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Ken Shroyer

Mehdi Damaghi. Photo from Stony Brook Hospital

By Daniel Dunaief

Do the birds on the Galapagos Islands, with their unique coloration, differently shaped beaks and specific nesting places, have anything to do with the cancer cells that alter the course of human lives?

For Mehdi Damaghi, Assistant Professor in the Department of Pathology at the Renaissance School of Medicine at Stony Brook University, the answer is a resounding, “Yes.”

Damaghi uses the same principles of evolutionary biology to understand how cancer, which resides within human genes, works to adapt, as it tries to win the battle to survive.

“What we try to understand is the Darwinian principals of cancer,” said Damaghi. Cancer “adapts and reprograms themselves” to their environment to survive.

Damaghi, who arrived at Stony Brook four months ago from Moffitt Cancer Center, plans to address numerous questions related to cancer. He recently received a $4 million grant from the Physical Science in Oncology program (PSON) through the National Institutes of Health/ National Cancer Institute. Working with cancer biologists, clinicians, and computational scientists, he plans to define and understand cancer’s fitness.

“We are trying to study the core evolution of cancer cells and the normal stroma around them,” said Damaghi. “We are looking at the evolution of the tumor and some of the host cells.”

Cancer biologists are trying to build mathematical and theoretical models to explore the playbook cancer uses when confronted with threats, either in the form of a body’s natural defenses against it or from therapies against which it can, and often does, develop resistance.

Treating cancer could involve using adaptive therapy, which could enable people to control and live with cancer longer, Damaghi suggested.

In studying cancer’s phenotype, or the way the disease is expressed and survives, he hopes to understand factors in the microenvironment. Many cancers, he reasons, become more problematic as people age. Indeed, centuries ago, cancer wasn’t as prevalent as it is today in part because life expectancy was shorter.

Damaghi also has an evolutionary model to explore metastasis, in which cancer spreads from one organ or system to other parts of the body. He is looking at the earliest stages of breast cancer, to see what factors some of these cancers need or take from the environment that enables them not only to develop into breast cancer, but also to spread to other systems.

Through the microenvironment, he is looking for biomarkers that might signal a potential tumor development and metastasis long before a person shows signs of an aggressive form of the disease.

“We look at the tumor as a part of a whole ecosystem that can have different niches and habitats,” he said. “Some can be hypoxic and oxidative, and others can be like a desert on Earth, where not much grows and then cancer evolves.”

Damaghi challenges cells in a culture or organoids, which are miniature, three-dimensional live models of human cells, with different microenvironmental conditions to see how they respond. He exposes them to hormones, immune cells, and hypoxic conditions.

“We try to understand what is the adaptation mechanism of cancer to this new microenvironment and how can we push them back to the normal phenotype,” he said.

Like other scientists, Damaghi has demonstrated that many of these cancer cells use sugar. Removing sugar caused some of the cancer to die.

Increasing the survival for patients could involve knowing what kinds of micro-environments cancer uses and in what order. Deprived of sugars, some cancers might turn to amino acids, dairy or other sources of food and energy.

Damaghi thinks researchers and, eventually, doctors, will have to approach cancer as a system, which might have a patient-specific fingerprint that can indicate the resources the disease is using and the progression through its various diseased stages.

Choosing Stony Brook

Damaghi appreciates the depth of talent in cancer sciences at Stony Brook University. He cited the work of Laufer Center Director Ken Dill and Cancer Center Director Yusuf Hannun. He also suggested that the Pathology Department, headed by Ken Shroyer, was “very strong.”

For their part, leaders at Stony Brook were pleased to welcome, and collaborate with, Damaghi. Hannun suggested Stony Brook recruited Damaghi because his research “bridges what we do in breast cancer and informatics.”

Shroyer, meanwhile, has already started collaborating with Damaghi and wrote that his new colleague’s focus on breast cancer “overlaps with my focus on pancreatic cancer.”

To conduct his research, Damaghi plans to look at cells in combination by using digital pathology, which can help reveal tumor ecosystems and niches.

He also appreciated the work of Joel Saltz, the Founding Chair in the Department of Biomedical Informatics. “In the fight against cancer, we all need to unite against this nasty disease,” Damaghi said. “From looking at it at different angles, we can understand it first and then design a plan to defeat it.”

