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Cancer Research

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From left, Sam Kleeman, Assistant Professor Tobias Janowitz, Miriam Ferrer Gonzalez and Emma Davidson. Photo by Caryn Koza/CSHL

By Daniel Dunaief

This part one of a two part series.

It’s a bit like shaking corn kernels over an open flame. At first, the kernels rustle around in the bag, making noise as they heat up, preparing for the metamorphosis.

That’s what can happen in any of the many laboratories scattered throughout Long Island, as researchers pursue their projects with support, funding and guidance from lab leaders or, in the science vernacular, principal investigators.

Sometimes, as happened recently at the benches of Cold Spring Harbor Laboratory Assistant Professor Tobias Janowitz, several projects can pop at around the same time, producing compelling results, helping advance the careers of developing scientists and leading to published papers.

PhD graduate Miriam Ferrer Gonzalez and MD/ PhD student Sam Kleeman recently published separate studies.

In an email, Janowitz suggested the work for these papers is “time consuming and requires a lot of energy.” He called the acceptance of the papers “rewarding.” 

In a two-part series, Times Beacon Record News Media will describe the research from each student. This week, the focus is on Ferrer Gonzalez. Check back next week for a profile of the work of Kleeman.

Miriam Ferrer Gonzalez

Miriam Ferrer Gonzalez. Photo by Caryn Koza/CSHL

Miriam Ferrer Gonzalez was stuck. She had two results, but couldn’t seem to figure out how to connect them. First, in a mouse model of the ketogenic diet — heavy on fats, without including carbohydrates —cancer tumors shrunk. That was the good news.

The bad news, which was even more pronounced than the good, was that this diet was not only starving the tumors, but was triggering an earlier onset of cachexia, in which bodies weaken and waste away. The cachexia overpowered the mice, causing them to die sooner than if they had a normal diet.

Ferrer, a student in residence from Spain who was conducting her research at Cold Spring Harbor Laboratory while earning her PhD at the University of Cambridge in the UK, thought the two discoveries were paradoxically uncoupled. A lower tumor burden, she reasoned, should have been beneficial.

In presenting and discussing her findings internally to the lab group, Ferrer received the kind of feedback that helped her hone in on the potential explanation.

“Finding out the mechanism by which a ketogenic diet was detrimental for both the body and the cancer was the key to explaining this uncoupling,” Ferrer explained.

The adrenal glands of mice fed a ketogenic diet were not producing the necessary amount of the hormone corticosterone to sustain survival. She validated this broken pathway when she discovered higher levels of corticosterone precursors that didn’t become functional hormones.

To test this hypothesis, she gave mice dexamethasone, which boosted their corticosterone levels. These mice had slower growing tumors and longer lives.

Ferrer recently published her paper in the journal Cell Metabolism.

To date, the literature on the ketogenic diet and cancer has been “confusing,” she said, with studies that show positive and negative effects.

“In our study, we go deeper to explain the mechanism rather than only talking about glucose-dependency of cancer cells and the use of nutritional interventions that deprive the tumor of glucose,” said Ferrer. She believed those factors are contributing to slower tumor growth, but are not solely responsible.

Thus far, there have been case studies with the ketogenic diet shrinking tumors in patients with cancer and, in particular, with glioblastoma, but no one has conducted a conclusive clinical trial on the ketogenic diet.

Researchers have reported on the beneficial effects of this diet on epilepsy and other neurological diseases, but cancer results have been inconclusive.  For the experiments in Janowitz’s lab, Ferrer and technician Emma Davidson conducted research on mouse models.

Ferrer, who is the first author on the paper, has been working with this system for about four years. Davidson, who graduated from the College of Wooster in Ohio last year and is applying to MD and MD/PhD programs, contributed to this effort for about a year.

Next steps

From left, Emma Davidson, Assistant Professor Tobias Janowitz, Sam Kleeman and Miriam Ferrer Gonzalez. Photo by Caryn Koza/CSHL

Now that she earned her PhD, Ferrer is thinking about the next steps in her career and is considering different institutions across the country. Specifically, she’s interested in eating behavior, energy homeostasis, food intake and other metabolic parameters in conditions of stress. She would also like to focus on how hormonal cycles in women affect their eating behavior.

Originally from a small city in Spain called Lleida, which is in the western part of Catalonia, Ferrer appreciated the opportunity to learn through courses and conferences at Cold Spring Harbor Laboratory.

Until she leaves the lab in the next few months, Ferrer plans to work with Davidson to prepare her to take over the project for the next year.

