2024-2025 Gateway Awardees

Kerim Cakir, Temple University

Mentor: Dr. Ellen Walker

Research Title: Chemical and Pharmacological Investigation to Prevent Adverse Consequences of Fentanyl Adulterated with Xylazine

The proposed project is to understand the chemical relationship between fentanyl and xylazine. The project consists of three phases: chemistry, in vitro assays, and if time allows an in vivo proof of principle. For the chemistry portion, Kerim will use metabolites or precursors of fentanyl as fentanyl itself is not particularly reactive. We anticipate attempting at least two compounds to combine with xylazine. For example, he will likely begin with the reactive metabolite of fentanyl, norfentanyl. The compound 1-boc-4-phenylaminopiperidine, will be converted into a reactive state through removal of the protecting boc group yielding N-phenylaminopiperidine. Thereafter, the resulting compounds can be characterized through LC-MS-MS, HPLC, and NMR for identification. One he has isolated the reactive compound, he will mix the isolated compound with xylazine and determine if a novel structure emerges. Once the novel compound is detected and isolated, Kerim can scale up the compound and test it in a MTT assay for cell metabolic activity and in microsomal stability assays. In the MTT assay, concentration-dependent loss of mitochondrial function will be measured as a marker for cytotoxicity. Microsomal stability will be assessed by incubating the isolated new compound at 37°C in the presence of rat liver microsomes and an nicotinamide adenine dinucleotide phosphate regenerating system according to standard procedures Both assays are readily available in standard kits. Finally, if time allows, we can test the compounds in a mouse model of pruritis in which the compound is injected in the scruff of the neck and the number of scratches counted and compared to Compound 48/80. 

 

Weiming Dong, University of California, San Diego

Mentor: Dr. Mark Bounthavong

Research Title: Cost-Utility Analysis of Eptinezumab for Episodic Migraine Headaches Patients in the United States

Eptinezumab is a new but costly medication for the management of migraine headaches. It can be used for episodic or chronic migraine headaches ($6600 to $20,000 per cycle for a total of four cycles in a year).11 Eptinezumab has a special mechanism that is designed to target the pathophysiology of migraine; these drugs are called calcitonin gene-related peptides (CGRP) monoclonal antibodies.9 Several studies have reported that eptinezumab reduces the amount of migraine headaches individual experiences.9,10 However, there are no studies that have evaluated the cost-effectiveness of eptinezumab compared to other similar agents. This study seeks to address that gap by performing a cost-effectiveness analysis of eptinezumab in migraine management. Cost-effectiveness analysis is an evaluation that seeks to quantify an intervention’s value and answers the question, “Is this good value for money?”13–15 In other words, “Is eptinezumab less costly and more efficacious than its comparators?” Our objective is to perform a cost-effectiveness analysis of eptinezumab compared to other migraine management treatments (e.g., erenumab, another CGRP monoclonal antibody; and botulinum toxin) among adults with episodic and chronic migraine headaches from the US healthcare payer and societal perspectives. To do this, we will construct a decision analytic model that will simulate the pathway individuals with migraine will experience. This decision analytic model will be constructed in two parts: decision tree and Markov model. The decision tree will model the short-term efficacy of ponezumab over 6 months, which will then feed the Markov model where the long-term management is modeled over 10 years. We will quantify the total costs and benefits generated by each strategy and then compare them to each other. For example, we will compare eptinezumab to erenumab and measure the incremental costs and benefits, and we will calculate the incremental cost-effectiveness ratio (ICER). If the ICER is less than the payer’s willingness-to-pay, then eptinezumab is considered a cost-effective strategy. If the ICER is greater than the payer’s willingness-to-pay, then eptinezumab is not a cost-effective strategy. The findings from this study will inform healthcare policy makers to make decisions about drug benefits and formulary decisions. 

 

David Ferguson, Howard University

Mentor: Dr. Indiran Pather

Research Title: Stability of synthetic curcumin derivatives used as novel sunscreen agents.

The mentor has developed and patented a natural sunscreen. The mentor now wishes to use a slight chemical modification of the natural substance because it is more stable. The mentor has also identified a second natural product that has useful sunscreen properties and this substance will be combined with the first substance. The role of the student will be to test the stability of the natural substance, curcumin, and its chemical derivatives alone and in combination with the second natural substance, which also has sunscreen properties. These natural substances have a long history of safety and are anticipated to be more acceptable to consumers. Since the final formulation will not be white (most current sunscreen formulations are white), they will not leave a white residue or give the wearer a ghost-like appearance. This is especially important for people with darker skins, although this undesirable effect is observed on light-skinned individuals as well. Due to certain skin conditions, some people need to wear sunscreen daily and the white residue causes them not to do so as regularly as they shouldIn addition, there is concern about atmospheric pollution, especially of the ocean and protection of sea life from sunscreen that washes off swimmer’s bodies. In particular, coral is especially susceptible and coral reefs need to be protectedThe applicant’s role in this larger project is to test the stability of the natural substance and to compare it with slightly modified substances. The applicant will learn to use the equipment, to write a scientific protocol, will have a large role in deciding the parameters of the experimental method and will compile and present the results and conclusions from this study. The applicant has a master’s degree in chemistry and is well qualified to do this work. He is naturally curious and has an interest in learning more and of being involved in research. This project will help him further develop his research skills as well as cement his pathway to a research career. Such a career would likely involve his educational background in the field of Pharmacy (which involves a great deal of patient interaction and instruction) and training in bench science. 

