Education:
Ph.D. University of Glasgow
M.Sc. University of Warwick
M.Res. Keele University
B.Sc. Keele University
Post-doctoral Fellowship:
University of Vermont (American Heart Association, 20POST35220017)
Research Interests:
Parasite pathogenesis, parasite developmental biology, stage development, molecular genetics, novel antiparasitic drug development.
Contact Information:
Lab: BMSB 1041
Office: BMSB 1041
Email: Robyn-Kent@ouhsc.edu
Phone: 405-271-2133 Ext: 46655
Research Interests:
One third of the world’s population is chronically infected with the apicomplexan parasite Toxoplasma gondii. Majority of these cases remain subclinical with people experiencing only mild flu-like symptoms upon infection. However, if a chronically infected person becomes immunosuppressed the infection can rapidly reactivate causing debilitating disease that can result in toxoplasmic encephalitis and even death.
Current treatments for toxoplasma are unable to clear the chronic infection and can only eliminate the parasites actively causing disease. This results in repeated cycles of latency and disease with many immunosuppressed patients becoming intolerant of the current drugs over time. Additionally hyper virulent strains have been recently identified that cause severe ocular disease, that can result in vision loss, in immune competent individuals.
These factors highlight the need for novel drug development, particularly for treatments that could eliminate the chronic stages.
The Kent lab studies how the chronic stage of Toxoplasma gondii can survive long term in different host tissues with very different microenvironments and stressors and the process of reactivation where parasites convert from the chronic to actively infecting form resulting in disease. We are currently working on three major exploratory projects to understand these processes.
- Define the common and tissue specific transcriptome of chronically infecting bradyzoites in vivo. The cysts of T. gondii, that cause a life-long chronic infection in more than 20% of Americans, persist in several different tissues in hosts. To date, little is known about how the parasites survive in these disparate environments that likely exert different pressures on the parasite. In this project we will use cutting edge transcriptional and proteomic technologies to define the constant and tissue specific differences in parasite responses that enables their long-term survival. For any novel treatment to be effective at preventing reactivation of the chronic infection or to eliminate the cysts, it must be efficacious against parasites surviving throughout the host. A better understanding of the core survival pathways in T. gondii chronic stage parasites will be critical to fulfil this requirement.
- Define the tissue specific transcriptional response to T. gondii cysts in vivo. Acute infection with T. gondii elicits a robust and well described immune response in immunocompetent hosts. This response is characterised as a pro inflammatory Th1 response and results in parasite conversion from their actively infecting form into a more dormant, chronically infecting encysted form called bradyzoites. In neurons, the only host cell infected long term by cysts in the brain, and in vitro models of muscle cells a robust change in gene and protein expression has been shown in response to these cysts. Additionally, the immune response to these persistent cysts has been described in the brain with intact cysts largely overlooked by the infiltrating and surveying immune cells. However, the in vivo cellular and immune response to long term infection with T. gondii cysts has not been comprehensively investigated across the many different tissues and cell types that the parasite infects. Using spatial transcriptomics, flow cytometry, immunohistochemistry, and immunofluorescence microscopy we will profile the transcriptional response of infected and neighbouring cells to the presence of a cyst in different tissues and define the immune cell populations that respond to the cyst over time. This understanding of the cellular and immune response to a chronic T. gondii infection will provide valuable insight into how the host responds to this infection that is so extensively infects different cells and tissues.
- Profile T. gondii reactivation in vivo. Following immune dysregulation parasites within the chronically infecting T. gondii cysts undergo stage conversion from the more dormant stage to the rapidly replicating stage responsible for the initial acute infection and leave the encasing cyst. This stage transition has never been profiled in vivo, and our preliminary data suggests that there are substantial changes in gene expression following immune dysregulation and that the structure of cysts rapidly changes resulting in parasite population expansion. Recent data also suggests that excystation of the chronic stage bradyzoites does not occur following the same pathways as egress of the acute stage tachyzoites making this process a novel and vital pathway to process and an exciting new target for cyst elimination or a possible means to prevent reactivation. In this work we will carry out single cell RNA sequencing analysis of stimulated reactivation in vivo to map the process of stage transition and uncover novel pathways involved in excystation building upon exciting new preliminary data.
Alongside these exploratory projects we have developed exciting new in vivo and in vitro models that allow us to explore the role of existing and newly identified candidates that may be required for long term cyst survival and/or for reactivation following immune dysregulation.
Current Lab Personnel:
Emma Franklin
Research Technician
CURRENT EMPLOYMENT OPPORTUNITIES:
Postdoc Scholar / Staff Research Associate
Lab Assistant (part-time position)
Graduate and medical students admitted to the OUHSC GPiBS and MD/PhD programs may contact Dr. Kent about setting up a rotation.
Selected Publications:
Kelsen A*, Kent RS*, Snyder AK, Wehri E, Bishop SJ, Stadler RV, Powell C, Martorelli di Genova B, Rompikuntal PK, Boulanger MJ, Warshaw DM, Westwood NJ, Schaletzky J, Ward GE. MyosinA is a druggable target in the widespread protozoan parasite Toxoplasma gondii. PLoS Biol. 2023 May PMID: 37155705
Kent RS*, Modrzynska KK*, Cameron R, Philip N, Billker O, Waters AP. Inducible developmental reprogramming redefines commitment to sexual development in the malaria parasite Plasmodium berghei. Nature Microbiology. 2018 November PMID: 30177743
For full publication record see:
https://pubmed.ncbi.nlm.nih.gov/?term=robyn+kent&sort=date&size=200