The follow up experiments will include pharmacologically inducing ferroptosis of cancer cells in mice fed a ketogenic diet. They hope to demonstrate that early induction of ferroptosis, or a type of programmed cell death, prevents tumor growth and prevents the tumor-induced reprogramming of the rest of the body that causes cachexia.

These experiments will involve working with mice that have smaller and earlier tumors than the ones in the published paper. In addition, they will combine a ketogenic diet, dexamethasone and a ferroptosis inducing drug, which they didn’t use in the earlier experiments.

Janowitz has partnered with Ferrer since 2018, when she conducted her master’s research at the University of Cambridge. As the most senior person in Janowitz’s lab, Ferrer has helped train many of the people who have worked in his lab. She has found mentoring rewarding and appreciates the opportunity to invest in people like Davidson.

Ferrer, who is planning a wedding in Spain in September, is a fitness and wellness fan and has taken nutrition courses. She does weight lifting and running.

Ferrer’s parents don’t have advanced educational degrees and they supported their three children in their efforts to earn their degrees.

“I wanted to be the best student for my parents,” said Ferrer, who is the middle child. She “wanted to make my parents proud.

The hand off

Emma Davidson and Miriam Gonzalez Ferrer examine an adrenal gland sample section from a cachectic mouse. Photo by Caryn Koza/CSHL

For her part, Davidson is looking forward to addressing ways to implement further treatment methods with a ketogenic diet and supplemental glucocorticoids to shrink tumors and prevent cachexia. 

Davidson appreciated how dependable Ferrer was during her time in the lab. Just as importantly, she admired how Ferrer provided a “safe area to fail.”

At one point, Davidson had taken all the cells she was planning to use to inject in mice. Ferrer reminded her to keep some in stock.

“Open lines of communication have been very beneficial to avoid more consequential failures,” Davidson said, ”as this mistake would have been.”

Davidson developed an interest in science when she took a high school class called Principles in Biological Science and Human Body Systems. When she was learning about the cardiovascular system, her grandfather had a heart attack. In speaking with doctors, Davidson acted as a family translator, using the language she had studied to understand what doctors were describing.

Like Ferrer, Davidson lives an active life. Davidson is preparing for the Jones Beach Ironman Triathlon in September, in which she’ll swim 1.2 miles, bike 56 miles and run a half marathon. She plans to train a few hours during weekdays and even more on weekends for a competition she expects could take about six hours to complete.

Davidson started training for these events with her father Mark, an independent technology and operations consultant and owner of Exoro Consulting Group.

Longer term, Davidson is interested in medicine and research. After she completes her education, she will try to balance between research and clinical work.

 

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Chengfeng Yang Photo by Zhishan Wang

By Daniel Dunaief

This is part two of a two-part series.

As Erin Brockovich (the real life version and the one played by Julia Roberts in the eponymous movie) discovered, some metals, such as hexavalent chromium can cause cancer in humans.

Chengfeng Yang and Zishan Wang

Environmental exposure to a range of chemicals, such as hexavalent chromium, benzo(a)pyrene, arsenic, and others, individually and in combination, can lead to health problems, including cancer.

In March, Stony Brook University hired Chengfeng Yang and Zhishan Wang, a husband and wife team to join the Cancer Center and the Pathology Departments from Case Western Reserve University.

The duo, who have their own labs and share equipment, resources and sometimes researchers, are seeking to understand the epigenetic effect exposure to chemicals has on the body. Yang focuses primarily on hexavalent chromium, while Wang works on the mechanism of mixed exposures.

Last week, the TBR News Media highlighted the work of Wang. This week, we feature the work of Yang.

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When he was young, Chengfeng Yang was using a knife to make a toy for his younger brother. He slipped, cutting his finger so dramatically that he almost lost it. Doctors saved his finger, impressing him with their heroic talent and inspiring him to follow in their footsteps.

Indeed, Yang, who earned an MD and a PhD from Tongji Medical University, is focused not only on answering questions related to cancer, which claimed the life of his mother and other relatives, but also in searching for ways to develop new treatments.

A Professor in the Department of Pathology at the Renaissance School of Medicine at Stony Brook University and a member of the Stony Brook Cancer Center, Yang has his sights set on combatting cancer.

“Our research always has a significant clinical element,” said Yang. “This is related to our medical background.”

He is interested in studying the mechanism of cancer initiation and progression and would like to develop new strategies for treatment.

Yang and his wife Zhishan Wang recently joined the university from Case Western after a career that included research posts at the University of Pennsylvania, Michigan State University, and the University of Kentucky.

