Research

Linskey Glioma Brain Tumor Research Laboratory

The UCI Brain Tumor Research Laboratory, established in 2006 by Mark Linskey, MD, is an in vitro primary and secondary cell culture and molecular biology laboratory, including real-time PCR, that also works with in vivo subcutaneous and intracranial stereotactic nude mice human brain tumor xenograft models. 

Since its inception, the team has focused on applying biological principles learned from normal neuronal-glial stem cell biology and molecular pathways to the study of human malignant glioma biology. This includes growing primary and secondary human glioma cultures and cell lines with chemically defined, serum-free media under both adherent and nonadherent spheroidal culture conditions and Matrigel cell invasion assays. A couple of current research projects the lab is working on include the following:

Chromosomal Instability of Chromosome 7 and Malignant Glioma Subpopulation Dynamics

The most recent major interest of the Brain Tumor Research Laboratory relates to studying the cellular subpopulation interdynamics between the malignant glioma mass-like cell (TMC) subpopulation and the stem-like tumor initiating cell (STIC) subpopulations — specifically, how these subpopulations relate to resistance to standard therapies and tumor reemergence/recurrence after standard therapies are completed. 

EFEMP1 Variant as a Novel New Malignant Glioma Therapeutic Agent

Researchers found that EFEMP1, a protein regulated by PAX6, can inhibit cell division, reduce new blood vessel formation and prevent tumor recurrence in gliomas. They created a variant called hFV3v that maintains these beneficial effects without promoting cell migration. The resulting protein, ZR30, shows promise for treating malignant gliomas and has been patented.

LINKSEY FACULTY PROFILE

Mohyeldin Brain Tumor Research Lab

The Mohyeldin Brain Tumor Research Lab, led by neurosurgeon-scientist Ahmed Mohyeldin, MD, PhD, has a unique philosophy that leverages the utility of thinking about our patients’ medical problems from both a basic science and clinical perspective. The research group is driven by a fundamental purpose to better elucidate the understanding of brain tumors while also improving the surgical outcomes of the patients they serve. This unique mindset allows for a synergistic approach to characterize and decipher how brain tumors arise and how they behave, which in turn allows the team to discover better therapeutics for patients. The challenges they observe in the operating room help frame and focus the questions they ask in the laboratory, and this formula has been critical to their success.

The team’s research focuses on primary tumors of the brain, pituitary gland and skull base. Their collective expertise in the surgical management of complex brain tumors, cell culture engineering, animal tumor models, cell signaling, computational biology, bioinformatics and spatial omics allows them to directly utilize brain tumor tissue from the operating room — with the consent of patients — for rigorous laboratory investigation. This powerful workflow allows them to study brain tumors up close and probe their complexity directly, instead of relying on artificial models or surrogates.

MOHYELDIN FACULTY profile

Yuki Research Lab

Novel Liquid Embolic System for the Treatment of Hypervascular Tumors and Vascular Malformations

Trans-arterial embolization is a procedure used to stop blood flow to specific areas of the body, often to treat abnormal blood vessels or tumors. By inserting a catheter into an artery, small particles, liquid embolic materials (LEMs) or coils are injected to halt blood flow. This procedure is commonly used to reduce bleeding during surgery or to shrink large hypervascular tumors. However, current embolic materials have limitations.

Microparticles are a commonly used embolic material, but they have drawbacks such as limited tissue penetration and poor visibility under X-ray. LEMs offer advantages over microparticles, including better tissue penetration and permanent vessel closure. However, FDA-approved LEMs like n-butyl cyanoacrylate (nBCA) and Onyx — which contain ethylene vinyl alcohol (EVOH) dissolved in dimethyl sulfoxide (DMSO) — are not suitable for many treatments due to their limitations. nBCA is a strong adhesive with a significant risk of catheter entrapment, and its pro-inflammatory nature is not suited for tumor treatment. Similarly, the organic solvent DMSO used in Onyx carries strong tissue toxicity. Thus, none of the existing LEMs are FDA approved for treating conditions such as hypervascular tumors or trauma-related vessel injuries.

To address this, the Yuki Lab team developed a novel LEM called Aqua Embolic System (AES), a single-component water-based LEM. AES, made of biocompatible polysaccharides, forms a solid hydrogel cast triggered by blood calcium. It offers excellent tissue penetration, can be delivered with any single-lumen microcatheter and contains no toxic solvents like DMSO. AES shows promise for treating vascular malformations or hypervascular tumors, with the potential for delivering multiple chemotherapy agents. The research team includes Ichiro Yuki, MD, Parisa Khosropour, Shuichi Suzuki, MD, PhD, and Frank P.K. Hsu, MD, PhD. The material is provided by polymer scientist Kousaku Ohkawa, MD, from the Institute for Fiber Engineering, Shinshu University, Japan. 

