2021-2022 Gateway Awardees

Rachel Allen, The University of Tennessee

Mentor: Dr. Justin Gatwood

Research Title: Addressing Glaucoma Medication Nonadherence through Tailored, Mobile Messaging

“In the United States, nearly 3 million people have glaucoma and the annual costs to treat this condition and its associated complications are nearly $6 billion. Although multiple treatment options exist, nonadherence to glaucoma medications is suboptimal; some estimates suggest that adherence in glaucoma may be as low as 20%, depending on the metric used. However, the extent of glaucoma-related nonadherence has likely been underreported due to inefficient means of collecting patients’ medication-taking information. Currently, popular forms of adherence measurements include patient self-report and pharmacy claims data, both of which are significantly biased and may report conflicting information. Previous attempts to use electronic devices, such as the Medication Event Monitoring System (MEMS) or Travatan Dosing Aid, have been wrought with challenges and provide only delayed information. To address unmet needs in measuring and combating nonadherence to eye medications, a new technology, Kali Care, was developed that provides real-time, wirelessly relayed data with on-demand metrics focused on patients’ topical medication use. Importantly, this new device does so while adding minimal bulk to a standard eye drop bottle making it easier for patients to transport and use medication. The proposed work will provide an initial set of tailorable messages using established, tested techniques to create and then test intervention content that, if successful, can be expanded to inform a larger program that can be replicated by health systems across the country.”

Meghna Bhatt, University of Maryland, School of Pharmacy

Mentor: Dr. Fadia Shaya

Research Title: Predictors of COVID-19 outcomes as a function of resource access

“The aim of this project is to see how pharmacies are distributed across the country and to analyze how accessible they are to the public. This is important to look at, especially in current times because community pharmacies are often the first line of healthcare access with the ongoing pandemic. While looking at the number of pharmacies in a given area, the project will also involve analyzing some of the characteristics of the area including household income, race, ethnicity, age, gender, and education. Analyzing the number of pharmacies in the area along with the characteristics of the area will help determine trends in how resources are distributed and determine if there are any gaps in care that need to be addressed at a pharmacy level.”

 

Brian Kam, Binghamton University, The State University of New York

Mentor: Dr. William Eggleston

Research Title: Impact of a Naloxone Training Device on Secondary Community Naloxone Training

“Opioid overdose is a significant source of morbidity and mortality in the United States. Expanded access to naloxone has been identified as a key strategy for reducing overdose death and complications. However, despite increased access, many training programs continue to focus on patients at highest risk for opioid overdose. Although this increases access among high risk patients, typically these patients will rely on their secondary contacts and support networks to administer the naloxone to them in the event of an opioid overdose. The results of our research will provide community training programs and pharmacy with critical, and scalable knowledge to improve resources for their patients and reduce opioid overdose related morbidity and mortality. The results of this research would also provide us with crucial information to assess the need for next steps to evaluate the impact of naloxone training on opioid overdose morbidity and mortality in our community.”

David McChesney, The University of New Mexico

Mentor: Mr. Pavan Muttil

Research Title: Microencapsulation of Amorphous Solid Dispersions of Clofazimine using Spray Drying

“Tuberculosis (TB) is the world’s leading infectious disease, and the rates of drug-resistant cases are rising. This disease is easily spread between individuals and the treatment requires lengthy multidrug therapies spanning from months, to years. Also, there are other challenges to overcome including the availability of treatments in remote regions, trained people to administer treatments (giving injection shots), and treatment compliance of TB patients with these long-lasting therapies. These problems are especially prevalent in low and middle-income countries and have created huge economic burdens within these already struggling regions. Therefore, the goal of this study is to create a new formulation of an existing drug that will provide a safe and effective treatment option against TB and will also be needle-free (no shots required).

An analogy to help understand our goal in the formulation is to imagine the compound as a chocolate chip cookie that is currently made with an old recipe, and we will change the ingredients and how it is cooked to bake a cookie that tastes better and doesn’t spoil.”

 

Danial Mehranfard, Nova Southeastern University

Mentor: Dr. Robert Speth

Research Title: Anti-proliferative and Anti-inflammatory effects of the Renin-Angiotensin System Modulators as Novel Therapeutic Agents for Rheumatoid Arthritis Treatment

“Abnormal synoviocytes are the mediators of rheumatoid arthritis (RA), a crippling disease that causes pain and joint damage leading to incapacitation. This study will investigate possible pathophysiological influences on cultured normal human fibroblast-like synoviocytes (HFLS), which are in the healthy lining of a joint structure, compared to abnormal HFLS – Rheumatoid Arthritis (HFLS-RA), which are highly expressed in affected joint structures. HFLS-RA cells eventually cause joint inflammation leading to destruction of the joint cartilage.

