Pilot Project Recipients

Internal mentor: Dr. Song Gao  Title:  Professor of Pharmaceutical Sciences, Texas Southern University, College of Pharmacy and Health Sciences

External Mentor: Dr. Ming Hu    Title: Professor of Pharmaceutics, College of Pharmacy, University of Houston

Project title: Alleviating Mycophenolic acid (MPA)-induced Toxicity in the GI tract using Dietary Supplement

Project summary: the project hypothesizes that wogonin and chrysin attenuated MPA-induced diarrhea could be related to UGT1A1 and/or anti-inflammation based on the preliminary study. To test this hypothesis, we design the experiment to develop a mouse model for MPA-induced diarrhea to better mimic the diarrhea symptom in humans and develop more effective wogonin/chrysin dosing regimens for diarrhea attenuation and determine the UGT1A1 expression and the TNF-a level in the gut to reveal the mechanism.

TSU Mentor: Omonike A. Olaleye, PhD, Professor of Pharmacology  

External Mentor: May E. Elebeoba, PhD (University of Wisconsin)  

Project Title: A Systems Biological Approach for Discovery of Potent Inhibitors Against SARS-CoV-2 Infection 

Project Summary:   

The objective of this study is to discover and develop promising and potent compounds that can inhibit the transmission and replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Previously, our group reported on the repurposing of Clioquinol (CLQ) and its two derivatives as potential therapeutics against SARS-CoV-2. CLQ and its analogues inhibited SARS-CoV-2 infection induced cytopathic effect (CPE) at low micromolar concentrations. Due to the emergence of different variants of SARS-CoV-2, there is an urgent need to discover and develop novel therapeutics (small molecules) that can inhibit viral-host interaction and viral target proteins. These potential novel agents could be potent and selective blockers of molecular interactions between SARS-CoV-2 spike proteins and the human ACE2 receptor; and inhibit viral replication, transcription, and maturation. The fusion and translocation of SARS-CoV-2 into the host cell, specifically results from the binding of the virus spike S1 protein to the human angiotensin converting enzyme 2 (hACE-2) enzymatic domain on host cells surface. This binding is crucial to transmission of SARS-CoV-2 from one host to another. Furthermore, like majority of RNA viruses, RNA-dependent RNA-polymerase (RdRp) enzyme is essential for viral replication and transcription of the viral genome, and the protease enzyme (Mpro) plays a vital role in viral protein maturation.  Therefore, our overall hypothesis is that therapeutic inhibition of the molecular interactions between SARS-CoV-2 spike proteins and the hACE2 receptor, and vital target proteins (RdRp and Mpro) by small molecules can stop and/or reduce the replication and transcription of viral genomes, and assembly of mature viral particles, Ultimately, this approach could provide new treatment option for COVID-19. 

Award amount: $50,000 (direct cost)  

Dominique Guinn, PhD, Assistant Professor in College of Education, Department of Health, Kinesiology and Sports Studies

TSU Mentor: Shirlette Milton, PhD, Professor Pharmaceutical Sciences

External Mentor: Terry D. Stratton, PhD, Professor in Behavioral Sciences (University of Kentucky College of Medicine)

Project Title: “The Roots Study: Understanding Young Adult Barriers to Biomedical Prevention”

Project Summary:
The Centers for Disease Control and Prevention (CDC), report that 60% of American adults have received at least one dose of a vaccine for the coronavirus. Additionally, CDC data indicates that younger adults have been the least likely to get vaccinated. More than 80 million cases of infection and 2 million deaths have been reported worldwide. In the United States, a familiar more disturbing trend is that people of color, particularly African Americans, are experiencing more serious illness and death due to COVID-19 than their White counterparts. Many African Americans distrust the American healthcare system. These deeply held beliefs and stereotypes concerning the healthcare system reduce confidence and inhibit adoption of biomedical prevention strategies. There is a need for research interventions to address uptake of biomedical prevention, specifically vaccine hesitancy, and uptake among racial and ethnic minorities. The primary aim of this study is to explore the various cultural and psychosocial factors underlying younger African Americans’’ reluctance to engage in established biomedical preventive measures-namely, COVID19 vaccine hesitancy. The study will utilize focus groups and quantitative survey results to elicit information on the health locus of control, demographic covariates, and beliefs of college students, 18 and older. The goal is to develop a targeted, evidence-based intervention to encourage individual participation in prevention-oriented public health initiatives by strategically allaying barriers and bolstering benefits. This proposal is significant because it explores the various cultural and psychosocial factors underlying younger African Americans’ reluctance to engage in established biomedical preventive measures – namely, COVID-19 vaccine hesitancy and uptake.

