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Cushion Laboratory


Proposed life cycle of Pneumocystis of Pneumocystis jirovecii
Fig. 1: Proposed Life Cycle of Pneumocystis jirovecii

Dr. Cushion's lab has over 30 years of research dedicated to investigating fungal pathogens in the genus, Pneumocystis.  Fungi in this genus cause an oftentimes lethal pneumonia (PCP) in humans and other mammals with compromised immune status. The niche of these fungi includes patients with underlying chronic diseases such as COPD or HIV and those receiving anti-inflammatory or immunosuppressive agents. PCP is not responsive to standard antifungal therapy with few treatment alternatives besides trimethoprim-sulfamethoxazole. The laboratory focuses on pre-clinical drug development that includes discovery of potential new targets by understanding the metabolism of these obligate fungi; in silico or in vitro screening of inhibitors to identify potential new drugs; evaluation of toxicity in vitro, and eventually evaluation in rodent animal models of this fungal pneumonia (see Alan Ashbaugh's and Sandy Rebholz's summaries below). Besides depending on the mammalian host for vital nutrients and survival, we recently discovered that these fungi must also replicate through the sexual cycle to survive in the lung.  Thus, we recently identified that the sexual cycle could be a potential drug target and will be evaluating the processes involved in mating to further extend knowledge in this area (See Aaron Albee’s summary below). A major impediment in Pneumocystis research has been the lack of a continuous in vitro growth system for these obligate pathogens. The lab is constantly evaluating the effects of supplements based on the understanding of its metabolic capacities derived from genomic studies as well as other platforms including alveolar organoids, cell-based co-cultures, and delivery by extracellular vesicles (see Steve Sayson’s summary below).

Cyst forms scanning
Fig. 2: Differential
Interference micrograph
of Pneumocystis carinii

A new direction in the lab has been to facilitate research in wound healing, mainly through different types of electrical stimulation.  Dr. Cushion collaborates with Dr. Daria Narmoneva to assess novel wireless electric field stimulation using a porcine wound healing model that includes infection with Staphylococcus aureus and Pseudomonas aeruginosa. In a second project, she collaborates with Drs. Greg Harris and Leyla Esfandiari to investigate regenerative rehabilitation solutions for peripheral nerves. The goal will be to identify a self-powered, tissue-specific therapeutic scaffold for peripheral nerve regeneration using piezoelectric biomaterials. Mechanical deformation of the material results in the endogenous polarization of ions or charges, which induces an electric potential for wound healing.

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Melanie T. Cushion, Ph.D.
Senior Associate Dean for Research
University of Cincinnati College of Medicine
Senior Research Career Scientist, VAMC
Phone: 513-558-7540