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Stony Brook University

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John Haley photo from SBU

By Daniel Dunaief

Once they reach their destination, they wreak havoc, destroying areas critical to life. All too often, when cancer spreads, or metastasizes, through the body, it becomes fatal.

John Haley, a Research Associate Professor in the Pathology Department at Stony Brook, is trying to figure out how cancer become metastatic and, even further, what they do to avoid recognition by the immune system.

Haley is “working on the mechanisms by which metastasis occurs,” he said. He is also studying the “immune recognition of tumor cells and, in the near future, wants to link the two.”

Understanding the way metastasis works can greatly reduce mortality in cancer, Haley said. Researchers are currently attempting to develop therapies that target metastatic cells, but these are often more difficult to kill than their primary counterparts, Haley explained.

The stakes are high, as 90 percent of cancer deaths are due to complications from the spread of cancer rather than the primary tumor itself, he said.

About 80 percent of human cancers are carcinomas, which are derived from epithelial cells. Those are the cells that make up the skin, and line the stomach and intestines.

“As cancers become metastatic, those cells have the ability to shape shift,” he said.

They become much more like fibroblasts, which are underneath the skin and glue the skin to bone and make up connective tissue layers. Haley said he has made some progress in understanding the molecular mechanism that allows cells to shift from epithelial to fibroblastic cells. They have “defined factors which promote” this transition, with differences in survival and growth pathways.

Haley works with a machine called a mass spectrometer, in which he identifies proteins in complex biological samples and measures how changes in composition alters function. He spends about half his time working on his own research and the other half assisting other researchers who are seeking to get a clearer view of key changes in proteins in their work.

In his own research, he wants to understand how cancers modify a cell’s proteins. He has helped define how cancers can change their protein signaling pathways to become drug resistant, which suggests targets for drug therapies.

Haley is tapping into an area of science that many other researchers are exploring, called bioinformatics. Using statistics and mathematical models, these scientists are cutting down on the number of genes and proteins they study, honing in on the ones that have the greatest chance to cause, or prevent, changes in a cell.

“We’re taking the data sets we’ve generated and trying to predict what we should look for in human patient samples,” Haley said. “We can find a tumor cell that have mutations or this expression profile and find drugs they are sensitive to.” Once scientists find those drugs, researchers can test them in cell cultures, then in mouse models and eventually in people, he said.

“We try to isolate someone’s cancer to understand what the molecular drivers are that occur in that cancer,” Haley said. The approach, as it is much of modern medicine, is to understand the patient’s genetics and biochemistry to select for a drug that would be effective against the particular mutations present in their tumor.

A resident of Sea Cliff, Haley is married to Lesley, whom he met while he was pursuing his PhD at Melbourne University. A native Australian, Lesley was completing her Masters in Opera when the couple met at a tennis match. They still play today. Lesley has sung at New York premieres for several living composers at concert venues including Avery Fischer Hall. She teaches music at her studio in Sea Cliff. Their children share their interests. John is a freshman studying biochemistry at Stony Brook University and Emma, who is a senior at North Shore High School, plans to study science and singing.

As for his work, Haley would like to see his efforts culminate in cancer therapies and diagnostics. Any novel therapy might also become a product for a start up company which could create jobs on Long Island. “There are some fabulous scientists” at the university, he said. “A major goal of the Center for Biotechnology and Diane Fabel, its director, is to create small businesses here in New York. I’m trying to help them in that goal.”

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Scott Powers with his wife Diane at a recent Cancer Research Gala. Photo by Julie Skarratt

By Daniel Dunaief

He spent 20 years looking at the problem in one way. Now, he’s ready for a change and Stony Brook officials stand behind him. After working in genomics at several locations, including for a decade as director of human cancer genomics at Cold Spring Harbor Laboratory to find therapeutic targets for human tumors, Scott Powers recently embraced the opportunity to find better ways to diagnose different types of cancer.

“A major driver for me coming to Stony Brook was to work on earlier detection,” Powers said.

Working with pathology department Chairman Ken Shroyer and Stony Brook obstetrician/gynecologist Michael Pearl, Powers is hoping to develop a prototype test for early detection of ovarian cancer so it can be removed by “simple surgery,” he said.

Powers has worked in numerous ways to isolate or identify mutations that might lead to cancer. That work focused on finding drug targets or developing therapies. One of the many challenges in studying genomics is that some mutations are bystanders, which means they likely don’t have a role in causing cancer or even, necessarily, in enabling cancer to spread. They make it harder to know whether they have a role or are merely different from the range of normal in a genetic sequence.

Some of the ways Powers has understood the potential part mutations play is by taking a computational approach, which can take many forms, including finding gene networks that are frequently altered. This approach has helped find various targets for therapies and improve the classification of tumors.

