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Power of Three

Priya Sridevi with her golden doodle Henry. Photo by Ullas Pedmale

By Daniel Dunaief

Priya Sridevi started out working with plants but has since branched out to study human cancer. Indeed, the research investigator in Cold Spring Harbor Laboratory Cancer Center Director David Tuveson’s lab recently became the project manager for an ambitious effort coordinating cancer research among labs in three countries.

The National Cancer Institute is funding the creation of a Cancer Model Development Center, which supports the establishment of cancer models for pancreatic, breast, colorectal, lung, liver and other upper-gastrointestinal cancers. The models will be available to other interested researchers. Tuveson is leading the collaboration and CSHL Research Director David Spector is a co-principal investigator.

The team plans to create a biobank of organoids, which are three-dimensional models derived from human cancers and which mirror the genetic and cellular characteristics of tumors. Over the next 18 months, labs in Italy, the Netherlands and the United States, at Cold Spring Harbor Laboratory, expect to produce up to 150 organoid models.

The project officially started in January and the labs have been setting up the process through June. Sridevi is working with Hans Clevers of the Hubrecht Institute, who pioneered the development of organoids, and with Vincenzo Corbo and Aldo Scarpa at the University and Hospital Trust of Verona.

Sridevi’s former doctoral advisor Stephen Alexander, a professor of biological sciences at the University of Missouri, said Sridevi has had responsibilities beyond her own research. She was in charge of day-to-day operations in his lab, like ordering and regulatory reporting on radioactive material storage and usage, while he and his wife Hannah Alexander, who was Sridevi’s co-advisor, were on sabbatical. “She is hard working and determined,” said Alexander. “She knows how to get things done.”

In total, the project will likely include 25 people in the three centers. CSHL will hire an additional two or three scientists, including a postdoctoral researcher and a technician, while the Italian and Netherlands groups will also likely add another few scientists to each of their groups.

Each lab will be responsible for specific organoids. Tuveson’s lab, which has done considerable work in creating pancreatic cancer organoids, will create colorectal tumors and a few pancreatic cancer models, while Spector’s lab will create breast cancer organoids.

Clevers’ lab, meanwhile, will be responsible for creating breast and colorectal organoids, and the Italian team will create pancreatic cancer organoids. In addition, each of the teams will try to create organoids for other model systems, in areas like lung, cholangiocarcinomas, stomach cancer, neuroendocrine tumors and other cancers of the gastrointestinal tract.

For those additional cancers, there are no standard operating procedures, so technicians will need to develop new procedures to generate these models, Sridevi said. “We’ll be learning so much more” through those processes, Sridevi added. They might also learn about the dependencies of these cancers during the process of culturing them.

Sridevi was particularly grateful to the patients who donated their cells to these efforts. These patients are making significant contributions to medical research even though they, themselves, likely won’t benefit from these efforts, she said. In the United States, the patient samples will come from Northwell Health and the Tissue Donation Program of Northwell’s Feinstein Institute of Medical Research. “It’s remarkable that so many people are willing to do this,” Sridevi said. “Without them, there is no cancer model.”

Sridevi also appreciates the support of the philanthropists and foundations that provide funds to back these projects. Sridevi came to Tuveson’s lab last year, when she was seeking opportunities to contribute to translational efforts to help patients. She was involved in making drought and salinity resistant rice and transgenic tomato plants in her native India before earning her doctorate at the University of Missouri in Columbia.

Alexander recalled how Sridevi, who was recruited to join another department at the University of Missouri, showed up in his office unannounced and said she wanted to work in his lab. He said his lab was full and that she would have to be a teaching assistant to earn a stipend. He also suggested this wasn’t the optimal way to conduct research for a doctorate in molecular biology, which is a labor-intensive effort. “She was intelligent and determined,” Alexander marveled, adding that she was a teaching assistant seven times and obtained a wealth of knowledge about cell biology.

Sridevi, who lives on campus at CSHL with her husband Ullas Pedmale, an assistant professor at CSHL who studies the mechanisms involved in the response of plants to the environment, said the transition to Long Island was initially difficult after living for six years in San Diego.

“The weather spoiled us,” she said, although they and their goldendoodle Henry have become accustomed to life on Long Island. She appreciates the “wonderful colleagues” she works with who have made the couple feel welcome.

Sridevi believes the efforts she is involved with will play a role in understanding the biology of cancer and therapeutic opportunities researchers can pursue, which is one of the reasons she shifted her attention from plants. In Tuveson’s lab, she said she “feels more closely connected to patients” and is more “directly impacting their therapy.” She said the lab members don’t get to know the patients, but they hope to be involved in designing personalized therapy for them. In the Cancer Model Development Center, the scientists won a subcontract from Leidos Biomedical Research. If the study progresses as the scientists believe it should, it can be extended for another 18 months.

