|Education||DVM, Ohio State University|
Dr. Muth comes to the program with a DVM from Ohio State and is researching cellular and extracellular microRNAs in HIV-1 elite suppression. This project is made possible by an ongoing collaboration with Dr. Joel Blankson, also of CMM.
In the absence of antiretroviral therapy (ART), HIV-1 infection is typically followed by declining CD4+ T-cell counts, elevated viral loads, and eventual progression to AIDS and death. By means of incompletely understood mechanisms, a minority of individuals maintain plasma viral loads under the clinical limit of detection (50 copies/mL) over the long term, even without ART. A better understanding how these elite suppressors (ES) restrain virus replication may aid in developing effective vaccines and new treatments. A class of short nucleic acids known as microRNAs (miRNAs) contribute to post-transcriptional regulation. miRNAs are also exported from the cell and are thought to be sufficiently stable in circulation to establish cell-to-cell communication.
We previously reported that PBMC miRNAs cluster HIV-1-positive chronic progressors from healthy controls and ES. In this study, we aim firstly to profile miRNA expression in CD4+ and CD8+ naïve, effector memory, and central memory cells and characterize their networks of direct regulatory targets. Secondly, we aim to characterize extracellular (plasma) miRNAs, which circulate in vesicles, lipoprotein particles, and protein complexes, and determine whether specific miRNAs are associated with abundance and/or size profiles of plasma particles that derive from CD4+ or CD8+ T-cells. The findings of this project will have relevance for basic miRNA science and will advance HIV-1 clinical science through biomarker discovery and determining the feasibility of potential miRNA-based therapies based on the ES phenomenon.
- Muth DC, McAlexander MA, Ostrenga LJ, Pate NM, Izzi JM, Adams RJ, Pate KA, Beck SE, Karim BO, Witwer KW: Potential role of cervicovaginal extracellular particles in diagnosis of endometriosis. BMC Veterinary Research 2015, 11:187.
- Garrett CM, Muth D, Watson J: Effects of medicated diet to eradicate Helicobacter spp. on growth, pathology, and infection status in Rag1-/- and nude mice. J Am Assoc Lab Anim Sci, 2014 53(3):238-45.