Two UAB Pathology faculty members' proposals were selected for faculty development grants by the Provost and Faculty Senate in the 2024-25 cycle. Andrea Comba, Ph.D., Assistant Professor, Neuropathology, and Liyun Cao, Ph.D., Assistant Professor, Laboratory Medicine.
Comba's project, "Unraveling mesenchymal transformation in glioma through spatial transcriptomics,” has been funded for $10,000, with funding split between the Office of the Provost and the Heersink School of Medicine.
Cao's project, “Development of a machine learning algorithm to predict free valproic acid concentration in adult epileptic patients,” has been funded for $10,000.
According to Comba's proposal, gliomas remain among the most prevalent and aggressive brain tumors, with a median survival rate of 15-19 months post-diagnosis, and resistent to conventional treatments. Leveraging the department's extensive brain tumor archive, Comba proposes a pilot screening study of diverse human glioma formalin-fixed paraffin-embedded (FFPE) specimens. The goal is to "unravel the morphological and molecular signature of mesenchymal transformation using digital histopathological evaluation combined with molecular spatial transcriptomics methods such as RNA-scope, a multiplex in-situ hybridization method, in primary and recurrent glimoa specimens. The project aims to demonstrate the feasibility and effectiveness of spatial transcriptomics analysis in glioma tissue through RNA-scope."
Cao's proposed rationale for her study is to develop a machine-learning algorithm that accurate predicts fVPA concentration to decrease turn-around time, optimize drug efficacy and minimize toxicity, and ultimately improve epilepsy patients' outcome.
According to her proposal, epilepsy is the fourth most common neurological disorder following migraines, stroke, and Alzheimer’s Disease. Valproic acid, (VPA) an antiepileptic drug, is highly protein-bound, with 90-95% bound to albumin. The unbound free VPA (fVPA) is the bioactive form responsible for the pharmacologic effects, but also for toxicity. In patients with low albumin level, the fVPA level will increase when the total VPA (tVPA) level is normal or less than normal. Therefore, to optimize the clinical outcome, measuring fVPA level is required in the presence of hypoalbuminemia. However, fVPA measurement is not available in many laboratories due to the complexity of the test. In most situations, patients’ blood samples are sent to a reference laboratory to measure the fVPA concentration. The send-out test usually takes 4-7 days of turnaround time to get the results, which is inconvenient for the clinicians/pharmacists to adjust the dosage of the drug. In addition, non-epilepsy drugs are prescribed to treat comorbidities of the patients. The drug-drug interaction can result in a change of the free drug concentration. Furthermore, the free drug concentration varies non-linearly with increases in total drug concentration.
Cao was promoted to assistant professor from instructor in Lab Medicine, in 2021, and Comba is one of our newer faculty, having joined the department in 2023. Congratulations to both doctors on their newly funded projects.