Originally from Tehran, Iran, Damaghi is the oldest of five brothers. He said his parents encouraged them to explore their curiosity.

Damaghi, whose wife Narges and two daughters Elissa and Emilia are still in Tampa and hope to join him before long, has hit the ground running at Stony Brook, where he has hired three postdoctoral researchers, a lab manager, four PhD students, two master’s candidates, and three undergraduates.

Damaghi is inspired to conduct cancer research in part because of losses in his family. Two grandparents died from cancer, his aunt has breast cancer, and his cousin, who had cancer when he was 16, fought through the disease and is a survivor for 20 years.

Damaghi bicycles and plays sports including soccer. He also enjoys cooking and said his guests appreciate his Persian kebobs.

As for his arrival in Stony Brook, he said it was “the best option for me. It’s a great package and has everything I need.”

Above, microscopic image showing brown, antibody-based staining of keratin 17 (K17) in bladder cancer. Image from Shroyer Lab, Stony Brook University

By Daniel Dunaief

Detectives often look for the smallest clue that links a culprit to a crime. A fingerprint on the frame of a stolen Picasso painting, a shoe print from a outside a window of a house that was robbed or a blood sample can provide the kind of forensic evidence that helps police and, eventually, district attorneys track and convict criminals.

Kenneth Shroyer MD, PhD                  Photo from SBU

The same process holds true in the world of disease detection. Researchers hope to use small and, ideally, noninvasive clues that will provide a diagnosis, enabling scientists and doctors to link symptoms to the molecular markers of a disease and, ultimately, to an effective remedy for these culprits that rob families of precious time with their relatives.

For years, Ken Shroyer, the Marvin Kuschner Professor and Chair of Pathology at the Renaissance School of Medicine at Stony Brook University, has been working with a protein called keratin 17.

A part of embryological development, keratin 17 was, at first, like a witness who appeared at the scene of one crime after another. The presence of this specific protein, which is unusual in adults, appeared to be something of a fluke.

Until it wasn’t.

Shroyer and a former member of his lab, Luisa Escobar-Hoyos, who is now an Assistant Professor at Yale, recently published two papers that build on their previous work with this protein. One paper, which was published in Cancer Cytopathology, links the protein to pancreatic cancer. The other, published in the American Journal of Clinical Pathology, provides a potentially easier way to diagnose bladder cancer, or urothelial carcinoma.

Each paper suggests that, like an abundance of suspicious fingerprints at the crime scene, the presence of keratin 17 can, and likely does, have diagnostic relevance.

Pancreatic cancer

A particularly nettlesome disease, pancreatic cancer, which researchers at Stony Brook and Cold Spring Harbor Laboratory, including CSHL Cancer Center Director David Tuveson, have been studying for years, has a poor prognosis upon diagnosis.

During a process called surgical resection, doctors have been able to determine the virulence of pancreatic cancer by looking at a larger number of cells.

Shroyer and Escobar Hoyos, however, used a needle biopsy, in which they took considerably fewer cells, to see whether they could develop a k17 score that would correlate with the most aggressive subtype of the cancer.

“We took cases that had been evaluated by needle biopsy and then had a subsequent surgical resection to compare the two results,” Shroyer said. They were able to show that the “needle biopsy specimens gave results that were as useful as working with the whole tumor in predicting the survival of the patient.”

A needle biopsy, with a k17 score that reflects the virulence of cancer, could be especially helpful with those cancers for which a patient is not a candidate for a surgical resection.“That makes this type of analysis available to any patient with a diagnosis of pancreatic cancer, rather than limiting it to the small subset of cases that are able to undergo surgery,” Shroyer said. 

Ultimately, however, a k17 score is not the goal for the chairman of the pathology department.

Indeed, Shroyer would like to use that score as a biomarker that could differentiate patient subtypes, enabling doctors to determine a therapy that would prove most reliable for different groups of people battling pancreatic cancer.

The recently published report establishes the foundation of whether it’s possible to detect and get meaningful conclusions from a needle biopsy in terms of treatment options.

