2022-2023 Gateway Awardees

Sydney Blackmer, Drake University

Mentor: Dr. Brian Gentry

Research Title: Elucidating the Mechanism of Action of Filociclovir against Human Adenovirus

“Human adenoviruses are pathogens responsible for a variety of disease states including respiratory and gastrointestinal infections (chest colds and “the stomach flu”).  For the majority of the public with functioning immune systems, this virus is annoying, but overall, relatively harmless.  For patients with compromised immune systems (organ transplant patients, patients on cancer chemotherapy, infants and toddlers), adenovirus infections can be problematic and sometimes fatal.  Currently there are no good drugs for the treatment of this disease.  Ganciclovir and cidofovir have been used, but both carry a high burden of adverse effects and have limited utility.  Filociclovir is a novel compound that has demonstrated activity against adenoviruses without any observed adverse effects.  In other words, this drug works and is safe.  Currently in clinical trials for the treatment of another viral disease, filociclovir has demonstrated very few adverse effects at concentrations necessary to treat viral diseases.  However, the mechanism by which this drug combats human adenovirus infections is currently unknown.  It was initially thought that this drug works in the same manner it does against other viral diseases, but recent evidence suggests otherwise.  Therefore, the goal of this project is to examine the mechanism by which filociclovir elicits an effect against human adenovirus.”

Annagabriela Figueroa, University of Colorado

Mentor: Dr. Manisha Patel

Research Title: Identifying redox and metabolic targets in an in vitro model of neuronal excitability

“Epilepsy is a common and debilitating central nervous system condition in which brain activity becomes abnormal and causes individuals to have recurring seizures. Studies have illustrated an energetic shift in cells of the nervous system, neurons, which leads to an increase in the use of an important metabolic sugar, glucose. The observed increase in the utilization of glucose, helps support the abnormal activity of neurons, which subsequently results in the formation of agents that cause oxidative damage and an increase in the expression of factors that promote inflammation in the brain of an individual affected by epilepsy. However, the mechanism that links factors of inflammation, metabolic and oxidative changes to the increase in neuronal activity remains elusive. This project will explore the role of glucose-driven neuronal activity, formation of reactive oxygen species, and expression of immune system factors that facilitate cell-to-cell communication. Ultimately, the study of the intersection of these factors is critical in better understanding the development of this debilitating disorder.”

 

Cierra Fujimoto, University of Hawaii at Hilo

Mentor: Dr. Leng Chee Chang

Research Title: Hawaiian medicinal plants and green-synthesis of silver nanoparticles of Waltheria indica as potential antimicrobial agents against methicillin resistant Staphylococcus aureus

“Bacteria Pathogens exhibiting resistance to antimicrobial agents are common causes of morbidity and mortality and impose a significant economic burden on health care worldwide. In recent years, Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging deadly pathogen of the skin or soft-tissue infections that can lead to life-threatening pneumonia or septic shock, especially for those limited exposures to health care. In 2017, the Centers for Disease Control (CDC) reported 120,000 S. aureus bloodstream infections, and 20,000 cases of deaths were associated with infections occurring in the United States. The occurrence of MRSA bloodstream infections has declined over the years, in contrast, methicillin-susceptible S. aureus (MSSA) infections are increasing in the community by 4% yearly. Antibiotics resistant to MRSA include b-lactams, aminoglycosides, fluoroquinolones, and macrolides. In 2019, there were increases in the rise of Staph infections in the community reported as MRSA. Further, the recent emergence of community-associated-MRSA (CA-MRSA) is of interest due to its effect on healthy individuals within the community. In hospitals, MRSA infection is a problem that clinicians will be confronting ongoing, increasingly frequent basis. Hawai’i has twice the national average of MRSA infections, with native Hawaiians, minorities, and groups subject to health disparities are more prone to staphylococcal infections. MRSA infections are often associated with biofilm formation, contributing to antibiotic resistance. MRSA treatment is challenging due to antibiotic resistance and overused, and relapses following therapy are common resulting in substantial morbidity and mortality. There is an urgent need for novel treatment approaches for MRSA and CA-MRSA infections. Natural products obtained from Hawaiian medicinal plants could represent a new treatment approach. For example, natural product extracts from Hawaiian medicinal plants exhibit antimicrobial activity. This project proposes to examine natural product-derived from Waltheria indica and Osteomeles Schwerin as antibacterial agents to control MRSA. 1) our expertise in natural product chemistry; 2) ease of access to Hawaiian medicinal plants via the local community; 3) the ability to directly test the activity of natural products against MRSA both isolated from the Hawai’i environment and the clinical settings with MRSA infections. It hypothesizes that natural products from Hawaiian medicinal plants may show antimicrobial activity against MRSA isolates.”

Michelle Grose, West Virginia University

Mentor: Dr. Heather Johnson

Research Title: Measuring the impact of a protocol that improves PHQ9 Completion Rates in patients on medication for depression

“Depression is an underrecognized and undertreated disease state in the United States. Inadequate treatment for depression has negative results. Patients may have depressive symptoms that affect their daily life. Uncontrolled depression can also hurt their ability to take care of their other disease states and can make them less motivated to seek help from their doctor.  The community is affected because patients with undertreated depression miss more work and have higher health care costs. The purpose of this project is to increase the number of patients being screened for symptoms of their depression in one family medicine practice.”

