Graduate NIH Training in BiotechnologyTrainees
Melanie Ruffner
Project Description Currently I am working in Dr. Paul Robbins’ lab on a project involving exosomes. Exosomes are nanovesicles produced in the late endosome and secreted by various cell types, including dendritic cells (DC) and other antigen presenting cells. Studies have demonstrated that tumor-derived exosomes are capable of suppressing host anti-tumor immune response and placental-derived exosomes play an important role in establishing maternal immune tolerance toward the fetus. Our lab has demonstrated previously that exosomes derived from DC transduced with adenoviral vectors containing anti-inflammatory molecules such as IL-10, IL-4 and FasL are capable of suppressing antigen-specific immune responses in multiple disease models, such as delayed type hypersensitivity and collagen-induced arthritis. My work in the lab thus far has had several parts. My first project has been to examine the ability of DC and DC-derived exosomes to halt the progression of diabetes in the NOD model of autoimmune diabetes. DC transduced with IL-4 were able to prevent the onset of diabetes with a single treatment to either 5- or 10-week old NOD mice, similar to our previous results. Interestingly, treatment of NOD/LTJ with DC-derived exosomes also prevented the onset of hyperglycemia. These results suggest that exosomes from immunosuppressive DC are able to block progression of diabetes in NOD mice and thus could be used clinically to treat type I diabetes. I am currently repeating this experiment and will also be beginning a series of experiments using a mouse multiple sclerosis model to determine if these vesicles have a therapeutic effect in that model as well. I have also been working on developing a fusion protein to enable our laboratory to track exosomes in vivo. Lactadherin is a membrane associated protein that has been shown to be present on the surface of vesicles from multiple cell types. I am currently working on creating a construct which replaces a non-essential domain of this protein with a FLAG tag, and will then make andeno- and retroviral vectors to stably deliver this tagged protein to cells. We hope to elucidate the role that exosomes play in vivo by transducing cells, like DC or tumor lines, with this tagged protein and tracking the interaction of secreted exosomes with the host immune system. Course work Intro to Statistical Methods 1—John Wilson—Fall 2005—3 credits—Letter Math Methods in Bioengineering—TK Hung—Spring 2006—3 credits— Hemodynamics and Biotransport Biomaterials and Biocompatibility Advanced Biomaterials Molecular Cell Biology and Biophysics 1— Comprehensive Immunology Fundamentals of Biochemical Engineering Stem Cells Molecular Cell Bio I Biomaterials and Biocompatibility
Peer Reviewed Publications
Book Chapters
Abstracts
Attended the first two meetings and presented posters #1 and #2 Seminars I have attended several of the Immunology and Molecular Genetics and Biochemistry Seminars as part of my involvement in this training program. These are outside of my home department, which is Bioengineering. Advisor Paul Robbins Professor of Molecular Genetics and Biochemistry and Orthopaedic Surgery School of Medicine University of Pittsburgh |
Biotechnology Program
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