2021-2022 Pre-Doctoral Fellows

2021-2022 Pre-Doctoral Fellow Projects by Research Category

Clinical and Translational Sciences (includes pharmacotherapy, experimental therapeutics, PK/PD, modeling and simulation)

Kabir Ahluwalia, University of Southern California

Mentor: Dr. Stan Louie

Research Title: Mechanistic Dissection of Stem-Cell-Derived Factors on Atrophic Age-Related Macular Degeneration

“Age-related macular degeneration (AMD) is the leading cause for vision loss in the United States. 80% of AMD patients, who have a specific form of AMD called dry AMD, have no approved therapy. There are several causes of AMD and treatments to target one of these causes is not enough to treat the disease. Recently, an implant made of living cells was developed and is in clinical trials. This therapy will be implanted into the back of the eye to replace the dying cells in the eye. This research found the cell implant supports nearby cells in the eye which indicates the implanted cells can communicate with the surrounding area. The difficulty with this implant is the complexity of surgery which excludes patients with early forms of AMD. As such, we are investigating the communication signals, called the secretome, to develop a more widely available therapy and treat AMD before vision loss occurs. We have shown that the secretome can protect eye cells in a petri dish and in animal experiments. In this project I propose to investigate how the secretome protects the eye by targeting two key causes for AMD, oxidative stress and inflammation. Using a range of biology, chemistry, and animal experiments I plan to probe these two areas to further understand how the secretome can be utilized in treating AMD and similar diseases.”

 

Aaron Devanathan, University of North Carolina at Chapel Hill

Mentor: Dr. Angela Kashuba

Research Title: Identifying factors influencing antiretroviral pharmacology and HIV eradication in the spleen

“While the introduction of medicines to treat individuals living with HIV has significantly extended life expectancy, HIV cannot yet be cured. One of the hallmark principles of HIV infection is that HIV will persist in areas of the body known as HIV reservoirs, such as the brain, lymph nodes, and spleen. These reservoirs contain persistent HIV despite 100% adherence to the medicines to treat HIV. One reason for this HIV persistence is that medicines to treat HIV may not adequately reach and penetrate these reservoirs. The goal of this proposal is to identify factors that affect antiretroviral distribution in the spleen to understand viral persistence in lymphoid organs and to develop more targeted medicines.”

 

Screen Shot 2020-06-17 at 11.25.57 AM

 

Mansour Dughbaj ,University of Southern California, Second Year Fellow

Mentor: Dr. Paul Beringer

Research Title: Design of Therapeutic Cyclotides for Cystic Fibrosis Infection and Inflammation

“The priority for this upcoming year is to complete the in vivo testing of the lead peptides. I will continue my full focus on my investigation to develop an
antimicrobial and immunomodulatory pharmaceutic for CF use. The PG-1 cyclotides will be assessed through susceptibility studies for their antimicrobial activity against various CF pathogens, including S. aureus, P. aeruginosa, Achromobacter xylosoxidans, Stenotrophomonas maltophilia, and Burkholderia cepacia. PG-1 derivatives will be assessed for their safety using hemolytic and cytotoxicity assays using red blood and lung epithelial cells (e.g., A549, CuFi), respectively. The in vivo activity of the most potent antimicrobial cyclotide will be performed using an established murine model of chronic P. aeruginosa lung infection, as previously conducted in Dr. Beringer’s lab. This murine model closely mimics the advanced chronic pulmonary disease course of CF and can be used both for pathogenesis studies and for novel therapeutic evaluations. ”

 

Screen Shot 2020-06-17 at 11.29.40 AM

Jacqueline Gerhart, UNC-Chapel Hill, Second Year Fellow

Mentor: Dr. Daniel Gonzalez

Research Title: Application of Physiologically-Based Pharmacokinetic (PBPK) Modeling to Understand Drug Disposition in Children with Obesity

“One in six children in the United States are currently obese, but doctors have little guidance on if or how to adjust the dosing of medicines for these patients. This is because conducting the clinical trials necessary to determine the right dose in children, let alone children with obesity, is very ethically and logistically challenging. My project aims to use novel mathematical modeling and simulation techniques to optimize the dosing of six commonly used drugs in children with obesity. To do this, I will 1) develop a virtual population of children that reflects the actual demographics and physiology of actual children with obesity, 2) use this virtual population and what we know about the medicine in adults to develop these models, then 3) use the models to simulate different dosing scenarios in children with obesity in order to predict which dose results in concentrations that are both safe and efficacious for this vulnerable patient population.”

