Rethinking the War on Cancer

jones for web.jpgA two-day symposium taking place today and tomorrow at Northwestern University, June 6 and 7, is bringing together internationally renowned scholars working at the intersection of the physical sciences and oncology to share insights about rethinking the War on Cancer.

Sponsored by Northwestern’s Physical Sciences-Oncology Center, the events are taking place in the auditorium of the Pancoe Life Sciences Building, 2200 N. Campus Drive.

A standing-room-only crowd gathered early on Monday to hear talks by Alexander Ruthenburg from the University of Chicago, Peter Jones from the University of Southern California and Northwestern’s Richard Carthew. Later sessions will feature presentations by Lucy Godley and Chuan He from the University of Chicago, Leonid Mirny of MIT, Frank Pugh of Penn State, Olivier Elemento of Cornell University and Ji-Ping Wang of Northwestern.

“Experienced and aspiring investigators are coming together inspired by the knowledge that a new understanding of cancer is necessary,” said Jonathan Widom, the principal investigator of Northwestern’s Physical Sciences-Oncology Center. “The center is based on the belief that such an understanding will help secure a conclusion to what has been a difficult and prolonged war.”

Supported by a five-year, multi-million dollar grant from the National Cancer Institute, the Physical Sciences-Oncology Center represents a dramatic attempt to fundamentally rethink approaches to fighting cancer.

The center operates under the leadership of Widom, who holds the William Deering Professorship in Biological Sciences in the department of molecular bioscience, is a member of the Chemistry of Life Processes Institute and holds appointments in the Robert H. Lurie Comprehensive Cancer Center and the departments of biochemistry, molecular biology and cell biology; and Jonathan Licht, the center’s senior co-investigator, chief of the division of hematology/oncology in the Feinberg School of Medicine and associate director for clinical sciences at the Lurie Cancer Center.

By importing techniques, ideas and methods from the physical sciences into the unfamiliar terrain of tumor biology and oncology, the center and its eleven sibling research centers are creating new insights into cancer by revealing the physical and chemical forces shaping the emergence and progression of the disease at all levels.

“Breaking from the orthodoxy of established thought, the center is eschewing cell- and organ-specific studies to develop a systemic or global understanding of how cancer functions from carcinogenesis to metastasis,” the center’s senior co-investigator Licht said.

The reappraisal underway at the center is undergirded by a series of analytical approaches, including nano- and sub-atomic microscopy, advanced optics, mathematical modeling and high-level computational power that will generate the raw data necessary to solving perplexing and lethal riddles.

“The importance of the center’s work is best highlighted by the elusive nature of cancer itself,” said Will Kazmier, education, training and outreach coordinator in Northwestern’s Chemistry of Life Processes Institute.

“Forty years after President Richard Nixon famously opened a “war on cancer” that has required the commitment of enormous financial and scientific resources, survival rates for most forms of the disease remain largely unchanged,” he added.–Pat Vaughn Tremmel

Dhwanil Damania Wins PS-OC Young Investigators’ Award

Dhwanil_web.jpgAlthough the Northwestern University Physical Sciences-Oncology Center (PS-OC) was established only last fall, Dhwanil Damania, a PhD student in the university’s Department of Biomedical Engineering, believes his experience as an NU PS-OC trainee has already had a significant impact on his research  skills. As Damania explains, both the NU PS-OC and its eleven sibling research centers, which rely on physical sciences-based approaches to understand and control cancer, strongly advocate “interdisciplinary collaboration” to achieve their goals. This emphasis on collaborative science, he says, has helped him think “more creatively” both in his approach to problem-solving and in the way he envisions future paths for his work.

Over the next twelve months, he will have a new opportunity to apply this creativity. At the recently held PS-OC National Investigators’ Meeting in Bethesda, MD, a team comprised of Damania and two trainees from the Scripps Physical Sciences-Oncology Center, Kevin Phillips and Joseph Aslan, won a one-year, $10,000 Young Investigators’ Research Award for their proposal to develop a novel method for characterizing the pathophysiological features of circulating tumor cells (CTCs). CTCs have long been known to play a key role in the metastasis of cancer by detaching from existing tumors, traveling through the bloodstream, and forming secondary tumors in new locations.

Funded by the National Cancer Institute, which is  supporting the PS-OC network through a series of five-year, multimillion-dollar grants, the Young Investigators’ Award was created to help cultivate innovative cancer research among a new generation of interdisciplinary scientists working in the laboratories of senior PS-OC investigators. The most notable feature of the competition was its collaborative focus. To be eligible to compete for one of three grants, trainees from across the network were required to work in teams by developing proposals that incorporated at least two students or postdoctoral fellows from separate PS-OCs. By encouraging trainees to grapple with and overcome the institutional and disciplinary barriers frequently impeding scientific progress, competition organizers hoped the application process would function as a catalyst for sustained partnerships and, eventually, meaningful scientific advances. These aspirations, in turn, guided the award selection process.

