Buffalo Translational Consortium News
UB-led study of postmenopausal women finds that those at highest genetic risk of fracture benefit most from HT
BUFFALO, N.Y. – Women at the highest genetic risk for fracture benefit the most from hormone therapy, according to a first-of-its-kind study led by researchers at the University at Buffalo.
The study included nearly 10,000 participants from the Women’s Health Initiative (WHI), a national, long-term study of more than 150,000 women.
“We found that women who are genetically at the highest fracture risk can enjoy the greatest protection from fracture when they use hormone therapy,” said Heather Ochs-Balcom, associate professor of epidemiology and environmental health in UB’s School of Public Health and Health Professions, who led the research team.
The findings were published online ahead of print in the Journal of Clinical Endocrinology and Metabolism. The paper’s first author, Youjin Wang, conducted the research as a doctoral candidate in epidemiology and environmental health at UB.
“This study provides a better understanding of who can benefit the most in terms of bone health from hormone therapy use,” Ochs-Balcom said, adding that the results have implications for personalized medicine. “It’s important information as women and their doctors make decisions about hormone therapy use.”
The study, believed to be the first to investigate gene-hormone therapy interaction on fracture in postmenopausal white women, utilizes the largest set of known genes linked to fracture risk from a meta-analysis of genome-wide association studies.
Researchers looked at a subset of 9,922 women from among the more than 27,000 who had participated in WHI hormone therapy clinical trials. They wondered whether women who are more genetically susceptible to fractures could benefit from hormone therapy.
“This is important because, as previous WHI studies have identified, there are risks and benefits with hormone therapy,” Ochs-Balcom said. “This is where precision or personalized medicine comes in — the attempt to get the right drugs to the right person to ensure the most benefit and least harm.”
As women age, their bone mineral density (BMD) decreases, leaving them at greater risk of breaking bones from falling, which also increases as they age. But some women also are more genetically prone to fractures.
“Our study represents a first look at how inherited predisposition to fracture is related to hormone therapy use,” said Ochs-Balcom, who also holds a faculty appointment in the Department of Genetics, Genomics and Bioinformatics in UB’s Jacobs School of Medicine and Biomedical Sciences.
Wang notes that “further studies on gene-therapy interaction are warranted to evaluate the advantages of targeted interventions based on genetic profile.” The research team is currently analyzing other gene-environment interactions and recently published another paper on the association of calcium plus vitamin D supplementation and genetic risk of fracture.
In addition to Wang and Ochs-Balcom, other UB co-authors include Jean Wactawski-Wende, dean of the School of Public Health and Health Professions and SUNY Distinguished Professor and professor of epidemiology and environmental health; and Leah Preus, Kathleen Hovey and Jing Nie from the School of Public Health and Health Professions.
Additional co-authors include Lara Sucheston-Campbell, Rebecca Jackson and Samuel Handelman, The Ohio State University; Rami Nassir, University of California, Davis; and Carolyn Crandall, University of California, Los Angeles.
The Women’s Health Initiative began in 1991 and consisted of a set of clinical trials and an observational study. Combined, they included more than 161,000 generally healthy postmenopausal women aged 50 to 79.
One of 40 WHI centers nationwide, the University at Buffalo serves as the Northeast Regional Center, managing data collection and scientific coordination among nine WHI-affiliated institutions in the mid-Atlantic and Northeast regions. UB has received WHI extension funding to conduct follow-up studies on the original participants, many of whom are now between ages 67 and 100.
The WHI is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health.
2017 Creative Scientist Workshop: “Innovations in Recruitment to Clinical Trials,” March 14-15, 2017
A group of about 50 biomedical researchers gathered in Buffalo in March to examine the state-of-the-science on recruitment to clinical trials and to explore approaches for developing and evaluating improved methods.
Participants came from Buffalo Translational Consortium partner institutions and a range of other CTSA hubs and institutions, including the University of Rochester, Vanderbilt University, Johns Hopkins University, University of Pennsylvania, The Ohio State University and Case Western Reserve University.
The need is massive. At present, recruitment of participants represents the single largest obstacle to successful clinical trials. Consensus among this diverse group was reached on at least one topic: the need for more empirical data, rather than guesswork and anecdotes, about what actually does and doesn’t work.
Workshop organizer Larry Hawk, PhD, a professor of psychology at UB who conducts clinical trials to help cigarette smokers kick the habit, reviewed the modest literature on evidence-based best practices in recruitment and led the push to improve it: “We need to build a research base for better recruitment as opposed to the usual hand-wringing, throwing money at it, et cetera,” he said.
The 2017 Creative Scientist Workshop, “Novel Approaches to Clinical Trials Recruitment,” was sponsored by the University at Buffalo Clinical and Translational Science Institute (supported by the National Center for Advancing Translational Sciences of the NIH under award number UL1TR001412). It was held over two days, despite a late-winter snowstorm that socked most of the East Coast, including Buffalo. Attendees heard from national experts on recruitment strategies and formed small work groups to share ideas and formulate strategies.
The conference employed a facilitated workshop format now being used by the National Science Foundation, National Institutes of Health and the National Center for Advancing Translational Sciences to catalyze scientific innovation. Workshop attendees brought a diverse set of perspectives to the table, presenting a range of informative case studies and suggested best practices.