Powers said the “poster child” for success of this method was the development of the Oncotype DX test for breast cancer, which allows patients with node-negative, ER-positive breast cancer to determine whether they need to take chemotherapy.

He has also compared the gene sequences for similar cancer types across different species. He and Scott Lowe, who is now at Memorial Sloan Kettering Cancer Center, found this approach could “help identify drivers and, in a sense, help filter out passengers,” he said. This has been successful on a basic science level but hasn’t yet led to the identification of a viable new therapeutic strategy, he said.

Powers’ focus now is to direct his expertise toward developing a test that might address early detection and, in some cases, improved diagnosis.

“It’s a brand new set of things for me to think about,” Powers said. The effort, he believes, should prove reinvigorating. The intellectual challenge of coming up with a solution that improves or enhances someone’s life motivates him.

Powers supports Stony Brook’s effort to add staff and develop a pool of researchers who can develop techniques and tools to aid in the diagnosis and treatment of cancer. “I am very hopeful for Stony Brook to build up an intellectually interesting environment that will attract a new generation of cancer scientists to come on board,” he said.

Powers believes cancer is a complex disease that has many different variations. “Many random events occur that sometimes give the cancer cell a competitive survival advantage,” he explained. “Everyone’s tumor has its own unique combination of 10 to 25 genetic alterations that are driving it.”

In addition to working with Shroyer on developing diagnostic tools for the genomics of cancer, Powers has turned his attention toward other researchers on the campus with different backgrounds. He is planning a collaboration with Sasha Levy, who works at the Laufer Center for Physical and Quantitative Biology and is an assistant professor of biochemistry and cell biology, to study cancer evolution. He said they’ll be using experimental methods Levy has developed on yeast.

Yusuf Hannun, the director of the Cancer Center, has recruited Powers to participate on the tumor board, which is where physicians from different areas come to discuss specific patients in a multidisciplinary fashion.

“There are numerous discussions and plans to expand upon this growing trend to use genetic testing in developing a personalized strategy for each patient,” Powers said.

Powers and his wife Diane, who works in fundraising with Patricia Wright at Stony Brook in the anthropology department, live in Greenlawn with their daughter Camille, who is a sophomore at Harborfields High School. Their other children are Alexander, 25, who works for a nonprofit in Brooklyn called the Social Science Research Council, and Douglas, 21, who is a junior studying applied math at Harvard.

Powers was looking for two things that he found when he came to Stony Brook: “the chance to develop diagnostic tests” and to “enter new fields by finding new collaborators with scientists doing interesting things.”

Geoffrey Girnun hiking in the White Mountains of New Hampshire. Photo from Girnun

By Daniel Dunaief

He hopes to use their addictions against them. By taking away what they depend on for survival, he would like to conquer a disease that ravages and, all too often, kills its victims.

Geoffrey Girnun, an associate professor in the pathology department and the director of cancer metabolomics at Stony Brook University, is looking closely at the addictions cancer has to certain pathways that normal cells do not. “It is really about starving the cancer,” he explained. “Perhaps what you feed the patient can starve the cancer.”

Cancer has a ramped-up metabolism that handles nutrients differently, Girnun explained. Differences between normal cells and cancer can provide scientists and doctors with opportunities to develop selective treatments.

Using mouse models, Girnun is exploring the role of different proteins that either promote or prevent various cancers. Recently, he has been studying one particular protein in the liver cell. This protein classically regulates the cell cycle, which is why finding it in the liver, which has non-dividing cells under normal conditions, was unusual.

Girnun discovered that it promotes how the liver produces sugar, in the form of glucose, to feed organs such as the brain under normal conditions. In diabetic mice, the protein goes back to its classic role as a cell cycle regulator.

“We’re using genetic and pharmaceutical mechanisms to dissect out whether increases in liver cancer associated with obesity in diabetics is dependent on this protein,” Girnun said. If he and other scientists can figure out how the protein that functions in one way can take on a different role, they might be able to stop that transformation.

“It’s like a linebacker becoming a quarterback,” Girnun said. He wants to figure out “how to turn it back” into a linebacker.

Girnun is exploring the metabolic pathways and signatures for liver cancer. If doctors are targeting one particular pathway, they might develop “personalized therapy that would help avoid treatments that wouldn’t be effective.”

Girnun’s peers and collaborators said he has contributed important research and insights in his laboratory.

Girnun is “considered a rising star, especially in the area of the downstream signaling events that modulate gluconeogenic gene expression,” explained Ronald Gartenhaus, a professor of medicine and co-leader of the Molecular and Structural Biology Program at the University of Maryland Cancer Center. Gartenhaus, who has known Girnun for seven years and collaborated with him, said metabolomics is “rapidly exploding with novel insights into the perturbed metabolism of cancer cells and how this information might be exploited for improved cancer therapeutics.”