 

Abbie Leino, University of Michigan, AFPE-ASHP Fellowship

Mentor: Dr. Manjunath Pai

Research Title: Home-Based Therapeutic Drug Monitoring of Immunosuppression in Kidney Transplantation

“Personalized dosing of immunosuppressive drugs is critical to protect transplanted organs from immune-mediated damage while minimizing drug-associated morbidity and mortality. Unfortunately, the individual response to these drugs is highly variable, making dosing complicated. A greater understanding of total drug exposure is essential to improve treatment, but it is challenging to accomplish as currently, multiple blood samples obtained in the clinic via venipuncture are required. The overall research goal is to develop novel tools to enable home-based monitoring of immunosuppression. A new blood sampling device will be applied to allow patients to self-collect tiny, dried blood samples at home that can be mailed to the clinic for analysis. The specific goals of this project are to 1) optimize and validate an existing method to obtain the concentration of tacrolimus and mycophenolate from dried microsamples; 2) determine the best sample collection time points to estimate drug exposure; 3) evaluate the use of automated text messages to support sampling adherence and accuracy; and 4) understand patient-reported barriers and facilitators to home-based sample collection.”

 

Screen Shot 2020-06-17 at 11.47.55 AM

Dr. Teddy Jennaro, University of Michigan, Second Year Fellow

Mentor: Dr. Kathleen Stringer

Research Title: Identifying Altered Metabolic Signatures that Drive Mortality in Septic Shock: Steps Toward Precision Pharmacotherapy

“Sepsis is a life-threatening organ dysfunction that results from a bloodstream infection. The individual response to infection is highly variable, and the precise reasons why sepsis resolves in some individuals and is deadly in others is poorly understood. Sepsis is a ‘catabolic crisis’ and the body alters energy utilization pathways and perturbs metabolism to meet the rising energetic demand. I seek to apply novel statistical and bioinformatic approaches to understand metabolic changes over time in septic patients, which are related to mortality and drug response. I will use bioinformatic software to map these findings back to known biochemistry and molecular biology to inform rational drug discovery. I will also seek to explain interpatient variability in response to a promising, targeted sepsis-therapeutic, levo-carnitine, using patient-specific data.”

 

Jing (Daisy) Zhu, University of North Carolina at Chapel Hill

Mentor: Dr. Daniel Crona

Research Title: Development of a population pharmacokinetic model to optimize tacrolimus dosing in adult recipients of allogeneic hematopoietic stem cell transplant (HCT)

“Acute graft-versus-host disease (aGVHD) is a potentially fatal complication associated with bone marrow transplant that affects at least 35-50% patients within the first 100 days post-transplant. Tacrolimus is the cornerstone of aGVHD prevention, but the dosing range between what is effective and what is toxic is extremely narrow. Thus, patients require routine tacrolimus therapeutic drug monitoring to ensure efficacy and to prevent toxicity. But, inconsistencies in the way tacrolimus is absorbed, distributed, metabolized and eliminated from patient to patient makes accurate drug dosing difficult. My dissertation research focuses on developing a precision dosing model for tacrolimus that accounts for patient-specific clinical, demographic and genetic information so that dosing can be individualized to minimize aGVHD and tacrolimus-induced toxicities. This will be the first study to develop a comprehensive tacrolimus precision dosing model in adult bone marrow transplant patients. To do so, I will help lead a prospective clinical trial to collect real-time clinical data that can refine mathematical simulations and an overall precision dosing model. The data generated from the clinical study and the simulations will ideally provide guidance to the U.S. FDA, and to tacrolimus prescribers.”

 

Drug Delivery, Bioengineering (includes nanomedicine, devices, biotechnology, protein delivery and characterization, and biopharmaceuticals)

Jason Grunberger, The University of Utah, Dr. Paul B. Myrdal Memorial Pre-Doctoral Fellowship in Pharmaceutics

Mentor: Dr. Hamid Ghandehari

Title: Treatment of Hepatocellular Carcinoma Using Novel Double Shelled Silica Nanoparticles for Controlled Drug Delivery

“The standard of care for liver cancer treatment is a chemotherapeutic that has many adverse toxicities and low efficacy associated with the oral dosage form. The goal of my project is to develop a novel drug delivery system that will reduce toxicity and maximize efficacy using a nanocarrier for controllable drug release through intravenous administration.”

