Brain injury after subarachnoid hemorrhage
Name:
Dr. Brian Hoh
Email
brian.hoh@neurosurgery.ufl.edu
Phone
(352) 273-9000
Faculty Department/Division
Neurosurgery
This project is primarily:
Translational
Research Project Description:
We are studying pathophysiologic mechanisms of brain injury after subarachnoid hemorrhage.
Does this project have an international component or travel?
No
Formation and Rupture of Brain Aneurysms
Name:
Dr. Brian Hoh
Email
brian.hoh@neurosurgery.ufl.edu
Phone
(352) 273-9000
Faculty Department/Division
Neurosurgery
This project is primarily:
Translational
Research Project Description:
We are studying pathophysiologic mechanisms of brain aneurysm formation and rupture.
Does this project have an international component or travel?
No
Improving Aneurysm Treatment and Healing
Name:
Dr. Brian Hoh
Email
brian.hoh@neurosurgery.ufl.edu
Phone
(352) 273-9000
Faculty Department/Division
Neurosurgery
This project is primarily:
Translational
Research Project Description:
We are studying pathophysiologic mechanisms of aneurysm healing and developing biological endovascular devices for the treatment of aneurysms.
Does this project have an international component or travel?
No
Clinical development of novel immune checkpoint blockade for cancer therapy.
Name:
Dr. Jianping Huang
Email
jianping.huang@neurosurgery.ufl.edu
Phone
(352) 273-6835
Faculty Department/Division
Neurosurgery
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