What are we curious about?
Replicating complex human biology.
Remarkable advances in microphysiological systems technology and tissue engineering have opened up new possibilities to study human-specific biology and diseases. We are utilizing this progress to “humanize” medical research and develop approaches to mimic complex multiorgan physiology and systemic immunology.
Tissue homeostasis and regeneration.
Our early studies of ex-vivo multiorgan interactions show intriguing differences in tissue functionality and maturation when kept in isolation or in communication with other organs. We are interested to identify mediators responsible for this increased life-like behavior of various organ systems and contributors to their homeostasis to inform new paradigms in regenerative medicine.
Immunometabolism in health and disease.
We are passionate about understanding how fundamental disruption in tissue-tissue and tissue-immune crosstalk leads to the early emergence of immunometabolic and neurodegenerative disorders such as Inflammatory Bowel Disease, diseases of the liver and Parkinson’s disease. These remain some of the biggest challenges of our time.
Humanness and the pursuit of life
What does it mean biologically to be human and where does humanness start? As we are advancing human biomimetics and human-machine integration, these questions are as relevant as ever. We hope to contribute new theoretical concepts to the evolving notion of what biological life and being human means today and in the future.
Research
Metabolic and inflammatory disorders such as metabolic syndrome, autoimmune and neurodegenerative diseases, are increasing at alarming rates, with little progress made in untangling their causal connection or mitigation of mortality. Emerging human multiorgan microphysiological systems (MPSs), in combination with multiomics and systems biology, offer new exciting possibilities to provide clarity in metabolic and inflammatory diseases through controlled interaction of multiple MPSs as well as components of the innate and adaptive immune system. MPSs are reductionist in vitro models, comprising multiple cell types, specialized microenvironments, and perfusion, that capture salient features of in vivo organ behavior. We are focused on identifying causation in gut-liver-brain immunometabolic pathologies and explore how disruption of tissue-immune homeostasis leads to the emergence of metabolic diseases. While this approach might yield tangible targets in disease prevention and treatment, it will also contribute to our understanding of humoral physiology of the gut-liver-brain axis, the role of innate and adaptive immune cells for tissue regeneration, and susceptibility of the axis to metabolic perturbation.
Projects
Role of MR1-Restricted Lymphocytes of the Gut-Liver Axis in Health and Disease
Recently discovered MR1-restricted lymphocytes, such as MAIT cells, represent a heterogeneous population of immune cells that, interestingly, have a unique ability to recognize a number of metabolites as their antigen. Previous studies have found a connection between their migration and proliferation and several autoimmune disorders, however their exact role in either prevention or potentiation of these diseases remains to be established. Given their high frequencies in mucosal as well as hepatic tissue, we are interested in the role they might play in concurrent pathologies such as IBD and autoimmune liver diseases, as well as the therapeutic potential of engineered MR1-restricted lymphocytes.
Identifying immunometabolic modulators of Gut-Liver-Cerebral homeostasis..
Despite well described connections between the gut, liver and brain, many mechanisms contributing to their humoral metabolic, immunological and structural homeostasis remain unidentified. Our preliminary data suggest that the behavior and maturation of individual organ systems greatly differs during their interaction as opposed to isolation primarily due to metabolic changes and tissue-immune interactions. Identifying critical factors responsible for these phenomena would open new venues for therapeutic interventions, regenerative medicine and tissue engineering.
Deciphering the role of lipid metabolism and gut-liver-cerebral interactions in mitochondrial neurodegenerative pathologies
Evidence of ferroptosis and mitochondrial disfunction playing a role in the death of dopaminergic neurons is mounting and increased interest exists in the connection between neuroinflammatory conditions, ferroptosis and fatty-acid metabolism. Our preliminary work implicates changes in neuronal lipid metabolism due to increased local inflammation and activation of microglia, to further modulate disease progression. Our established model of the gut-liver-cerebral axis offers the opportunity to chart causal relationships between systemic alteration of lipid metabolism, immunity and neurodegenerative disease.
What we strive for
Publications
Multiorgan microphysiological systems as tools to interrogate interorgan crosstalk and complex diseases.
Trapecar, FEBS Letters 2021
Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases
Trapecar et al., Science Advances 2021
Gut-Liver Physiomimetics Reveal Paradoxical Modulation of IBD-Related Inflammation by ShortChain Fatty Acids
Trapecar et al., Cell Systems 2020
Meet the Team
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Martin Trapecar
PRINCIPAL INVESTIGATOR
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Merve Uslu
POSTDOCTORAL FELLOW
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Farhan Siddiqui
POSTDOCTORAL FELLOW
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Marissa McGilvrey
POSTDOCTORAL FELLOW
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Shereen Chew
PhD CANDIDATE
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Ronald Bronson
RESEARCH SPECIALIST
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Lorenzo Thomas
PROGRAM COORDINATOR
Open positions
We are always looking to expand our team by creative, motivated and kind members. If interested in joining, please respond with a CV and description of scientific interests to mtrapec1@jhmi.edu.
Postdoctoral training opportunites
The Laboratory of Human Biomimetics at the Johns Hopkins All Children’s Hospital and Institute for Fundamental Biomedical Research in St. Petersburg, Florida, is looking to hire multiple postdoctoral associates.
The focus of the group, led by Dr. Martin Trapecar, is the exploration of the fundamental origins of immunometabolic diseases, such as IBD, metabolic syndrome, and neurodegenerative disorders. The group is developing advanced multiorgan microphysiological systems (organs-on-chips) and uses tissue engineering and systems biology tools to recreate patient-specific models of diseases. Please consult https://humanbiomimetics.com for further information.
An ideal candidate will have strong conceptual and practical experience in at least two areas: stem cell biology, molecular biology, tissue engineering, and systems biology. The tissues and organs that the lab is particularly interested in are mucosal tissue and liver, pancreatic, neuronal, and adipose tissue. Standard techniques used in the lab are cell culturing (primary cells, organoids, iPS cells), flow cytometry and cell sorting, generation, and analysis of transcriptomic as well as metabolomic data (Chipseq, single-cell RNAseq…), confocal microscopy, multiplexed cytokine/chemokine analysis (ELISAs, Luminex) and use of bioengineered tools like multiorgan microphysiological system platforms and 3D bioprinting to study human multiorgan interactions.
Successful candidates must be capable of working in highly multidisciplinary research teams and have a demonstrated track record of success in independent scientific research. Strong applicants will exhibit significant basic science understanding, scientific rigor, motivation, and an ability to originate, carry out, and publish crucial original research in collaboration with their JHU mentors. Strong written and verbal English language skills are required.
The rapidly growing new Institute for Fundamental Biomedical Research is part of the Johns Hopkins All Children’s Hospital in St. Petersburg, Florida, and the Johns Hopkins University (JHU) School of Medicine ecosystem. It represents a superbly equipped research environment that aims to connect fundamental and clinical researchers to solve some of the most significant medical challenges. Trainees and postdoctoral scientists have full access to resources available at the main JHU Baltimore campus and are strongly encouraged to participate in JHU-wide activities and collaborations. The lab and institute are fully committed to the candidate’s career development and path to independence.
St. Petersburg offers an excellent quality of life in terms of affordability, pristine nature, proximity to Tampa bay’s international airport, and vibrant cultural life.
If interested in the position, please submit a CV and brief description of scientific interests to mtrapec1@jhmi.edu.