Grants We Funded

Abstract
Lymphatic regeneration is a vitally important, but poorly understood, physiologic process which plays a central role in lymphedema, inflammation, allograft rejection, and cancer metastasis. Our project uses a novel, non-surgical model to explore how lymphatic vessels regenerate after injury. This is of particular importance to plastic surgeons because injuries or abnormalities of this system result in lymphedema, play important roles in composite tissue transplant rejection, and significantly alter adipose tissue metabolism. If we can safely boost lymphatic regeneration we can improve outcomes in lymphedema and composite tissue transfers.
Our first is aim is to determine how lymphatics regenerate after non-surgical injury. This aim will test the hypothesis that lymphatic vessels regenerate spontaneously after toxin-mediated ablation, and that both remaining local lymphatics and bone marrow-derived cells play critical roles re-growing vessels. This aim is clinically relevant because knowing the sources of regenerating lymphatics is essential to developing the most effective therapeutic targets in diseases involving adult lymphangiogenesis.
Our second aim is to determine how lymphatic regeneration can be accelerated after injury. This aim will test the hypothesis that lymphangiogenesis can be improved by inhibition of the anti-lymphangiogenic forces, TGF-ß1 and IFN-?. This is clinically important in lymphedema because adding pro-lymphangiogenic cytokines, such as VEGF-C, risks inducing metastasis in a population of patients with a history of malignancy.
This approach is innovative because we are have developed a novel transgenic mouse model of toxin-mediated lymphatic ablation to induce profound destruction of the lymphatic architecture without surgery. Ablating lymphatics non-surgically avoids confounding postsurgical changes including inflammation and wound healing. Additionally, we will be using fluorescently labelled bone marrow and BrdU-labelled local lymphatics to identify the specific cell lineage of individual cells in regenerated lymphatic vessels. These are groundbreaking studies in lymphangiogenesis with broad clinical implications for the field of plastic surgery.

Biography
Jason Gardenier, MD was raised in McLean, VA and graduated summa cum laude with a BA in International Relations from the College of William and Mary. He went on to obtain his MD from the University of Virginia. After completing two years of general surgery residency at New York-Presbyterian Hospital, Weill Cornell Medical Center, he began a prestigious research fellowship at Memorial Sloan Kettering Cancer Center under the guidance of Dr. Babak Mehrara, MD, FACS. Dr. Gardenier has focused his research efforts on improving the scientific understanding of adult lymphangiogenesis and improving animal models of lymphatic disease. He has also focusing on identifying appropriate pharmacologic targets to improve surgical and nonsurgical treatment of lymphedema.