Kristen Hong, University of Michigan

Mentor: Dr. Anna Schwendeman

Research Title: Optimization of HDL Mimetic Micelle Composition for the Treatment of Atherosclerosis and Thrombosis

“Atherosclerosis and Thrombosis are two diseases that can lead to heart attack and stroke. Currently, medications that are used to treat these potentially fatal diseases have many side effects, and do not reduce the risk of cardiovascular events to a large extent. Therefore, our goal is to develop a more targeted and effective therapeutic to treat these diseases. We have particles in our body called high density lipoproteins (HDL) that are able to move cholesterol from the tissues and to our liver to be eliminated through our waste. Cholesterol buildup is one of the major contributors to the development of atherosclerosis and thrombosis. Therefore, HDL can be beneficial in these diseases by taking the extra cholesterol and removing it from the body. Due to this fact, synthetic HDL (sHDL) have been created by scientists in order to increase the transfer of cholesterol from tissues to the liver for elimination, reducing the development and progression of disease. Unfortunately, sHDL are expensive and difficult to make and this can be off-putting to pharmaceutical companies. This led to the idea to create a HDL mimicking nanoparticle that is more cost-friendly and easy to produce, and is able to have the same therapeutic capabilities as HDL. To mimic HDL, we decided to take the lipid components of sHDL, and remove the one component that makes the particle expensive, proteins, to achieve our micelles. One micelle has shown to have promising ability to remove cholesterol like HDL. We believe that we can improve the efficacy of our micelle by exploring different lipids that make up our micelle particles, which may change it’s activity. My project’s goal is to find a composition of micelles that shows the highest efficacy in treating atherosclerosis and thrombosis in hopes to reduce deaths and the cost burden for patients that suffer from these diseases.”

 

Drug discovery/medicinal chemistry

Maxwell Dillenburg, University of Minnesota

Mentor: Dr. Carston Wagner

Research Title: Development of Probes to Characterize the Role of HINT1 in Mu Opioid Receptor and N-Methyl-D-Aspartate Receptor Cross-Regulation

“Opioids have long been established as the most common and effective treatment for chronic pain in the United States, with more than one third of American adults reporting opioid use in 2015. While opioids have unmatched analgesia, their use can lead to the development of addiction, tolerance, and a host of dangerous side effects. This combination of rampant use and dangerous side effects have led to an urgent need for a better understanding of opioid mechanisms and the development of opioid alternatives. Recently, the histidine triad nucleotide binding protein 1 (HINT1) has been demonstrated to play a key role in the development acute opioid tolerance as well as neuropathic pain due to its interactions with the mu opioid receptor (MOR) and n-methyl-d-aspartate receptor (NMDAR), making it an exciting new target for pain therapy. My research goal is to build on our lab’s work in the development of small molecule HINT1 inhibitors in order to probe the impact of HINT1 inhibition on MOR and NMDAR interactions in addition to the effects on opioid tolerance and neuropathic pain.”

 

Jesse Wotring, University of Michigan, AFPE Regional Award

Mentor: Dr. Jonathan Sexton

Research Title: Identification and optimization of novel hepatic steatosis inhibitors using high-content screening and morphological cell profiling

“The long term goal for my project is to identify novel small molecules for the treatment of fatty liver disease using the techniques of high-content screening and medicinal chemistry. Thus far, I have identified 20 compounds from a bioactive compound library that have anti-steatosis activity in a novel cell based high-content model for liver steatosis. One of these 20 compounds was moved forward into a mouse model for steatosis and showed robust activity in vivo. This exciting result is the foundation for my research moving forward. The primary goal will be to use medicinal chemistry to optimize the potency and metabolic stability of the lead compound as well as elucidate a mechanism of action for the compound class.”

 

Pharmacology, Toxicology (includes cell biology, chemical biology, and pharmacognosy)

Matthew Le, The University of Texas at Austin, Herb and Nina Demuth Memorial Award in Pharmaceutics

Mentor: Dr. Maria Croyle

Research Title: Analytical Characterization of Viscosity and Moisture Content in a Thermostable Film

“The goal of this project is to improve upon a dissolvable film platform, which can deliver drugs or vaccines through the mouth.  This film is like a Listerine breath strip, where it can be placed inside the cheek or under the tongue and be easily dissolved.  This film has a much smaller packaging footprint compared to traditional vaccines, and it can be stored at room temperature.  This eliminates or reduces the logistical needs for refrigerators and freezers.  To improve the technology, I am studying how moisture content within the film impacts its stability.  I am also studying a variation of the film which can be easily dissolved in an IV bag, so that it can be used with existing IV therapies.”

