Antibodies are generated by the immune cells in the lymph nodes in response to infection, autoimmunity, and other maladies. Humoral immunity depends on the germinal center differentiation process in the B cell follicles of lymph nodes and spleen. In germinal centers, B cells rapidly proliferate and somatically mutated high-affinity antibody secreting cells, i.e. plasma cells, are generated from naïve B cells in response to T cell-dependent antigen. The stochasticity of the antibody formation process predisposes immune cells to turn into lymphomas. To date, the cross-talk between cellular, biochemical, and biomechanical factors in the lymph node microenvironment that regulate antibody formation and support lymphomas is poorly understood. In this talk, I will discuss my laboratory’s effort in developing tractable hydrogel-based ex vivo immune organoids for generating highly specific immune cells in a dish and to elucidate the role of epigenetic modifiers in humoral immunity against infection. I will subsequently describe designer bio-adhesive hydrogels and lymphatic-mimicking technologies for understanding the role of the lymphoid microenvironment in genetically diverse lymphomas and potential causes of drug resistance, including lymphoid tissue mechanics and lymphatic-like fluid flow. Finally, I will discuss the ongoing work on the development of engineered biomaterials for immunomodulation in metabolic syndrome conditions.
Prof. Singh is an Assistant Professor with joint appointments in Mechanical Engineering and Biomedical Engineering at Cornell University. He is the Associate Director on the NIH/NIBIB T32 training grant on Immune-Engineering at Cornell University. He is a standing member of the Englander Institute for Precision Medicine at Cornell Medicine (NYC) and has affiliations with Cornell’s Immunology and Infectious Disease Program. His “Immunotherapy and Cell Engineering” laboratory at Cornell is developing strategies to engineer adaptable, designer immune organoids and enabling technologies for the understanding of healthy and diseased immune cells and their immunomodulation. He has received funding from the National Institute of Health (NIAID, NCI), National Science Foundation, Department of Defense, and the Lymphoma and Leukemia Society, among others. He has published over 40 peer-reviewed journal articles, including those in Nature Methods, Nature Materials, Nature Communications, Cell Reports, PNAS, Blood, Nature Protocols, and Biomaterials. He is a recipient of several scientific awards including the NSF CAREER, Society for Biomaterials Young Investigator award, 3M Non-Tenured Faculty Award, and the Department of Defense Career award. In 2017, he received Cornell’s Teaching Excellence Award and in 2018, Cornell’s Research Excellence Award. His immune organoid research has been identified among Top 100 Discoveries of 2015 by the Discover Magazine. Prof. Singh is the founder and twice elected Chair of the Immune Engineering Special Interest Group (SIG) at the Society for Biomaterials. He is the current Chair of Immuno Delivery Focus Group at the Controlled Release Society. He currently serves on the editorial board of Science Translational Medicine and Nature's Scientific Reports.