Ulrich von Andrian, MD, PhD
Department of Pathology, Harvard Medical School
Adaptive immunity and leukocyte trafficking: lymphocyte activation; lymphatic system; intravital microscopy
Study how immunological memory is produced through the orchestration of the adaptive immune response, including initiation, regulatory mechanisms, and immune cell homing to organs; harnessing of this knowhow for the development of next generation vaccines
Dr. von Andrian's groundbreaking studies on the biology of immune cells will yield new approaches for tackling the most intractable medical challenges that exist today, including cancer, autoimmune disease, and viral infection.
Obtaining new insights into the role of specialized APCs, the recruitment and homing of subsets of immune cells to target organs for immune surveillance, the T-cell selection process in the thymus, the propagation of the adaptive immune response in lymph nodes, and the cellular and molecular mechanisms of blood cell and immune cell differentiation, will be tremendously important for laying the foundation for novel therapeutic approaches to diseases that involve the immune system. Also, the lab's findings have formed the basis for the development of a novel class of vaccines. Dr. von Andrian’s lab is experienced with industry collaborations, and the stellar work being performed in the lab is clearly evident from the lab’s published findings.
Current Research Interests
- Investigate the immune responses in lymph nodes, with a focus on how T-cell and B-cell-specific responses to antigen are initiated and how antigen is transported to the lymph nodes and presented by APCs.
- Delineate the profiles of specific subsets of lymphocytes, such as cytotoxic T cells, in terms of the operable regulatory constraints, and how a particular antigen context elicits responses and drives lymphocyte differentiation.
- Explore the migration and homing mechanisms for specialized immune cells trafficking to target tissues, and the highly regulated gatekeeper role that the endothelium plays in this process, including multi-step adhesion cascades at sites of infection and inflammation.
- Study the immune cell differentiation and selection; for example, how the thymus “approves” T-cells for release into the blood-stream while eliminating self-reactive T-cells.
- Investigate the different populations of APCs and their roles in immune responses.
- Explore new facets of contact hypersensitivity related to natural killer cell activity.
- Utilize advanced microscopy (for example, multiphoton intravital microscopy) to visualize heretofore unknown processes involving blood cells and immune cells.
- Employ custom-engineered mouse models that allow for immune cell observation.
Dr. von Andrian’s lab’s work has led to paradigm-shifting discoveries, as evidenced by publication of its research in prestigious journals such as Cell, Science, and Nature. The lab has demonstrated for the first time that circulating hematopoietic stem and progenitor cells (HSPCs) infiltrate peripheral organs, where they have the capacity to proliferate and differentiate into cell types, such as dendritic cells, thus providing a localized response to infection and inflammation. The HSPCs that do not undergo this differentiation can return back to the blood via the lymphatic system, a process dependent on the bioactive lipid sphingosine-1-phosphate.
The lab has also studied the mechanisms of platelet generation (that is, thrombopoiesis). Using advanced intravital microscopy, the lab visualized the previously obscure differentiation process within the bone marrow, whereby platelet precursors (proplatelets) are formed from megakaryocytes and then released into the circulation by the hydrodynamic shear force exerted by flowing blood.
Other experiments have uncovered the dynamics of T-cell interactions with antigen-presenting dendritic cells and identified a critical role for macrophages at the lymph-tissue boundary. These cells participate in the adaptive immune response by “chelating” viral particles in the lymph, and then engaging B cells in the adjacent follicles to trigger B cell activation.