The Clinical and Translational Science Institute (CTSI) announced the presentation of a new Buffalo Translational Consortium (BTC) Mentored Career Development Award in March.
Jason Davies, MD, PhD, assistant professor in the departments of Neurosurgery and Biomedical Informatics, Jacobs School of Medicine and Biomedical Sciences, will be researching better ways to predict who is most likely to have a stroke, and who is most likely to recover.
Since strokes have many causes and people are individually very different from one another, it’s difficult to know how much at risk any particular person might be. Davies’ project is designed to develop personalized risk predictions based on the combination of genetics and rich demographic, clinical and social data gleaned from electronic health records. All of these factors will be combined using artificial intelligence techniques to create new predictive models. If shown to be effective, these models could then be used to improve clinical practices and guide future health care policies based on constellations of risk factors that better represent individual patient risk.
Margarita L. Dubocovich, PhD, SUNY distinguished professor and senior associate dean for diversity and inclusion in the Jacobs School of Medicine and Biomedical Sciences, is the program lead of the CTSI Mentored Career Development Award Program. “Dr. Davies’ stellar training in neurological surgery and stroke -- combined with the expert guidance of outstanding mentors and the resources provided by the Clinical and Translational Science Institute -- will synergize his unique and novel research on personalized risk predictions for stroke,” she said.
Davies received his MD and PhD at Stanford University and was a resident in the University of California San Francisco Department of Neurological Surgery program. He joined University at Buffalo Neurosurgery as a fellow in 2015 and was named assistant professor in neurosurgery a year later.
The CTSI Mentored Career Development Award programs provide junior faculty with research and professional development mentoring under the guidance of experienced mentors to help their transition into independently funded clinical and translational investigators. BTC scholars receive support through the BTC to cover partial salary and research, tuition and travel costs for up to two years, as they submit for individual K or R awards.
Preference for funding awards is given to research that brings novel approaches towards reducing health disparities in clinical populations and applicants with experiences or attributes, which increase diversity in the clinical and translational workforce. Those goals align with the overall aims of the Clinical and Translational Science Institute (CTSI), which serves as the hub of the BTC.
More information about education and training in clinical and translational research can be found here.
The BTC award is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award numbers UL1TR001412 to the University at Buffalo. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
The University at Buffalo Clinical and Translational Science Institute (CTSI) Science Seminar Series is pleased to present renowned biophysicist and professor of structural biology Michael Levitt for the 2017 O.P. Jones Lecture entitled, “The Birth and Future of Multiscale Modeling of Macromolecules.” The lecture, co-sponsored by the Department of Biomedical Informatics in the Jacobs School of Medicine and Biomedical Sciences, is scheduled for Tuesday, May 2, at 3:30 p.m. in Butler Auditorium, 150 Farber Hall, on UB’s South Campus.
Levitt, along with Martin Karplus and Arieh Warshel, was awarded the 2013 Nobel Prize in Chemistry for the development of multiscale models for complex chemical systems. Levitt says the work leading to the prize began in 1967. “The simplifications used then at the dawn of the age of computational structural biology were mandated by computers that were almost a billion times less cost-effective than those we use today,” he said. “These same multiscale models have become increasingly popular in applications that range from simulation of atomic protein motion to protein folding and explanation of enzyme catalysis. In this talk, I describe the origins of computational structural biology and then go on to show some of the most exciting current and future applications.”
Born in South Africa in 1947, Levitt visited London at age 16 where he was “profoundly influenced” by John Kendrew's 1964 BBC TV series “The Thread of Life,” a program produced by the Royal College of Surgeons to explain the emerging field of molecular biology. After receiving a BSc in physics at King’s College London in 1967 and studying for a year with Prof. Shneior Lifson and his PhD student Arieh Warshel at the Weizmann Institute in Israel, Levitt joined the Laboratory of Molecular Biology (LMB), Cambridge, in 1968. His PhD thesis on Protein Conformation Analysis described the use of classical force-fields and introduced energy refinement. Levitt worked with Francis Crick as a visiting scientist at the Salk Institute in La Jolla, CA for two years in the late 1970s. Following appointments in the Weizmann Institute in Israel and the MRC Laboratory of Molecular Biology in Cambridge in the 1980s, he joined the faculty of the Department of Structural Biology at Stanford University in 1987, where he remains to this day an active programmer -- “a craft skill of which I am particularly proud,” he says.
Levitt’s “diverse interests” have included: RNA and DNA modeling, protein folding simulation, classification of protein folds and protein geometry, antibody modeling, x-ray refinement, antibody humanization, side-chain geometry, torsional normal mode, molecular dynamics in solution, secondary structure prediction, aromatic hydrogen bonds, structure databases and mass spectrometry.
A Fellow of the Royal Society since 2001 and a member of the National Academy of Sciences since 2002, Levitt continues to pursue his dual ambitions: “to work as single-mindedly as I did in the mid-1970s on hard problems and to help today’s young scientists gain the recognition and independence that my generation enjoyed.”
Please join the CTSI and the Department of Biomedical Informatics in welcoming him to UB this May.