UCSF Scientists Help Guide Cancer Research to a Melding of Physics & Biology
Two separate grants from the National Cancer Institute (NCI), each totaling more than $15 million, will feature UCSF scientists as the senior cancer researchers.
The grants, announced by the NCI last week, are among 12 new awards that will promote collaborations among universities, and among scientists from different disciplines.
One of the two new centers being co-led by UCSF cancer biologists is the result of a successful proposal submitted by University of California collaborators from UC Berkeley, UCSF, the Lawrence Berkeley National Laboratory (LBNL) and the California Institute for Quantitative Biosciences (QB3), and will be administered from UC Berkeley. The other is based at Princeton University.
The unusual aim of the NCI’s solicitation for research proposals that led to the grant awards was to engage physicists as the leaders in a new initiative in the fight against cancer. The NCI is fostering the fusion of physics and traditional cell biology, to inject new knowledge and ways of thinking into the war against this leading killer. The 12 grants mark the establishment of a network of Physical Sciences Oncology Centers.
"I truly believe the initiative's objective of applying physical sciences and engineering perspectives and principles to cancer will lead to paradigm-shifting science toward understanding and, ultimately, treating the disease," says Larry Nagahara, PhD, NCI’s program director for the new centers. "I'm very excited with the team of world-class researchers assembled in these centers and that they will be working together as a collaborative network."
“The NCI wanted to do things differently,” says UCSF’s Thea Tlsty, PhD, director of the Cell Cycling and Signaling Program at the UCSF Helen Diller Family Comprehensive Cancer Center. “What they required for these research proposals is that a physicist be a principal investigator, and that a cancer biologist be a senior scientific investigator.”
Tlsty teamed up with physicist Robert Austin, PhD, of Princeton University to put together a research agenda focused on exploring the evolution of cancer -- how a tumor and its environment changes during the course of disease. The two will now lead the Princeton University Physical Sciences Oncology Center.
“It is the evolution of cancer -- the switch to drug resistance and a metastatic mode that can spread disease to distant parts of the body -- that causes it to become deadly in so many cases,” Tlsty says.
Not only physicists, but also mathematicians, chemists and engineers are among the physical scientists who will work together with cancer biologists at the new centers.
Weaver has been at the forefront of interdisciplinary research between physicists, bioengineers, mathematicians, cancer cell biologists and clinicians for the past 10 years. The UC research team will explore the role of mechanical force in the growth and spread of cancer.
All cells sense and respond to mechanical force at multiple levels – and these forces change dramatically as tissues transform. This phenomenon has been observed for several decades, Weaver says, and it permits the easy palpation of tumors such breast cancer. However, researchers have only recently implicated mechanical force in the pathogenesis of tumors.
“The work builds upon ground breaking studies conducted in several team-member laboratories, including recent studies demonstrating how mechanical force drives breast cancer and how inhibiting tissue tension can inhibit cancer progression and metastasis,” Weaver says.
Several additional researchers and institutions are guiding research projects within the centers. At the UC Berkeley center, studies of how cancer cells send and receive signals will be led by Joe W. Gray, PhD, the director of the Division of Life Sciences at LBNL, who is also a UCSF faculty member; along with Frank McCormick, PhD, FRS, the director of the Helen Diller Family Comprehensive Cancer Center; Jay Groves, PhD, of UC Berkeley, LBNL and the Howard Hughes Medical Institute; and another leading LBNL researcher, Mina Bissell, PhD.
Liphardt, Groves and Gray have developed unique methods to precisely manipulate individual molecules, and to measure physical properties that are of interest to biologists such as Weaver and McCormick. Their studies emphasize how physical forces affect molecular organization, which in turn influences how cells signal. The studies may shed light on how changes in cellular signaling in cancer lead tumors to become resistant to treatment.
The physical scientists affiliated with the Princeton center, led by Austin and James Sturm, PhD, director of the Princeton Institute for the Science and Technology of Materials, will use microfabrication techniques to design and build specialized silicon structures, or microhabitats. Within these microhabitats, clusters of cancer cells and the cells that normally surround them can be grown in tightly controlled conditions to precisely measure the effects of physical variables on cells, cellular interactions and cell growth and movement.
For research at the Princeton center, Tlsty and Austin will be joined by UC Santa Cruz scientists David Haussler, PhD, director of the Center for Biomolecular Science and Engineering, and biomolecular engineer Nader Pourmand, PhD; Johns Hopkins researchers Robert Getzenberg, PhD, and Donald Coffey, PhD; and Beverly Emerson, PhD, from the Salk Institute for Biological Studies.
Thea Tlsty
Interdisciplinary Approach to Cancer
The principal investigator for the new UC Berkeley Physical Sciences Oncology Center is physicist Jan Liphardt, PhD, and the senior scientific investigator is UCSF Helen Diller Family Comprehensive Cancer Center member Valerie Weaver, PhD, who also is the director of the Center for Bioengineering and Tissue Regeneration at UCSF.Valerie Weaver