For his part, Damania is confident that his project with Phillips and Aslan has the potential to realize the competition’s objectives. “What is most exciting to me about the work with Scripps is that it will help us understand the varying tumorigenic capabilities of different classes of CTCs—or their uneven capacity to cause metastasis in cancer patients,” he says. From a clinical perspective, identifying the CTCs capable of causing metastasis is particularly important because doing so could potentially help physicians provide early and effective care to cancer patients possessing the most virulent kinds of cancer-spreading cells. In other words, “this is something that could potentially improve current methods for understanding–and eventually treating–the spread of cancer,” Damania concludes.

To carry out its work, the team will synthesize important advances made in the labs of senior researchers at Scripps and Northwestern. As Damania explains, his collaborators “have been involved with pioneering research to isolate and tag CTCs in the bloodstream using fluorescent microscopy.” This feat, accomplished in the laboratory of Dr. Peter Kuhn, is particularly impressive, he continues, “because CTCs can be found in the bloodstream only in very small concentrations, roughly at the level of one per thousands or more normal blood cells.” Consequently, the extensive CTC samples obtained by the Scripps team occupy the status of rare commodities in the world of cancer research.

But while Scripps researchers have been able to isolate CTCs, they have yet to identify the physical characteristics that reveal their metastatic potential. To help accomplish this goal, Damania and his colleagues at Northwestern will assist his Scripps teammates in constructing a partial-wave spectroscopic microscopy system. An innovative optical technique developed in the Northwestern laboratory of Professor Vadim Backman, one of Damania’s faculty advisors, partial-wave spectroscopy (PWS) has been used to identify subtle tumorigenic changes in human cells even when those same cells appear normal using conventional microscopy. Because Backman’s research group has shown that these changes are linked to the degree of disorder present within cell nano-architecture, a quantifiable PWS marker obtained by translating backscattered light from human cell samples, Damania believes that a similar approach can be used on CTCs. The goal here, then, will be to correlate cellular disorder strength among CTCs with their metastatic potential. If that work can be accomplished, his team will have established a novel approach for characterizing CTCs and, potentially, a new way of understanding cancer.

While Damania is extremely excited to begin making progress on his collaborative project, he is also grateful for the lesson he learned while preparing his proposal with Aslan and Phillips at the National PS-OC Meeting. Due to the team emphasis of the Young Investigators’ competition, Damania concedes that for the first time in his academic career, he attended a professional meeting while “considering the possibility that the event’s other participants could be potential collaborators rather than potential competitors.” Yet when he did so, he realized how much could be learned “from ordinary attendees instead of just the meeting’s official speakers.” It was instructive to realize, he adds, how important “a change in perspective can be. I immediately began to have new ideas about how to advance my research and consider new possibilities for the directions in which my research could progress.” Damania has already begun to realize the benefits of such a change in perspective through the Young Investigators’ Award. In the future, it is possible that the broader cancer research community will benefit from this change as well.

Center Funds Important New Pilot Studies

The Northwestern Physical Sciences-Oncology Center (NU-PSOC), under the leadership of Prof. Jonathan Widom, recently awarded a total of nearly$300,000 to NU investigators for one-year pilot studies related to the Center’s theme of “Coding, Decoding, Transfer and Translation of Information in Cancer.”  The Center awarded an additional $100,000 to support the incorporation of needed expertise into existing Center research projects.

The NU PS-OC is one of 12 such Centers established by the National Cancer Institute in 2009 to apply concepts and methodologies from the physical sciences and engineering to the study of cancer biology. Under the terms of its $12.5 million award from the National Cancer Institute, the NU PS-OC must devote some of these funds each year to support  pilot projects that complement and expand the Center’s five main projects.  In its second round of underwriting these studies, the NU-PSOC selected three promising pilot projects for support.  Marcus Peter, Dept. of Medicine/Hematology-Oncology, received $100,000 for his project “Development of Novel Tools to Detect and Inhibit MicroRNAs.  MicroRNAs, a recently discovered species of non-coding RNA, play an important role in the mis-regulation of gene expression in cancer cells, and agents that can block microRNA action may have therapeutic benefit in cancer. However, there are many closely related microRNAs whose actions and targets are very hard to distinguish, complicating the development of effective blocking agents. Dr. Peter proposes a novel approach using antibody fragments that may allow individual microRNAs in a family to be detected and inhibited, with the ultimate goal of developing these antibody fragments as cancer therapeutics.

A second $87,500 award was given to Dr. Carol LaBonne, Dept. of Molecular Bioscience, for her project “Epigenetic Regulation of the Stem Cell State, and Relation to EMT and Invasiveness ($87,500).  In these studies, Dr. LaBonne will use a model organism, the zebra fish, to examine the epigenetic marks that accompany and may contribute to a critical embryological transition, the establishment of the neural crest stem cell population.  Neural crest cells exhibit migratory and invasive behaviors, which are required for their normal function during embryogenesis.  Importantly, metastatic tumors cells reacquire these motile and invasive behaviors that are normally confined to embryological development, with deadly consequences for cancer patients.  Epigenetic marks are modifications to either the DNA or the protein components of chromatin.  These modifications are heritable and can alter gene expression, but they do not involve changes to DNA sequence and are therefore not classified as mutations.  In this project, Dr. LaBonne will examine specific modifications to histones, proteins that form a core around which DNA is wrapped in the nucleus.

