Scholars in the NIH Oxford-Cambridge Scholars Program recently experienced a career development field trip to the Novartis Institutes for BioMedical Research (NIBR) located in Cambridge, Massachusetts. The trip to NIBR, sponsored by the Alliance and thoughtfully coordinated by Drs. Eric Svensson and Jang-Ho Cha of Novartis, spanned a full day at the newly constructed $600 million campus in Cambridge. The agenda included research presentations made by both NIH OxCam Scholars and Novartis scientists, a synopsis of the Novartis Malaria Program, neuroscience and physician scientist career path panels, an overview of the NIBR Post-Doc Program, and a walking tour of the Novartis facilities. Patricia Gruver, Senior Science & Innovation Officer at the British Consulate General in Boston, made a morning visit to greet and welcome the Scholars. NIBR’s dynamic president, Dr. Jay Bradner, addressed the Scholars during their visit. Scholar Career Development Field Trips are a newly created initiative aimed at exposing Scholars to a variety a career options as well as providing an opportunity for Scholars to conduct formal presentations on their research.
To infinity and beyond! It’s not such far out concept as Scholars learned on a recent career development field trip to NASA’s Goddard Space Flight Center in Greenbelt, Maryland. Established in 1959 and named for American rocketry pioneer Dr. Robert H. Goddard, it is home to the nation’s largest organization of scientists, engineers, and technologists who build spacecraft, instruments, and new technology to study Earth, the sun, our solar system, and the universe. Goddard is home to Hubble operations and the upcoming James Webb Space Telescope. Goddard manages communications between mission control and orbiting astronauts aboard the International Space Station. Goddard scientists stare into the sun, grind up meteorites for signs of life’s building blocks, consider the farthest reaches of space, and untangle the mysteries of our changing world.
The Goddard visit was focused on astrobiology (one of the many topics of science that NASA researches). Astrobiology is the study of the origins and evolution of life in the universe and on Earth. Astrobiology addresses whether life exists outside Earth and how we can detect signs of life in other areas of the universe. This field employs many of the scientific techniques that traditional biologists (like those at the NIH) use to understand the chemistry and evolution of life, but it also employs techniques developed to study the universe such as those used in astronomy, astrophysics, and aerospace engineering. For example, one of the NASA missions presented to the Scholars during their visit was OSIRIS-Rex, which involved using a satellite to intercept an asteroid and return a sample to Earth. Scientists believe that some of the precursor molecules important to life on Earth may have had origins in space. The researchers at NASA Goddard wanted to sample compounds from the asteroid to see if such molecules could be found on it.
Scholar Lindsey Rosen shared that astrobiology is more physics and analytical chemistry than it is biology: “Their aim is to study specimens retrieved from meteorites and asteroids for organic and inorganic compounds, thus determining if such environments are suitable for life (single-celled organisms and such). We also heard from folks who design instruments that are sent to Mars or used for meteorite/asteroid specimen collection. Such instruments are the result of international collaborations where many different institutions around the world contribute various devices.”
For many of the Scholars, space exploration has been an inspiring area of science from the time they were children. The fundamental questions that NASA seeks to answer are important to all of us: How did the universe form? Are there other life forms out there? Additionally, the advanced and diverse technology that NASA uses in its research is exciting and fascinating.
Scholar Keval Patel noted that “personally, space exploration was one of the main reasons for my pursuit of an engineering and science education. My lifelong dream is to travel to space and perform science that pushes the limits of human space exploration.”
During his fifteen years as chancellor, Dr. Ralph Snyderman helped create new paradigms for academic medicine while guiding the Duke University Medical Center through periods of great challenge and transformation. Under his leadership, the medical center became internationally known for its innovations in medicine, including the creation of the Duke University Health System—which became a model for integrated health care delivery—and the development of personalized health care based on a rational and compassionate model of care. In A Chancellor’s Tale Snyderman reflects on his role in developing and instituting these changes.
