Using spleen tissue, the life gift from the transplant organ donors, we aim to reconstitute immune response in vitro. Our unique platform enables us to test hundreds of different conditions in parallel and assess their impacts on human immune responses, such as antibody production. We aim to leverage the systemic and causative understanding of human immune system to inform the rationale design of vaccine and immunotherapy.
Immunotherapy and vaccine save lives. In just 3-5 generations back, diseases like measles and polio, are major causes of mortality and morbidity. They left horrors town after town and claimed millions of lives. However, nowadays, most physicians have never seen a single case of measle or polio in their lifetime, thanks to the advent of effective vaccines.
However, old technology (inactivated vaccine) does not always generate highly effective vaccine (e.g. COVID-19). Meanwhile newer generations of immunotherapies (such as monoclonal antibodies and CAR-T) emerge. To test and to understand the mechanism of new vaccine and immunotherapy has been challenging. Immune response, such as the protective antibody response generated in a vaccine response, requires a relay of antigen information between multiple different cell types (antigen presenting cells, multiple types of T cells, B cells). The conventional culture typically consisting of a single cell type was unable to capture the cooperativity between different cell types. As a result, these cultures were also unable to model the multi-step immune function.
Spleen organoid is an in vitro multi-cell-type culture re-capitulating key features of human immune response in vivo. Spleen is the largest lymph node in a human body. Due to the concern of allograft rejection, spleen from the transplant organ donor is typically treated as medical waste. Mark Davis lab at Stanford University/HHMI pioneered organoid technology to harness the immune reaction potential of the spleen. During my postdoc research there, I further developed the technology to allow massively parallel culture of hundreds of organoids derived from the same donor. As an example, we screened the vaccine adjuvant activity among 19 different cytokines in 3 different concentrations across 5 different donors. The screening identifies robust candidates undergoing engineering development.
At the Medical College of Wisconsin, we are building up robotic screening pipeline to further increase the throughput of spleen organoid to 1000+ organoids per day. I also hold a joint appointment at the Versiti Blood Research Institute, a regional Organ Processing Organization (OPO). With the support from VBRI, we are also building up a spleen biobank covering diverse donor age groups and ethnicities. The overall goal of our lab is to develop high-throughput spleen organoid assays, enabling a systemic and causative/functional understanding of the human immune system. The knowledge will inform rationale design of vaccine and immunotherapies.
Principal Investigator | Title of Research Study Awards / Publications / Presentations |
---|---|