By Chinaza Egbuta, PhD
On Wednesday, April 25, 2018, the Graduate Research Organizations for Biotechnology (GRO-Biotech) held its third annual conference at the NYU Langone Health Campus. The event featured a plethora of speakers and panelists from different sectors of the biotech industry. The overarching theme of the first session – from the opening remarks of Dr. Robert Schneider (Professor & Associate Dean for Therapeutics Alliances, NYU Langone Health), to the last talk of the session by Dr. Kate Merton (J & J Labs) – was that a non-traditional career in the life sciences industry is the new black. It is up to graduate students and postdoctoral research fellows to ride the cusp of this change and become better scientists as a result.
Dr. Aris Economides is the Vice President of Research at Regeneron Pharmaceuticals Inc. and was the first invited speaker. He presented a roadmap of his research on Fibrodysplasia Ossificans Progressiva (FOP), a rare disease characterized by episodic heterotropic bone formation—that is, bone formation in aberrant tissues—in soft tissue as result of inflammation. In addition to reminding the audience that some of the most successful therapeutics for difficult-to-treat-diseases were discovered because bench scientists paid close attention to the physiological consequences of gene alterations, he emphasized that biomedical research education and training at the bench is a viable path to a career in the life science industry. Dr. Economides’ successful non-traditional career in the biotech sector has spanned over 25 years. He joined Regeneron in 1992, after the completion of his doctorate in Biochemistry from Michigan State University. He attributed his career success to re-writing his job description every five years, and not being afraid to go to places where he was considered unqualified.
Dr. Economides described the challenges that led to the discovery of a novel mechanism that explains a key aspect of FOP pathophysiology. The novel mechanism of note is a gain-of-function mutation in the bone morphogenetic protein receptor ACVR1 that leads to enhanced specificity for the injury-related factor activin. Now, this mechanism is being used to develop effective targeted therapies, including the blockade of activin, for the disease. Importantly, Dr. Economides discussed the weaknesses of initial assumptions related to FOP. A major assumption was that ACVR1 is constitutively active. This assumption was due to a lack of robust genetics techniques to generate quality data, and a failure to subject data to “pressure tests” that are particularly critical for drug development projects. The biggest red flag for Dr. Economides and his team was that data from previous research on hyperactive ACVR1 could not explain the human phenotype of the FOP. By using a genetically humanized mouse model, Dr. Economides and his team were able to elucidate the mechanism by which mutant ACVR1 drives heterotropic bone formation, and evaluate neutralizing antibodies that prevent activin binding to mutant ACVR1. He emphasized that these findings were possible because he and his team allowed the physiology of the disease to guide their discoveries. He ended by sharing two valuable quotes that helped map their course: “imagination is more important than knowledge” (Albert Einstein), and “chance favors the prepared mind” (Louis Pasteur).
The next speaker was Dr. Aron Jaffe, a Cambridge Regenerative Medicine Hub Leader from the Developmental and Molecular Pathways Department at Novartis Institutes for BioMedical Research (NIBR). Dr. Jaffe joined Novartis in 2008. Prior to this, he completed his doctoral research in Cellular and Molecular Biology at the University of Pennsylvania School of Medicine and moved to the Medical Research Council Laboratory for Molecular Cell Biology in London, UK for his postdoctoral training. He relocated with the lab of his postdoc mentor to the Memorial Sloan Kettering Cancer Center in New York City, where he continued his work on 3D-culture models of intestinal epithelial morphogenesis—the process that generates the different shapes and patterns of epithelia across tissues.
Dr. Jaffe began his talk by introducing the audience to NIBR schemes as they relate to different diseases and the NIBR drug discovery pipeline. For the rest of his talk, he discussed his current research, which focuses on elucidating airway epithelial morphogenesis in vitro and understanding signaling pathways that dictate epithelial morphogenesis. The data from these studies are instrumental in identifying novel druggable targets for tissue integrity, tissue repair, and tissue regeneration. In order to enhance the audience’s understanding of the system, Dr. Jaffe described some key players such as the airway basal cell, which is an important progenitor of the cells that line human airways outside the lungs. He described results in which these basal cells differentiated into bronchospheres via organotypic cell culture. This is a type of cell culture system in which two or more separately cultured cell types, derived from the same tissue or organ, are recombined in a common culture environment so that they can interact as they normally would in the organ. In this instance, the culture consisted of the human bronchial epithelium used in modeling growth, repair, and differentiation of the human airway epithelium. Notably, Dr. Jaffe described his research as “translational medicine” that bridges from the bench to the bedside and back, thereby creating avenues to reinvent or redefine hypotheses and experimental approaches.
Leading the third and final session was Dr. Stephane Peluso, Senior Director of External Innovation at Ipsen. Dr. Peluso described the focus of Ipsen as “…building a sustainable pipeline in oncology, neuroscience and rare diseases of the endocrine system.” Dr. Peluso graduated with a doctorate in Chemistry from the University of Lausanne in 1999 and completed a postdoctoral fellowship in the laboratory of Dr. Barbara Imperiali at the Massachusetts Institute of Technology a year later. He entered the biotech/pharma space as a Scientist with Millennium Pharmaceuticals for four years. He then joined Infinity Pharmaceuticals where he ascended the ranks from Senior Scientist to Senior Director for Drug Discovery over a period of twelve years before being recruited to Ipsen for his current position. Dr. Peluso described how the external innovation model of Ipsen differs from traditional R&D models through its aims to increase the size and diversity of the pipeline by searching for innovative drug targets. He concluded by sharing information on the vast array of opportunities for PhDs in the life sciences and emphasized team spirit, agility, result-orientation, and accountability as drivers for success in biotech.
In conclusion, the speakers encouraged the audience to keep their fingers on the pulse of the different changes occurring in the life science industry such as the increase in investing in high technologies, increase in the availability of diverse training programs for students and fellows, and increase in the opportunities to collaborate with other scientists from different fields.
About the author: Chinaza Egbuta is a biomedical research scientist trained in pharmacology, structural biology (macromolecule crystallization and x-ray crystallography), endocrinology, cell biology, and drug development. She is currently a postdoctoral fellow at New York University School of Medicine and will transition into a career in the biotech space after postdoc-ing. During her spare time, she enjoys cooking, physical exercise (running, cycling, yoga, kickboxing) and volunteering with organizations that promote STEM awareness for minorities. Find her LinkedIn here: https://www.linkedin.com/in/drchinazaegbuta/