The tandem, who share lab resources and whose research staffs collaborate but also work independently, are focused specifically on the ways exposures to carcinogens in the environment cause epigenetic changes that lead to cancer.

Specifically, Yang is studying how hexavalent chromium, a metal commonly found in the environment in welding, electroplating and even on the double yellow lines in the middle of roads, triggers cancer. It is also commonly used as a pigment to stain animal leather products.

Yang is focused mainly on how long cancer develops after exposure to hexavalent chromium.

People can become exposed to hexavalent chromium, which is also known as chromium 6, through contaminated drinking water, cigarette smoking, car emissions, living near superfund sites and through occupational exposure.

Yang has made important findings in the epigenetic effect of metal exposure. His studies showed that chronic low-level chromium six exposure changed long non-coding RNA expression levels, which contributed to carcinogenesis. Moreover, his studies also showed that chronic low level exposure increased methylation, in which a CH3 group is added to RNA, which also contributed significantly to chromium 6 carcinogenesis.

“It is now clear that metal carcinogens not only modify DNA, but also modify RNA,” Yang explained. Metal carcinogen modification of RNAs is an “exciting and new mechanism” for understanding metal carcinogenesis.

By studying modifications in RNA, researchers may be able to find a biomarker for the disease before cancer develops.

Yang is trying to find some specific epigenetic changes that might occur in response to different pollutants.

Stony Brook attraction

Yang was impressed with the dedication of Stony Brook Pathology Chair Ken Shroyer, whom he described as a “really great physician scientist. His passion in research and leadership in supporting research” helped distinguish Stony Brook, Yang said.

Yang is confident that Stony Brook has the resources he and Wang need to be successful, including core facilities and collaborative opportunities. “This is a very great opportunity for us, with strong support at the university level,” he said.“We plan to be here and stay forever.”

Yang is in the process of setting up his lab, which includes purchasing new equipment and actively recruiting scientists to join his effort.

“We need to reestablish our team,” he said. “Right now, we are trying to finish our current research project.”

He hopes to get new funding for the university in the next two to three years as well. After he establishes his lab at Stony Brook, Yang also plans to seek out collaborative opportunities at Cold Spring Harbor Laboratory, which is “very strong in RNA biology,” he added.

A return home

Returning to the Empire State brings Yang full circle, back to where his research experience in the United States started. About 23 years ago, his first professional position in the United States was at New York University.

Outside of work, Yang likes to hike and jog. He is looking forward to going to some of Long Island’s many beaches.

He and Wang live in an apartment in South Setauket and are hoping to buy a house in the area. The couple discusses science regularly, including during their jogs.

Working in the same area provides a “huge opportunity” for personal and professional growth, he said.

Yang suggested that his wife usually spends more time training new personnel and solving lab members’ technical issues. He spends more time in the lab with general administrative management and support. Wang has “much stronger molecular biology skills than I have,” Yang explained in an email, whereas he has a solid background in toxicology.

Growing up, Yang said he had an aptitude in math and had dreamed of becoming a software engineer. When he applied to college, he received admission to medical school, which changed his original career path.

Once he started running his own experiments as a researcher, he felt he wanted to improve human health.“Once humans develop disease, in many cases, it’s very expensive to treat and [help] people recover,” he said. “Prevention could be a more cost effective way to improve health.”

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Zhishan Wang. Photo from Chengfeng Yang

By Daniel Dunaief

This is part one of a two-part series.

As Erin Brockovich (the real life version and the one played by Julia Roberts in the eponymous movie) discovered, some metals, such as hexavalent chromium can cause cancer in humans.

Chengfeng Yang and Zhishan Wang

Environmental exposure to a range of chemicals, such as hexavalent chromium, benzo(a)pyrene, arsenic, and others, individually and in combination, can lead to health problems, including cancer.

Recently, Stony Brook University hired Chengfeng Yang and Zhishan Wang, a husband and wife team to join the Cancer Center and the Pathology Departments from Case Western Reserve University in Ohio.

The duo, who have their own labs and share equipment, resources and sometimes researchers, are seeking to understand the epigenetic effect exposure to chemicals has on the body. Yang focuses primarily on hexavalent chromium, while Wang works on the mechanism of mixed exposures. 

In part one, TBR News Media highlights the work of Wang. Next week, we will feature the efforts of Yang.

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In certain areas and specific job sites, people can be exposed to environmental pollutants.