Beginning his faculty career at Duke in 1972, Dr. Snyderman made major contributions to inflammation research while leading the Division of Rheumatology and Immunology. When he became chancellor in 1989, he learned that Duke’s medical center required bold new capabilities to survive the advent of managed care and HMOs. The need to change spurred creativity, but it also generated strong resistance.
Among his many achievements, Dr. Snyderman led ambitious institutional growth in research and clinical care, broadened clinical research and collaborations between academics and industry, and spurred the fields of integrative and personalized medicine. Snyderman describes how he immersed himself in all aspects of Duke’s medical enterprise as evidenced by his exercise in “following the sheet” from the patient’s room to the laundry facilities and back, which allowed him to meet staff throughout the hospital. Upon discovering that temperatures in the laundry facilities were over 110 degrees he had air conditioning installed. He also implemented programs to help employees gain needed skills to advance. Snyderman discusses the necessity for strategic planning, fund-raising, and media relations and the relationship between the medical center and Duke University. He concludes with advice for current and future academic medical center administrators.
The fascinating story of Snyderman’s career shines a bright light on the importance of leadership, organization, planning, and innovation in a medical and academic environment while highlighting the systemic changes in academic medicine and American health care over the last half century. A Chancellor’s Tale will be required reading for those interested in academic medicine, health care, administrative and leadership positions, and the history of Duke University.
Dr. Snyderman joined the Alliance Board of Directors in 2012 and has served as a member of the sub-committee on Strategic Planning/Vision. In May of 2015 he was the keynote speaker at the inaugural Lasker Lessons in Leadership, a lecture series which is a collaborative effort between the Albert and Mary Lasker Foundation, the Alliance, and the NIH Oxford-Cambridge Scholars Program. Dr. Snyderman takes a personal interest in the research conducted by the scholars and has attended the annual Scientific Research Colloquium and spearheaded Mentoring Days for student in the NIH OxCam program. He is Chancellor Emeritus, Duke University, James B. Duke Professor of Medicine, and Director of the Center for Research in Personalized Health Care at the Duke University School of Medicine. He previously served as Chancellor for Health Affairs at Duke University and as the founding President and CEO of the Duke University Health System; Dean of the School of Medicine at Duke University; Chair of the Association of American Medical Colleges; Senior Vice President, Medical Research and Development, Genentech, Inc.; Director, Laboratory of Immune Effector Function, Howard Hughes Medical Institute; Chief, Division of Rheumatology and Immunology at Duke; and Senior Investigator, National Institutes of Health.
Dr. Snyderman has received numerous honors, including the Personalized Medicine World Conference Pioneer Award (2016), the North Carolina Life Sciences Leadership Award (2014), the Association of American Medical Colleges David E. Rogers Award (2012), the Industrial Research Institute Medalist Award (2008), the Ellis Island Medal of Honor (2003), and the CIBA-GEIGY Award for Lifetime Achievement in Inflammation Research (1992). He has authored almost 400 manuscripts and is the editor or co-editor of several books.
Since 2012, the NIH Oxford-Cambridge Scholars Program has enabled future scientists to work with NCATS researchers to explore the translation of promising new therapies for cancers and tuberculosis. Most recently, OxCam — an accelerated, individualized doctoral training program for outstanding students committed to biomedical research careers — has supported the work of three M.D./Ph.D. students in NCATS’ Division of Pre-Clinical Innovation.
Unlike traditional U.S. doctoral programs, which require two years of courses and research training prior to the start of thesis work, OxCam enables scholars to begin thesis research immediately upon starting the program. The trainees split their research time over four years with scientific mentors at NIH and at Oxford University or Cambridge University in the U.K.
NCATS mentors share their translational science expertise with the scholars, enabling them not only to focus on a specific scientific question but also to learn how to apply translation approaches to research more broadly.
