Origin, classification and function of mononuclear phagocytes: macrophages, dendritic cells and monocytes in mouse and man.
- Regulation of the adaptive immune response by lymphoid and non-lymphoid dendritic cells and monocytes.
- Efferocytosis and cross-presentation by antigen presenting cells.
- The role of mononuclear phagocytes in transplant rejection and cancer immunology.
The human respiratory system is the body’s largest interface exposed to ambient air, and it continuously encounters particles, allergens and microbes. The aims of this project is to functionally characterize human pulmonary dendritic cells in the lung and lung-draining LNs, which play crucial roles in lung immunity against foreign material, with the hopes that we will gain insight into designing new vaccines and developing novel immune therapies, including the treatment of forms of cancer that are now incurable.
The immune system has evolved to recognize mutations and alterations of minor antigens (mAgs) produced by cancerous tumors, but this adaptive immune response carries costs: The immune system can reject the body’s own tissues, as occurs in autoimmune disorders, or other needed tissues, as with organ transplantation. We do not yet understand how endogenous antigen-presenting cells recognize, coordinate and induce immunological responses against mAg-mismatched cells, particularly in the absences of pathogen-associated molecular patterns (PAMPs) that mark foreign agents. If we can uncover the sequential cellular cascade that leads to mAg-mismatched cell rejection, then we can design drugs to prevent tissue rejection, with benefits for transplant surgery, autoimmune disorders, and more.
Cancer is one of the most enduring health problems of the modern era. A major new direction in cancer treatment is the development of anti-cancer vaccines, which would educate the body’s immune system to recognize and kill cancer cells. If successfully developed, vaccines could provide long-lasting or permanent remission of a cancer without requiring radiation, chemotherapy, or other treatments with adverse long-term effects. We have projects that lay a scientific foundation for developing anti-cancer vaccines based on selective targeting of dendritic cells, which can train other parts of the immune system to destroy tumor cells. We have recently discovered that educating a specific type of dendritic cell in a particular way elicits an immune response that nearly completely eliminates metastatic cancer in the lungs of mice. The goal of our current project is to characterize and outline the fundamental mechanism of this system and achieving this will provide critical steps towards developing this approach as a treatment for cancer in humans