Charlette Berkes, Ph.D.

Office: Mendel 352
Tel: 978-837-5000 ext 5281
Email: BerkesC@merrimack.edu

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Courses Taught
Principles of Biology I, Immunology, Genetics, Senior Thesis Research

Research Interests
 Macrophage cells form our body’s first line of defense against infection by phagocytosing and destroying potentially harmful microorganisms. The word “macrophage” means “big eater” in Greek, but the roles played by macrophages within the immune system are far more complex than their simple name suggests. Macrophages express a network of evolutionarily conserved sensor molecules, generally referred to as pattern recognition receptors, that enable them to detect microbes and activate appropriate downstream signaling, gene expression and cytokine production tailored to the particular infection.

Transmission electron microscopy image of a mouse macrophage infected with four H. capsulatum yeast cells (indicated with red arrowheads)

While the defense and early warning functions provided by the macrophage are normally sufficient to combat infection, many of the world’s most notorious pathogens are able to subvert the potent anti-microbial mechanisms of macrophages and live within them, essentially hidden from the immune system. My research focuses on one of these intracellular pathogens: a fungus called Histoplasma capsulatum. H. capsulatum is found in soils throughout the Midwestern United States, and is a common cause of fungal respiratory infection in these areas. When inhaled by a mammalian host, H. capsulatum spores transition to a budding yeast form that parasitize lung macrophages, replicating robustly within the phagosome, and ultimately lysing them. Recent work has shown that a secreted Histoplasma protein encoded by the CBP1 (c alcium b inding p rotein 1) gene is required for stimulating lysis of host macrophages. Furthermore, CBP1 stimulates a macrophage gene expression program associated with stress response and activation of programmed cell death, suggesting a potential mechanism by which H. capsulatum manipulates macrophage biology to promote its own dissemination (Berkes et al., in preparation). Future work in my lab will investigate the mechanisms by which H. capsulatum stimulates macrophage stress responses via CBP1, and the role of these responses in modulating macrophage death.

Another area of interest involves examining interactions between amoeba cells and intracellular pathogens. Amoebae have many attributes in common with mammalian professional phagocytes, including chemotaxis and the ability to phagocytose and destroy foreign particles. Since many potentially pathogenic microbes co-habit soil and aquatic environments along with amoebae, it has been suggested that amoebae have provided a mechanism for selection and maintenance of virulence traits throughout evolution. The social amoeba Dictyostelium discoidium is genetically tractable and its genome contains homologs of many mammalian genes, including macrophage pattern recognition receptors. Its similarities to mammalian professional phagocytes, combined with the ease of culturing and genetic manipulation, makes it an excellent model with which to dissect the fundamental cellular processes of intracellular pathogenesis. My recent work has shown that the Dictyostelium amoebae efficiently phagocytose Histoplasma capsulatum cells, and further characterization of this interaction is currently underway.

Recent Publications
 Berkes, C. A.*, Isaac, D. T.*, Hocking Murray, D. R. and Sil, A. The fungal pathogen Histoplasma capsulatum utilizes the virulence factor Cbp1 to elicit a unique host transcriptional response and trigger cell death in infected macrophages. In preparation *These authors contributed equally to this work.

Inglis, D. O,, Berkes, C. A, Hocking Murray, D. R. and Sil, A. 2010. Conidia but not yeast of the fungal pathogen Histoplasma capsulatum trigger a type I interferon innate immune response in murine macrophages. Infection and Immunity 78(9):3871-82.