“A key part of NCATS’ mission is to work collaboratively with disease and biology experts on projects designed to demonstrate ways to improve translational research processes and ultimately speed development of new treatments,” said Anton Simeonov, Ph.D., NCATS scientific director. “Mentoring OxCam students in translational science helps form collaborations between NIH and Oxford or Cambridge.”
Developing a new therapy for patients is a multistage process in which the potential therapy is translated from basic research, pre-clinical research, clinical research and clinical implementation to affect public health. As such, multidisciplinary collaborations are crucial for successful translation; no individual or organization can succeed alone. NCATS studies the science of translation to understand the scientific and operational principles underlying each step of the translational process and develops innovative approaches to make the process more efficient. One major area of collaboration at NCATS involves working with disease experts to generate chemical probes for studying human biology, focusing specifically on new therapeutic targets.
Chemical probes are small molecule compounds that can be used to increase or decrease the activity of a biological target in cells or animals. Investigators use these compounds to “probe” the function of molecules such as proteins to understand their roles in health and disease. If appropriate, probes can be optimized to become potential drug candidates. Generating these probes requires the specialized expertise and facilities that NCATS can provide.
The OxCam program provided a new avenue for launching collaborations. With their U.K. mentors and lead mentor Craig Thomas, Ph.D., who heads NCATS’ Chemistry Technology program, three students — Monica Kasbekar, Michael Gormally and Ian Goldlust — have harnessed NCATS’ assay development and high-throughput screening capabilities to identify potential new therapeutics.
For her thesis project, Kasbekar set out to develop a small molecule to probe the metabolism of Mycobacterium tuberculosis, the bacterium that causes tuberculosis, a potentially life-threatening infectious lung disease. In her lab at Cambridge, under the mentorship of biological chemist Chris Abell, FRS, FMedSci, Kasbekar developed an assay to look for the activity of an enzyme called fumarate hydratase, which is involved in the bacterium’s metabolism. She then took the assay to Thomas’ lab to find an inhibitor to block fumarate hydratase. Kasbekar used NCATS’ robotic technology to perform high-throughput screens of a library containing more than 400,000 small molecules.
Unexpectedly, Kasbekar found an inhibitor that was selective for the bacterial version of fumarate hydratase but not the human version. The compound’s selective nature makes it an ideal tuberculosis drug candidate because it would be unlikely to cause toxic side effects in patients. Kasbekar published the results of this work in the July 5, 2016, issue of the Proceedings of the National Academy of Sciences (link is external).
“The OxCam program enabled me to leverage the differing expertise of the Cambridge and NCATS labs to approach problems from different angles, which ultimately led to this discovery,” Kasbekar explained.
The same year that Kasbekar began her work at Cambridge, Goldlust arrived at NCATS to perform high-throughput screens for potential ovarian cancer drugs, using the NCATS Pharmaceutical Collection and the Mechanism Interrogation PlatE (MIPE) library of approved and investigational drugs. Goldlust was searching for agents that could kill ovarian tumor spheroids, tiny clusters of cancer cells that often remain and spread (metastasize) throughout the body after surgical removal of an ovarian tumor.
The screens identified a possible match called elesclomol, a drug originally developed to treat metastatic skin cancer. GoldIust brought the compound to his Cambridge lab and worked with cancer research physician and mentor James Brenton, FRS, FMedSci, to determine the mechanisms by which elesclomol kills ovarian cancer spheroids.
Goldlust noted that these discoveries might not have been possible in a traditional training program. “The OxCam program provides a level of independence that many scientists do not achieve until they are assistant professors,” he said. “We were given almost unlimited access to the resources we needed to answer questions that interested us. That freedom was indispensable.”
Gormally used the OxCam learning environment to explore an even broader research objective: He wanted to find a drug to block FOXM1, a protein that is overactive in many types of cancer. At Cambridge, under the mentorship of biological chemist Shankar Balasubramanian, FRS, FMedSci, Gormally designed an assay to test for FOXM1 activity. Then he brought the assay to NCATS to run a high-throughput screen of a library of more than 54,000 drug-like small molecules.