What encouraged Girnun to consider the professional move to Stony Brook was the opportunity to create something larger. “I want to build a program in cancer metabolism,” he said. “I want to build something beyond my own lab.”

When he first spoke to the leadership at Stony Brook, including Ken Shroyer, the head of the pathology department, Yusuf Hannun, the director of the Cancer Center, and Lina Obeid, the dean of research at the School of Medicine, he felt as if he’d found a great match.

Girnun has been so busy working with other researchers that managing collaborations has become a part-time job, albeit one he finds productive and exciting.

Hannun said Girnun has identified “key investigators who are working on developing the field of nutrition and metabolomics.” Girnun is heading up a symposium on May 13th that focuses on innovations in basic and translational cancer metabolomics. The keynote speaker is Harvard Professor Pere Puigserver.

While Girnun changed jobs, he hasn’t moved his family yet from Baltimore. Every week, he commutes back and forth. Girnun and his wife Leah have five children, who range in age from preschool to high school. He hopes his family will move within the next year or so.

Girnun enjoys Stony Brook, where he said he has an office that overlooks the Long Island Sound and where he can run. When he’s hiking on Long Island, he said he has a chance to “think through my experiments.”

His commute from several states away shows “how much I was sold on Stony Brook,” he said. “We believe Stony Brook is moving up to the next level.”

He remains focused on the applications of his research toward people. “Something may be cool mechanistically, but, unless it’ll have a biologically meaningful result and affect how patients are treated or diagnosed, to me, it doesn’t matter,” he said.

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Counterclockwise from front row left, John Haley, Geoffrey Girnun, Scott Powers and Patricia Thompson. Photo from Stony Brook University

When local teams bring in superstars, the typical sports fan salivates at the prospect of winning a national championship. At the player level, success often breeds success, as other stars and talented players are eager to join teams where they believe in the philosophy of management and the talent of their teammates.

With considerably less fanfare to the typical Suffolk County resident, Stony Brook University has lured some promising researchers from around the country to its growing pathology department. What’s more, the newest members of the team not only have big plans for themselves and their department — they want to help Long Islanders who are battling cancer.

Their research aims to give doctors tools to make a more informed cancer diagnosis, create jobs by developing start-up companies and contribute to the Cancer Center’s goal of receiving a National Cancer Institute designation, which would allow Stony Brook to bid on multimillion dollar grants.

“We are looking for new ways to advance the practice of pathology that will improve the quality of health care nationwide and worldwide,” said Ken Shroyer, the head of the pathology department.

When Shroyer arrived in 2007, he said his first goal was to bring together the talent that was already working at the university. Like siblings who grow apart after they leave home, the clinical research and basic research efforts were working in parallel, rather than together.

After finding common ground for those groups, Shroyer added staff on the clinical side. His next priority, he said, was to boost the research department, which had only one externally funded investigator. That number now stands at 12, with four of the new staff coming in the last 18 months.

The newest researchers joined the pathology department and became leaders in the Cancer Center. “Each of these four individuals has a national reputation and special expertise in a particular area of cancer research,” Shroyer explained, saying he combed the research landscape to find the right experts in their field.

For their part, the new staff share an enthusiasm for the department and a vision for where it’s heading. An expert in finding biomarkers that help identify patients at risk of cancer recurrence, Patricia Thompson plans to encourage basic scientists to make discoveries that affect patient care.

Geoffrey Girnun, meanwhile, continues to study how cancer’s metabolism works, hoping to find differences between cancer cells and normal cells that can become targets for intervention and therapy.

After two decades searching for therapeutic targets for cancer, Scott Powers shifted gears and is now looking for ways to detect cancer earlier.

John Haley is concentrating on exploring how cancer cells escape detection from the immune system and become metastatic.

The director of the Cancer Center, Yusuf Hannun said the partnership with the pathology department is “key to bridging basic research discoveries to cancer specific research and then to human applications,” which could include biomarker discoveries, new therapeutics and individualized and personalized genomic cancer research.

Hannun believes the Cancer Center will continue to push the envelope in diagnosis, treatment and prevention. “We want to bring more special and unique abilities in the war against cancer,” Hannun said. “The inroads in cancer are happening.”

Stony Brook could become involved in prevention, where doctors and scientists work with patients before they develop any signs of the disease. “That domain is clearly within the scope of the Cancer Center,” Hannun said. “We are working on novel biomarkers that could detect very early cancer.”

Hannun described Shroyer as his “alter ego” in the Cancer Center. “He is a very capable leader and does very exciting cutting edge research with a steeped history in early diagnostics.”

Shroyer focuses his work on the discovery of biomarkers that can be used to improve diagnostic accuracy, provide prognostic information and identify more effective treatments for cancer, he said.

Five years from now, the success of the effort will be reflected by the extent to which the group can enhance the national standing of Stony Brook Medicine and the Cancer Center as leading institutions in basic and translational cancer research, Shroyer said.