Sometimes, the introduction of a metal or element can cause cancer after long term exposure. The effect of another carcinogen can be synergistic in triggering disease, triggering a stronger progression of cancer than an individual exposure alone.

Zhishan Wang, who joined Stony Brook in March and is a Professor of Research in the Department of Pathology, is trying to understand what changes this mixed exposure creates at a molecular level.

“If we find out some gene or pathway change, we can try to intervene,” said Wang, who is a member of the Stony Brook Cancer Center and earned MD and PhD degrees from her native China.

Among the many possible environmental triggers, Wang chose to study arsenic, which is common in rock soil and water and is present in some places in drinking water.

“People living in high exposure areas to arsenic and [who] are also cigarette smokers have a significantly higher risk of lung cancer,” she said.

Arsenic can cause three different kinds of cancer: skin, bladder and lung cancer. For skin cancer, Wang explained that direct contact can lead to the kind of irritation that promotes the disease. 

As the heavy metal works its way through the body, parts of it get excreted through the urine system, which means that bladder cells come into contact with it as well.

For a long time, scientists knew arsenic exposure through drinking water caused lung cancer. The underlying mechanism for the development of that cancer was not well understood. 

Wang’s lab studies the mechanism by which arsenic and benzo(a)pyrene (or BAP) co-exposure increases lung cancer risk. Exposure to arsenic alone causes cancer, but it takes a long time in animal models. Arsenic and BPA co-exposure significantly increases lung cancer risk.

Wang’s study showed that co-exposure increases lung tumor burden and malignancy. She plans to continue to study the mechanism of how arsenic and BAP co exposure increases lung cancer risk.

“That’s our big goal: to try to find some useful method to prevent this tumor from happening,” she said.

Wang believes the cancer cells caused by the mixed exposure increases the number of cancer stem cell-like cells, which could mediate therapeutic resistance.

Wang explained that generating the mouse model took considerable time and effort. She tried to find the exposures during particular windows of time that lead to cancer.

“By using this model, we can do a lot of data analysis” including single cell analysis and can determine which cluster or pathway will change.

Choosing SBU

Wang suggested she and her husband chose Stony Brook for several reasons. The couple would like to help the University earn a National Cancer Institute (NCI) designation, which would give scientists the ability to compete for ambitious, well-funded, multidisciplinary efforts.

Both Wang and Yang “lead NCI-funded research programs that will enhance the [Cancer Center’s] eligibility for NCI designation,” explained Kenneth Shroyer, chair of the Pathology Department at Stony Brook.

Shroyer, who described both researchers as “highly competitive candidates with the potential to enhance the status of any cancer center,” is looking forward to working with his newest recruits.

Wang is eager to use the tissue bank at Stony Brook, which Shroyer explained has also attracted other cancer research scientists recruited to the Renaissance School of Medicine at Stony Brook.

The new scientists also hope to tap into the expertise at nearby Cold Spring Harbor Laboratory, which has become one of the leading centers in creating organoids. 

In the early years of her training during her MD and PhD years in China, Wang developed her technical skills. Through her career, she has worked on several genes that play important roles in carcinogenesis. Down regulation of the gene known as SOCS3, for suppressor of cytokine signaling 3, plays an important role in arsenic and BAP co-exposure caused lung tumorigenesis.

Early in their careers, Wang worked in her husband’s lab for seven years until she received her own research funding.

Outside of work, Wang enjoys playing badminton and ping pong. She also cooks every day. She and her husband bring her home cooked meals to work.

When she was in high school, Wang had ambitions to become a writer. Her teachers regularly read her work out loud to the class.

Her father, who was a lawyer, had encouraged her to join the legal profession. She had heard that people called others “smart” when they joined the fields of Science, Technology, Engineering and Mathematics. “I want people to call me smart,” she said, so she changed her career and went to medical school at Tongji Medical University where she earned top scores. 

Her father had a stroke, surviving afterwards for seven years. When she was in medical school, Wang hoped to learn ways to help him. Wishing she could have done more, she pursued clinical research in the lab. She passed the tests to become a practicing physician in the United States, but she was more inspired to work as a scientist.

As for her work at Stony Brook University, Wang appreciates the beauty of Long Island. She hopes this is their “last move,” as they continue their careers.

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CSHL’s David Spector (center) and postdoctoral fellows Rasmani Hazra on left and Gayan Balasooriya on right. Photo courtesy of CSHL

By Daniel Dunaief

One came from India, the other from Sri Lanka. After they each earned their PhD’s, they arrived on Long Island within seven months of each other about seven years ago, joining a lab dedicated to studying and understanding cancer. Each of them, working on separate projects, made discoveries that may aid in the battle against heart disease.