The study will assess the involvement of the renin-angiotensin system (RAS) in both normal and abnormal human fibroblast-like synoviocytes physiology. Our hypothesis is that the RAS in normal (HFLS) and abnormal (HFLS-RA) synoviocytes differs, and that this may contribute to RA pathology. To test our hypothesis, we will treat the cells with an Angiotensin II receptor type 1 antagonist (losartan), an angiotensin II receptor type 2 agonist (C21), and an Ang-(1-7) analog (AVE0991) to try to normalize the abnormal synoviocytes and decrease the production of proinflammatory cytokines which promote joint inflammation in HFLS-RA cells. We anticipate that these agents will block the pathophysiological actions of the RAS in HFLS-RA thereby restoring their normal HFLS function.”

 

Madison Ricco, The University of Colorado

Mentor: Dr. Tom Anchordoquy

Research Title: Oral Chemotherapy – An Exosome Approach

“All cells in the body are constantly taking in material and shedding material. Until about a decade ago, it was thought that the tiny vesicles that cells released (exosomes) were simply a mechanism to rid the cell of cellular “garbage”. It has recently become apparent that cells use exosomes to transfer material from one cell to another as a form of communication and coordination. It is now recognized that all cells (animal, plant, bacteria, fungi) produce exosomes, and it is hypothesized that exosomes can be used to pass information among very different types of organisms (e.g., bacteria to human). In fact, a clinical study in 2014 demonstrated that molecules in cow milk are passed into the blood of humans, and that those molecules alter the function of human genes! The extent to which life on this planet communicates via exosomes is slowly becoming apparent, and the project attempts to take advantage of this transfer mechanism to deliver therapeutic molecules. Madison’s project involves hijacking exosomes from cow milk to pass chemotherapeutics through the gastrointestinal tract, thereby enabling cancer patients to consume their medicine in the convenience of their own home instead of being required to travel to a hospital for daily intravenous infusions. In addition to easing the trauma of undergoing chemotherapy, this project has the potential to save the healthcare system tens of billions of dollars each year and improve outcomes for patients by allowing them to avoid travel and contact with other sick people. After loading drugs into freshly-isolated exosomes, these will be administered orally to mice to determine the efficiency with which drugs are absorbed into the blood for the treatment of cancer. This approach has the potential for rapid clinical adoption due to the use of a ubiquitously-consumed material (milk) combined with drugs that are already approved for cancer treatment. In addition to chemotherapeutics, this approach could enable many injectable drugs to be taken orally, and we are currently in discussions with several pharmaceutical companies about this technology. This situation allows Madison to master laboratory research skills, while also becoming familiar with issues associated with intellectual property and commercialization.”

 

Jacob Robinson, University of North Carolina at Chapel Hill

Mentor: Dr. Daniel Crona

Research Title: Epithelial mesenchymal transition mechanisms in metastatic prostate cancer: the role of MPP8

“Prostate cancer (PC) is a common, deadly disease with treatment options that vary based on the patient’s disease severity. Men diagnosed with metastatic PC (mPC) have significantly reduced survival compared to those diagnosed with localized disease. Moreover, 20% of all PC patients originally diagnosed with localized disease will relapse and progress to mPC. Androgen deprivation therapy (ADT) is standard-of-care in mPC, but ADT resistance typically occurs within 18-24 months, resulting in progression to castration-resistant mPC (mCRPC). Despite treatment advances for mCRPC patients such as with enzalutamide, >20% will develop treatment resistance and potentially progress further, substantially decreasing their overall survival. Therefore, despite treatment advances, mCRPC remains incurable and there is an urgent and unmet public health need to establish long term effective treatment options for these patients.

The data obtained from this research have the distinct potential to be highly impactful towards the development of a novel therapeutic that could extend the lives of mCRPC patients. We ardently believe that, through our approach to combat epigenetic dysregulation and the effects of EMT, we will ultimately reverse treatment resistance in mCRPC to limit its lethality. This research could be truly groundbreaking and result in a treatment that positively impacts the health and well-being of patients.”

