Management and Outcomes of Cerebral Vasculopathy in Children with Sickle Cell Disease: a Retrospective Registry
Dr. Philipp Aldana
Phone
(904) 633-0991
Faculty Department/Division
Pediatric Neurosurgery
This project is primarily:
Case Review
Research Project Description:
Children with sickle cell disease (SCD) are at significant risk for stroke despite best medical management. Cerebral revascularization surgery (CRS) is effective in other diseases in the prevention of stroke due to cerebral vasculopathy, such asMoyamoya syndrome (MMS) – one of the types of vasculopathy seen in SCD. While preliminary studies have shown that these interventions can possibly reduce the risk of stroke in pediatric SCD, they have been mainly single center case series with small sample sizes. The patients identified to be at high risk for stroke have been managed via existing protocols to diagnose them with cerebral vasculopathy and referred for neurosurgical evaluation when appropriate. Following neurosurgical evaluation, surgical intervention may be recommended to the appropriate patient. These interventions can include CRS procedures as well as obliteration of cerebral aneurysms. However, the role of CRS in this patient population is not clearly defined. Thus, this study aims to compare the stroke outcomes in pediatric patients with SCD and MMS following best medical management alone to those additionally undergoing CRS.
As a multi-center, retrospective cohort study, the objective is to determine the role of CRS in this patient population by examining the surgical indications, techniques, outcomes and adverse events of the procedure. Patient characteristics and stroke occurrence will be compared between those who underwent CRS and those who underwent conservative treatment. Medical students would have the opportunity to analyze data and assist with data accuracy of research data between institutions.
Does this project have an international component or travel?
No
Co-opting TME lactate signal to benefit T cell therapy
Dr. Loic Deleyrolle
Email
loic.deleyrolle@neurosurgery.ufl.edu
Phone
(352) 273-9381
Faculty Department/Division
Neurosurgery
This project is primarily:
Translational
Research Project Description:
Complex alterations of energy pathways have been described in cancers and originate from the Warburg hypothesis, whichpostulates that the majority of cancer cells derive their energy from aerobic glycolysis. This specific metabolic reprogramming ofstrong engagement in the glycolytic pathway is a hallmark of glioblastoma (GBM). As part of their high glycolytic rate, GBMsecrete metabolic byproducts such as lactate, which acts as an important oncometabolite and immunosuppressor. Capitalizing onour current knowledge of tumor metabolism and how metabolic pathways affect immune response, the goal of this project is totest an innovative therapeutic modality based on reprograming the metabolic qualities of anti-tumor immune cells to enhanceimmunotherapy for the treatment of GBM. We hypothesize that co-opting lactate signal may be a useful approach to overcomemetabolically driven tumor-imposed immunosuppression and for developing efficient immunotherapies. This project investigatesthe efficacy of lactate receptor genetic engineering in T cells in the context of adoptive cell therapy to treat GBM.
Does this project have an international component or travel?
No
Enhancing metabolic fitness of T cells to treat brain cancer
Dr. Loic Deleyrolle
Phone
(352) 682-1961
Faculty Department/Division
Neurosurgery
This project is primarily:
Translational
Research Project Description:
Adoptive T cell transfer (ACT) has emerged as a viable therapeutic for brain tumors. While promising, the efficacy of this approachis often limited by a complex immunosuppressive tumor microenvironment. These complexities mean that more sophisticated Tcell products are necessary for the treatment of such malignancies.
T cell functions are metabolically regulated and undergo metabolic reprogramming upon activation marked by an increasedglucose uptake to support their greater bioenergetic and biosynthetic needs. Brain tumors are supported by a microenvironmentcharacterized by tumor-imposed metabolic restrictions with fierce nutrient competition, especially for glucose.
We hypothesize that brain tumor cells outcompete adoptively transferred T cells for metabolic substrates like glucose, directlylimiting their survival/activation and function.
We propose that by enhancing T cell glucose metabolism through genetic manipulation (overexpression of key glucosetransporters) and in vitro metabolic conditioning that we can modulate the metabolic fitness of T cell products and enhance theirantitumor efficacy. The effects of these metabolic manipulations will be tested in mouse models of high-grade glioma.
Does this project have an international component or travel?
No
Mechanisms of Cerebral Aneurysm Formation and Rupture
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:
Our laboratory is studying mechanisms of cerebral aneurysm formation and rupture.
Does this project have an international component or travel?
No
Cerebral Aneurysm Healing
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:
Our laboratory is developing novel methods to treat brain aneurysms and studying mechanisms of cerebral aneurysm healing.
Does this project have an international component or travel?
No
Mechanisms of subarachnoid hemorrhage associated acute brain injury, vasospasm, and delayed cerebral ischemia
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:
Our laboratory is studying mechanisms of subarachnoid hemorrhage associated acute brain injury, vasospasm, and delayed cerebral ischemia.
Does this project have an international component or travel?
No
Cerebral aneurysms and SAH
Dr. Brian Hoh
brian.hoh@neurosurgery.ufl.edu
Phone
(352) 273-9000
Faculty Department/Division
Neurosurgery
This project is primarily:
Translational
Research Project Description:
My laboratory studies: 1) the biological mechanisms of how cerebral aneurysms form and how they rupture; 2) the development of
improved therapies and devices to treat aneurysms; 3) the biological mechanisms of acute neural injury from subarachnoid
hemorrhage when aneurysms rupture.
Does this project have an international component or travel?
No