Multiorgan MicroPhysiological Systems in Studies of Immunity and Metabolism.

Date/Time
Date(s) - 10/27/2025
3:00 pm - 4:00 pm

Location
Communicore, C1-007

Martin Trapecar, Ph.D., Assistant Professor; Division of Endocrinology, Diabetes and Metabolism; Johns Hopkins University School of Medicine

The Laboratory of Human Biomimetics engineers donor-matched, immunocompetent multi-organ microphysiological systems (MPS) to interrogate how tissue-resident immune niches shape human metabolic and inflammatory responses. In this seminar, I will overview two complementary platforms and the insights they enable. First, an autologous gut–liver axis with resident immune compartments is coupled to single-cell RNA/TCR profiling of donor-matched colon (intraepithelial and lamina propria), liver, and blood. Controlled challenges (LPS, poly(I:C), 5-OP-RU) reveal that tissue-resident T cells exhibit distinct transcriptional states, clonal architectures, and response dynamics compared with circulating cells, illuminating how local niches govern the balance between surveillance and tolerance. Second, a six-tissue MPS (intestine, liver, pancreas, skeletal muscle, adipose, brain) establishes physiologic inter-organ crosstalk under fasting- and Western-diet-mimicking conditions and during treatment with metformin (AMPK activation) and semaglutide (GLP-1 agonism). Integrated readouts—multiplex hormones/cytokines, imaging, and bulk or single-cell transcriptomics—demonstrate that connected tissues mount more human-like, coordinated responses than isolated cultures: fasting drives hepatic gluconeogenesis with glucagon release, Western diet elevates insulin and hepatic inflammatory signaling, and drugs correct dysfunction via mechanistically distinct pathways. Together, these autologous, immune-competent models provide a causal bridge between single-cell atlases and organ-level physiology, offering a tractable, human-relevant route to dissect inter-organ inflammatory cascades and immune–metabolic coupling. I will discuss implications for inflammatory bowel disease, metabolic liver disease, and therapy evaluation, and highlight how these platforms advance non-animal methods, enable personalized experimentation, and accelerate discovery of targeted interventions that leverage tissue-resident immune biology.

Bio:

Assist. Prof. Martin Trapecar is the leader of the Laboratory of Human Biomimetics at Johns Hopkins University School of Medicine and serves as the associate director of the Johns Hopkins Center of Microphysiological Systems. He obtained his Ph.D. in Biomedical Engineering at the University of Maribor and pursued postdoctoral training at Gladstone Institutes and the Massachusetts Institute of Technology. His team is developing new precision models of multiorgan human biology and tissue-resident immune environments to learn how interorgan crosstalk navigates autoimmunity, metabolic disorders and neurodegeneration.. The laboratory is supported by the NIH MIRA Award, funding from NASA and DOD as well as collaborations with industry partners.