Grants We Funded

Abstract
Vascularized composite allotransplantation (VCA) is a recently developed method for reconstructing patients with complex and severe disfigurements. However, patients must take immunosuppressants for the rest of their life. Immunosuppressants have many drawbacks, including risks of cancer and severe metabolic and endocrine disturbances. Therefore, much attention is being given to methods that reduce the need for immunosuppression. One such method may be inhibiting the lymphatic system at the time of transplantation. Lymphatics act as highways for immune cells in the skin to reach the lymph node and activate the immune response. Inhibiting lymphatics has already been shown to reduce the threat of graft rejection in several other organ transplant models. However, it may be particularly powerful in VCA because the skin component, which the recipient's immune system attacks most vigorously, has an extensive network of lymphatic vessels. In this proposal, we will: 1) study how inhibiting lymphatic regeneration affects skin rejection, 2) how immunosuppressants affect lymphatic regeneration, and 3) how inhibiting lymphatic regeneration affects immune cell trafficking. To study our first aim, we will transfer skin from transgenic mice with no lymphatics in their skin to normal mice and measure the time to skin rejection. To study our second aim, we will treat mice receiving skin grafts with different immunosuppressants, and assess how regeneration patterns and levels of lymphatic-specific growth factors are affected. Finally, to study our third aim, we will use a laser to ablate lymphatics and then track the movements of immune cells to see if their trafficking is inhibited. If successful, our work will demonstrate that inhibiting lymphatic reconstitution indeed holds promise to reduce the threat of acute rejection in VCA. Future work may determine whether we can use this to reduce the dose of immunosuppression, increasing the availability of VCA.

Biography
Justin M. Sacks, M.D. is an Assistant Professor in the Department of Plastic and Reconstructive Surgery at the Johns Hopkins University School of Medicine. A graduate in biology and society from Cornell University, Dr. Sacks received his medical degree from the Mount Sinai School of Medicine in New York City, where he also completed his combined general surgery and plastic surgery residency. He is currently faculty at Johns Hopkins where he works with his mentor, Dr. Lee, to help contribute to fundamental advancements in the field of vascularized composite allotransplantation, specifically focusing on the hand, face and abdominal wall reconstruction. His clinical interests include the reconstruction of all forms of acquired and oncological defects ranging from the head and neck to the breast, chest, abdomen, pelvis and extremities. He serves on the editorial boards of Plastic and Reconstructive Surgery, and has been an invited speaker at multiple institutions. He is fellow member of the American College of Surgeons and a member of the American Society of Plastic Surgeons, American Society of Reconstructive Microsurgery and Plastic Surgery Research Council. He is a founding member of the American Society of Reconstructive Transplantation.