Samira Pal, University of Wisconsin-Madison

Mentor: Dr. Quanyin Hu

Research Title: Develop ferritin degrader to induce pyroptosis for enhanced immunotherapy in triple-negative breast cancer

There are currently many cancer treatments and therapies in use and development. These therapies come in a multitude of forms, such as radiation therapy, chemotherapy, immunotherapy, and more traditional surgeries. The current problem a majority of cancer patients face is that many of the available cancer treatments cause harmful and even deadly side effects, all in hopes of eradicating the cancerous cells and preventing recurrence and metastasis, the spread of cancer. The research to be conducted consists of immunotherapy. The proposed treatment involves a previously designed small molecule compound to target the malignant cells and induce iron stress. Iron stress is caused when the small molecule drug breaks down the protein ferritin, which stores iron ions intracellularly. Our previous study demonstrates iron excess stress induces pyroptosis, a form of regulated cell death accompanied by inflammation factor release. The small molecule compound that serves as the drug is encapsulated in a nanoparticle formulation, which will flow to the specific tumor site and be taken up into the malignant cells after intravenous injection. The drug in the malignant cells will break down ferritin and cause iron ion accumulation, thereby inducing iron stress and initiating the pyroptosis sequence to kill malignant cells selectively. Thus, this treatment holds the potential to suppress tumor growth, relapse, and metastasis safely and efficiently. This ferritin degrader treatment has previously shown promising effects in reducing melanoma, a form of skin cancer. This project will focus on developing a combination treatment regimen between ferritin degrader and immunotherapy against triple-negative breast cancer (TNBC), which is a much more aggressive form of solid tumor cancer. 

 

Soutsada Sikhounchanh, Touro University California

Mentor: Dr. Shane Desselle

Research Title: Using Work Paradigmatic Approaches to Uncover Nuanced Issues Driving Turnover in Academic Pharmacy

This project involves in-depth interviews of formerly well-established pharmacy faculty who left academia to take on a job in industry, consulting, clinical practice, or other. This is unique from past research that examined turnover intentions of existing faculty. It will be the first to examine turnover among those who have already left. Rather than acquring cursory information, we will acquire highly nuanced and rich information by using open-ended questions generated from high-level foundational theories to get more deep into the phenomenon than the surface-level issue usually discussed, such as pay and stress. The issue of actual turnover, particularly when leaving entire industries/roles (eg, leaving academia for a pharmaceutical company) are much more complex than these surface-level issues. Moreover, providing more pay and reducing stress are often not very much in the academic manager’s (eg, dean’s or department chair’s) control. Getting these more nuanced solutions can help these decision-makers provide more effective governance as well as professional organizations proffer more substantive and feasible solutions to this problem. 

 

Tyler Vaglivelo, University of Connecticut

Mentor: Dr. Gregory Sartor

Research Title: Characterizing Toxicity and Treatments for the Fentanyl and Xyalzine Crisis 

Opioid use disorder (OUD) inflicts enormous emotional and economic cost to the individual, families, and society. Despite the clinical importance of limiting the development of drug dependence, currently there are few effective treatments available for patients suffering from OUD. Recently, the opioid crisis has evolved and now certain adulterants (e.g., xylazine) are being added to fentanyl, leading to additional overdoses and other health complications. In this proposal, we will investigate the behavioral and toxicological effects of fentanyl + xylazine use and test new treatments to reduce fentanyl + xylazine dependence. The student will gain didactic and hands-on experience in animal models of OUD and will test the effectiveness of novel therapies for OUD. Results from these experiments may lead to new therapeutic avenues for the treatment of opioid use disorder. 

 

Lyle White, University of Connecticut

Mentor: Dr. Robin Bogner

Research Title: Development of a Stable Aspirin Suspension

Aspirin is used as an effective therapy for prevention of heart attackFor patients who have a lot of difficulty swallowing, a liquid aspirin would allow them to maintain their heat attack prevention even though they can no longer swallow tabletsHowever, aspirin degrades quickly in water, so there is no aspirin syrup availableRecently, a syrup containing no water has become available for drugs that are not stable in waterThe proposed project will evaluate how long a non-water-containing aspirin syrup can be stored after being prepared for a patient in the pharmacy.