From left: Gad Getz, Chuan He, and Aviv Regev are the three winners of the 2017 Paul Marks Prize for Cancer Research.
The 2017 winners are Gad (Gaddy) Getz, PhD, of the Broad Institute of MIT and Harvard, the Massachusetts General Hospital (MGH) Cancer Center, and Harvard Medical School; Chuan He, PhD, of the University of Chicago; and Aviv Regev, PhD, also of the Broad Institute.
Gad (Gaddy) Getz
Gad (Gaddy) Getz, PhD, is an Institute Member and director of Cancer Genome Computational Analysis at the Broad Institute. He is also director of Bioinformatics at the MGH Cancer Center and Department of Pathology. In addition, he is an Associate Professor of Pathology at Harvard Medical School and the Paul C. Zamecnik Chair in Oncology at the MGH Cancer Center.
He uses computational biology to study the genomic changes that allow normal cells to evolve and become cancerous, and the continuing evolutionary processes by which they become increasingly aggressive and come to dominate their environment.
Dr. Getz explains that his research falls under two umbrellas. The first is characterization, which involves analyzing the genomic changes in an individual patient’s tumor sample. “We want to learn what events and mutational processes got them to that place,” he says.
The second part is interpretation, which involves studying data from many samples to look for patterns. “From a single patient, it’s hard to look at a sample and know which mutations are driving the tumors and which are passengers,” he adds. “We need statistical models and samples from many patients to determine which genes and pathways are mutated at a higher rate than what you would expect to see by chance.”
Dr. Getz, who has been involved in a number of multicenter cancer sequencing projects, including The Cancer Genome Atlas and the International Cancer Genome Consortium, stresses the importance of collaboration in his research. “The future of this field is only going to be more collaborative,” he says. “To have the statistical power to find these cancer drivers, we need to look at data from all over the world. Including greater numbers of patients is key to making a difference in this field.”
In addition, he notes, it’s important to involve clinicians, who are able to help connect genomic changes observed in the lab with what happens in patients, and to translate findings into new treatments that can be tested in the clinic.
Dr. Getz earned his doctorate in physics from the Weizmann Institute of Science in Israel.
View Gad Getz’s webpage at the Broad Institute.
Chuan He
Chuan He, PhD, is the John T. Wilson Distinguished Service Professor in Chemistry, Biochemistry, and Molecular Biology at the University of Chicago; director of U of C’s Institute for Biophysical Dynamics; and a Howard Hughes Medical Institute (HHMI) investigator. He is also director of the Synthetic and Functional Biomolecules Center at Peking University in China.
He is an expert in the field of cancer epigenetics and RNA modification biology. Epigenetics involves variations in the way that genes are expressed that don’t affect the actual DNA sequence. “The human genome contains 3 billion base pairs but only roughly 20,000 genes,” he says. “We have tens of trillions of cells, and about 200 different tissue or cell types. Epigenetics facilitates cell differentiation into different identities, despite having the same genetic sequence in an individual human being.”
His major contribution to the field is that he was the first to put forward the idea that modifications to RNA are reversible and can control gene expression. Control of RNA, the molecule that carries DNA’s “message” to the protein-making machinery of the cell, is one of the major ways that affects the outcomes of gene expression.
“When I started this work back in 2008 and 2009, we knew that proteins called writers could install modifications to RNA molecules that altered their function, but no one knew that there were also proteins called erasers that could undo these changes,” Dr. He explains. His team went on to identify for the first time the eraser proteins, and in later work characterized a series of reader proteins that explain how RNA methylation functioned.
“This research laid down the mechanistic pathways for our current understanding of how these modifications impact biological outcomes, including those related to cancer,” he says. “Cancer and other diseases can hijack aberrant RNA methylation to gain a survival advantage, allowing cells to proliferate and grow out of control.”
These types of RNA changes are known to play a role in many types of cancer, including endometrial cancer, acute myelogenous leukemia, and glioblastoma. Dr. He’s work forms some of the foundations for developing potential future therapies that target RNA methylation effectors against human cancer.
He earned his doctorate in chemistry from MIT.
View Chuan He’s webpage at the University of Chicago.
Aviv Regev
Aviv Regev, PhD, is director of the Klarman Cell Observatory at the Broad Institute, a professor in the biology department at MIT, and an HHMI investigator. She is also one of the leaders of Human Cell Atlas, an international effort to build a collection of maps that will describe and define the cellular basis of health and disease.
She has been a pioneer in developing experimental and computational methods for the genomic analysis of single cancer cells, especially using the process called RNA sequencing (RNA Seq). Because RNA Seq looks at RNA rather than DNA, it enables investigators to determine which genes are being expressed, or “turned on,” in particular cells.
Dr. Regev explains that to leverage the full benefits of next-generation sequencing, it’s important to look at cells on the individual level, rather than looking at the makeup of an entire tumor. “You can think of the way tumors have traditionally been analyzed as a fruit smoothie. All the cell types are mixed together, and it’s hard to determine what makes up the mixture,” she says. “Single-cell analysis is more like looking at a fruit salad. You can not only characterize each fruit individually, but also determine how much of each type is present.”
Dr. Regev’s has made discoveries thus far in two types of cancer: brain tumors and melanoma. By using this single-cell method, her team has discovered that although oligodendroglioma and astrocytoma, two types of brain cancer, appear to be very different, they both contain the same cancer stem cells. These stem cells account for what makes them difficult to treat and could yield insights into how targeted therapies could be developed that would be effective against both cancers.
In melanoma, her lab has determined that a small subset of tumor cells is resistant to therapy before treatment has even started. These findings offer new clues about how to best treat individual patients.
In addition to her own research, Dr. Regev is also active in helping many other investigators to use the methods she has developed. “These insights will help everyone who works in this area to develop better diagnostics and better therapies,” she says.
She earned her doctorate in computational biology from Tel Aviv University in Israel.
