Graduate Students’ Discoveries Shine During Best Research Awards
Each year, the University of Miami Miller School of Medicine’s Medical Faculty Association honors Ph.D. students with Best Research Awards. This year, students researching cancer, HIV and cerebral amyloid angiopathy garnered the awards.
“The annual Best Research Awards highlight the powerful and innovative research our Ph.D. students conduct,” said Ana Fiallos, Ph.D., director of career services for the Office of Graduate Studies. “While we can only have four winners, the recognition is a testament to the hard work and creativity our students and faculty show every day.”
Fighting Brain Tumors
Fourth-place awardee Jiaqi Liu studies gliomas, a type of brain tumor, in the Zhai Lab. Her work has shown that the protein NMNAT, an enzyme crucial in the final step of nicotinamide adenine dinucleotide (NAD+) synthesis, plays a significant role in the growth and progression of gliomas.
Experiments with fruit flies which were validated in human glioma cells showed that increased NMNAT activity allowed glial cells with harmful mutations to survive and multiply. This work could offer two advantages. NMNAT could be used as a biomarker to identify patients at high risk for cancer progression. It could also be used as a therapeutic target.
“It’s possible to develop an inhibitor that targets this protein to suppress brain tumors before they become deadly,” said Liu. “We could potentially use such an inhibitor in the brain after surgery to help eliminate residual cancer.”
HIV-Associated Neurocognitive Disorders
Third place went to Oandy Naranjo in the Toborek Lab. Naranjo investigates the consequences of HIV-1 infection and focuses on HIV-associated neurocognitive disorders. He is studying cells in the blood-brain barrier (BBB), called pericytes, that harbors HIV and may contribute to cognitive loss.
Anti-retroviral drugs do not penetrate the BBB as well as other parts of the body. Infected cells produce viral particles, which generate inflammation. Though HIV patients can live almost normal life spans, this long-term inflammation can have a powerful impact on the brain. Naranjo wants to understand how pericytes behave differently when infected and hopes these insights will lead to treatments.
“We created a big database of latent, active and uninfected cells and how they’re different from each other,” said Naranjo. “This could give us insights into how specific genes could be used to treat HIV-associated neurocognitive disorders.”
Cerebral Amyloid Angiopathy
Olivia Osborne, who placed second, also works in the Toborek Lab, studying the molecular mechanisms that affect post-stroke neurogenesis (brain tissue growth) in people with cerebral amyloid angiopathy (CAA). Osborne was awarded an F31 fellowship from the National Institutes of Health to advance her dissertation on “Ischemic Stroke in Cerebral Amyloid Angiopathy: Microvascular Injury and Recovery.”
In CAA, amyloid beta (Aβ) proteins, which have been linked to Alzheimer’s disease, weaken small blood vessels, sometimes causing bleeding. Osborne wants to understand how these mechanisms affect people who have suffered a stroke.
“My central hypothesis is that Aβ accumulation in cerebral vasculature exacerbates ischemic stroke outcomes and delays post-stroke recovery,” said Osborne. “My work focuses on the blood vessels after damage occurs. There’s some sort of dysregulation that might disrupt signaling to other cells in the area and delay recovery. If we can find that signaling pathway, we could potentially target it therapeutically.”
Chronic Lymphocytic Leukemia
Skye Montoya from the Taylor Lab won top Best Research Award honors. She studies mutations in chronic lymphocytic leukemia (CLL), focusing on Bruton’s tyrosine kinase (BTK), an enzyme that drives cancer growth.
Montoya wants to identify small molecules that could regulate BTK and slow or even stop CLL. Cancers have a bad habit of learning how to resist targeted therapies, and Montoya and colleagues are trying to figure out ways to overcome that resistance. Montoya was first author on a recent paper, published in the journal “Science,” that identified previously unknown BTK mutations and showed a potential therapy (NX-2127) could be effective.
“Each BTK mutant we study can cause resistance to multiple BTK inhibitors, which can really limit therapeutic options for patients harboring these mutations,” said Montoya. “We were all excited to see positive responses in both cell lines and patients, regardless of BTK mutational status.”