As for her work, Sridevi doesn’t look back on her decision to shift from plants to people. While she enjoyed her initial studies, she said she is “glad she made this transition” to modeling and understanding cancer.

Front row, from left, Liliana Dávalos, Heather Lynch and Christine O’Connell; back row, from left, Robert Harrison, IACS director and STRIDE PI, Arie Kaufman, and Janet Nye. Photo from Stony Brook University

By Daniel Dunaief

If Stony Brook University has its way, the university will stand out not only for the quality of the research its graduate students produce but also for the way those budding scientists present, explain and interpret their results to the public and to policy makers.

Pulling together faculty from numerous departments across the campus, Robert Harrison, the director of the Institute for Advanced Computational Science, created a program that will teach graduate students how to use big data sets to inform difficult decisions.

The institute recently received a $3 million grant from the National Science Foundation Research Traineeship for this effort, called Science Training & Research to Inform DEcisions, or STRIDE. The grant will be used for students in the departments of Applied Mathematics and Statistics, Biomedical Informatics, Computer Science, Ecology and Evolution and the schools of Journalism and Marine and Atmospheric Sciences.

“This is unique,” said Arie Kaufman, a distinguished professor and chair of the Department Computer Science at Stony Brook. “It’s a new kind of approach to training and adding value to Ph.D. students.” Indeed, the students who complete the STRIDE training will earn their doctorates and will also receive a certificate for their participation in this program. Students in the participating departments will need to apply for one of the 10 positions available in the program next year. The partners involved in this program expect it to expand to 30 students within five years.

Kaufman said what enabled this collaboration was the range of skill sets across Stony Brook, including the Alan Alda Center for Communicating Science, which is a growing program that already offers the type of training more typical for an actor studying improvisation techniques than for a scientist studying neurotransmitters or DNA.

The Alda Center is “creating a new course,” said Christine O’Connell, an associate director at the center and assistant professor in the School of Journalism. She is currently working on developing the course description, which will include communicating to decision makers. O’Connell, who has a doctorate in marine and atmospheric sciences, sees her work with the Alda Center and with STRIDE as the “perfect combination in bringing the decision making piece to work with scientists to help them talk about their research.”

Scientists who take courses at the Alda Center with STRIDE learn how to understand their audience through various role-playing scenarios. They will also develop their abilities to present their goals or messages in a visual way and not just talk about their work.

Heather Lynch, an associate professor in the Department of Ecology and Evolution who is also a co-principal investigator on the STRIDE grant, will help design the program, mentor students and develop courses. She’s been involved with this proposal since its inception, over three years ago. “In many ways,” she explained in an email, “my interest stems from my own difficulties communicating effectively with policy makers, and finding tools and visualizations that are compelling to a non-scientist.” Lynch recounted her frustration with presenting science to help a policy making body, such as a committee, with the kind of analysis she believed they were seeking. After she did her best to answer the question, the committee sometimes dismissed her work as not being what they wanted. “That’s frustrating because that means I failed at the outset to define the science question and that’s what I hope we can teach students to do better,” Lynch explained.

Lynch said she wishes she had the training these students will be getting. For scientists, computers are an invaluable tool that can help delve into greater breadth and depth in analyzing, interpreting and collecting information. The STRIDE effort includes a greater awareness of the way computers can inform political or social science. Researchers generate “tremendous amounts of data that can be used to analyze trends or detect diseases,” Kaufman said. “The data science is tremendous in every discipline.”

The faculty who are a part of this program said they have already benefited from the interactions they’ve had with each other as they’ve developed the curriculum. “I know a few people in Ecology and Evolution and I know more people in Marine Sciences, but these particular individuals were new to me,” said Kaufman. “We have already been communicating about ideas for how to use the Reality Deck for other projects.”

Completed in late 2012, the Reality Deck is a $2 million rectangular room in the Center of Excellence in Information Technology building. The room has hundreds of monitors that cover the wall from floor to ceiling and provides a way for researchers to study images in exquisite detail.

Other scientists in the program include Liliano Dávalos, an associate professor in the Department of Ecology and Evolution, Janet Nye, an assistant professor in the School of Marine and Atmospheric Sciences, Joel Saltz, the founding chair of the Depatment of Biomedical Informatics, Erez Zadok, a professor in the Department of Computer Science and Mighua Zhang, a professor in the School of Marine and Atmospheric Sciences.

Lynch said the program will bring in people who are working on real-world problems, including those in government, industry and nongovernmental organizations who are “in a position to take science and use it for practical purposes.” As a part of the program, the scientists will monitor the progress of the STRIDE candidates, O’Connell said.

The evaluations will check to see if “they become better communicators and better at interpreting their data for different audiences,” O’Connell said. “The evaluation piece built in will help us assess the program.”