At this point, Shroyer isn’t sure whether these results increase the potential clinical benefit of a needle biopsy.

“Although this paper supports that hypothesis, we are not prepared yet to use k17 to guide clinical decision making,” Shroyer said.

Bladder cancer

Each year, doctors and hospitals diagnose about 81,000 cases of bladder cancer in the United States. The detection of this cancer can be difficult and expensive and often includes an invasive procedure.

Shroyer, however, developed a k17 protein test that is designed to provide a reliable diagnostic marker that labs can get from a urine sample, which is often part of an annual physical exam.

The problem with bladder cancer cytopathology is that the sensitivity and specificity aren’t high enough. Cells sometimes appear suggestive or indeterminate when the patient doesn’t have cancer.

“There has been interest in finding biomarkers to improve diagnostic accuracy,” Shroyer said. 

Shroyer applied for patent protection for a k17 assay he developed through the Stony Brook Technology Transfer office and is working with KDx Diagnostics. The work builds on “previous observations that k17 detects bladder cancer in biopsies,” Shroyer said. He reported a “high level of sensitivity and specificity” that went beyond that with other biomarkers.

Indeed, in urine tests of 36 cases confirmed by biopsy, 35 showed elevated levels of the protein.

KDx, a start up biotechnology company that has a license with The Research Foundation for The State University of New York, is developing the test commercially.

The Food and Drug Administration gave KDx a breakthrough device designation for its assay test for k17.

Additionally, such a test could reveal whether bladder cancer that appears to be in remission may have recurred.

This type of test could help doctors with the initial diagnosis and with follow up efforts, Shroyer said.“Do patients have bladder cancer, yes or no?” he asked. “The tools are not entirely accurate. We want to be able to give a more accurate answer to that pretty simple question.”

Felicia Allard

By Daniel Dunaief

Stony Brook University recently added a wife and husband team to its Pathology Department. Felicia Allard and Eric Yee are joining SBU from the University of Arkansas.

Allard and Yee will “replace an individual who had moved to a leadership position at another institution and to meet increased caseloads in surgical pathology and cytopathology,” Ken Shroyer, the chairman of the Pathology Department, explained in an email.

Times Beacon Record News Media will profile Allard and Yee over the next two weeks.

Felicia Allard

Eric Yee and Felicia Allard. Photo by Joshua Valencia

A self-described “mountain girl” from Colorado, where she attended medical school and met her husband Eric Yee, Felicia Allard had only been to Long Island three times before accepting a job at Stony Brook.

She came once when she was interviewing for a residency and twice during the interview process.

Allard and Yee accepted the jobs in the middle of February and weren’t able to look at potential homes during the height of the lockdown caused by COVID-19.

For now, the couple have moved into temporary housing in Port Jefferson Station, as they look for longer term living options.

Allard, who will be an Associate Professor at SBU, said the move started with Pathology Department Chair Ken Shroyer, who was looking to fill two positions and reached out to Yee.

Shroyer was involved in a type of cancer work that interested her.

“The active pancreatic cancer research group was a big draw for me as I am hoping to expand my research career,” Allard explained in an email.

Allard said she was particularly interested in pancreatic cancer, in large part because of its intractability and the poor prognosis for most patients.

“It was clear to me that this is one of the areas where we had a lot of work to do in terms of being able to offer any type of meaningful treatment to patients,” she said.

Allard said she, like so many others in the medical community, entered the field because she wanted to make a difference. She searched for areas where the “greatest good could be done, and pancreatic cancer is still one of those.”

In her initial research, she studied the pancreatic neoplasm, exploring how cells went from pre-invasive to invasive to metastatic conditions. She is interested in how the tumor interacts with the patient’s immune system.

While Allard will continue to provide clinical services, she plans to collaborate with Shroyer in his lab. “I’m hoping naturally to be integrating into Dr. Shroyer’s group,” Allard said.

Shroyer welcomed Allard to the department and to his research team.

Allard is “a highly-qualified surgical pathologist with subspecialty expertise in GI tract pathology,” Shroyer wrote in an email. “She has a specific interest in pancreatic cancer, which will also complement our translational research program,” he said.

