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Beth Tamburini Lab


Research Team

Beth Tamburini, PhD - Assistant Professor of Medicine and Immunology
Jeffrey Finlon - Professional Research Assistant
Erin Lucas - Graduate student - Immunology Graduate Program
Andrew Winter - Graduate student, Biomedical Sciences and Biotechnology Masters Program

Job Posting

We are looking for a post-doctoral fellow to join our research team.
Please follow the link if you are interested and apply through the CU careers page.
Or go to:

 

Research Summary

The goals of my research are to understand how interactions between LECs and canonical immune cells shape immune responses to infections, cancer, and chronic inflammation.  The following three areas of interest aim to expand the field of stromal cells in immunity by understanding the function of the lymphatic endothelium across tissues and systems.  First, my discovery that lymphatic endothelial cells in the lymph node have the capacity to hold onto antigens for long periods of time in order to educate memory T cells led me to become interested in how the lymphatic endothelium interacts with immune cells.  My data suggest that antigens disappear from the lymph node on the order of four weeks post immunization or infection.  Interestingly, antigen specific T cells continue to divide 6-8 weeks post immunization or infection in response to archived antigen.  Thus, one of the remaining questions is how lymphatic vessels interact with immune cells outside of the lymph node, in the tissue.  As lymphatic vessels are also made up of LECs it seems likely that there may be storage of antigen within the vessels in addition to antigen retention on lymph node LECs.  Most of the cells passing through the lymphatic vessels are memory phenotype T cells and dendritic cells, which fits well with our data that naïve T cells are deleted after stimulation with archived antigen while memory T cells are stimulated.  Furthermore, my work was the first to demonstrate antigen hand-off from LECs to hematopoietic cells and is often confused with other work showing LECs as antigen presenting cells.  These different functions of LECs lead to questions about how LECs handle different types of antigens.  When do LECs themselves present antigen (e.g. self-antigens), when do LECs hand-off antigen (e.g. foreign antigens), and how do LECs handle multiple antigens.  Thus, understanding the activation state of LECs, and the signals which activate LECs to take up antigen and induce antigen hand off (such as division and death), may allow us to manipulate the function of LECs.


In addition to understanding the role of antigen retention by the LECs we aim to understand the role the lymphatic vessels have in interacting with the immune system during breast cancer.  Studies to evaluate the role of lymph node LECs within a tumor draining lymph node as well as tissue lymphatics are currently underway in a collaboration with Traci Lyons, PhD in the context of breast cancer and mammary gland involution.  Our prediction is that increased lymphangiogenesis in Sem7a expressing tumors affects not only tumor lymphatics but also lymph node lymphatics.  As published by Dr. Lyons, Sem7a expressing tumors not only increased metastatic potential, but also increased tumor take and lymphatic vessel density.  In collaboration, we discovered that the tumor draining lymph nodes are increased in size and LEC number.  This increase in LEC number results in increased PD-L1 expressed by the lymphatic endothelium and indeed increased expression of PD-1 on CD8 T cells.  Our hypothesis and future work will test whether increased lymphatics in the lymph node and tumor affects the PD-L1/PD-1 axis leading to a more tolerogenic tumor microenvironment and increased metastatic potential.  Furthermore, this work will predict if patients whose tumors express Sem7a may be candidates for PD-1/PD-L1 immunotherapies.

Lastly, our recent data in collaboration with Matthew Burchill, PhD and Hugo Rosen, MD suggests there is a correlation between liver disease progression, lymphangiogenesis, and tertiary lymphoid structures.  There is a significant gap in our understanding of both liver disease progression and the effect lymphangiogenesis has during liver disease.  We find that there is an increase in the number of CD45+ lymphoid clusters from patients with liver disease and that these clusters are associated with increased disease severity as measured by increased fibrosis and clinical designation of liver function.  Furthermore, these lymphoid clusters are highly associated with lymphatic vessels and we are investigating what role lymphatic vessels may play in these lymphoid clusters.  Concurrently, it seems likely that the normal lymphatic vessels associated with the portal triad which are important for lymphatic flow away from the tissue may be damaged due to chronic inflammation caused by increased fat, cholesterol, or chronic infection.  Thus we aim to understand the relationship between normal lymphatic vessel function in the liver as well as the recruitment/generation of lymphatic vessels to lymph node like tertiary lymphoid organs within the liver and mucosa.  Using a number of therapeutic methods we will evaluate first when and if increased lymphangiogenesis associated with lymphoid clusters promotes progression of liver disease and second whether we can alter liver disease progression by increasing normal lymphatic vessel function and determine if increased lymphatic vessels are important for lymphoid cluster formation and inflammation.
Taken together, my current and future work strive to answer questions regarding the role of the previously underappreciated lymphatic stroma in immune function.  I expect the bridge between the lymphatic stroma and the immune system to be of utmost importance to future vaccine development, understanding of infection, cancer immunotherapies, and chronic diseases.