Top-Five Awards to Brigham Researchers Open Up New Opportunities, Directions
In 2018, MGH and the Brigham ranked first and second, respectively, on the list of top free-standing hospitals to receive federal research funding from the National Institutes of Health. This tremendous honor is not all that surprising—the institutions have held the top two spots for the last 25 years. In 2018, the Brigham’s research revenue totaled $707 million, almost one-quarter of the Brigham’s entire revenue.
In late 2018, Paul Anderson, MD, PhD, chief academic officer and senior vice president of Research and Education, shared these statistics with the Brigham community at a series of forums including the monthly Research Connection Live Lunch and Research Oversight Committee meetings. Anderson also highlighted the five Brigham projects and researchers who received the largest research awards in 2018, illustrating new opportunities and directions that Brigham researchers will pursue starting in the year ahead.
siRNA Points the Way
The top award for the Brigham in 2018 is for a project led by Marc Sabatine, MD, chair of the Thrombolysis in Myocardial Infarction (TIMI) Study Group. TIMI and colleagues at the University of Oxford will lead HPS-4/TIMI 65 ORION-4, a large cardiovascular outcomes trial of inclisiran, an investigational new drug being developed by the Medicines Company. Inclisiran targets a well-known molecule called PCSK9, a key player in the metabolism of LDL (or “bad”) cholesterol. Several inhibitors have been developed to block PCSK9 and reduce risk of heart disease, but inclisiran represents a new approach. Unlike previously developed monoclonal antibodies (also studied by Sabatine), which typically need to be dosed every two weeks, inclisiran is a short-interfering RNA (siRNA) molecule that only needs to be injected every six months to cut LDL cholesterol levels in half. The design of the clinical trial itself is novel, too. It will be conducted at high-enrolling sites using a streamlined, quality-by-design approach, reducing the cost of the trial and allowing it to run for a longer period.
All in for All of Us
Brigham investigators were among the recipients of a grant to fund the New England Precision Medicine Consortium of the All of Us Research Program, a historic effort to gather data over many years from one million or more Americans (www.joinallofus.org). All of Us New England is supported by a $12 million grant from the National Institutes of Health’s Office of the Director. Partners HealthCare System and its founding hospitals, MGH and the Brigham, lead All of Us New England, which was launched in May 2018. Boston Medical Center is an equal partner in All of Us New England.
All of Us is intended to serve as a national resource for researchers to inform studies on a wide variety of health conditions to help researchers learn more about how individual differences in lifestyle, environment and biological makeup can influence health and disease. The program aims to engage a community of participants that reflects the diversity of the U.S., including people who have been historically underrepresented in biomedical research, medically underserved or have experienced disparities in health due to systemic social disadvantages.
“All of Us will create a unique longitudinal cohort, building on the tradition of cohorts like the Framingham Heart Study and the Nurses’ Health Study that have contributed so much to our understanding of human health,” said Elizabeth Karlson, MD, MS, a principal investigator for the project and director of Rheumatic Disease Epidemiology at the Brigham, noting that All of Us will include comprehensive data from surveys, mobile sensors, apps, biomarkers and genetic markers.
Risk of Asthma: A Role for Vitamin D and the Gut Microbiome?
Most cases of asthma are diagnosed before age 6, suggesting that early life or even prenatal exposures may contribute to the development of asthma and allergies. Scott Weiss, MD, co-director of the Systems Genetics and Genomics Section of the Channing Division of Network Medicine, will lead an investigation into the role of two potential risk factors: vitamin D and the intestinal microbiome. The team will determine patterns and changes in the early intestinal microbiome in children up to age 6 and will determine if such changes are related to vitamin D deficiency before and immediately after birth. Researchers will also study whether these changes are associated with an asthma diagnosis by age 6. The work will be funded with a $2.6 million grant from the NIH’s Office of the Director.
“Findings from this project will point to potential mechanisms by which early environmental exposures interact with the developing intestinal microbiome and the host to confer risk for asthma,” said Weiss.
Connecting the Research Community
Award funding from both federal and non-federal sources totaling $2.3 million will support the continuation of the Harvard Clinical and Translational Science Center. Part of the Harvard Catalyst established in 2008, the center supports innovative clinical and translational science and provides training opportunities for the next generation of researchers. The center offers courses and educational programs, research consulting, tools for study design and clinical trial collaboration, guidance on regulatory issues and pilot funding for novel, high-impact projects. All this support is available to trainees, fellows and faculty. Lindsey R. Baden, MD, the director of the Center for Clinical Investigation (which is the home of Harvard Catalyst at the Brigham), serves as the principal investigator of the Harvard Catalyst at the Brigham and co-leads the Harvard Catalyst Connector and Network programs.
Finding Treatments for Genetic Tumor Syndromes and Cancers
Hamartoma syndromes are rare, genetic tumor syndromes in which benign growths occur in many different organs that can have lethal effects. These syndromes are caused by mutations in classic tumor suppressor genes (TSC1, TSC2, PTEN, LKB1), which are also involved in many adult cancers. For the past 10 years, David Kwiatkowski, MD, PhD, and colleagues have been dissecting the wiring of the mTOR signaling pathway affected by mutations in these genes and how this causes tumor development. With this renewal in funding of $1.8 million from the National Cancer Institute, the team will focus on development of therapeutic strategies for the tumors and cancers caused by mutations in these genes.
“This P01 Award represents team science at its best, with important contributions from all seven principal investigators. I am optimistic our work will lead to changes in care for one or more of these tumor types,” said Kwiatkowski.
Anderson congratulated the top award winners as well as all investigators in the research community who have garnered new funding in the last year.
“Research is critical to this organization. It has helped create the Brigham’s reputation, discoveries, breakthroughs, new therapies and clinical trials,” said Anderson. “I want to thank you all for your work, your efforts and your commitment to research at the Brigham.”