Shroyer expects that Allard will be integrated into several cancer research programs and he is “looking forward to having her join my team that is focused on the validation of prognostic and predictive biomarkers for pancreatic cancer.”

Shroyer’s lab, which includes Luisa Escobar-Hoyos, who is an Assistant Professor in the Department of Pathology, will work with Allard to advance the translational aspects of keratin 17 research, building on earlier work to understand the mechanisms through which K17 causes tumor aggression, he explained.

As for her clinical work, Allard said she analyzes biopsies and resections from the esophagus, stomach, intestines, liver, and pancreas. She has also used cytopathology to look at pap smears and to analyze salivary tumor aspirations.

The time to consider any of these slides varies broadly. Sometimes, she receives a slide and the diagnosis is unequivocal within 30 seconds. Other times, a biopsy from a six-month old patient with diarrhea, for example, can have an extensive list of differentials. In that case, the diagnosis can take considerably longer, as a baby could be sick because of an autoimmune disorder, inflammatory bowel disease or an infection.

She said she can “perseverate for hours or even days” over the subtle clues that may help with a diagnosis.

Allard likened the diagnostic process to reading a detective novel, in which the reader might figure out the perpetrator on page three, while other times, the culprit isn’t discovered until page 300.

Allard said she and her husband have a similar clinical background.

Yee is “more of a tech geek than I am,” she said. “He understands artificial intelligence, computer science and bioinformatics more than I do. He is also interested in administrative and leadership to a greater degree.”

Allard said she and Yee may have professional overlaps, but they have unique interests, backgrounds and perspectives that they bring to work that give them each different strengths.

Allard said she knew she wanted to go into medicine in her junior year of high school. When Doctors Without Borders won the Nobel Peace Prize in 1999, she recalls being impressed with that distinction.

In medical school, she said the field of pathology appealed to her because she appreciated the marriage of clinical care and basic science in the field.

She and Yee started dating just before medical school started for her. Yee was two years ahead in school. They continued their relationship from a distance while he did his residency at Beth Israel Deaconess Medical Center at Harvard Medical School. While she was a resident, Allard said Yee had the “distinct pleasure of trying to train me.”

She likes to explore the boundaries of diagnosis to understand the nuances and all the data that factor into interpretations, to tease the art from the science.

Outside of her work, Allard enjoys reading and calls her Kindle one of her favorite possessions. She hopes to learn how to sail while a resident of Long Island.

Allard is excited to start working at Stony Brook. Shroyer was “very persistent and once he got us up to New York to interview, he was persuasive with respect to the type of career growth we could both potentially have,” she said.

From left, Luisa Escobar-Hoyos, Lucia Roa and Ken Shroyer Photo by Cindy Leiton

By Daniel Dunaief

The prognosis and treatment for cancer varies, depending on the severity, stage and type of disease. With pancreatic ductal adenocarcinoma, the treatment options are often limited and the prognosis for most patients by the time doctors make a diagnosis is often bleak.

Researchers at the Renaissance School of Medicine’s Pathology Department at Stony Brook University have been testing for the presence of a protein called keratin 17, or K17, by staining tissue specimens or needle aspiration biopsy specimens. This measures the proportion of tumor cells that have high levels of expression.

This protein is typically active during embryological development or in stem cells, which are a type of cell that can differentiate into a wide range of other cells. It is also active in pancreatic cancer.

Ken Shroyer, department chairman; Luisa Escobar-Hoyos, assistant professor of pathology; and Lucia Roa, assistant professor of pathology recently published a paper in the journal Scientific Reports in which they documented how the level of this protein can indicate the prognosis for patients. K17 above a certain level typically suggests a worse prognosis.

The Stony Brook scientists want to understand why some pancreatic cancers are more aggressive than others, with the hope that they might be able to develop more effective ways to treat the most aggressive form of the disease.

In the recent research, the level of K17 not only indicated the prognosis for the most aggressive form of the disease, but it is also considered a “cause of making the tumors more aggressive,” Escobar-Hoyos added, which confirmed their previously published research and which unpublished data also supports.

Shroyer suggested that this research paper has been a validation of their plan to pursue the development of K17 as a way to differentiate one form of this insidious cancer from another.

