Pilot Project Leaders

Pilot Project 1 - Transcriptomic predictors of the immune response to vaccination

The Bates Laboratory studies the in vivo biology at the interface of innate and adaptive immunity. We are currently performing single cell RNA-sequencing of antigen-specific CD4+ T cells to define the molecular pathways that govern adjuvant-mediated differences in T cell survival, proliferation, and function. Separately, use of spatial transcriptomics provides us a comprehensive view of the in vivo transcriptional landscape associated with immune cells and their interactions. Defining how these early transcriptional profiles affect intermediate outcomes like germinal center formation and longer-term outcomes like antigen-specific antibody titers will contribute to the development of vaccines that elicit more protective and longer-lasting immunity.  Both of these avenues of research rely heavily on the expertise of UMMC Core Labs. All transcriptomic assays are being performed in the UMMC Molecular and Genomics Core Facility. The Research, Computing, Bioinformatics and Biostatistics Core in the UMMC Molecular Center for Health and Disease provides crucial support for data analysis. 

Pilot Project 2 - Role of monocytes in oncoviral infection and associated cancer

Ramona Moles, PhD Assistant Professor of Cell & Molecular Biology rmoles@umc.edu

 Monocytes are mononuclear phagocytes, which historically have been considered crucial in suppressing tumor growth by recognizing and killing tumor cells. However, the immune system does not eliminate transformed cells in cancer patients. Emerging evidence shows that in vivo monocytes exhibit an immunosuppressive phenotype that promotes cancer development rather than disease progression. Transcriptomic analyses of circulating monocytes isolated from different cancer types revealed alteration in gene expression. However, most pathways identified are not involved in the immunosuppressive phenotype, demonstrating that further studies are needed to fully understand the functional role of monocytes in cancer.

Dr. Moles' project will aim to investigate the role of monocytes in the neoplastic disease induced by the oncogenic virus HTLV-1. Adult T cell leukemia (ATL) is an incurable condition induced by the retrovirus HTLV-1. The main cellular targets of the virus are CD4+. Evidence suggests that the innate response, specifically monocytes, might be involved in HTLV-1 pathogenesis. Monocytes isolated from HTLV-1 infected individuals and ATL patients display functional alterations in their ability to differentiate and release cytokines. Our data demonstrates that HTLV-1 infected cells are resistant to monocyte-mediated engulfment. This evidence shows that the virus targets and manipulates the monocytes' functions; however, its role in HTLV-1 pathogenesis is poorly understood and represents a scientific gap in the field. Our hypothesis is that the oncovirus HTLV-1 reprograms monocytes to favor the progression of infected cells towards leukemia and support immune evasion of transformed cells. 
The engulfment mediated by monocytes is a process that can be divided into three steps: phagocyte recognition of the "eat me/don't eat me" signals on the surface of target cells, and the engulfment and degradation of cargo. This proposal aims to study (Aim 1) how HTLV-1-infected cells impair the "don't eat me" signal to escape monocyte recognition, (Aim 2) studying the fate of monocytes following phagocytosis and (Aim 3) characterize the functional phenotype of monocytes in ATL patients.