Regulatory T cells (Tregs) play a critical role in immunosuppression and therefore have the potential to reduce or prevent harmful autoimmune and inﬂammatory immune responses. Using Tregs from mice, humans and, most recently dogs, the Garden & Luo Immune Regulation Laboratory has identiﬁed the critical role of several signaling cascades, including those involving phosphoinositide-3-kinase p110δ, cytokines utilizing the common gamma chain, and microRNA -155 ·15b/16, in the induction, function, and development of Tregs.
The Garden & Luo Immune Regulation Laboratory was also the ﬁrst to document a key defect in the ability of conventional (non-regulatory) T cells to be regulated by Tregs in a murine model of systemic lupus erythematosus, a pathomechanism subsequently demonstrated in other murine models and T cells from human patients. Moreover, the laboratory team showed that reduced T cell receptor α chain diversity of Tregs in NOD mice, a murine model of type I diabetes mellitus, compromised peripheral tolerance and enhanced disease. By discovering these mechanisms, their work has highlighted pathways that may underlie defects of Treg function in disease, potentially identifying novel targets by which these cells may be manipulated for therapeutic gain.
Our current research focuses on the role of regulatory cells of lymphoid and myeloid origin in the pathogenesis of cancer and autoimmune disease. We love dogs, not only because they are wonderful companions and members of our own families, but also because natural canine diseases offer insightfulmodels for a plethora of human diseases -- and studying canine disease can help both dogs and humans, embracing our over-arching ethos of One Health, One Medicine. It is something we take very seriously in the Garden Immune Regulation Laboratory and at Penn Vet in general!
We have ongoing research on canine Tregs and myeloid-derived suppressor cells in various canine cancers, including diffuse large B cell lymphoma, and autoimmune diseases, including myasthenia gravis and immune-mediated hemolytic anemia. One of our exciting new areas of research is the influence of the intestinal microbiome, a key component of the exposome, on the pathogenesis of autoimmune disease in dogs. We collaborate widely, within both the veterinary and biomedical research communities. Please contact us if you would like to reach out with a proposal for a collaboration, or just for a chat about your complementary research activities over a coffee. The following figure summarizes our current research themes.
The Garden & Luo Immune Regulation Laboratory is home to Senior Research Investigator and Laboratory Manager, Dr. Jie Luo; Post-Doctoral Scientist and Research Specialist, Dr. Julia Wu; Research Assistant, Mr. Brandon Lawson; and a number of long-term undergraduate students on work study placement, including Mr. Andrew Pham. We are also delighted to collaborate with Drs. Eric Lancaster and James Riley. Recent laboratory alumna and Howard Hughes Medical Institute Fellow, Sabina Hlavaty, also periodically still visits the laboratory while pursuing her VMD/PhD degree at Penn Vet.
Our principal focus is on developing novel animal models and immunotherapies for autoimmune disease, with a particular focus on myasthenia gravis and autoimmune encephalitides. Our dynamic autoimmune team is led by Dr. Jie Luo and includes Dr. Julia Wu, Brandon Lawson, and Andrew Pham. Julia Wu also has an interest in the role of lymphoid and myeloid regulatory cells in canine diffuse large B cell lymphoma and other cancers, yielding a number of recent publications.
Successful student projects
To date, six PhD students, five BSc students, and 14 MSc students have successfully graduated following projects carried out within the Garden & Luo Immune Regulation Laboratory. Of the MSc students, ten gained Distinctions for their projects, and all but two have completed – or are currently completing – successful PhD projects. Of the PhD students, all completed their theses within three or four years (depending on the program) and have carved out successful careers in research, medical practice, or (in one case) patent law.
Most recently, Sabina Hlavaty was awarded the Howard Hughes Medical Institute-Burroughs Wellcome Fund Medical Research Fellowship for 2018/2019.
The laboratory has also employed two Research Technicians, who both moved on to prestigious Research Associate posts – one at King’s College London and the other at University College London. Another post-doctoral Fellow (Dr Dammy Pinheiro), moved to a senior post-doctoral post within the School of Biological Sciences at the University of Reading. Dammy is currently a Post-Doctoral Research Associate at Imperial College London.
Key expertise and funding
Key techniques for which the Garden & Luo Laboratory has specific expertise include:
- T cell culture, including sophisticated Treg assays in vitro
- Multi-color analytical flow cytometry and flow-assisted cell sorting
- ELISAs, ELISpots, and enhanced electrochemiluminescent assays of a number of Th1 and Th2 cytokines
- Protein techniques, including Western blots
- Molecular biological techniques, including PCR, cloning and transduction of constructs into mammalian cells
- Peptide synthesis and purification
Total extra-mural grant income since 2003 has been ≈ $2.5m, including industrial sources, the Medical Research Council, Mizutani Foundation for Glycoscience, Commonwealth Scholarship Commission, Biotechnology and Biological Sciences Research Council (BBSRC), European College of Veterinary Internal Medicine (ECVIM), Italian Ministry of Health, American College of Veterinary Emergency and Critical Care (ACVECC), Wellcome Trust, Petplan Charitable Trust (PPCT), AKC-CHF, and The British Kennel Club. Current funding includes grants from the British Kennel Club, National Institutes of Health (National Eye Institute), and various commercial sponsors.
Delivering for industry
The Garden & Luo Immune Regulation Laboratory has successfully worked with nine major industrial partners over the past ten years, consistently delivering on-time and within budget – for both product-orientated projects and blue-sky research. The laboratory has a dynamic, forward-looking, innovative, and committed work ethic – with an unquestionable dedication to its team members, to its academic funders, and to its industrial partners. Our mantra is simple: “How can we help you?”
Members of the Garden & Luo Immune Regulation Laboratory have been recognized by prestigious international awards:
- Oliver won an International Canine Health Award presented by the Kennel Club, one of the most distinguished veterinary awards in the world. The award was given to Oliver in recognition of his tireless work as a small animal internist and immunologist.
- Sabina was awarded an NIH/Boehringer-Ingelheim Summer Research Scholarship from Penn Vet. This program is designed to expose students in their first or second year of veterinary school to all phases of biomedical research. More recently, Sabina was awarded a Howard Hughes Medical Institute-Burroughs Wellcome Fund Medical Research Fellowship for 2018/2019, which she concluded in July 2019. Sabina has now resumed her VMD/PhD program at Penn Vet.
- Oliver's publication on a review of systemic inflammatory response syndrome and sepsis, for which the first-named author is Dan Lewis, won an award for being one of the top five most downloaded publications in the Journal of Veterinary Internal Medicine in 2013, being downloaded a total of 6,372 times in this time period.
- Oliver's study of duodenal lesions in diet-responsive chronic enteropathy, for which the first-named author is David Walker, won a European Emesis Council/European Society of Comparative Gastroenterology award for the best gastrointestinal publication from a European research group in 2013.