We integrate chemistry, library technology, bioengineering, immunology, advanced noninvasive imaging methods, and animal models to best design –and interactively fine tune– nanotherapies for immune-mediated diseases, such as cancer, cardiovascular and infectious diseases.
Bridging the translational gap
In addition to mouse models, we focus strongly on translational research in large animals.
While hundreds of nanomedicine studies are produced every year, very few formulations are clinically approved. This is partly due to an undue reliance on murine studies, which suffer from limited value in accurately predicting translational efficacy in humans. To combat this experimental hindrance, our lab established a translational nanomedicine program with large animal models, ranging from rabbits to swine to non-human primates. It involves scaling up production and testing while in the preclinical phase, which provides a unique framework in preparing for clinical studies. We have the unique infrastructure to study our therapies and probes in large animal models while performing imaging studies using some of the most advanced multimodality systems available.
– https://www.ncbi.nlm.nih.gov/pubmed/31434756
– https://www.ncbi.nlm.nih.gov/pubmed/30936448
– https://www.ncbi.nlm.nih.gov/pubmed/27236528
– https://www.ncbi.nlm.nih.gov/pubmed/28091604
Cardiovascular nanoimmunotherapy
Immunomodulation therapies to tackle the most prominent range of cardiovascular ailments.
Atherosclerosis, a chronic diseases of the large arteries, is one key underlying cause of myocardial infarction and stroke. Driven by cholesterol accumulation and subsequent inflammation in the vessel wall, atherosclerosis has been clinically treated by lipid-lowering treatments, but remains a major threat to human health worldwide. Over the past 20 years, insights into cardiovascular immunopathology have opened up a range of potential therapeutic targets to reduce the risk of cardiovascular disease, which has shifted the focus from lipids to inflammation. Continually inspired by the excitement surrounding and results from the 2017 CANTOS trial, which first demonstrated the possible efficacy of immunotherapeutics in reducing prevalence of cardiovascular disease, our lab has honed in on nanotechnology approaches to facilitate the specific targeting of innate immune cells. With continued research efforts focusing on this crucial and promising field, we believe our approaches can generate more effective immunomodulatory treatments to induce disease regression and prevent the recurrence of cardiovascular events.
– https://www.ncbi.nlm.nih.gov/pubmed/24445279
– https://www.ncbi.nlm.nih.gov/pubmed/26295063
– https://www.ncbi.nlm.nih.gov/pubmed/30209355
– https://www.ncbi.nlm.nih.gov/pubmed/30936448
– https://pubmed.ncbi.nlm.nih.gov/33692130/
Chemical engineering of nanomaterials
Designing and producing ever-expanding libraries of highly biocompatible nanomaterials.
The design, synthesis, and characterization of our nanomaterials is the cornerstone of our research and group. Our lab has its origin story deeply intertwined with the field of nanomedicine, and we’re proud of the contributions we’ve made towards pioneering its application for immunotherapy. Our designs include, but are not limited to apoA-1-based nanobiologics, nanoemulsions, liposomes drug-loaded block-copolymer micelles, and nanocrystal-core lipoproteins. We have established a library of A1-based nanomaterials, which is used to develop tailored immunotherapeutics using pharmacological approaches, RNA therapeutics and proteins for the treatment of cardiovascular diseases, cancer, and transplantation.
– https://www.ncbi.nlm.nih.gov/pubmed/27791119
– https://www.ncbi.nlm.nih.gov/pubmed/29281244
– https://www.ncbi.nlm.nih.gov/pubmed/28112478
– https://www.ncbi.nlm.nih.gov/pubmed/27071376
– https://pubmed.ncbi.nlm.nih.gov/33674313/
Visualizing the immune system
Multimodality preclinical and clinical approaches to image immune response using novel innovative probes.
Complex immune responses result in the production and distribution of a variety of immunological precursors and cells throughout multiple organ systems. In order to further illuminate the local and systemic cellular function and migration patterns, our group has a special develops non-invasive immuno-imaging methods. Being part of the Biomedical Engineering and Imaging Institute, we are fortunate to have access to a fleet of dedicated preclinical and clinical imaging systems, including PET/MR, PET/CT, high field MR and optical imaging, which can be utilized to study disease status in murine, swine, rabbit and non-human primate models. Using novel radiotracers, we have establshed approaches to non-invasively monitor immunological processes. Among different applications, we have studied the induction of trained immunity, the egress and migration of myeloid cells in ischemic heart disease and cancer, amygdala metabolic activity as a predictor for cardiovascular events, and local macrophage proliferation and monocyte production as a biomarker for the progression of atherosclerosis. Our lab revels at the opportunity to visualize the (immunomodulatory) effects of our carefully designed nanoimmunotherapeutics using a range of highly advanced imaging scanners.
– https://pubmed.ncbi.nlm.nih.gov/33899016/
– https://www.ncbi.nlm.nih.gov/pubmed/32313216
– https://www.ncbi.nlm.nih.gov/pubmed/28091604
– https://www.ncbi.nlm.nih.gov/pubmed/28088338
– https://www.ncbi.nlm.nih.gov/pubmed/26394773
Empowering the immune system
Combatting disease with novel nanoimmunotherapeutics that target trained immunity.
Trained immunity, a de facto innate immune memory, describes the process by which innate immune system activation results in enhanced responsiveness to subsequent triggers. Trained immunity naturally occurs through mechanistic epigenetic and metabolic reprogramming of innate immune cells. Our research focuses on how this immunological phenomenon can be purposefully induced or downregulated using our novel nanoimmunotherapeutics, as an approach to treating maladies including cancer, bacterial/viral infection, cardiovascular diseases, autoimmune disorders, and allograft rejection in organ transplantation. Through widespread collaboration with other leading researchers in the cutting-edge field of trained immunity, we continue to explore therapy regimens in which our nanoimmunotherapeutics can lead to improved clinical outcomes.
– https://www.ncbi.nlm.nih.gov/pubmed/32132681
– https://www.ncbi.nlm.nih.gov/pubmed/31561273
– https://www.ncbi.nlm.nih.gov/pubmed/30967658
– https://www.ncbi.nlm.nih.gov/pubmed/30413362
– https://pubmed.ncbi.nlm.nih.gov/33125893/
I started working in the field of nanomedicine as a chemistry student in The Netherlands, more than twenty years ago. Since then, I have been captivated by the application of nanotechnology in medicine, particularly in immunology.
During my tenure at Mount Sinai, which started in 2006, and since the beginning of 2021 at Radboudumc and TU/e in The Netherlands, we have established a unique multidisciplinary ecosystem. It allows young scientists from diverse backgrounds to flourish and mature into the engineers, scientists, and medical doctors of tomorrow by participating in and driving innovative science today.
By exploring the biological, chemical, and experimental knowledge that interconnects chemistry, imaging, and immunology, our lab creates nanomaterials to tackle detrimental medical conditions such as cancer, atherosclerosis, stroke, and organ transplantation. We strive to make these technologies available to patients through entrepreneurship BIOTRIP.nl
