Drs. Josh Hill, Josh Schiffer, Keith Jerome and Michael Boeckh, an interdisciplinary group of investigators from Fred Hutchinson Cancer Research Center's Vaccine and Infectious Disease Division, have received a $1.7 million grant from Chimerix Inc. to study the risk factors for and cumulative impact of reactivated infections after transplantation with donor adult stem cells. Chimerix Inc. is a biopharmaceutical company led by University of Washington-trained infectious disease physicians who got their start in research careers at Fred Hutch.
Lifelong latent infections, normally held in check by a healthy immune system, can reactivate in a patient whose immune system has been destroyed by the intense chemotherapy and radiation pre-transplant conditioning regimen required to make room for transplanted immune cells to grow. Current screening and prevention strategies have reduced but not eliminated complications caused by these pathogens. At the same time, the increased use of cord blood cells and T-cell depletion, while expanding access to stem cell transplantation, has led to a rise in viral reactivation because of the later engraftment and delayed restoration of immune function that accompany these procedures.
One of the barriers to broader prevention is a poor understanding of the cumulative effects of multiple viral reactivations and the toxicities of currently available medications, Hill said.
“If you have one virus and get another, does it change the natural history of the infection?” he said. “And does reactivation of more than one virus increase the risk of significant complications, such as graft-vs.-host disease, pulmonary disease, or death?”
In the study proposed by Hill, blood samples obtained weekly for the first 100 days after transplantation will be tested by the UW Molecular Virology Laboratory for cytomegalovirus, human herpesvirus-6A and 6B, adenovirus, Epstein-Barr virus and BK virus. Quantitative polymerase chain reaction will be used to detect reactivated viruses and examine their cumulative impact. In collaboration with the Schiffer group, the investigators will develop mathematical models to predict outcomes and guide treatment.
“We’ll be looking at viral interactions and how that changes the life cycle of infection,” Hill said. “We can use mathematical models to predict this and let this data guide us on how to intervene and treat.”
This will be the most comprehensive study of the epidemiology, viral dynamics and clinical impact of multiple reactivated viruses in a contemporary group of stem cell transplant recipients. The data generated by this proposal will be instrumental in designing randomized prevention and treatment clinical trials with emerging broad-spectrum drug or immunologic therapies.
Dr. Joshua Roth, an investigator in the Hutchinson Institute for Cancer Outcomes Research, is among six recipients of the International Society for Pharmacoeconomics and Outcomes Research 2015 Scientific Achievement Awards. He received the Award for Excellence in Application of Pharmacoeconomics and Health Outcomes Research last month during ISPOR’s 20th annual meeting in Philadelphia.
Specifically, he won the award for a paper he wrote describing the economic return from the Women's Health Initiative landmark combined hormone therapy trial; his analysis was published last year in Annals of Internal Medicine.
Roth is an assistant member of the Public Health Sciences Division at Fred Hutch and an affiliate assistant professor in the Pharmaceutical Outcomes Research and Policy Program at the University of Washington.
His primary research interest is in the application of comparative effectiveness research methods to inform translation of lung and breast cancer therapeutics and diagnostics, including observational study design, decision modeling, randomized controlled trial design, systematic review, and meta-analysis. His current research focuses on evaluating patient perspectives on lung cancer screening and applying value of information analysis to identify high-value study designs for future lung cancer screening research.
The annual ISPOR meeting focused on the theme of “Integrating Big Data, Patient Data, and Cost-Effectiveness into Clinical Practice: Promise and Prospects.” More than 3,700 professionals from research and academia, and policy makers, payers, and patient representative groups attended.
Dr. Patrick Mitchell, who recently completed his doctorate research in the laboratories of Drs. Harmit Malik and Michael Emerman, has received the 2015 Raymond W. Sarber award, a prize given by the American Society for Microbiology to honor exceptional graduate and college students in the field of microbiology. Mitchell was nominated by Malik, Emerman and their collaborator Dr. Otto Haller of the University of Freiburg. He received the award recently at the ASM general meeting in New Orleans.
Mitchell spent his graduate years studying an antiviral protein known as MxA, part of the body’s immune defense against influenza and other viruses. This protein is unique among virus-fighting molecules in that it is able to recognize and form a barrier against many different types of infections by targeting a variety of viral proteins. Most antiviral proteins are more specific, and scientists didn’t understand the reason why MxA was able to effectively block so many different types of viruses.
Mitchell, who describes himself as “part evolutionary biologist and part molecular virologist,” brought the idea to work on MxA to Malik, who studies other aspects of the interplay between the immune system and viruses but had not previously worked on this protein. Mitchell decided to look at which pieces of MxA rapidly evolve as an innovative way to understand how the protein works. The researchers found that, unlike other antiviral proteins, MxA works like a “Swiss Army knife,” Malik said, using different sections of itself to recognize different viruses.
“Patrick is extremely persistent. He recognized that this is a very important problem,” Malik said. “He basically established an entirely new research program in my lab … That’s unusual for a graduate student to have that level of ambition.”
Along with his graduate research, Mitchell has had a longstanding interest in early science education and literacy, particularly for students from underserved communities. Through the Hutch’s Science Education Partnership, he participated in a training program to improve science education in Washington high schools and has served as an instructor for the Technology Access Foundation Academy, a STEM-focused public high school in Federal Way, Washington. In September, Mitchell will join the laboratory of Dr. Russell Vance at the University of California, Berkeley, for a postdoctoral fellowship where he will apply evolutionary perspectives to understanding bacterial infections.
“It’s wonderful to be recognized and get this kind of affirmation from the microbiology community,” Mitchell said. “The community here has a lot of avenues to promote science and, in particular, to influence early science education. It’s been awesome and enriching to share those meaningful experiences with up-and-coming scientists.”
The Pew Charitable Trusts selected Dr. Jesse Bloom among this year’s 22 early-career researchers named Pew scholars in the biomedical sciences. The award, announced today, includes a four-year grant of $240,000 to support Bloom’s research on influenza’s evolution and its interaction with the human immune system.
“This new class of remarkable scientists is emblematic of all that is unique, exciting, and compelling about this initiative,” Rebecca W. Rimel, Pew’s president and CEO, said in a statement. “We are proud to provide a launching pad for the adventurous minds represented here.”
The Scholars Program in Biomedical Sciences was launched 30 years ago and includes more than 600 scientists, including six other Fred Hutch researchers. Pew scholars are faculty members at the assistant professor level and are nominated for pursuing high-risk, high-reward research.
The funding will help support Bloom’s ongoing research on influenza evolution in which he and his team systematically mutate every amino acid in different flu proteins and then ask how those mutations affect the virus itself and its ability to infect cells in the laboratory. Understanding not only how the virus has evolved to date but how it is likely to evolve in the future, through research like Bloom’s, could lead to better seasonal flu vaccines.