Gurung focuses on new preventative target in leishmaniasis

Prajwal Gurung, PhD, assistant professor in Infectious Diseases, received a five-year, $2.64M NIH R01 grant from the National Institute of Allergy and Infectious Diseases. Gurung will use this funding to investigate possible infection prevention for leishmaniasis, a disease affecting more than a billion people in Africa, the Middle East, Mexico, Asia, and South America.

Leishmaniasis is caused by Leishmania spp., a protozoan parasite, which manifests as skin lesions (in cases of cutaneous infections) and other internal symptoms such as fever, enlarged spleen, enlarged liver and more (in cases of systemic infections). However, treatment and prevention methods for the disease are still limited.  

“To understand the pathogenesis of this disease, we have used L. major infection of mice as a model system to mimic cutaneous leishmania infection in humans,” Gurung said. “We found that RIPK2-deficient mice are highly susceptible to L. major infection.”

Receptor interacting protein kinase 2 (RIPK2), an enzyme that plays a crucial role in bacterial, viral and fungal infections, has also been observed by Gurung’s team to play an important role during Leishmania major-induced skin diseases, but the molecular mechanisms remain undetermined. Gurung’s preliminary work suggests that understanding RIPK2 mechanisms may provide novel insights to combating the spread of L. major.

Furthermore, RIPK2 is downstream of cytoplasmic sensors NLRC1 and NLRC2. In the preliminary work, Gurung found that deficiency in NLRC1, NLRC2, or both NLRC1/NLRC2 had no impact on the course of L. major infection in mice. This suggests a new sensor functioning upstream of RIPK2. In this new study, Gurung’s research team will examine the novel signaling axis, Dectin-1/RIPK2/CARD9, and investigate how this signaling axis impact immunity to leishmaniasis. 

“This project aims to identify a novel pathway that is required for providing protection during L. major infection,” Gurung said. “The hope is that by understanding and elucidating this pathway, we will able to target specific molecules to provide protection against cutaneous leishmaniasis.”

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