Osteoimmunology: Bone tissue is in a constant flux of bone formation and bone resorption, which is regulated by bone forming cells (osteoblasts) and bone resorbing cells (osteoclasts). Using knockout mice, the Dennis Laboratory, in collaboration with Dr. Feng Lin of the Cleveland Clinic, showed that cells lacking complement signaling formed fewer osteoclast cells than wild type mice. The Dennis Laboratory is now testing the hypothesis that reduced complement signaling can protect post-menopausal women from bone loss (osteoporosis). Using a mouse model of post-menopausal estrogen deficiency, they are quantifying the effects of complement signaling on bone structure, bone density and on the number of osteoblasts and osteoclasts found within bone tissue. The hope is that these results may lead to new treatments for osteoporosis.
Cell Targeting: Therapeutic cells are coated by one of two “cell painting” methods where either an antibody is attached to the cell surface via a Two-Step method using palmitated protein G and an antibody, or by a One-Step method using a synthetic cell targeting molecule composed of a targeting peptide sequence, a linker and a lipid moiety that inserts into the cell membrane. The coated cells are then infused into the patient where they will preferentially bind to the target tissue or organ.
Inflammatory Bowel Disease (IBD): Mesenchymal stem cells (MSCs) have been shown to be able to modulate the immune response. The Dennis Laboratory is working on methods to deliver MSCs to the gastrointestinal tract as a method to treat IBD. Using a unique “cell painting” methodology, MSCs are coated with antibodies that direct cells to bind to inflamed epithelium where the MSCs then produce factors that down regulate the inflammatory process. Using the cell painting methodology, the Dennis Laboratory has shown significant improvement in mortality, body weights, and reduced tissue damage in a mouse model of IBD. The long term goal of these studies is to develop treatments for ulcerative colitis and Crohn’s disease.
Trachea Tissue Engineering: Recently, there have been several anecdotal reports in the media about the implantation of tissue engineered tracheas into people. However, none of the results have demonstrated a reproducible method to produce living engineered cartilage, and most patients have required multiple operations and long hospital stays. The Dennis Laboratory is developing methods to produce completely autologous tissue engineered tracheas from a patient’s own cells as a means to produce functional tissue engineered tracheas with no artificial scaffolds. This entirely scaffold-free tissue engineering method is currently being tested in a rabbit model. The long term goal of this study is to produce functional, tissue engineered tracheas to be used in people with severe tracheal injuries from trauma, congenital defects, or cancer.
The Dennis Lab:
James Dennis, PhD
Danielle MacKay, PhD
Thomas Kean, PhD
Mark Jakob, MD
G. Adam Whitney