Immune Regulation Laboratory
Professor Oliver Garden’s laboratory based at the School of Veterinary Medicine at the University of Pennsylvania, Philadelphia specializes in cellular immunology, with a specific expertise in regulatory T cell (Treg) and myeloid-derived suppressor cell (MDSC) biology. Oliver started his laboratory with the aid of a Wellcome Trust Advanced Fellowship in 2001 within the Department of Immunology, Imperial College London, Hammersmith Campus, following post-doctoral training at the University of South Carolina School of Medicine and a Residency in Small Animal Internal Medicine at Cornell University College of Veterinary Medicine.
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 laboratory has identiﬁed the critical role of several signaling cascades, including 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 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 (SLE)¹, a pathomechanism subsequently demonstrated in other murine models and T cells from human patients. Moreover, they 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 insightful models 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 at Penn Vet!
We have ongoing research on canine regulatory T cells and myeloid-derived suppressor cells in various canine cancers, including diffuse large B cell lymphoma, and autoimmune diseases, including immune-mediated haemolytic anaemia and myasthenia gravis. 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 and cancer 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 laboratory is home to PhD student (Julia Ying Wu), Research Assistant (Sabina Hlavaty), and Senior Research Investigator (Dr. Jie Luo). Julia is studying the role of lymphoid and myeloid regulatory cells in canine diffuse large B cell lymphoma. Sabina's project focuses on understanding the role of myeloid-derived suppressor cells in cancer, with a special emphasis on using the dog as a model to study these cells. Jie is working to advance his prior research related to myasthenia gravis into clinical patients (dogs), with the aim of developing novel antigen-specific immunotherapies for both canine and human patients. Research Specialist Brandon Lawson will join the Garden Laboratory on June 11, 2018 in a joint venture with Dr. James Perry, Surgical Oncology at Penn Vet. Student workers Andrew Phan and Lee Avery are also expanding their studies working in the Garden Laboratory.
Successful student projects
To date, six PhD students, five BSc students and 14 MSc students have successfully graduated following projects carried out within Oliver’s 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 – following the conclusion of their contracts, and one postdoctoral Fellow (Dr Dammy Pinheiro), who has moved on to a senior postdoctoral post within the School of Biological Sciences at the University of Reading.
Key expertise and funding
Key techniques for which Oliver’s laboratory has specific expertise include T cell culture, including sophisticated Treg assays in vitro; multi-colour analytical flow cytometry; ELISAs and enhanced electrochemiluminescent assays of a number of Th1 and Th2 cytokines; and molecular biological techniques, including PCR, cloning and transduction of constructs into mammalian cells.
Total extra-mural grant income since 2003 has been ≈ £1.6m, including industrial sources, the Medical Research Council, Mizutani Foundation for Glycoscience, Commonwealth Scholarship Commission, Biotechnology and Biological 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 PPCT and various commercial sponsors.
Delivering for industry
Oliver’s laboratory has successfully worked with seven (7) major industrial partners over the past ten (10) 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.
Lab members have been recognized by many 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 the NIH/BI Summer Research Scholar from Penn Vet. The program is designed to expose students in their first or second year of veterinary school to all phases of biomedical research. Sabina Hlavaty was also recently awarded the Howard Hughes Medical Institute-Burroughs Wellcome Fund Medical Research Fellowship for 2018/2019.
- 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.