Grants We Funded
Grant applicants for the 2022 cycle requested a total of over $2.9 million dollars. The PSF Study Section subcommittees of Basic & Translational Research and Clinical Research evaluated 115 grant applications on the following topics:
The PSF awarded research grants totaling almost $550,000 to support 19 plastic surgery research proposals.
ASPS/PSF leadership is committed to continuing to provide high levels of investigator-initiated research support to ensure that plastic surgeons have the needed research resources to be pioneers and innovators in advancing the practice of medicine.
Search The PSF database to have easy access to full-text grant abstracts from past PSF-funded research projects 2003 to present. All abstracts are the work of the Principal Investigators and were retrieved from their PSF grant applications. Several different filters may be applied to locate abstracts specific to a particular focus area or PSF funding mechanism.
Immunosuppressive Properties of Lymphatics in Promoting Melanoma Growth
Memorial Sloan Kettering Cancer Center (MSK)
Pilot Research Grant
Other, General Reconstructive
Project Summary: The advent of immunotherapy for the treatment of metastatic melanoma has dramatically increased survival for a fatal and incurable disease. However, not every patient responds to immunotherapy initially, and of the ones who do, most will eventually develop secondary resistance to the treatments, rendering them ineffective. There remains a gap in our knowledge of the molecular mechanisms of immunotherapy failure that underscores tipping of the balance between the immune system and cancer in favor of the tumor. The overall objective of our proposed study is to gain insights into the molecular crosstalk between the tumor microenvironment, lymphatics, and host immunity. Specifically, our proposal seeks to clarify the role of lymphatics in modulating the immune system to fight cancer, which may underlie mechanisms of immunotherapy failure. Previous research has shown that one of the cell types that can promote a favorable environment for tumor growth are lymphatic endothelial cells (LECs), which make up the lymphatic system. This discovery stemmed from the finding that LECs express on its surface major immunohistochemistry class I (MHC-I) and II (MHC-II) molecules, critical molecules that present either exogenous or endogenous antigens to naïve immune cells to activate them in the fight against foreign cells or defective innate cells. In a mouse model of melanoma, we have found that tumor growth is decreased when MHC-II is bioengineered to be deleted from LECs. Based on these novel findings, we hypothesize that melanoma tumor cells co-opt the immunosuppressive properties of LECs to scavenge and present tumor antigens to host immune cells as a mechanism of evading the antitumor response. To investigate this hypothesis, we have two specific aims: (1) to identify the mechanisms by which the tumor microenvironment activates the antigen-presenting and immunosuppressive capabilities of LECs and (2) to identify the mechanisms of how LECs modulate the host antitumor immune response in an MHC-II dependent manner. These aims are based on previous studies demonstrating increased immunosuppressive properties of LECs in response to tumor-directed immune cells, resulting in a negative feedback loop. To test these aims we will examine the effects of various cytokines secreted by tumor-specific immune cells on LECs grown in culture. Subsequently, we will investigate the effects of LEC-specific MHC-II deletion on immune cells in melanoma-bearing mice using flow cytometry. Impact Statement: Melanoma is the fifth most common cancer in men and women in the United States. Patients with melanoma are taken care of by a team of highly specialized physicians, including medical oncologists and surgeons. Plastic surgeons, especially, are involved in both the direct surgical treatment of melanoma and the reconstructive efforts afterwards. Therefore, improving therapies for melanoma is impactful in the field of plastic surgery and can have long-lasting effects on related reconstructive needs.
Claire Li, MD, is a research fellow in the Lymphatic Biology Laboratory directed by Babak J. Mehrara, MD, at Memorial Sloan Kettering Cancer Center (MSK) in New York, NY. Under Dr. Mehrara’s mentorship, she is focused on characterizing the relationship between lymphatics and cancer in promoting tumorigenesis. Dr. Li was raised in Columbia, Maryland, and completed her undergraduate studies in biology, with a concentration in genetics, at Duke University, NC, in 2013. She subsequently obtained her medical degree from the University of Maryland School of Medicine in Baltimore, MD, in 2017. Prior to her current research fellowship at MSK, Dr. Li completed two years of general surgery residency at New York Presbyterian/Weill Cornell Medical Center. Her long-term career goal is to pursue a career in academic surgery in the field of surgical oncology.