Discovering and evaluating the factors that influence how therapeutic agents work
We work to optimize drug therapy through the generation, integration, and translation of scientific information between the bench and the bedside, the patient and the population. We advance clinical practice through innovative translational research and through the education and training of clinical scientists and current practitioners.
DPET is focused on collaborative clinical and translational research projects, with a particular emphasis on developing world-class programs in pharmacogenomics, quantitative pharmacology, and experimental therapeutics. Current research centers around the following therapeutic areas: cardiology, hepatology/gastroenterology/transplant, infectious disease, oncology/hematology, and pulmonology. Our program develops scientists who excel at conducting innovative and clinically relevant translational research that integrates biomedical and pharmaceutical sciences in a laboratory- and computer-based environments that leverage preclinical and clinical investigations.
Our research focuses on the following therapeutic areas:
- Infectious disease
UNC Precision Dosing Initiative
A primary focus of the Division of Pharmacotherapy and Experimental Therapeutics (DPET) is the optimization of drug therapy. With new federal interest in precision medicine, and given the expertise contained within DPET, we have built a precision dosing initiative into our 2016 strategic plan. This initiative is based on the premise that standard doses of many drugs evaluated in Phase III studies do not meet the needs of all patients, and lead to poor response or unnecessary side effects. Our focus is to improve patient outcomes and lower healthcare costs by transforming how medication dosing is selected and optimized at the time of prescribing. This premise is not new – therapeutic drug monitoring which targets patient variability has been used for decades for certain drugs, and pharmacists are adept at providing this monitoring. However, with the widespread implementation of the electronic medical record, and the expansion of pharmacometrics into modeling appropriate dosing for special populations, we believe initial dosing strategies could be better optimized at the time the prescription is written.
Certain drug classes, such as anticoagulants, antiinfectives, anticancer agents, and opioids are ideal candidates for individualized dosing due to their common use in high-risk patient populations, narrow therapeutic window, and substantial variability in response between patients.
To launch the Precision Dosing Initiative, we are establishing a multidisciplinary research network that converges expertise in clinical and quantitative pharmacology, data science, medicine, implementation science, and innovative clinical practice models to transform how medication dosing is optimized in individual patients. This involve Phase IV studies in real world patient populations, validating pharmacometric models and the appropriate covariates in these diverse populations, incorporating these models into the electronic medical record, studying optimal approaches for implementing the dosing tools, and evaluating the clinical and financial impact of early dose optimization.
Comprehensive PGx Test Panel
The Eshelman Institute for Innovation has funded a proposal from Tim Wiltshire, Ph.D., director of the Center for Pharmacogenomics and Individualized Therapy (CPIT). The Center has developed a unique and comprehensive test panel called DNA2Rx. The 22 genes included on this panel were selected because they are associated with definite actionable guidance that can be provided for the clinician/patient to optimize drug dosing. Dr. Wiltshire has proposed to initiate pilot studies in five specialist areas of medicine (Anesthesia/Pain, Cardiology, Oncology, Psychiatry and Transplant) to discover the usefulness of providing preemptive PGx information to physicians.
Most drugs do not work effectively in all people and may have excessive side effects or toxicity. The variation people show in response to a drug, whether it is for efficacy or toxicity, can often be explained in their genetic makeup. Understanding the interactions of genes and drugs enables us to identify the most appropriate drug or dose for each individual.
To develop this project, the Center for Pharmacogenomics and Individualized Therapy has used a methodology called MIPs, which stands for molecular inversion probes. This data produces a report for each patient which details their responses to over 100 drugs that can then be used to provide the guidance for “the right drug or the right dose of drug” on an individualized basis. An example of this report can be viewed by downloading a QR scanner application like, “QR Reader” or “i-nigma QR code”, and scanning our sample report viewed here.
Dr. Wiltshire’s Eshelman Institute for Innovation Award will develop a model that explores how to maximize the reach and impact of PGx information in five major Divisions/disease areas in the School of Medicine and explore how it can be integrated into clinical practice models. It will provide:
- Specific and relevant PGx tests for a specialist physician.
- Comprehensive testing that can follow a patient through into different specialist areas.
- Information regarding the frequency of actionable variants
- Information regarding comorbidities and the spectrum of medications that are prescribed.
- Educational information for both patients and clinicians.
- A data set to initiate the appropriate EMR inclusion.
- A data set to evaluate the pharmacoeconomic impact of preemptive sequencing for a multi-gene test.
- Interactions with primary care physicians to assess their engagement as “holders” of a patients PGx data.
- Precise genetic information for actionable genes that would be incorporated into new models being developed for precision therapy.
The long-term goal of this proposal is to demonstrate that a preemptive PGx testing program is cost-effective. That the outlay cost of testing is outweighed by cost savings in improved prescribing regimens and that this will ultimately lead to direct improved health outcomes for patients: this is precision therapy. Precision medicine therapies are becoming expected. Tools have become available to consider how to provide the appropriate therapy on an individual basis, and this project will be part of the mechanism of putting this in place at UNC and more broadly in healthcare for North Carolina. This is one part of what will need to be a larger initiative to achieve precision therapy, and it would integrate genetic information into the broader DPET proposal for a multidisciplinary convergence to develop, implement and evaluate innovative tools to individualize drug dosing.