 

Raul Salazar, The University of New Mexico

Mentor: Dr. Matthew Campen

Research Title: Evaluation of WS1442 on Systemic Inflammation and Blood Brain Barrier

“Supplements, in general, are extensively used among patients with the purpose of increasing their quality of life. Many patients, such as hypertensive patients, often chose over-the-counter therapy (supplements) in addition or as a substitute to pharmacologic therapy. Many supplements do not undergo rigorous FDA testing for efficacy, especially those marketed as antioxidants or anti- inflammatories, as such outcomes may not be as readily testable as therapeutics for more concrete symptoms or diseases. Nonetheless, it is important to assess the therapeutic impact of supplements in various diseases or comorbidities to better understand their benefits and to demonstrate whether or not patients should be taking supplements in combination or alone for these disease states. Regardless of the outcome of this study, this information will open explorations into the pathways in which WS 1442 is used in drug therapy.”

Maureen Shin, University of California, San Francisco

Mentor: Dr. Nancy Sambol

Research Title: Comparison of Precision Dosing Methods of Tacrolimus in Lung Transplant Patient

“Tacrolimus is a medication used to prevent organ rejection after transplant surgery. Though the drug is quite effective, it has a narrow margin between safety and efficacy, and requires careful dosing so that blood levels are maintained within a specific range. For example, high tacrolimus blood levels can cause harm to the kidneys or cause diabetes. Current practices for tacrolimus dosing are rather imprecise because they usually do not consider the effects of patient variables, such as genetics, on drug absorption and elimination. While some transplant centers are beginning to incorporate genetic factors into tacrolimus dosing, another, perhaps better, method uses computer models that take into account genetics in addition to other factors, such as concomitant medication and concurrent diseases. Model-based dosing is a bit more complex, however, because it requires special software and updates its algorithm with patient-specific data (e.g., prior tacrolimus blood levels) as they become available.  The purpose of this study is to compare two methods of tacrolimus ‘precision’ dosing, genetics-only dosing and model-based dosing, with respect to patient outcomes in lung transplant patients.”

 

Vy Tran Luu, California Northstate University

Mentor: Dr. Bernadette D’Souza

Research Title: Targeted miR-146a; an innovative treatment modality for shear stress-induced vascular inflammation & atherosclerosis.

“Heart attacks and other critical health problems like stroke and other vascular diseases are usually the result of stiffening of the major blood vessels which supply these essential body organs. Stiffening of these major blood vessels occurs due to inflammation of blood vessels, which has been found to be directly related to the nature of blood flow that occur in specific areas of blood vessels. Using a simple analogy of a “water hose” to describe blood flow; If the blood flow occurs in one direction with high speed, the blood vessels stays healthy with minimal stiffening. Vice versa, when blood flow is is turbulent in nature and lower in speed, then the blood vessel becomes inflamed, which is the first step needed to develop the blood vessel stiffness. Within the blood vessel tissues, there are specific molecules that are responsible for responding to these mechanical changes in blood flow. Of these molecules, our research group is interested in studying a specific molecule that is called micro-RNA146a (miR-146a). High levels of miR-146a are found in areas of blood vessels that are subjected to the healthy kind of high speed, one direction blood flow. Which in turn, can suppress the inflammatory molecules in the blood vessel wall and keep it healthy. Therefore, our group is interested in studying two research goals: (1) whether turbulent blood flow results in decreased levels of miR-146a, and hence increased inflammation of the blood vessels. (2) In addition, our group is also interested in studying whether supplying back high levels of miR-146a to areas of blood vessels that are subject to turbulent flow using specific carriers can be used as a tool to treat inflammation and Stiffness of affected blood vessels.

In order to study research goal (1), our group will study endothelial cells isolated from human aorta and artificially cultured in the lab in a circular dish. These endothelial cells will be shaked in a circular motion to simulate two areas of blood flow: High speed area at the edges of the cell culture dish, versus, turbulent area with low flow speed in the center of the dish. Afterwards, cells will be studied to determine the levels of miR-146a and inflammation, and evaluate whether treated the endothelial cells with high levels of miR-146a can suppress inflammation in the turbulent flow areas. In parallel, In order to study research goal (2), laboratory mice will be subjected to a unique surgery to induce a localized area of turbulent flow in their aorta by making a slight constriction in it using a specially designed clip. As a result, the aorta tissue becomes more inflamed and lower levels of miR-146a are expected, compared with the other healthy areas with normal blood flow. Afterwards, these mice will be treated with specific carriers that can deliver high levels of miR-146a to the specific areas of turbulent flow of the aorta, then we will evaluate the remaining levels of inflammation and stiffness in these treated blood vessels.”