Breaking Boundaries

Taking a synergistic and multidisciplinary approach, investigators in the Harrison College of Pharmacy’s Department of Drug Discovery and Development span the spectrum of the drug discovery process and are working together every day to advance medicine and improve health outcomes.

Formerly referred to as the Department of Pharmacal Sciences, the unit was renamed several years ago to better represent the full drug discovery process that takes place, covering the disciplines of pharmacology, pharmaceutics and medicinal chemistry.

“Drug discovery and development epitomizes team science,” said Dr. Tim Moore, associate dean for research in the Harrison College of Pharmacy (HCOP). “While the research is integrated in terms of the overall goal to design and develop a drug that can be used to satisfy an unmet medical need, there are still elements of hand-off points as a molecule moves through the pipeline to becoming a medicine.

“This requires collaboration and multidisciplinary expertise at all points along the way.”

With the addition of the Pharmacy Research Building in 2017, the department now encompasses more than 40,000 square feet of research laboratory space for more than 20 faculty members and more than 40 graduate students. The department additionally delivers a graduate education curriculum that has integrated required coursework necessary to understand the multidisciplinary scientific approach needed to accomplish drug discovery and development.

With the construction of the Pharmacy Research Building, the lab spaces were left open and shared with dedicated procedure rooms to encourage collaboration and innovation among the investigators. With the advancement of the laboratory space, the college has seen its National Institutes of Health portfolio double in the amount received per year since the building’s opening.

“The collaborative environment that exists there along with modern cell culture space, open bench space, and dedicated closed spaces needed for specific research activities has greatly improved grant reviewers’ opinions of our research environment,” said Moore. “In addition, it has allowed for more space in Walker to be used for medicinal chemistry, pharmaceutics and natural products research activities.”

With this foundation, the department has embraced a collaborative, multidisciplinary and innovative approach to the drug discovery process, bringing molecules to medicine, conducting purpose-drive research and bringing synergy with partners in the pharmaceutical industry.

Collaboration and Teamwork

The drug discovery process can be divided into four main areas: discovery, pre-clinical studies, clinical development/clinical trials and market approval. While this can look like a neat sequence, it is actually integrated with processes happening at each stage.

The expertise within the HCOP, coupled with other Auburn University and industry partners, uniquely positions the college to be present in all phases of the drug discovery process.

“The expertise and emphasis on biomedicinal chemistry and pharmaceutics research are unique features for our college, and coupled with our pharmacology expertise, we possess all the fundamental sciences needed to design and conduct drug discovery-driven research efforts that advance discovery and many components of pre-clinical studies,” said Moore. “This collective expertise also makes us attractive to partners engaged in drug discovery and development.”

With strong foundations in areas like medicinal chemistry, pharmacology and pharmaceutics, the college also has faculty experts in other areas that can help assess unique measurements and inform drug mechanisms and potential treatment outcomes.

Examples include behavioral science, imaging, pharmacogenomics and natural products. Dr. Miranda Reed, co-director of the Center for Neuroscience, conducts studies that measure cognitive performance and behavioral outcomes, which are important for informing the discovery of therapeutic interventions targeting Alzheimer’s Disease. Meanwhile, Dr. Peter Panizzi is a director of Project ALIAS, the Auburn Laboratory for Imaging Animal Systems, which can be an informative resource for drug efficacy, particular in cancer.

Dr. Amit Mitra leads the Center for Pharmacogenomics and Single-Cell Omics, an initiative that works to develop algorithms to help formulate strategies to repurpose existing drugs for use in other disease conditions and is part of the growing trend of personalized medicine.

Dr. Angela Calderón is a sought-after expert in natural products, evaluating their pharmaceutical properties to study how substances derived from natural products can provide health benefits or if they actually interfere with the actions of prescription pharmaceuticals.

Embracing Innovation

On average, it can take between 10 and 15 years and millions upon millions of dollars to advance a new drug from initial discovery to the market. While those facts are not changing anytime soon, HCOP investigators are embracing new technologies and methods, such as artificial intelligence, additive manufacturing and personalized medicine to make the process more efficient.

In silico (computer) modeling has long been a tool in drug development, helping investigators predict drug-receptor interactions and informing medicinal chemists that synthesize potential drugs. Using these new technologies can provide a greater understanding of these interactions and qualities.