Global Engagement Initiative
Amanda Corbett, PharmD, a Clinical Associate Professor with DPET, was named Associate Director of the Office of Global Engagement. Dr. Corbett has been involved with the Office of Global Engagement since 2014, when she helped spearhead the Global Pharmacy Scholars (GPS) program. In her new role, her primary focuses are the GPS and the new China initiatives.
The Global Pharmacy Scholars program began in 2014 when two UNC PharmD students were selected as a pilot for the GPS program. At the time, Dr. Corbett had a standing relationship with Malawi as part of her HIV patient and pharmacology work as the Global Pharmacology Coordinator for the Institute for Global Health and Infectious Diseases. With guidance from Dr. Corbett, these students visited Malawi in the first year of the Global Pharmacy Scholars program. The mission of GPS is to enable students to learn about global health care issues, expose students to various cultures and healthcare systems, and develop global leaders in pharmacy. Since 2014, the program has expanded to nine different sites (Malawi, Australia, Ethiopia, India, Japan, Moldova, United Kingdom, Zambia and, most recently, China). In 2018, it is expected that at least one third of the students in their fourth year of the PharmD program will be able to participate in the Global Pharmacy Scholars program as one of their advanced pharmacy practice experiences.
This summer, Dr. Corbett visited China as part of her role with global engagement. Dr. Corbett and UNC students participated in a two-week Traditional Chinese Medicine and Chinese Culture Summer Program with ShangHai JiaoTong University, followed by two-weeks of pharmacy practice in the hospital setting within China. This visit was particularly interesting to Dr. Corbett as she has pioneered Integrative Medicine at the pharmacy school where she developed an elective in 2011 focusing on teaching pharmacy students the perspective of combining Western and traditional medicine in caring for patients in a holistic way. During this visit, Dr. Corbett was able to speak and share her knowledge of integrative health to students from all over the world through the summer program. The visit was also associated with the Office of Global Engagement’s new China Initiative, that will focus on collaborative efforts with Chinese academic institutions and entrepreneurial groups that are working to promote healthcare, education, and pharmacy within China.
Research Facilities and Capabilities
DPET is located in Genetic Medicine Building and Kerr Hall on the health sciences campus at UNC Chapel Hill.
Genetic Medicine Building
Researchers in the UNC Eshelman School of Pharmacy occupy approximately 75,000 square feet of laboratory space on the first and second floors of GMB, allowing them to work closely with colleagues in Medicine and giving Pharmacy a strong presence in the heart of Carolina’s health sciences campus..
Each of the GMB’s seven floors has a footprint of about one acre. The two lower floors house vivaria, and the five above-ground floors house faculty and staff.
The labs in the GMB are shared, open labs that are typically 10,000 to 12,000 square feet and contain seating areas for lab personnel, lab bench areas, fume hood rooms, tissue culture rooms, equipment rooms and cold rooms.
The center of the building provides space for some shared equipment, microscopy rooms, dark rooms, autoclaves, limited additional freezer storage, chemical storage, and meeting rooms. A space for a small nuclear magnetic resonance spectrometer is located on the first floor. The entire building is supplied with emergency power.
Dr. Brouwer directs an NIH-funded research program focused on hepatobiliary drug disposition and development and refinement of in vitro model systems to predict in vivo hepatobiliary disposition, drug interactions, and hepatotoxicity.
Cao’s group is interested in developing system pharmacology platforms (models) integrating PK/PD to facilitate drug development and optimize therapeutics for cancers and autoimmune diseases.
His translational research program focuses on how genetic variations can lead to differences in the pharmacokinetics and pharmacodynamics of therapeutic treatments used in oncology, and how inter-individual differences in clinical pharmacology measures can affect survival and drug toxicity phenotypes.
Her primary research interest is the pharmacokinetics/pharmacodynamics of antiretrovirals.
His research interests include pediatric clinical pharmacology and the application of mathematical modeling and simulation techniques to characterize the pharmacokinetics and pharmacodynamics of drugs, guide dosage selection, and improve drug safety in children.
The Heinzen Lab focuses on the genetic and genomic basis of epilepsy disorders, including analyses of the role of germline mutations, somatic mutations, and how regulation of the cellular transcriptome influences the risk and presentation of seizures.
Dr. Innocenti’s NIH-funded research program is currently focused on the discovery of genomic determinants of efficacy and toxicity of cancer chemotherapy, integrating clinical genomic investigation with functional evaluation of gene variation.
Klarissa Jackson’s research interests focus on drug metabolism and toxicology to better understand the mechanisms and risk factors of adverse drug reactions and improve drug safety.
Dr. Kashuba’s research focuses on the clinical pharmacology of drugs used in the treatment, prevention, and cure of HIV infection.
His research focuses on cytochrome P450 metabolism, cardiovascular experimental therapeutics, and precision medicine/pharmacogenomics.
