Patrick Kelly successfully defends PhD thesis

Patrick Kelly & Mary Wilson

On April 7, 2017, Patrick Kelly successfully defended his thesis titled "A Punch to the Midgut: Leishmania Interactions with the Sand Fly Gut Microbiome:." He is pictured with his mentor Dr. Mary Wilson.

Research

The Leishmania spp. are kinetoplastid protozoan parasites that cause a spectrum of highly prevalent and neglected tropical diseases known as leishmaniasis. The parasites must undergo two life forms during their life cycle, the first being the extracellular promastigote life stage within the gut of the sand fly vector. During this stage, other organisms that co-inhabit the sand fly gut, collectively known as the microbiome, interact with parasites during their development. Based on the hypothesis that the gut microbiome can influence parasites during their extracellular life stage, he sequenced midgut microbiomes of the sand fly Lutzomyia longipalpis with or without L. infantum infection. The data revealed microbial richness and phylogenetic diversity of the gut microbiome progressively decreases in infected sand flies over time. Importantly, antibiotic-mediated perturbation of the gut microbiome halts parasite replication and development to infectious metacyclic forms and bacterial conditioned media inoculated to parasite cultures in vitro suppresses total metacyclic populations. Collectively, these data suggest the sand fly midgut microbiome is a critical factor for Leishmania growth and differentiation prior to disease transmission.

The second life stage of Leishmania is the intracellular amastigote life stage after internalization of host phagocytic cells, such as macrophages. Characterization of exosomes from Leishmania-infected human macrophages and their effect on the immune response has not been extensively investigated. Proteomic LC-MS/MS stable isotopic dimethyl labeled comparisons of infected and uninfected MDM exosomes identified 484 human and 21 Leishmania spp. proteins between four donors. Proteins significantly less abundant in exosomes derived from infected MDMs were HLA-II, and galectin-3 binding protein, whereas proteins more abundant included serotransferrin and Galectin-9. Exosomes from infected MDMs treated on naïve MDMs did not induce resistant to L. infantum infection or displayed increased gene expression of the pro-inflammatory cytokines. To date, this work is the first to comprehensively identify the proteome in primary human MDM exosomes during Leishmania infection, and to determine the impact of these exosomes on the immune response of other naïve human MDMs.

About Patrick

As the eldest of three, Patrick grew up in the small village of Roscommon in northern Michigan. His passion for insects and science began as a young child while accompanying his father on an insect collection project for an entomology class at the local community college. From there, his interest and curiosity in entomology grew immensely. During his time in elementary school, one could find Patrick saving ants and grasshoppers from the torment of other students on the playground. In his later years, he even convinced his mother to keep an active wasp nest alive since the nest would be abandoned in the subsequent winter months anyway.

The entomological force was strong within Patrick, and he graduated from Michigan State University with a BS in entomology in three years. During his tenure at MSU, he worked on a project studying the mosquito transmission of West Nile Virus in migratory bird populations in Chicago, IL, and subsequently joined the Wilson lab and the Department of Microbiology at the University of Iowa to study Leishmania and their interaction with gut bacteria within their sand fly vector. After graduation, Patrick has plans for a post-doc at the National Institutes of Health in Rockville, MD in the lab of Dr. Jesus Valenzuela continuing his work on the sand fly gut microbiome.

Outside of the lab, Patrick is typically playing with his beloved Pomeranian-Chihuahua Iggy, attending music concerts and festivals, or finding excuses to travel. He has traveled to ten different countries and speaks three languages. At the moment he is an active crossfitter and is currently training for a 100-mile ultramarathon.

Date: 
Monday, April 10, 2017