, TRAIL).  In addition to revealing an unappreciated role for NK cells during influenza virus infection, this project has enormous potential to better define the relationship between NK cells, DC, and NKT cells in a wide variety of infectious and tumor immunity models.



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