After 16 wonderful years at Pfizer, I joined Takeda overseeing the Drug Metabolism and Pharmacokinetics (DMPK) group. This new role was a both a continuation of my scientific area of expertise held at Pfizer and an extension into managing a team of talented researchers who discover and develop transformative therapies for patients.
My scientific career journey began after receiving my undergraduate Bachelor’s degree in Biochemistry with an emphasis in mathematics and a Doctorate degree in Biochemistry with an emphasis in Pharmacology. I then became more immersed in studying drug metabolizing enzymes through a post-doctoral fellowship. From a young age, I had a keen interest in the human body and specifically on the mechanisms of how the body functions from an enzyme perspective. So, when it came time to start a career beyond my formal education, I focused on obtaining a research position in drug metabolism. You may be asking, “What are the primary responsibilities of the DMPK department?” The overall mission of a DMPK department is to characterize the fate of a therapeutic in the body. Using pre-clinical systems in the drug discovery phase prior to human testing, i.e. the design phase for the therapeutic, researchers predict the extent to which the therapeutic will reside in the body and for long, as well as how the body will modify the therapeutic, a process otherwise known as metabolism.
As a DMPK researcher, we characterize and optimize the extent and duration of exposure anticipated to provide the desired pharmacological effects, in collaboration with pharmacology colleagues, and undesired toxicological effects, in collaboration with our safety colleagues. During this phase, DMPK researchers have a critical role in partnering closely with other scientific disciplines to design in the ideal properties of the therapeutic, innovatively bringing the best medicines to the intended patient. Once in human clinical trials, DMPK researchers further characterize the fate of the molecule in the human body and any associated undesired interactions that may affect exposure, safety, and efficacy of the therapeutic. We are fortunate today that many world class DMPK scientists over the past two to three decades have improved our understanding of how best to design the attributes that are best for the therapeutic and for patients, particularly for small molecule therapeutics, and this practice is likely to continue for years to come. As one can imagine, characterizing and optimizing the drug metabolism and pharmacokinetic properties of a molecule for the human body requires broad scientific knowledge of biology, organic chemistry, biochemistry, analytical chemistry, mathematics, anatomy, and physiology. This diversity of scientific areas was aligned with my formal education that spanned biochemistry, pharmacology and mathematics, and was inclusive of the scientific areas needed. Consequently, my education provided the experience beneficial for partnering in cross functional and scientific teams comprised of deep biology and chemistry experts. While this diverse educational background lends itself to a broad role in DMPK in Research and Development, researchers with deep expertise are also critical to successfully discovering and developing safe and effective therapies. In the DMPK discipline, these include scientific core areas such as pharmacokinetics, metabolism, enzymology, drug transporters, and bioanalytical. There are also roles that leverage expertise in areas that include mathematical modelling of pharmacokinetics, pharmacodynamics and drug distribution, imaging; molecular biology; and proteomics. It is the deep expertise in these areas that are not only essential to designing and developing highly beneficial and safe medicines for patients, but also drive innovation and research in novel areas particularly as diverse therapeutics move beyond small molecules and antibodies such as peptides, oligonucleotides, vector-based gene therapies, cell therapies based therapeutics, and nanoparticles. Scientific knowledge in these novel modalities is continually deepening especially with respect to translatable properties from pre-clinical to clinical and thus predictiveness to humans. More specifically, defining the properties, pre-clinically, that accurately predict how the therapeutic will behave in human with regards to exposure, distribution, residence time, and effective concentration for pharmacology and toxicity continues to emerge as more and more of these diverse modalities are studied in human subjects. Consequently, a key to successful innovation is having a scientifically inquisitive mindset with a solid educational foundation.
Equally important, is creating the climate for researchers to learn and develop in new scientific areas. To this end, there are couple actions we take at Takeda that intentionally facilitate achieving an innovative culture. Firstly, researchers are encouraged to participate in, and present at, scientific conferences enabling them to deepen their knowledge in DMPK core sciences as well as in these emerging areas with the additional benefit of growing their network. By building their network, this has the opportunity for Takeda researchers to build effective partnerships to achieving business goals. As second approach we take is provide researchers with cross-training opportunities within and outside the department in an effort to diversify their experience and enable them to develop in these emerging areas of science. Thirdly, we’ve established scientific training programs for our team members in contemporary areas related to novel therapeutic space. While these opportunities to develop researchers take time to establish and implement, the outcome and growth in colleagues is highly impactful and needed as we evolve our scientific understanding. More specifically and as I reflect on the past three decades of my career in drug metabolism, there are several notable shifts in how we design and develop therapeutics from a DMPK perspective. Working with a diversity of modalities towards biologics as mentioned earlier is certainly one apparent shift, where an understanding of protein chemistry is more critical today than it previously was within DMPK, when the majority of the therapeutics where small molecules. Another shift is in the advent of predictive tools generated through retrospective evaluation of human data. As an example, today we have access to micro-physiological systems and more human-like models that enable researchers to design, optimize and characterize molecules that meet patient needs. Thus, having a learning mindset and developing in novel areas is key innovation, keeping in mind, that despite the shift, the objective remains the same for DMPK: to define the fate of the molecule and the associated interactions with the intended target as well as the unintended targets in the human body.
In closing, building a career in DMPK at Takeda starts with have a passion about the science of the human body and a desire to discover and develop life changing therapeutics for patients that have ideal exposure needed to drive the intended pharmacology safely. How do you know this career is right for you? I’d encourage those who have an interest to connect with DMPK researchers such as myself or others who work in the field and ask them about their education, what they do on a day-to-day basis, and what excites them about the work they do. In the end, DMPK is a broad discipline and leverages all types of science. Hence, if a person is more excited about chemistry, biology, chemistry, or mathematic modelling, there’s a career for you awaiting.
Dr. Natalie A. Hosea currently leads the Takeda California research facility and the Department of Drug Metabolism & Pharmacokinetics (DMPK) at the San Diego-based site. Each day, Natalie strives to lead talented, diverse, and highly engaged teams focused on accelerating the innovation and delivery of transformative medicines to patients.
Natalie received her Ph.D. in Biochemistry and Pharmacology at the University of California, San Diego, and completed a research fellowship at Vanderbilt University in Nashville, TN. Thereafter, she joined Pfizer in 1999, where she worked until 2015. After 16 years at Pfizer, Natalie took a new position leading the DMPK function in Takeda San Diego. Since then, here team has grown to include the development DMPK team in Boston where she and her team continue to impact drug discovery and development of both small molecule and biological therapeutics in Neuroscience and GI disease areas from new target through registration and life cycle management. In June 2020, Natalie was appointed as the site head of the Takeda research facility located in San Diego, overseeing the Facilities, Environmental Health & Safety and Administration functions. Outside of Takeda, Natalie is an advocate of professional development, mentorship, and STEM outreach at all educational levels.