“Any tool, such as machine learning algorithms or AI programs, helps facilitate a greater understanding of the fundamental mechanisms underlying disease, the molecular interactions of potential drug candidates and biological systems or the pharmacokinetics and pharmacodynamics profiles of potential new drugs, can be used in the drug discovery research,” said Moore.

Along with Mitra, faculty like Drs. Raj Amin and Forrest Smith are working with these technologies and applying them in the omics space, facilitating precision or personalized medicine. By utilizing pharmacogenomics, investigators can look at the role of the genome in drug response how a particular person may react to a drug.

“Modern health care seeks to practice precision or personalized medicine, meaning understanding a person’s genome and all the gene variations or mutations that are possessed within that individual can help with the development of more tailored drugs to treat certain diseases,” said Moore. “Finding the right drug for the right person has become particularly true for cancer drug discovery and HCOP has strategically invested in both pharmacogenomics and in our cancer research portfolio over the past few years.”

Several HCOP faculty members have worked in the cancer research space over the years, including Drs. Rusty Arnold, Alexei Kisselev and David Riese. Part of the growing investment included the recruitment of Dr. Gary Piazza and his team (Drs. Xi Chen, Adam Keeton and Yulia Maxuitenko) to HCOP and the establishment of a Cancer Research Center.

Along with a precision approach to the development of medicines, HCOP has also taken a precision approach to drug compounding, blending classic pharmaceutics with 3D printing and additive technology to develop improved ways to delivery medicines to the target area.

“Additive manufacturing has introduced a new modality for thinking about drug delivery,” said Moore. “For example, HCOP researchers are studying how 3D-printed implants, such as might be used for orthopedic medicine, can be loaded with drugs that help treat pain and inflammation associated with an orthopedic surgical procedure.”
Much of this work is being done in the lab of Dr. Jay Ramapuram with Arnold also involved in the use of nanoparticles in drug delivery.

“Being able to deliver drugs directly to the site where they are needed reduces the higher drug doses and side effects that often accompany treating surgical recoveries with oral or IV medicines,” said Moore. “Modern drug discovery research occurring at HCOP seeks to fulfill the goal of the right drug for the right person at the right site.”

Purpose-Driven Research

The academic work going on at HCOP and around the country is vital to supporting the pharmaceutical industry ad bringing new drugs to market. Investigators can put together experimental models that are predictive of clinical models, developing and refining in vitro and en vivo models along the way.

Academic drug discovery aims to identify and develop drug candidates and tools to the point at which there is sufficient novelty and potential to attract commercial investment and establish sufficient scientific evidence to advance the research into clinical trials and pharmaceutical manufacturing, providing companies a proof-of-concept.

“New drug candidates can be brought to a point through the drug discovery and development pathway in academia, through milestone-driven research projects, such that company-based drug discovery entities will have higher levels of confidence that a potential new drug can be financially supported to proceed to clinical trials, and ultimately be brought to market to treat disease,” said Moore.

Moore noted that while milestone-driven research is quintessential for the drug discovery and development process, scientific discovery is also vital for identifying disease mechanisms that may be amenable for new drug development.

“As an academic department, Drug Discovery and Development faculty also conduct robust, hypothesis-driven biological and pharmaceutical sciences basic research that is stimulated by the goal of improving health and well-being,” said Moore.

Educating the Next Generation

Just as vital as the work in the lab spaces is the training that goes on to educate and train the next generation of pharmaceutical scientists. Along with providing foundational instruction to those in the doctor of pharmacy program, the department provides research-intensive instruction to those in the master’s and Ph.D. programs, placing graduates in careers in the pharmaceutical industry, government agencies and academia.

To further that mission, the college also recently announced the creation of a bachelor’s degree in drug and biopharmaceutical sciences. The first-ever bachelor’s degree offered by the college in this space, it is addressing a growing need for personnel in the biomedical field in areas like education, health care, public administration, technical services, drug manufacturing, food sciences, social services, and others.

Developed by senior faculty in the Department of Drug Discovery and Development, Drs. Murali Dhanasekaran, Jack Deruiter and Randall Clark, the degree program will welcome its first students this fall.

“Undergraduate students will experience an innovative instructional and research-intensive academic environment, providing a deeper understanding of drug development and pharmaceutical sciences at a much earlier point in their educational careers,” said Moore. “The program will produce graduates with the abilities to fulfill roles in industry, regulatory, professional and advanced degree programs.