 

Social and Administrative Sciences

Screen Shot 2020-06-17 at 11.21.01 AMBrandy Davis, Auburn University, Second Year Fellow

Mentor: Dr. Kimberly Garza

Research Title: Training Rural Pharmacists to Implement Depression Screening Services.

“The purpose of this study is to develop and deliver a depression screening training program for rural community pharmacies considering current practices, unique barriers/facilitators to rural populations, and preferred implementation strategies using 2 aims. Aim 1: Investigate current practices, barriers and facilitators, and preferred implementation strategies to implementing a depression screening service in rural pharmacies by using an online survey. Aim 2: Design, deliver, and assess a training program to improve knowledge, intention, self-efficacy, and attitudes towards implementing a depression screening service in rural pharmacists.”

Cassidi McDaniel, Auburn University, Second Year Fellow

Mentor: Dr. Chou Chiahung

Research Title: Improving access to quality care for rural residents with diabetes: developing a framework for care transitions and policy implications

“Patients with diabetes who are transitioning from hospital care back to their home are vulnerable to hospital readmissions, and this transitioning is referred to as transitions of care. A gold standard for transitions of care practices in patients with diabetes is lacking. Therefore, the goals of the proposed project are to develop an understanding of how to improve transitions of care in patients with diabetes and provide scientific knowledge to identify the gold standard for transitions of care practices. Through a mixed-methods approach, we will consider both large population-based data and perspectives of healthcare providers and patients to identify factors impacting the risk of high readmission rates among populations with diabetes. Machine learning techniques will be applied to population-based data to identify the factors attributing to patients’ risks for hospital readmissions, and framework analysis will be applied to provider and patient perspectives to understand how transitions of care may be improved among these patients. Through the integration of these results, we will gain a better understanding of how to improve transitions of care in patients with diabetes. Findings from this work will inform the design of a transition of care program, and the program will be examined for effectiveness to reduce hospital readmission rates in clinical practice. Overall, this study aims to determine which factors should be considered in intervention design and how these factors inform framework and program development. In conclusion, the overall goal of the proposed project is to provide further direction towards developing a gold standard intervention for transitions of care to advance health outcomes through amelioration of hospital readmissions for patients with diabetes.”

 

Tyler Wagner, Virginia Commonwealth University, Pre-Doctoral Fellowship in Health Outcome Disparities

Mentor: Dr. Teresa Salgado

Research Title: Predictive and Pharmacoeconomic Modeling of Pharmacy Services in Primary Care

“Primary care is facing a physician shortage, with a projected shortage of between 21,100 and 55,200 physicians by 2032. In 2016, Americans made nearly 490 million primary care visits, a number expected to continue to rise due to an aging population and projected population growth. More and more research has shown that pharmacists, when involved in patient care teams, can effectively manage chronic disease management. Our project aims to analyze patient data from a local health system to determine what characteristics – whether social, demographic, or clinical – contribute to a patient not achieving optimal patient outcomes or quality measure achievement. An example of quality measure achievement in hypertension is reducing a patient’s blood pressure to < 140/90 mmHg or in diabetes, reducing a patient’s hemoglobin A1c% to < 9% or lower. Quality measures are rooted in appropriate disease state management and are a way for health plans or health systems to determine how well they are providing care for their patients. We plan to take these identified characteristics to develop a referral tool for health systems, allowing them to more readily identify patients that could benefit from additional care from a pharmacist. Second, we want to identify any health disparities that exist within the data to better address gaps in care. Literature from the Centers for Disease Control and Agency for Healthcare Research and Quality have shown that patient care and associated outcomes can vary significantly by racial and ethnic groups, by sex, and by insurance status. Lastly, we plan on analyzing the cost of staffing pharmacists within primary care clinics and will compare the outcomes of patients from clinics with pharmacists to the outcomes of patients from clinics without pharmacists. We aim to determine if pharmacists within primary care provide value and if so, are they affordable.”