James Ross, Ph.D. (joining Fall 2025)

I (Dr. Ross) completed my graduate training with Dr. Dolores Hambardzumyan, a leading expert on myeloid cells in brain tumors. I studied tumor associated macrophages and microglia (TAMs) in high-grade glioma (HGG), how tumor driver mutations shaped the immune microenvironment in the pediatric context and studied TAMs in vivo using two-photon microscopy. I discovered there are molecular subtype-specific differences with regards to TAMs and T cells in pHGG, and demonstrated the existence of TAM heterogeneity in these tumors. For my post-doctoral training, I worked with Dr. Rafi Ahmed, a pioneer in T cell immunology and a founding father of checkpoint blockade therapy. Here, I studied T cell immunity in the context of the brain and meninges during chronic viral infection using the lymphocytic choriomeningitis virus (LCMV) mouse model. I examined the mechanism and effects of checkpoint blockade in this setting and discovered, given the right context, checkpoint blockade is highly effective in the central nervous system with regards to boosting T cell immunity and promoting viral clearance. In my lab I plan to combine this unique training with macrophages, microglia, and T cells to develop a deeper understanding of systemic anti-tumor immunity in high-grade glioma and diseases of chronic antigen exposure in the brain.

The goals of our research are to understand how neuro-immune interactions in high-grade gliomas allow for immune escape and to harness this knowledge to develop novel therapeutics. Despite aggressive therapeutic regimens, high-grade glioma is one of the deadliest human cancers with a median survival of just 11-15 months. To better understand the mechanisms underlying tumor progression, immune escape, and therapeutic resistance we utilize a combination of immune-competent mouse models, human patient samples, high-dimensional flow cytometry, single cell sequencing technologies, in vivo intravital imaging, and more. We are particularly interested in tumor associated macrophages and microglia as culprits of disease progression and aim to engineer these cells to disrupt immune-suppressive mechanisms within the brain. Other areas of interest include studying tumor and immune cell metabolism and profiling human blood for biomarkers of disease status and progression.

Another key interest of the Ross lab is studying central nervous system immunity during chronic antigen exposure, including viral infection and neurodegeneration. During chronic viral infection with LCMV peripheral organs clear infectious virus within 60 days while the brain and meninges remain infected for upwards of a year or longer. We have found checkpoint blockade therapy is beneficial in the CNS under the right circumstances and will utilize this knowledge to design more effective immunotherapies to aid with reinvigorating the immune response to boost viral clearance. Further, we aim to study the role of glia and meninges in regulating CD8 T cells in this setting. Any meaningful insights from these studies will then be applied to neurodegenerative disease.

https://scholar.google.com/citations?user=CoUaHlwAAAAJ&hl=en

I will be accepting graduate students and trainees at all levels starting fall 2025. I place a heavy emphasis on mentoring and seek to empower my trainees for success and getting to the next step in their careers. Your success = my success!

If you are interested in joining my lab, please reach out at james.ross@virginia.edu.