Biomedical Research: (Disease-related Research) 

Fungal and Neurodegenerative Disease in the Brain:

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Fungal Pathogenesis:  In our lab we study a fungal organism that is an important human pathogen, but that also is very closely related to fungi that inhabit forest niches and that decay wood. Cryptococcus neoformans evolved from these wood decay fungi, in ways currently not well understood, to attack the brain and other organs of mammals and other animals. C. neoformans' natural habitat is the forest and it can be found growing in niches in the bark of forest trees. However, after invading the lungs of a host, the fungus can move to the brain, and it thrives in the lysosomes of cells to cause Cryptococcal meningitis; a disease which kills 600,000 people each year. 

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The mechanisms that Cryptococcus employs in pathogenesis are also not well known, but considerable prior research has demonstrated that oxygen radicals are involved. The fungus grows in a yeast form, and it produces a very thick layer of extracellular polysaccharide known as the capsule.  This capsule appears to protect the fungus from the harsh, low pH environment that the fungus helps in generating during pathogenesis in the brain.  We are exploring the extracellular redox chemistries generated by fungus to better understand pathological conditions of importance, and are conducting our research in cooperation with colleagues at the UMass-Medical School. A key focus is exploring whether the CMF mechanisms, known to be active in certain brown rot wood decay fungi (see Bioconversion Research page) also play a role in pathogenesis.

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Neurodegenerative Disease:  This is a developing area of research in the lab, focussed on triggers for lysosomal dysfunction that may be associated with the low pH redox cycling of certain metal binding compounds produced within the lysosomes. Many mechanisms leading to lysosomal dysfunction are described in the literature, but redox cycling with metals has not been well explored. There is increasing evidence that triggers for lysosomal dysfunction are associated with pathogenesis in neurodegenerative disorders, and redox cycling may play a role.