While other cancers, such as cervical cancer, have proven quicker and easier to use K17 for its predictive power, the current work reflects the lab’s focus on pancreatic cancer. As such the research is a “great step forward to generate our first pancreatic cancer paper,” Shroyer said. His lab had previously published papers on other biomarkers in pancreatic cancer.

Escobar-Hoyos indicated that she and Shroyer anticipate that K17, which is one of a family of 54 different types of keratins in the human body, likely plays numerous roles in promoting cancer.

Indeed, K17 may promote the invasiveness of these cells, allowing them to spread from the original organ, in this case the pancreas, to other parts of the body. They are testing that concept through ongoing work in their lab.

The researchers believe that K17 may accelerate metastasis, but that line of thinking is “still at a relatively early stage,” Escobar-Hoyos said.

This protein may also change the metabolism of the cell. They believe K17 blocks the uptake of certain drugs by enhancing specific metabolic pathways. 

Additionally, K17 causes the degradation of p27, which is a tumor suppressor that controls cell division.

The researchers used two different ways to monitor the levels of protein, through mRNA analysis and through immunohistochemical localization. In the latter case, that involved staining the cells to look for the presence of the protein.

Roa, who is the first author on the paper, stained the slides and worked with Shroyer to score them.

The assistant professor, who came to Long Island with her daughter Laura who earned her bachelor’s degree and master’s in public policy at SBU, had been a pathologist and medical doctor when she lived in Colombia. She learned the IHC staining technique at Yale University just after she graduated from medical school and worked for six years as a postdoctoral fellow on several projects using IHC.

Roa is thrilled that she’s a part of a supportive team that could help develop techniques to improve patient diagnosis and care.

“We care deeply about developing a tool that will help us to treat patients and we value working together to accomplish this,” Roa explained in an email.

At this point, Shroyer and his team have identified key factors that cause K17 to be overexpressed. They are pursuing this line of research in the lab.

“We think K17 expression is dictated by something different than genetic status,” said Escobar-Hoyos. “This is speculation, but we think it might be triggered based on a patient’s immunity.”

After this study, the pathology team is looking to validate their results through different cohorts of patients. They are working with the Pancreatic Cancer Action Network and their scientific collaborators at Perthera Inc. to process tissue sections from these cases for K17 staining in their lab.

They are also at the early stages in the development of a collaboration with investigators at MD Anderson Cancer Center.

“If we can validate that K17 IHC testing is able to predict a response to the standard of care, then we’ll have permission to start a prospective analysis linked to a clinical trial,” Shroyer said.

Shroyer’s team is trying to understand how K17 becomes activated, what happens when they block that activation, and how it impacts the survival and tumor growth in animal models of pancreatic cancer.

In collaborations with other researchers, they are exploring how K17 impacts the therapeutic vulnerability of pancreatic cancer to over 2,000 FDA-approved compounds.

“There are a discrete list of compounds that are able to kill K17 positive cells,” Shroyer said. He is aiming to start phase 0 trials to validate the molecular model. If the data is sufficiently convincing, they can apply to the FDA to begin phase 1 trials.

He hopes this study is the first of many steps the lab will take in providing clues about how to diagnose and treat pancreatic cancer, which has been an intractable disease for researchers and doctors.

“This paper helps establish and confirm that K17 is an important and promising prognostic biomarker in pancreatic cancer,” Shroyer said. “For us, this is foundational for all the subsequent mechanistic studies that are in progress to understand how K17 drives cancer aggression.”

Brendan Boyce, center, with Xiangjiao Yi, left, and Jinbo Li, who are graduate students at the University of Rochester. Photo by Jianguo Tao.

By Daniel Dunaief

Chances are high you won’t see Dr. Brendan Boyce when you visit a doctor. You will, however, benefit from his presence at Stony Brook University Hospital and on Long Island if you have bone or soft tissue lesions and you need an expert pathologist to diagnose what might be happening in your body.

A professor at the University of Rochester for 20 years, the internationally renowned Boyce joined the Renaissance School of Medicine at SBU in November, splitting his time between Rochester and Long Island.