 

Christina Kazarov, University of Pittsburgh

Mentor: Dr. Sandra Kane-Gill

Research Title: Differences in reporting characteristics adverse drug events for prescription versus natural products

“The project will be looking at adverse event reporting data from Canada and the United States to assess the different habits in reporting side effects from natural products versus prescription products. The student will use statistical software to clean and analyze reports from these two countries’ databases in order to find key differences in the type and content of reports between natural products and prescription products and differences between reports in 2 countries.”

 

Yezan Salamoun, University of Kansas

Mentor: Dr. Ryan Funk

Research Title: Erythrocyte Metabolomic Profiling of Disease Activity and Methotrexate Response in the Collagen-Induced Arthritis Mouse Model

“In the treatment of juvenile idiopathic arthritis (JIA) early control of disease activity to prevent permanent joint damage and long-term disability continues to be a major goal of drug therapy. However, in current practice, response to drug therapy is characterized by a markedly delayed onset of action with a highly variable and unpredictable response profile, often necessitating multiple iterations of drug therapy modification to identify an effective therapy. Methotrexate (MTX) continues to be the mainstay of therapy, but the onset of action is in the range of weeks to months with approximately one in three patients failing to adequately respond to initial treatment. To date, efforts to identify biomarkers to guide drug dosing and selection have been unsuccessful and drug therapy remains a trial-and-error process. A critical need exists to identify laboratory biomarkers to guide clinicians in the early selection and optimization of drug therapy, but has been hampered by an incomplete understanding of the mechanism of action of MTX in the treatment of autoimmune arthritis. With the central hypothesis that MTX efficacy is mediated through inhibition of one-carbon metabolism, we believe intermediates of these pathways will represent biochemical markers of MTX response that can be utilized in the care of patients. The objective of this proposal will be to apply a metabolomics to define metabolic pathways and their intermediates that are associated with disease activity and therapeutic response to MTX using the collagen-induced arthritis (CIA) mouse model.  To test our central hypothesis and achieve this objective we will identify circulating metabolomic markers of disease activity and MTX response in the CIA mouse model.”

 

Jenna Schabacker, University of Montana

Mentor: Dr. Jenner Minto

Research Title: Implementation of Urinary Tract Infection treatment protocols based on facility-specific resistance data in Skilled Nursing Facilities.

“In Skilled Nursing Facilities, antibiotic prescriptions are frequently written for urinary tract infections (UTIs). Routine antibiotic use within these facilities has the potential to foster increasingly resistant strains of bacteria, especially if inappropriate or unnecessary antibiotics are prescribed. Resistant bacteria can lead to increasingly severe infections that threaten the health of residents and people in the community.   The CDC considers antibiotic resistance to be one of the most dangerous threats to public health. Many Skilled Nursing Facilities operate separately from hospitals and use different prescribers who may favor different antibiotics to treat UTIs. Thus, Skilled Nursing Facilities may develop unique patterns of antibiotic resistance within their facilities. With the guidance of Dr. Jenner Minto, Pharm.D. ,  pharmacy student Jenna Schabacker will investigate possible patterns of antibiotic resistance within three local Skilled Nursing Facilities. She will analyze and compare antibiotic prescription and resistance data before and after pharmacist recommendations were presented. We predict that in response to pharmacist recommendations, prescribers will have reduced the frequency with which they prescribe certain overused antibiotics. In the long-term, we hope to see reduced antibiotic resistance to these drugs in urine cultures.”

 

Melissa Stein, University at Buffalo, The State University of New York

Mentor: Dr. Raymond Cha

Research Title: Characterization of Treatment of Diabetes in COVID-19 Hospitalized Patients

“Diabetes has been established as a risk factor for developing severe outcomes including the development of acute respiratory distress syndrome, ICU admission, mechanical ventilation, and an increased risk for mortality following infection with SARS-CoV-2. There is conflicting information on whether long term glucose control and use of certain classes of glucose lowering medications have an effect on outcome, however higher blood glucose upon hospital admission and within the first week of admission was associated with worse patient outcomes. Looking at biomarkers to guide prediction of outcome and treatment is largely unexplored. Knowledge on how to manage blood sugar in this circumstance is sparse. This study seeks to characterize treatment of diabetes in the hospitalized population. Treatment approaches will be detailed within multiple hospitals and between the US and Jamaica. Models will be applied to determine the pertinence of different severity of disease, different populations, the influence of biomarkers, and different COVID variants.”

 

Angela Su, University of Connecticut

Mentor: Dr. Marie Smith

Research Title: An Interdisciplinary Healthcare Team Perspective on Improving Emergency Department Medication Reconciliation Processes

“This project is focused on improving emergency room medication reconciliations, which is the process of creating a patient’s up-to-date and accurate medication list. The medication reconciliation process is complex and often involves reaching out to sources of information beyond the patient and their caregiver, such as community pharmacies or doctor’ offices. If a patient’s medication list is not updated or has incomplete information, the prescribers and nurses who are treating the patient in the emergency room may make harmful or ineffective treatment decisions.”

 

Wai Chun Olivia Yip, University of California, San Diego

Mentor: Dr. Mark Bounthavong

Research Title: Cost-Utility Analysis of Academic Detailing Outreach on Naloxone Prescribing for Patients at Risk of Opioid-Related Overdose or Death

“This project will assess the value generated by academic detailing interventions to increase naloxone distribution to patients who are at risk for an opioid overdose or death. Currently, there are no studies to evaluate the cost-effectiveness of academic detailing impact on naloxone distribution. Given that naloxone itself is a cost-effective strategy, it is critical for public health officials to know whether academic detailing could enhance naloxone distribution thereby increase the health benefits to society. Our study will measure the increased health benefits of academic detailing in addition to its incremental costs to allow for comparisons with other strategies.”