This immunofluorescent image shows two distinct subclonal populations of cells (red and green) that may cooperate in this chimeric tumor. | Allison Cleary and Edward Gunther
Allison Cleary, a cancer research pioneer who demonstrated that subpopulations of breast cancer cells cooperate to enable tumor growth, has been named the 2015 Grand Prize winner of the Science & SciLifeLab Prize for Young Scientists.
Significant challenges remain to fight breast cancer; for example, recent studies have revealed that multiple genetically distinct subclones, or tumor cell subpopulations, coexist within individual human breast cancers, which makes them difficult to treat.
Many scientists have thought that this heterogeneity is a consequence of tumor evolution, and that the subclones commonly observed in breast cancers compete with each other within a tumor to be the "fittest." But as a graduate student in the laboratory of Edward Gunther at the Pennsylvania State University College of Medicine, Cleary investigated another possibility — that subclones actually cooperate with each other to promote tumor growth and development.
"We all assume that tumors arise from a single cell — heterogeneity arises through an evolution process — but could it be possible that tumors arise from two separate cells that are interacting with each other?" she asks in her grand-prize winning essay, "Teamwork: The Tumor Cell Edition," which appears in the 4 December issue of Science.
To explore this question, Cleary and colleagues focused on a mouse model of breast cancer known to produce tumors made of two distinct cell populations. Using gene sequencing and molecular biology techniques, Cleary and her team showed that these two populations actually represent two genetically distinct subclones, each with its own active cancer-causing gene.
Allison Cleary | Allison Cleary
Cleary then assessed whether the different subclonal tumor cell populations were capable of re-growing tumors, separately or as a mixture, by transplanting the cells back into the mammary glands of mice. Animals receiving either subclone alone failed to develop tumors, she observed, whereas the cell mixture containing both subclones was highly conducive to tumor formation.
"The results not only raise interesting questions about the nature of tumor progression but may ultimately have implications in the development of new cancer therapies," said Cleary. "It will be very interesting to find out whether these types of cooperative interactions are occurring within human breast tumors. If that is the case, I think there could be an opportunity to develop novel treatments for breast cancer that work to uncouple those cooperative interactions within the tumor."
Cleary is continuing her studies at the Pennsylvania State University College of Medicine in their combined M.D./Ph.D. program. She is finishing her M.D. degree and is in the process of applying to Pathology Residency Training Programs on the Physician-Investigator Track.
Cleary originally intended to pursue a career as a skeletal muscle physiologist, but was drawn to study in Gunther's cancer biology laboratory after she did a rotation in his laboratory. "I was hooked from the very first day — it was seriously like falling down the rabbit hole," said Cleary. "The thing about cancer that I find so interesting is that it's made up of our own cells that have been sort of hijacked and reprogrammed and are now working against us."
"Allison Cleary's work was a clear example of a young investigator who became fascinated with a theory that went against the dogma of the field and who designed elegant experiments to determine the reality of the science," said Barbara Jasny, deputy editor of Science.
Marcia McNutt, editor-in-chief of the Science family of journals, further reflected on Cleary's contribution. "Once again in 2015," McNutt said, "the judges were presented with an outstanding slate of candidates whose research is exciting, relevant, and original. While the SciLifeLab Prize may have been conceived to boost the careers of young scientists, it also serves to boost the confidence of all of us that the future of science is in good hands."
Cleary will receive the award for her research in the field of cell and molecular biology in Stockholm, Sweden, on 9 December, during an award ceremony and dinner at the Grand Hôtel in the Hall of Mirrors, which hosted the first Nobel Prize ceremony in 1901.
"I am truly impressed with the awardees' accomplishments and look forward to meeting them in Stockholm soon," said Olli Kallioniemi, director of SciLifeLab. "After three years the prize is now fully established thanks to the kind support of the Knut and Alice Wallenberg Foundation and we are excited to continue rewarding young scientists in the coming years."
The Science & SciLifeLab Prize for Young Scientists recognizes promising early-career scientists who conduct groundbreaking life-science research and includes a grand-prize award of US$30,000, supported by Science for Life Laboratory, a coordinated effort among four universities in Sweden, and the journal Science. The 2015 award also recognizes three runners-up winners, each receiving US$10,000. Their essays are also published online in Science.
The 2015 runners-up are:
Adam T. Ford | S. Colla
Adam T. Ford: For his essay on the topic of ecology and environment, "The Mechanistic Pathways of Trophic Interactions in Human-Occupied Landscapes." Ford is a wildlife ecologist interested in how predator-prey interactions are shaped by human-modified landscapes. He received a B.Sc. from the University of Victoria (British Columbia), a M.Sc. from Carleton University (Ontario), and his Ph.D. from the University of British Columbia with Assistant Professor Jacob Goheen. Ford is currently a Liber Ero Postdoctoral Fellow in Conservation Science, based at the Department of Integrative Biology at the University of Guelph (Ontario). The research described in his essay sheds new light on the relationships of people, large carnivores, their herbivore prey, and plants in an East African savanna.
F. Johannes Scheid | Jonathan Abraham M.D. Ph.D.
F. Johannes Scheid: For his essay on the topic of translational medicine, "HIV Specific B cell Response in Patients with Broadly Neutralizing Serum Activity." Growing up in New York and Germany in a family of scientists, Scheid was fascinated early in life by the career of a physician scientist. During medical school at the Charité Berlin, he decided to pursue a Ph.D. at The Rockefeller University. In his Ph.D., he investigated the observation that some HIV patients develop very potent antibodies against HIV. The Ph.D. was awarded the 2012 Harold Weintraub award. His work in the laboratory was inspired by interactions with study participants and he was excited to see some of his work now go into clinical trials. After completing medical school and his Ph.D., he worked for one year as a Clinical Scholar at The Rockefeller University and is now continuing his clinical training at the Massachusetts General Hospital in Boston.
Ludmil Alexandrov| Ludmil Alexandrov
Ludmil Alexandrov: For his essay on the topic of genomics and proteomics, "Understanding the Origins of Human Cancer: Mutational Signatures." Alexandrov is an Oppenheimer Fellow in the Theoretical Biology and Biophysics Group at Los Alamos National Laboratory. He earned his Bachelor of Science degree in Computer Science from Neumont University and received his M.Phil. in Computational Biology as well as his Ph.D. in Cancer Genetics from the University of Cambridge. Alexandrov is a recipient of the 2015 Weintraub Award for Graduate Research and, in 2013, he was listed by Forbes magazine as one of the "30 brightest stars under the age of 30" in the field of science and healthcare. Alexandrov's work is focused on understanding the mutational processes responsible for human cancer and human aging. In 2015, his research was highlighted by the American Society of Clinical Oncology as an important step forward in the fight against cancer.
SciLifeLab, Science for Life Laboratory, is a Swedish national center for molecular biosciences, with the mission to develop, use and provide advanced technologies for applications in health and environmental research. The center was established in 2010 and became a national resource in 2013, making technologies and expertise available to researchers in all of Sweden and beyond. Today, the center comprises more than 1,200 researchers and personnel. We offer a cross-disciplinary research setting that interacts with healthcare, authorities and industry to meet the need for new clinical methods and a better environment. In addition, SciLifeLab provides education for students and researchers at all levels. SciLifeLab is hosted by four universities; Karolinska Institutet, KTH Royal Institute of Technology, Stockholm University and Uppsala University. The infrastructure is mainly located in Stockholm and Uppsala but we also offer services at other Swedish universities.