Dr. Ken Shroyer, the chair of the Department of Pathology, reached out to Boyce with an unusual bone tumor case last spring. After that discussion, the two considered the possibility of Boyce adding his bone and soft tissue pathology expertise to the growing department. Boyce was receptive to the idea, particularly because his daughter Jacqueline lives in Woodbury with two of his seven grandchildren.

For local patients, Boyce adds a relatively rare expertise that could shorten the time for a diagnosis and improve the ability for doctors to determine the best course of action during surgeries.

“While the patient is already undergoing a surgical procedure, the preliminary diagnosis can guide the process of the surgery,” said Shroyer. “That’s difficult to achieve if we are dependent on an outside consultant. It happens, more or less in real time, if Boyce can look at the slides as they are being prepared and while the patient is still on the operating table.”

Prior to Boyce’s arrival, Stony Brook functioned the same way most academic medical centers do around the country when it came to bone and soft tissue cancers or disorders.

“There are only a handful of soft tissue and bone surgical pathology subspecialists around the country,” Shroyer said. “There’s an insufficient number of such individuals to make it practical like this at every medical school in the country.”

Many of these cases are “rare” and most pathologists do not see enough cases to feel comfortable diagnosing them without help from an expert, Boyce explained.

Boyce “was recruited here to help this program at Stony Brook continue to grow,” Shroyer said. “He enhances the overall scope of the training we can provide to our pathology residents through his subspecialty expertise. Everything he does here is integrated with the educational mission” of the medical school.

While bone and soft tissue tumors are relatively rare compared to other common cancers, such as colorectal or breast cancer, they do occur often enough that Stony Brook has developed a practice to diagnose and treat them, which requires the support of experts in pathology. Stony Brook hired Dr. Fazel Khan a few years ago as the orthopedic surgeon to do this work.

“To establish a successful service, there needs to be a mechanism to financially support that service that’s not solely dependent on the number of cases provided,” Shroyer said.

Boyce’s recruitment was made possible by “investments from Stony Brook University Hospital and the School of Medicine, in addition to support from the Department of Orthopedics and Pathology.”

Shroyer was thrilled that Boyce brings not only his expertise but his deep and well-developed background to Stony Brook.

It was “important to me that he was not only a highly skilled surgical pathologist, but also was a physician scientist, which made him a very attractive recruit,” Shroyer said.

Indeed, while Boyce will provide pathology services to Stony Brook, he will continue to maintain a laboratory at the University of Rochester.

Boyce’s research is “focused on the molecular mechanisms that regulate the formation of osteoclasts and their activity,” Boyce said. He emphasizes the effects of pro-inflammatory cytokines and NF-Kappa B, which are transcription factors that relay cytokine signaling from the cell surface to the nucleus.

These factors drive osteoclast formation and activity in conditions affecting the skeleton, which include rheumatoid arthritis, postmenopausal and age-related osteoporosis and cancers affecting the skeleton.

Osteoclasts degrade bone, which carve out deformities or the equivalent of potholes in the bone, while osteoblasts help rebuild the bone, repaving the equivalent of the roads after the osteoclasts have cleared the path. There are over a million sites of bone remodeling in the normal human skeleton and the number of these increases in diseases.

Boyce has studied various aspects of how bone remodeling occurs and how it becomes disturbed in a variety of pathological settings by using animal models. He uses cellular and molecular biological techniques to answer these questions.

On behalf of Boyce and three other researchers, the University of Rochester Medical Center just finished licensing a compound to a company in China that he recently contacted, which will do animal studies that will test the toxicity of a treatment for myeloma.

At this point, Boyce is applying in July for another five-year grant from the National Institutes of Health for research in his Rochester lab. He hopes to renew another NIH grant next year, which he has for four years. After he renews that grant, he will continue writing up papers and studies with residents and collaborating on basic science at Stony Brook as well.

Boyce and his wife Ann, have three children and seven grandchildren. Originally from Scotland, Boyce has participated in Glasgow University Alumni activities in the United States, including in New York City, where he walked in this year’s Tartan Parade with his daughters and their children.

As for his work at Stony Brook, Boyce is enjoying the opportunity to contribute to the community.

“The setting and faculty are very nice and congenial and I’ve been made to feel welcome,” he said.