Texas Tech University faculty Peter Keyel and Kai Zhang are teaming up to build foundational knowledge concerning leishmaniasis, a common, but neglected protozoan parasitic disease.

They're doing so with support from the National Institutes of Health's National Institute of Allergy and Infectious Diseases, in the form of roughly $600,000 to be used over three years.

Leishmaniasis is a term that covers numerous tropical diseases transferred to humans, dogs and other mammals by tiny, infected phlebotomine female sandflies and affects millions of people worldwide, from Brazil to India to countries in Central Africa.

The cutaneous form is the most common; mucocutaneous leishmaniasis can lead to disability and disfigurement, and the visceral variation is over 90% fatal if left untreated.

Keyel and Zhang both teach in the College of Arts and Sciences' Department of Biological Sciences as an associate professor and professor, respectively. The project combines Keyel's research into the cell biology of membrane repair with Zhang's parasitology knowledge.

Keyel's typical research centers on how cells reseal after they get damaged.

There are several stressors that damage cells regularly, which require a membrane-repair process to avoid a cell leaking its contents and dying. Keyel has focused on pore-forming toxins (PFTs), capable of attacking immune cells, destroying cell barriers and promoting the spread of bacteria, since his postdoctoral days.

In the infancy of the duo's collaboration, they looked at using PFTs to put holes in Leishmania cells. They found the toxins they used didn't work without the removal of the parasites' key lipid component that contributes to the membrane structure.

"We built on that to try to figure out, 'Why are these guys protected? What are the mechanisms of damage?'" Keyel explained. "That's moved into, 'Do they repair membranes the same way?'"

The main restoration mechanisms in humans include linking enzymes and proteins to seal a hole, donating internal membranes to patch the external one, and sequestering and shedding toxins from the cell.

During this project, Keyel and Zhang will look for commonalities between mammalian cells and the Leishmania's unicellular eukaryotic structure and aspects that can be found in all Leishmania, as well as differences that will inspire new questions about the where and why.

After the study establishes a base understanding, then comes the translational phase of selectively targeting changes in repair, followed by the clinical process of using an inhibitor or other solution and determining its efficacy and safety.

"We certainly have an eye out for translation and clinical development," Keyel said. "But even if we don't get something right this round, if we learn more about these processes, they give us that next round of questions, and then we build up the mechanisms more."

He anticipates having a graduate student help kick off the project in the fall by leading training of undergraduates in biomedical techniques, with the cohort to participate in subprojects over the course of the research.

Keyel emphasizes giving undergraduates ownership of their ideas and the ability to explain their work.

"The goal is to get them involved and help them learn the assays, get the techniques, and then, 'Here's the why and how we're building it within that framework,'" Keyel said.