The project is currently undergoing preclinical evaluation, followed by clinical evaluations and FDA approval for commercialization.

YUKI Faculty profile

JW Chen Lab

Traumatic Brain Injury and Neurocritical Care

The team’s research efforts include:

• Primarily multimodal brain monitoring involving brain O2, cerebral blood flow and cerebral microdialysis.
• Decreasing cerebral vasospasm and post-subarachnoid hemorrhage hydrocephalus using up-front irrigation of the brain.

Normal Pressure Hydrocephalus Studies

Chen’s research team has recently explored:

• The role of brain compliance in NPH and post-traumatic hydrocephalus with the use of the noninvasive brain4care monitor.
• Auto-calculation of ventricular volumes to access changes after VP shunting.
• Molecular markers of NPH and post-traumatic hydrocephalus via analysis of CSF proteins.
• Genomic analysis of NPH via whole exome sequencing.
• The utility and role of NPH virtual support groups.
• The importance of NPH education in native languages.

JW Chen Lab webPAGE

CHEN FACULTY PROFILE

Hansen Bow’s research interests bridge engineering and neurosurgery. Specifically he is interested in simulation in surgical education, artificial intelligence in improving neurosurgical outcomes and spine outcomes research.

bow faculty profile

Skull Base Lab

Dennis Malkasian’s goal of the Skull Base Lab is to expose resident and fellowship trainees to an advanced level of surgical and functional neuroanatomy. A broad and dynamic operative and clinical exposure is critical in attaining these goals. Cadaveric dissections are additive to a neurosurgeon’s training. Moreover, it is essential in selecting, formulating and executing research endeavors. The Skull Base Lab is designed for a spectrum of eclectic approaches employed in one’s research selection.

Malkasian faculty profile

Spine Research

The UCI School of Medicine spine team, led by Michael Oh, MD, aims to pioneer medical advancements through meticulous, inclusive and innovative research endeavors. These initiatives span from enhancing medical education to critically evaluating treatment algorithms. The team's current research projects are highlighted below:

NeuroSim: A Portable and Cost-Effective Neurological Simulation Device

The team developed a patented training device using computer-aided design (CAD) modeling to replicate neurosurgical procedures. This simulation tool enriches medical education training, allowing trainees the opportunity to practice surgical techniques, enhance anatomical knowledge and develop fine motor skills.

Perioperative Optimization of Spine Surgery Patients

Oh's research team collects and analyzes data to evaluate preoperative risk factors associated with adverse outcomes in spine surgery. By identifying these risk factors, surgeons can adjust their clinical practices to minimize the likelihood of complications for patients.

Evaluation of the Treatment Algorithm for Spondylodiscitis

Spondylodiscitis, an infection of the intervertebral disc, poses diagnostic and management challenges. A systematic literature review revealed improved pathogen identification and reduced pain with percutaneous endoscopic debridement and drainage (PEDD) compared to CT-guided biopsy.

Implementation of AI to Improve Surgical Outcomes

In collaboration with a group of computer scientists, the team is developing a predictive model to identify patients at risk of poor outcomes in spine surgery. With the model's personalized guidance, they aim to mitigate complications and enhance patient care.

Educational Utility of Augmented and Virtual Reality Models for Patient Education

The group evaluated augmented reality models for patient education in the outpatient spine clinic. Preliminary findings indicate improved patient understanding and a preference for augmented reality over traditional imaging modalities. 

Single and Multicenter Retrospective Studies

In collaboration with UCI’s Office of Research, the team has developed an automated data extraction pipeline, significantly streamlining database creation for single-center retrospective studies.

Sponsored Clinical Research Studies

The team's ongoing clinical studies encompass innovative solutions such as Premia Spine’s TOPS System, Spineart’s BAGUERA C cervical disc replacement and Medtronic’s Infuse Bone Graft in transforaminal lumbar interbody fusion.

OH FACULTY PROFILE

Sumeet Vadera has an interest in brain-machine interface research and epilepsy surgery outcomes. He has received several grants, including the Epilepsy Foundation Grant and the Medtronic Grant for novel surgical techniques. Vadera’s commitment to research extends beyond conventional boundaries, including his interest in improving the value and reducing the cost of care provided.

VADERA FACULTY PROFILE