Ivan Dzhagalov
Lab of Cellular Immunology
Thymus
DAPI
Spic-GFP
TIM4
Image courtesy of Chih-Yu Lin
Thymic macrophages
Macrophages in the thymus are well-known for their enormous phagocytic ability, but our knowledge about these cells is fragmented. We have established that thymic macrophages are not monolithic but instead are composed of two different populations with distinct localization and origin. TIM4+ thymic macrophages are located in the cortex and are derived from embryonic progenitors, while TIM4- cells are in the medulla and appear after birth. The current questions we are actively exploring in this project are:
1. How are thymic macrophages maintained?
2. What roles do Interferons play in the development and functions of thymic macrophages?
3. Are thymic macrophages more than just scavengers of apoptotic cells? Do they participate in T cell selection?
The roles of Heparan sulfate and Heparin in the immune system
The immune response is a well-organized, dynamic, and compartmentalized process that requires carefully choreographed interactions between different cell types. The glycosaminoglycan Heparan sulfate (HS) can bind to many secreted signaling molecules and can participate in the communication between cells. We want to find out what is the role of HS in the immune system and how is the variation in its structure responsible for selective interaction with various key signaling molecules. We have found out that the cells that express HS at the highest level in immune organs are the fibroblasts, and we have created tools to genetically eliminate HS production in the thymus and other immune organs. Our studies have identified an important role for HS in the growth of the thymus and a requirement for the HS relative, Heparin, for the granules production in mast cells. The current directions of this project include:
1. Dissection of the importance of the different HS structures for leukocyte trafficking in the lymph nodes
2. How do mast cells without granules function?
Sindbis virus-based vaccine platform
SARS-CoV2 swept the world a few years ago and highlighted the need for high-quality, easy-to-manufacture vaccines. We are testing a Sindbis virus-based vaccine platform that can easily be customized to work against various pathogens.
Macrophage-based therapy for SLE
One of the theories for SLE pathogenesis is that defective clearance of apoptotic cells is at the root of the disease. We are trying to engineer macrophages with enhanced ability to remove dying cells.