Rao’s principal research interests surround quantitative systems pharmacology, and she is working to understand the processes of infectious diseases.
Dhiren Thakker’s research focuses on drug absorption and metabolism.
The institute focuses on developing innovative approaches to investigate the underlying mechanisms of rare or “idiosyncratic” toxicities that are often not discovered until late in clinical development.
The Wilshire Lab’s research focuses on taking the pharmacogenetic knowledge we already have and develop approaches for that information to be used effectively in clinical practice.
His research interests focus on the application of pharmacokinetic, pharmacodynamic, and pharmacogenetic principles in the optimization of the chemotherapeutic treatment of cancer.
Institute for Drug Safety Sciences
The Institute for Drug Safety Sciences (IDSS) focuses on developing innovative approaches to investigate the underlying mechanisms of rare or “idiosyncratic” toxicities that are often not discovered until late in clinical development.
IDSS has amassed top-level talent in the fields of pharmacometrics, pharmacogenomics, mouse genetics and biomarkers, and developed high-impact collaborations with industry, academia and the Food and Drug Administration.
The vision of IDSS is to make new drugs more affordable and safe, and expedite their availability by (1) solving safety problems encountered at any point in the life cycle of a new drug candidate, (2) improving the efficiency and accuracy of safety assessment during the drug development process, and (3) guiding the rational design of safe drugs, thereby eliminating risks to patients.
The Institute uses innovative tools that inform quantitative systems pharmacology modeling to decrease the risk for adverse reactions at all stages of drug development. The Organ Injury Biomarker Core (https://pharmacy.unc.edu/research/centers/idss/research-programs/) focuses on cutting-edge biomarkers for early detection and mechanistic insight of hepatic, renal and cardiac injury is a full service core offered by the Institute.
IDSS also offers a Translational Pharmacogenomics research program that focuses on novel in vitro and in vivo platforms coupled with a systems biology approach to identify mechanisms and risk factors associated with drug-induced liver injury. The Institute’s DILI-Sim Initiative uses quantitative systems pharmacology modeling to improve patient safety, reduce the need for animal testing and reduce the costs and time necessary to develop new drugs.
The purpose of the Clinical Pharmacology and Analytical Chemistry Laboratory (Core E) is to provide a centralized unit to facilitate the pharmacological and analytical studies of HIV/AIDS related clinical, translational, and basic science research at UNC-Chapel Hill and at our collaborating institutions, and to establish collaboration with AIDS investigators at other national and international institutions.
The Pharmacometrics Core assists investigators at each step in the pharmacokinetic/pharmacodynamic research process, from study design and data analysis to publication.
We offer a variety of fellowships sponsored by the NIH, pharmaceutical industry partners, and traditional academic-funded fellowships. Details regarding these fellowships can be found here.
Collaboration and Partnership
We are partnering across the campus, state, nation and around the world to advance research and advance knowledge and treatment for patients to discover solutions for the world’s most challenging health issues.
UNC Health Sciences Campus
The School is part of the University of North Carolina at Chapel Hill, a major research university with a large teaching hospital and schools of medicine, public health, nursing, and dentistry.
- Ranked 5th nationally for federal research among all universities
- $1.1 billion in sponsored research from all sources annually
- Eleventh largest research university in research volume and annual expenditures
Eshelman Institute for Innovation
The Eshelman Institute for Innovation was established in 2014 with a $100 million commitment from Dr. Fred Eshelman. The Institute encourages collaborations between universities, research institutions, foundations and industry that accelerate groundbreaking science from the bench to the patient by funding and translating ‘top tier’ scientific solutions to the market with speed. Learn more here.
Research Triangle Park
UNC anchors one corner of North Carolina’s famed Research Triangle Park, which hosts an abundance of pharmaceutical, biotech, and health-care companies. This environment offers many opportunities for collaboration in research, education, and patient care with partners in academia, industry, and health care.
The University of North Carolina at Chapel Hill and Deerfield Management have entered into a partnership to create Pinnacle Hill, a company seeking to discover new medicines to address the significant unmet medical needs of our times. Deerfield will invest up to $65 million of targeted funding through Pinnacle Hill, as well as providing significant drug development expertise to advance promising therapeutic research at UNC-Chapel Hill. Learn more here.
PharmAlliance is a unique international partnership between three global leaders in pharmacy education, the University of North Carolina at Chapel Hill, Monash University, and University College London. PharmAlliance partners work collaboratively to inspire and train tomorrow’s professional leaders and practitioners to transform education delivery and address major research challenges in pharmacy and the pharmaceutical sciences.
Structural Genomics Consortium
The SGC (Structural Genomics Consortium) is a not-for-profit, public-private partnership that performs basic science of relevance to drug discovery. Research is conducted at several sites around the world to produce reagents, proteins, antibodies, assays, and data that support exploration of the human genome. All material and intellectual output of the SGC is placed in the public domain for use without restriction. The first SGC laboratory to operate in the USA is located in the UNC Eshelman School of Pharmacy. Learn more here.