Tags Posts tagged with "Ken Shroyer"

Ken Shroyer

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making the tumors more aggressive,” Escobar-Hoyos added, which confirmed their previously published research and which unpublished data also supports.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.