Project Award: 49,800.00 Direct Cost

Anuoluwapo (Anu) Egbejimi - Omogbara, Ph.D.
Center for Biomedical and Minority Health Research (CBMHR) PD Research Scientist
Adjunct Faculty, Biomedical Science

TSU Mentor: Omonike Olaleye, Ph.D. MPH., Interim Associate Provost and Associate Vice President for Research, Professor of Pharmacology

External Mentor: Rosa A. Maldonado, D.Sc., Professor, Biological Sciences (University of Texas- El Paso)

Project Title: Discovery of Pharmacologic Mechanisms Underlying the Action of Clioquinol and Analogues as Novel Antiviral Agents against SARS-CoV-2 Infection

Project Summary:
The objective of this study is to understand the underlying pharmacologic mechanisms of Clioquinol (CLQ) and two of its derivatives in SARS-CoV-2 infection. Previously, our group reported that CLQ and its two derivatives, CLBQ14 and CLCQ inhibited SARS-CoV-2 infection induced cytopathic effect at the low micromolar range. CLQ and its derivatives, are established Zinc chelators and ionophores which modulate the molecular and physiologic machinery required for Zinc homeostasis. Zinc ions have been shown to be essential for proper activity of various proteins and the antiviral properties of Zinc have been described in various infections. The intracellular shuttling and sequestration of Zinc have been linked to its antiviral activity. Replication of SARS-CoV-2 requires the Zinc dependent viral RNA-dependent RNA polymerase (RdRp) enzyme. To date, the physiologic relevance of Zinc homeostasis in SARS-CoV-2 infection and COVID-19 remains to be elucidated. Moreover, it is unknown whether CLQ antiviral properties is linked to modulation of Zinc transport in SARS-CoV-2 infection. The CLQ pharmacophore may offer key insight into the relevance of Zinc homeostasis in SARS-CoV-2 infection and COVID-19. Hence, the objective of this study is to understand the underlying pharmacologic mechanisms of CLQ and two of its derivatives (CLBQ14 and CLCQ) in SARS-CoV-2 infection. Our overall hypothesis is that the CLQ pharmacophore are effective lead compounds series for targeting essential pathways for SARS-CoV-2 infection and survival. In this study we will assess the effect CLQ and derivatives on SARS-CoV-2 RdRp in the presence of Zinc. We will also interrogate the molecular mechanism of CLQ disruption of ACE2, a key zinc dependent metalloenzyme essential for viral entry, interaction with SARS-CoV-2 Spike protein receptor binding domain. Finally, we will examine the CLQ pharmacophore on host signaling pathways: NF-kB signaling and lysosomal pathway.

Award amount: $50,000 (direct cost)

Mahua Sarkar, PhD, Formulation Research Scientist

TSU Mentor: Huan Xie, PhD, Professor in Pharmaceutics

External Mentor: Diana Chow, PhD (University of Houston) 

Project Title: Development and Evaluation of Giα2 Inhibitor Formulations for Treatment of CRPC

Project Summary: 

Prostate cancer (PCa) is the second leading cause of cancer death in the United States among men and it occurs more in men older than 65 years and of African descent. The number of new cases diagnosed in African American men is nearly 80% higher than the number of new cases diagnosed in white men. For advanced PCa, androgen deprivation therapy (ADT) is the primary standard of care. Despite initial positive responses to drugs like Enzulatamide and Bicalutamide, treatment failure occurs in 15-25% of patients and develop metastatic castration-resistant prostate cancer (mCRPC). Currently, very limited therapeutic options are available for CRPC, however, the success of treatment is modest. Small molecule inhibitors of Giα2 were identified by computational docking analysis and two different classes of inhibitors have been synthesized at our collaborator, Dr. Oyelere’s lab at Georgia Tech University. Class I and Class II molecules are Phenolic ketimine (compounds 7,8), Phenoxyethyl-1H-indole (compounds 13,14), respectively. In vitro cell migration assays in prostate cancer cell lines demonstrated significant, dose-dependent inhibition of migration. The promising anti-tumor efficacy in PCa cells encouraged us to further characterize physicochemical and pharmacokinetic properties of these compounds (7,8,13 and 14), investigate their pharmacokinetics and bio specifically deliver the compounds to the tumor site, distribution behavior in rats, and develop novel delivery formulation. It is necessary to formulate an optimum drug delivery system that will ensure higher solubility, bioavailability, specifically deliver the compounds to the tumor site, and steadily release the drug at a controlled rate. Our specific aims are to characterize physicochemical properties of Giα2 inhibitors (solubility, logP, pKa, stability) and develop solution formulations to be used in pharmacokinetic studies; to characterize basic in vivo pharmacokinetic and biodistribution pattern of the compounds; to develop and characterize an optimum nano-formulation (solid lipid nanoparticle) of Giα2 inhibitors. Desired characteristics of optimum nanoformulation are uniform shape, small particle size, low polydispersity index (PDI), and high encapsulation efficiency. This project will seek support and evaluation from the CBMHR Administrative Core and utilize the Research Infrastructure Core to perform experiments. Research findings from this project will be shared with various TSU communities via Community Engagement Core (CEC). The successful execution of this research will result in potential advanced treatment for CRPC patients.

Award amount: $49,650 (direct cost) 

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

Project Summary:

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

Project Summary:

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)