UNT professors from the College of Engineering Department of Biomedical Engineering have earned nearly $3 million in recent grants from the U.S. National Institutes of Health.

Their work will bring new understanding to some of the world’s biggest health challenges — from cancer to dementia and epilepsy — and could have future implications for drug discovery and the prevention and treatment of diseases affecting millions of people across the globe.

Awardee: Brian Meckes, assistant professor in the UNT Department of Biomedical Engineering

Award Total: $1.8 million

About the Research: Meckes is studying how disease-related physical changes in tissue that accompany diseases like lung cancer or epilepsy impact nanotherapeutic delivery since they have the potential to cause therapies to fail. The physical properties of the tissue environment play an important role in numerous diseases/disorders, spanning cancer, pulmonary fibrosis and hypertension. Changes in these physical properties alter how nanotherapeutics interact with cells while creating new opportunities for targeting diseased tissue. Meckes will contribute to the understanding of how extracellular stiffness and dynamic forces alter nanoparticle efficacy. He’ll leverage these tissue properties to design novel nanoparticles that have improved targeting and trafficking in dysfunctional tissue to deliver an improved treatment outcome.

Impact Goal: “We are interested in creating real world nanotherapeutics that consider the influence of the extracellular matrix in their design. Conventional therapeutic screening does not allow for this in the early stages, and we want to change that,” Meckes says. “The long-term vision is for us to translate these discoveries into new classes of therapeutic carriers that are more potent while limiting accumulation in non-diseased organs or cells.”

Awardee:

• Neda Habibi, assistant professor in the UNT Department of Biomedical Engineering

Award Total: $540,000

About the Research: Habibi, along with students in her multidisciplinary nanomedicine laboratory, is exploring new therapeutic targets that could be used to develop treatments for triple-negative breast cancer, or TNBC. Accounting for 10-15% of all breast cancer cases, TNBC is a drug-resistant type of breast cancer that does not express the estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2) protein that are seen in other types of cancers.

Rather than focusing on these cell receptors like other cancer treatments do, Habibi and her team are investigating a new approach using self-assembling peptides — foundational ingredients of nanostructures that aid in more efficient and targeted drug delivery within the body. Specifically, they’re designing peptide substrates of the tyrosine phosphatase enzyme in TNBC that could selectively inhibit TNBC cell growth.

Impact Goal: “TNBC tumors are generally larger, are of higher grade and are more aggressive than other breast cancer types,” Habibi says. “This type of breast cancer also is unlikely to respond to hormonal therapy medicines and other medicines that target the HER2 protein that are currently being used. It is critical that we develop more effective therapies for TNBC and other drug-resistant breast cancers.”

“New treatments will require radically different approaches that rely on enzymatic reactions specific to TNBC cells rather than the cell receptors. Our research is looking at ways to make ‘smarter’ nanoparticles that can carry the anti-cancer drug more directly to the tumor cells for release, which could increase the drug’s effectiveness and reduce the impact on normal cells in the body.”

Awardee(s):

• Lin Li, assistant professor in the UNT Department of Biomedical Engineering
• Jerome Engel (principal investigator), Distinguished Professor in the Department of Neurology at University of California Los Angeles
• Keith Vossel, professor and director of the Mary S. Easton Center for Alzheimer's Research and Care at UCLA
• Richard Staba, professor in the Department of Neurology at UCLA
• Paul Thompson, professor at the Institute of Neuroimaging at University of Southern California

Award Total: $ 312,758 to UNT, which is part of a total grant of $6.2 million to all institutions involved

About the Research: Patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS), the most common drug-resistant form of epilepsy, have an increased risk of developing dementia, and patients with Alzheimer’s Disease (AD) are more prone to developing an epileptic condition than previously suspected, according to Li, who specializes in the development of new neuromodulation tools that modify or prevent neurological disease.

Li and his collaborators in California are investigating the relationship between seizures and cognitive decline in MTLE and AD. They plan to conduct studies with patients with adult onset MTLE as well as patients with AD and mild cognitive impairment (MCI). They’ll also examine a rat model of AD with epileptic seizures. Based on the results of these studies, they will continue exploring the fundamental mechanisms of epileptogenicity in AD, and the role of seizures in cognitive decline in AD and MTLE, to identify novel targets for treatment and prevention. Additionally, the team will pursue noninvasive approaches to identify biomarkers that predict cognitive decline in patients with MTLE and progression to AD dementia in patients with MCI to design cost-effective clinical trials of potential treatment and preventive interventions.

Impact Goal: “Dementia and epilepsy are among the top four primary diseases of the brain, according to the World Health Organization’s Global Burden of Disease ranking, based on disability adjusted life years,” Li says. “Our translational research could lead to new approaches for the prevention and treatment of seizures and dementia in these conditions, which could mean increased quality of life for millions of people affected by these conditions worldwide.”

Awardee(s):

• Moo-Yeal Lee, associate professor in the UNT Department of Biomedical Engineering
• Pranav Joshi (principal investigator), senior scientist at Bioprinting Laboratories Inc., a startup company founded in 2017 by Lee

Award Total: $285,000

About the Research: Lee and his research collaborator Joshi are working to generate normal and genetically engineered human liver mini-tissues or human liver organoids through microarray 3D bioprinting technology for use in drug discovery. They’ll use the organoids to investigate drug-induced liver injury (DILI) across various ethnic groups. Lee says unexpected adverse drug responses (ADRs), including DILI, are likely to arise from differences in patient-specific drug metabolism, including individual variability in levels and activities of drug metabolizing enzymes (DMEs) in hepatocytes, which are the cells in the liver that perform a wide range of biotransformation and associated drug toxicity. In their study, genetically engineered liver organoids will be used to overexpress and downregulate multiple DME genes to simulate different levels of drug metabolism to represent individual patients from different ethnic groups.

Impact Goal: “Our research is working to advance in vitro cell-based testing, which is vital in screening potential drugs and treatments for their efficacy,” Lee says. “Current in vitro liver models are used mainly for assessing general hepatotoxicity of drug candidates, but we’re developing our normal and engineered liver organoids to more easily accommodate genetic diversity in their testing. This approach could potentially simulate DILI in poor and ultrafast drug metabolizers in different ethnic groups.”