A third pilot project award of $87,500 was made to Dr. Neil Kelleher, Dept. of Molecular Biosciences,  for his project “Combining CHIP-Seq and Mass Spectrometry to Measure the Effects of Histone Methylation on Nucleosome Positioning and Aberrant Methyltransferases in Lymphoma.”    Dr. Kelleher is a recognized expert in the technique of mass spectrometry, a method to identify proteins based on precise measurements of the masses of charged peptides that are generated by ionizing the proteins.   This technique can be used to measure histone modifications.  In this pilot project, Dr. Kelleher will collaborate with the laboratory of Dr. Widom, which has demonstrated that the position of nucleosomes in the yeast genome is largely determined by DNA sequence.  Dr. Kelleher will now ask whether epigenetic changes, and in particular, the presence or absence of a particular histone modification, also affects nucleosome positioning.

These investigators will join the Center’s 27 faculty members in participating in quarterly Center research meetings, symposia, workshops, and annual NCI site visits.  Support for the NU-PSOC Pilot Project program comes from NCI grant 5U54CA143869-02, cost shared support from Northwestern University, and a generous contribution from the Robert H. Lurie Comprehensive Cancer Center.

In addition to funding pilot projects, the NU-PSOC also supports activities and small projects  designed to foster collaborations between Center investigators and investigators outside of the PS-OC network.  These smaller awards (ranging from $10,000 to $25,000) allow Center researchers to send students and postdoctoral researchers to labs outside of the PSOC network for additional training and to sponsor visits from researchers who will enable them to expand their current projects.  Outreach project funding has been awarded to:  Elizabeth Eklund, “Role of Transcriptional Accessibility of Hox Loci in Poor Prognosis AML” ($25,000); Alexandre DeLuna, (Center Collaborator: Adilson Motter)  “Understanding how Genes, the Environment, and their Interactions Determine Synthetic Rescue” ($25,000); John Marko, (Collaborator: Kazuhiro Maeshima),  “Technique Development for Isolation and Visualization of Mitotic Chromosomes” ($10,000); Milan Mrksich, (Center Collaborator: Jonathan Licht), “The Chemical Biology of MMSET” ($12,500); and Igal Szleifer, (Center Collaborator: Vadim Backman)  “Microscopic Modeling of Nanoarchitecture Changes in Cancer Cells” ($25,000).

 

PS-OC Kickoff Reception

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PS-OC investigators William Kath, Dirk Brockmann, Adilson Motter, and Jonathan Widom discuss their work at the Center’s kickoff reception.

A broad array of physical scientists, cancer researchers, university administrators, students, and staff gathered in Pancoe Hall on November 6th to celebrate the establishment of the Northwestern University Physical Sciences-Oncology Center. The event provided Center faculty and trainees with the opportunity to share some refreshments as they mingled and exchanged ideas about their work.

PS-OC  members are eagerly awaiting their next general meeting on May 10th, the date for the Center’s spring quarter “Science Jam.”  A day-long event comprised of research presentations, scientific dialogues, and a poster session, the Science Jam will allow researchers to share preliminary results and discuss obstacles and opportunities in their work as they move forward.

Center to Open New Directions for Cancer Research

EVANSTON, Ill. — Northwestern University has been awarded a $13.6 million five-year grant from the National Cancer Institute (NCI) to establish an interdisciplinary research center for the study of genes and their role in cancer. A better understanding of the mechanisms could lead to better diagnostics and therapeutics and open up new directions for research.

Northwestern’s Physical Sciences-Oncology Center (PS-OC), one of 12 established nationwide by the NCI, brings together physical scientists and cancer biologists to use non-traditional, physical-sciences based approaches to understand and control cancer.

“Our center will be studying the regulation and expression of genes in both normal health and development and in cancer,” said principal investigator Jonathan Widom, the William Deering Professor in Biological Sciences in the Weinberg College of Arts and Sciences. “We need to understand healthy cells to understand and control cancer.”

The PC-OS initiative is expected to generate new knowledge in order to identify and define critical aspects of physics, chemistry and engineering that shape and govern the emergence and behavior of cancer at all scales.

“By bringing a fresh set of eyes to the study of cancer, these new centers have great potential to advance, and sometimes challenge, accepted theories about cancer and its supportive microenvironment,” said NCI Director John E. Niederhuber, M.D. “Physical scientists think in terms of time, space, pressure, heat, and evolution in ways that we hope will lead to new understandings of the multitude of forces that govern cancer — and with that understanding, we hope to develop new and innovative methods of arresting tumor growth and metastasis.”

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