Pilot Project Recipients 2020-2021
Pilot Project Recipient #1:
Erica Cassimere, PhD, Assistant Professor in Biology
TSU Mentor: Mario Hollomon, PhD, Associate Professor in Biology
External Mentor: Michael Lewis, PhD (Baylor College of Medicine)
Project Title: Characterization of p27kip as an enhancer of stem-like properties in breast cancer stem cells
Breast cancer remains the second leading cause of cancer deaths among women in the United States. Strikingly, recent evidence has revealed significant health disparities amongst cancer patients, especially African-American (Black) women. The mortality rate of Black women is higher than Caucasian (White) women, and later diagnosis of advanced staged breast cancer among Black women leads to poor patient survival. Thus, understanding the molecular mechanisms of breast cancer is of great importance in order to find effective treatments to combat breast cancer. The long-term goal of this project is to understand how the cell cycle kinase inhibitor, p27KIP1 (termed p27), enhances a unique population of cells found in breast cancer, known as cancer stem cells (CSCs). Coordinated signaling of normal stem cells helps to maintain tissue homeostasis, but deregulation of these networks within tumors increases the CSC population and can lead to radio- and chemoresistance. p27 exerts canonical (cell cycle-dependent) and non-canonical (cell cycle-independent) functions based on subcellular localization, and its regulation is tightly controlled by protein stability. Moreover, cytoplasmic p27 has been identified to play a role in migration and metastasis in a variety of cancers, including breast cancer. Thus, identifying key factors which help to maintain stemness in CSCs is of great importance. Aim 1 will investigate whether subcellular localization influences p27 levels in breast CSCs populations derived from different breast cancer subtypes, including those from Caucasian and African-American women. Using in vitro mammosphere formation assays derived from several breast cancer cell lines, protein expression for p27 will be assessed by Western blot analysis. The subcellular compartment whereby p27 resides within the breast CSCs will be examined using immunofluorescence. Aim 2 will investigate the molecular factors which regulate p27 protein stability in breast cancer stem cells. Using site-directed mutagenesis, breast CSCs stably expressing p27 at residues known to regulate p27 protein stability will be generated, and protein stability, along with mammosphere formation, will be measured to identify potential upstream regulators of p27. Chemical inhibition and gene silencing of these factors will shed light on the molecular basis by which p27 enhances stem cell properties in breast cancer stem cells.
Award amount: $50,000 (direct cost)
Pilot Project Recipient #2:
Bai Li, PhD, Assistant Professor in Health Sciences
TSU Mentor: Zivar Yousefipour, PhD
External mentor: Dr. Robert Britton (Baylor College of Medicine), Dr. Anthony Maresso (Baylor College of Medicine)
Title: Exploring the link between COVID-19 and gut microbiome – a study of the TSU community
This study intends to explore the link between Coronavirus disease 2019 (COVID-19) and gut microbiome in our Texas Southern University (TSU) community, which is primarily composed of underrepresented minority groups. Typically, this would be done by measuring the prevalence dynamics of SARS-CoV-2, the virus that causes COVID-19, and the composition dynamics of the microbiome in fecal samples collected longitudinally from human subjects. However, it would be challenging to track down individual COVID-19 positive patients and ask for a series of samples amid the pandemic. Moreover, individuals' results are often hard to generalize for a population unless a large sample size is used. Instead, we propose an alternative approach that samples raw sewage in and around TSU regularly to look for SARS-CoV-2 and microbiome signatures. Sampling raw sewage is an approved approach to identify SARS-CoV-2 spikes before significant community spread of COVID-19. Expanding the test to the microbiome would offer more insight into the overall health of the community. Sewage samples from manholes will be collected biweekly throughout the year 2021. This period will likely span over three critical and unique stages of the COVID-19 pandemic, the back and forth of increased (infectious stage) and reduced (mitigation stage) community spread during our ongoing battle with the virus, and the elimination stage when the majority of the population is vaccinated. The samples will be processed into two equal portions to determine the dynamics of SARS-CoV-2 and microbiome, respectively. To maximize the community impact of our project, correlations between the SARS-CoV-2 and microbiome data will be explored in three contexts. One, the SARS-CoV-2 data will be used to help TSU with predicting community spread during the infectious and mitigation stages because the city's data has established wastewater testing as an effective COVID-19 early warning system. Two, the microbiome data will be leveraged to shed light on environmental injustice across Houston. This is because the City of Houston has already contracted with Baylor College of Medicine (BCM) to follow the dynamics of SARS-CoV-2 but not the microbiome across the city-wide wastewater systems. We will work with our collaborators at BCM to determine the microbiome dynamics in their collected samples and compare them to ours. This would enable a comparison of various populations of different ethnic groups and/or contrasting socioeconomic status, as the city samples are collected from all parts of the city. Finally, analyzing samples post-vaccination would reveal if and how fast the SARS-CoV-2 may disappear and the impact of vaccination on the microbiome.
Awarded amount: $49,999 (direct cost)
Pilot Project Recipient #3:
Hongmei Wang, PharmD, PhD Assistant Professor in Pharmacy Practice
TSU Mentor: Dong Liang, PhD
External mentor: Thomas Giordano, MD, MPH (Baylor College of Medicine)
Title: Approaches to Objectively Measure Antiretroviral Medication Adherence and Impact of Clinical Pharmacist on Medication Adherence
Project Summary: Although HIV treatment and prevention have been revolutionized due to the highly active antiretroviral treatment (HAART), HAART's efficacy depends highly on patient adherence to drug therapy. HIV-positive individuals who demonstrated near-perfect adherent with HAART are more likely to achieve undetectable viral load, improve immune function, and reduce the likelihood of transmission to uninfected sexual partners. However, HAART adherence remains a challenge in clinical practice. Non-adherence to HIV treatment has a negative impact on patients' health and the public by increasing the development and transmission of the virus's drug-resistant strains. Numerous barriers associated with poor adherence include but are not limited to stigma, substance abuse, treatment complexity, medication side effects, low level of health literacy, and concurrent psychological issues such as depression. Therefore, longitudinal interventions are needed for a multidisciplinary team to work collaboratively and develop an effective approach to build trust and support patients' complex needs, particularly their medication adherence related needs. As multidisciplinary team members, pharmacists optimize patient outcomes through clinical pharmacy interventions, including manage and adherence to medication regimens, ensure proper medication use, and assist in patients' transition across the continuum of care. Giving the complex HIV treatment regimen and critical barriers, pharmacists may be particularly valuable in the medication therapy management of HIV positive individuals. In addition, medication adherence measurement tools may include self-reports, event monitoring systems, and therapeutic drug monitoring (TDM). Therapeutic drug monitoring is useful to objectively measure HAART adherence. The purpose of this project is to conduct HAART medication therapy management (MTM) longitudinal services to improve medication adherence and development a new objective medication adherence monitoring tool. The Aims are to 1). Evaluate the impact of medication therapy management on medication adherence among people living with HIV. 2). Develop and validate a therapeutic plasma drug monitoring method using the ultra-high-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS). Successful completion of this project will result in generating critical foundational data on HAART medication adherence and a useful TDM tool that has the potential to shift significantly clinical practice in HIV treatment in vulnerable populations.
Award Amount: $50,000 (direct cost)