The experiment yielded several promising inhibitors of FOXM1. Gormally returned to Cambridge and continued to study and characterize the compounds, ultimately generating new insights into how FOXM1 and similar proteins work in cancer cells. He published the results in the Nov. 12, 2014, issue of Nature Communications (link is external).
“NCATS’ resources for high-throughput screening are second to none, and the automation and robotics enabled me to perform many more experiments than would have been possible otherwise,” Gormally said. “And, the training from the OxCam program provided excellent preparation for leading my own research lab in the future.”
All three students currently are finishing their Ph.D. work and will start medical school in fall 2016 to complete the second portion of their doctoral programs. Each anticipates establishing a clinically focused research career, through which they can continue the drug discovery efforts they began in the OxCam program. Meanwhile, their former Ph.D. labs will continue to pursue the therapeutic leads these students uncovered.
“These three students perfectly exemplify what the NIH OxCam Scholars Program aims to produce: young, ambitious and independent investigators who have achieved a high-quality, impactful and collaborative research experience — one they can take with them wherever they go next,” said Rick Fairhurst, M.D., Ph.D., director of the NIH M.D./Ph.D. Partnership Training Program. “I have no doubt that Kasbekar, Goldlust and Gormally each will develop and trial a new therapeutic for human disease at some point in their careers.”
Participation in the OxCam program is just one of the ways that NCATS prioritizes drug discovery collaborations. The focus on training future scientists — in the OxCam program and through other NCATS efforts — provides the nation with a pipeline of promising translational investigators. These critical thinkers will have the skills, experience and knowledge to transform groundbreaking basic research discoveries into therapeutic innovations that benefit more patients more quickly.
”The students who qualify for the OxCam program are remarkable,” Thomas added. “It has been a great experience for NCATS, largely due to their combined efforts and talents.”
(The article was published as a Featured Story on the News and Events page of the National Center for the Advancing Translational Science, August 2016, at https://ncats.nih.gov/pubs/features/oxcam-scholars)
The International Biomedical Research Alliance announced that Jeffrey I. Auerbach, PhD, is joining the Alliance’s board of directors. Dr. Auerbach is the founder and managing member of AuerbachSchrot LLC, an intellectual property (IP) law firm based in Rockville, Maryland.
“The International Biomedical Research Alliance is always looking for new ways to support the NIH Oxford-Cambridge scholars and broaden their postgraduate medical research training. By partnering with Dr. Auerbach, who has 30 years’ experience in patent licensing, and has provided counsel for some of the most complex biotechnology cases, we will help increase their knowledge of this important arena,” said Stephen M. McLean, chairman of the Alliance Board of Directors. “We are delighted that Dr. Auerbach has agreed to join our Board.”
“This is a wonderful opportunity to help mentor the next generation of medical researchers who are going to shape the future of healthcare,” said Dr. Auerbach. “As a medical researcher and a patent lawyer, I understand many of the questions and challenges that these scholars face and have the experience to be able to provide practical, tangible guidance.”
Dr. Auerbach prepares and litigates bioinformatics, diagnostics, genetics, microbiology, molecular biology and therapeutic patent applications. He is also an expert in protecting global patent rights. Furthermore, he has patents of his own for vaccine production and isothermal “rolling circle” nucleic acid amplification.
He is also an entrepreneur. Dr. Auerbach founded Replicon, Inc., a biotechnology company that used rolling circle amplification in diagnostics, genomics and therapeutics, in 1994 and served as its president for almost eight years until it was acquired by Biokit SA. He then founded DC Associates, LLC, a company that licensed nucleic acid amplification technologies, and was its president for more than a decade.
Dr. Auerbach has an MPhil and a PhD in molecular biophysics and biochemistry from Yale University. He also has a JD from the National Law Center of George Washington University.
