[email protected] launches with $9.5M federal grant to battle deadliest cancers

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Yale University researchers across a spectrum of disciplines are coming together to fight some of the deadliest forms of cancer with a novel approach that has gained support from the National Cancer Institute (NCI) of the National Institutes of Health (NIH).

Cancer Systems Biology @Yale ([email protected]), based at the university’s West Campus, will use a $9.5 million NIH grant to understand how cancer cells reach an aggressive state and begin damaging surrounding tissue. The initial focus will be on two particularly aggressive cancers: glioblastoma multiforme (brain cancer) and melanoma (skin cancer).

The initiative combines expertise from a variety of Yale programs. The Yale Systems Biology Institute and the Yale Cancer Biology Institute on West Campus will join forces with the Raymond and Beverley Sackler Institute for Biological, Physical and Engineering Sciences, the Yale Cancer Center, and Emory University to address fundamental questions at the core of cancer biology, using a diverse set of approaches. Yale faculty from three schools and seven departments will be primary investigators at [email protected], with research backgrounds in genetics, molecular biology, evolutionary biology, biochemistry, biomedical engineering, oncology, pharmacology, biophysics, and mathematics.

“Our approach will vary from the use of synthetic biology to evolutionary approaches, and will rely heavily on advances in engineering, mathematics, and physics, in addition to breaking new ground in biology and chemistry,” said principal investigator Andre Levchenko, the John C. Malone Professor of Biomedical Engineering and director of the Yale Systems Biology Institute.

The new program will address the specific problem of phenotypic plasticity. Cancer cells with the same genomic makeup can adopt different phenotypes or behaviors, switching from rapid division and growth to invasive migration and metastatic spread, for example. Furthermore, different phenotypes may co-exist in the same tumor, with cells exchanging signals among themselves and with surrounding normal tissues.

How a cell or group of cells alters its behavior is not completely understood — yet more than 90% of cancer-related mortality is linked to invasive and metastatic spread of cancer cells from the primary tumor. [email protected] will be devoted to understanding and manipulating the complex molecular networks governing such cell behaviors. The program also will focus on translational research aimed at identifying new targets for therapeutic intervention and the development of new drugs targeting invading cells.

“The next important goal in cancer therapeutics will be to control or correct signaling networks rather than targeting individual molecules, and [email protected] brings unique sets of expertise and perspective together to do this,” said Mark Lemmon, co-director of the Yale Cancer Biology Institute and the David A. Sackler Professor of Pharmacology at the Yale School of Medicine.

The new grant provides funding for five years. The NCI also is establishing new research centers at Stanford, Columbia, and Memorial Sloan-Kettering Cancer Center. These centers, along with the Yale program, will form a consortium linked by a coordinating center at Sage BioNetworks, a non-profit research group based in Seattle.

In addition to Levchenko and Lemmon, primary investigators at [email protected] will be:

• Lynne Regan, professor of molecular biophysics & biochemistry and chemistry

• Jesse Rinehart, associate professor of cellular and molecular physiology, and member of the Yale Systems Biology Institute

• Farren Isaacs, assistant professor of molecular, cellular, and developmental biology, and member of the Yale Systems Biology Institute

• Gunter Wagner, the Alison Richard Professor of Ecology and Evolutionary Biology, and member of the Yale Systems Biology Institute

• Murat Acar, assistant professor of molecular, cellular, and developmental biology, and member of the Yale Systems Biology Institute

• Michael Murrell, assistant professor of biomedical engineering at the Yale School of Engineering & Applied Science and member of the Yale Systems Biology Institute

• Sidi Chen, assistant professor of genetics at the Yale School of Medicine and member of the Yale Systems Biology Institute

• Rong Fan, associate professor of biomedical engineering at the Yale School of Engineering & Applied Science

• Kshitiz Gupta, associate research scientist in biomedical engineering at the Yale School of Engineering & Applied Science, and member of the Yale Systems Biology Institute

• Adam Marcus, a member of the Winship Cancer Institute, associate professor in the Department of Hematology and Medical Oncology at the Emory University School of Medicine

For more information about the National Cancer Institute of the National Institutes of Health, visit the website.

For more information about the Yale Systems Biology Institute, visit the institute’s website.

For more information about the Yale Cancer Biology Institute, visit the website.

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