The Effects of Perioperative Bone Health on Spinal Fusion and Surgical Outcomes
Faculty Information
Name:
Julie Chan
Email
julie.chan@neurosurgery.ufl.edu
Phone
(323) 308-5836
Faculty Department/Division
Neurosurgery
This project is primarily:
Clinical
Research Project Description:
Spinal disorders are the largest expenditure in the United States with 134 billion dollars spent on spine conditions each year, including 300,000 spinal fusions performed annually. Elderly patients make up a large part of this population, with 10 million people over the age of 50 suffering from osteoporosis in the US alone. Poor bone health often precludes surgical intervention leading to persistent disability, or when performed, failed surgical intervention requiring additional surgical intervention and further morbidity. Given the treatable nature of osteopenia and osteoporosis, focusing on ways to improve the detection and treatment of poor bone quality may lead to more appropriate surgical procedures and less disability and health care expenditure over the longer term.
Current guidelines regarding the optimal detection and subsequent management of osteoporosis in the setting of spine surgery are limited. In this retrospective review of spinal fusion patients with osteoporosis and osteopenia, we will evaluate preoperative modalities for diagnosis (DXA, FRAX, CT) and treatment modalities (bisphosphonate, anabolic, immunotherapy) to determine which are more effective in preventing complications following spine surgery. Outcome measures will include perioperative complications, radiographic findings, and patient reported outcome measures (ODI, NDI, mJOA, SF-36, SRS 22, and VAS).
The medical student will be responsible for assisting with data collection and review, manuscript preparation, and abstract submission to a national conference.
No funding is required for this project due to the retrospective nature. The medical student will be added to the IRB appropriately.
Does this project have an international component or travel?
No
Cancer Immunotherapy Development
Name:
Dr. Jianping Huang
Email
jianping.huang@neurosurgery.ufl.edu
Phone
(352) 273-6835
Faculty Department/Division
Neurosurgery
Project Information
Project Title
Associate Professor
This project is primarily:
Translational
Research Project Description:
Our research team is at the forefront of pioneering cancer immunotherapy development for brain tumors and other cancers. We’ve made notable strides with multiple high-impact publications, establishing that specific molecules, like CD70, when expressed in tumors, advance tumor growth through both a direct tumor-promoting effect and an indirect trigger of immunosuppression within the tumor microenvironment (TME). This creates a dual threat, or “double jeopardy,” within the tumor. Hence, by targeting these molecules, we can produce a potent antitumor response, neutralizing two major factors of oncogenesis and tumor advancement.
In our innovative approach, we’ve harnessed IL-8 release from tumors to amplify T-cell movement within tumors by crafting a CAR design, ensuring optimal antitumor activity with minimal side effects. Through our work, we’ve showcased that IL-8 receptor-modified CD70CAR (8R-70CAR) significantly boosts the trafficking and persistence of the CAR T cells in tumors, resulting in complete tumor elimination and sustained immunological memory in advanced models of GBM, ovarian, and pancreatic cancer. Currently, we are spearheading a phase I clinical trial (NCT 05353530, FDA IND#23881, Huang, J) for adults diagnosed with primary GBM.
However, challenges persist. In-depth studies into the glioma TME highlight the extensive immunosuppression and pro-tumor signaling orchestrated by tumor-associated myeloid cells (TAMCs), which comprise over half of the cell population in cancers. Contemporary therapies like checkpoint inhibitors, targeting immune inhibitory receptors such as CTLA-4 and PD-1, have revolutionized cancer treatment due to their broad application and lasting clinical impact when effective. Yet, some tumor’s resistance to these inhibitors indicates alternative immune evasion mechanisms. In our quest to understand this, we identified LAIR1 (or CD305) as a unique innate immune checkpoint responsible for TAMC’s immunosuppressive actions in cancer. Remarkably, inhibiting LAIR1 facilitates a transformation of M2-like TAMs into M1 phenotypes, disrupts the immunosuppressive loop between LAIR1, FXIII-A, and collagen, and minimizes collagen build-up that acts as a barrier against immune responses. This reshaping of the TME enhances tumor-T cell interaction, making tumors more vulnerable to immune attacks. By implementing LAIR1 knockout or antibody-blocking, we observed enhanced antitumor responses, especially in models resistant to PD-1 blockade.
Together, our findings pave the way for innovative therapeutic strategies, bringing hope to those battling cancer.
Does this project have an international component or travel?
No