Working for principal investigator David Spector at Cold Spring Harbor Laboratory, postdoctoral fellow Rasmani Hazra, who grew up in Burdwan, India, found a link between a gene that affects cancer in mice that also can lead to a problem with the development of heart valves.

Hazra worked with two long noncoding RNAs that are highly expressed in mouse embryonic stem cells, which have the ability to differentiate into many different types of cells.

Specifically, she found that mice that didn’t have Platr4 developed heart-related problems, particularly with their valves.

At the same time, postdoctoral fellow Gayan Balasooriya, who was born and raised in Sri Lanka, discovered that a single, non-sex gene is governed by different epigenetic mechanisms based on whether the gene is inherited from the mom or the dad.

While it was known that males are more susceptible to heart disease than females, researchers did not know which copy of the gene related to those diseases are expressed. This discovery could help in understanding the development of heart defects.

“Although we ended up at heart development” in both of these published studies, “we didn’t initiate” looking for heart-related information, said Spector. “The science led us there.

Spector, however, expects that the lessons learned about differentiation in the context of the developing heart can also “impact out knowledge about tumors” which he hopes will eventually lead to advances in how to treat them.

He added that any clinical benefit from this work would take additional research and time.

An on and off switch

In Hazra’s study, which was published in the journal Developmental Cell, she worked with Platr4 because humans have several possible orthologous genes. 

When Platr4 expression, which shuts down after birth, is deleted from cells or embryos, the mice died from heart valve problems.

The human equivalent of Platr4 is located on chromosome 4. At this point, clinical case studies have connected the deletion of this chromosome to cardiac defects in humans.

Hazra said her project initially examined the function of these long non-coding sections of RNA. She was exploring how they affected differentiation. She found this link through in vitro studies and then confirmed the connection in live mice.

Spector explained that this work involved extensive collaborations with other researchers at Cold Spring Harbor Laboratory, including teaming up with researchers who can do electrocardiograms on mice and who can assess blood flow.

A shared mouse imaging resource also helped advance this research.

“One of the advantages of Cold Spring Harbor Laboratory is that we have over 10 shared resources, each of which specializes in sophisticated technologies that scientists can use on their own projects,” he said. Each lab doesn’t have to learn and develop its own version of these skills.

Hazra plans to continue to study other long noncoding RNA. She is also working on glioblastoma, which is a form of brain cancer.

Hazra plans to start her own lab next fall, when she completes her postdoctoral research.

Inactive gene

Balasooriya, meanwhile, published his research in the journal Nature Communications.

He used RNA sequencing to identify numerous genes. He also looked at whether the RNAs originated from the mom or dad’s genes in individual cells.

Also planning to start his own lab next fall, Balasooriya found changes that alter gene expression between the alleles from the mother and the father experimentally and through data mining approaches.

“What was most surprising in my studies is that [he identified] the gene from the father’s side and the mother’s side are regulated in a different manner,” Balasooriya said. “I’m interested in following up on that finding.”

The next step for him is to look not only at the heart, but, more broadly, at how monoallelic gene expression changes the way regulators affect development and disease.

“I want to do a deep dive to find out the mechanisms” involved in this expression of a single copy of the gene, Balasooriya said, which could provide ways to understand how to control the process.

In the long run, this kind of research could provide insights into ways to treat heart disease as well as other diseases like cancer and immune diseases.

Growing up in the North Western Province in Sri Lanka, Balasooriya was interested in math and science. After he finished his bachelor’s degree in biology in Sri Lanka, he earned a master’s in molecular biology at the University of Hertfordshire in England. He “got so excited about biology and exploring new fields” that he decided to pursue his PhD at the University of Cambridge, England.

After college, he worked in computer science for a while and realized he was not passionate about it, which encouraged him to do his master’s. The experience in computer science helped him with bioinformatics.

As for Spector, he is pleased with the work of both of his postdoctoral researchers. “This is what being a principal investigator is all about, having young people join your lab, sitting down with them, discussing a potential project, not really knowing where it’s going to go,” he said.

He described both members of his team as “extremely successful” who were able to make discoveries that they shared in prestigious journals. Balasooriya and Hazra both laid the groundwork to go and start their own careers. 

“Seeing the fruits of their work is the most rewarding experience” as the leader of a lab, Spector said.

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County legislator discusses major initiatives coming out of her office

Suffolk County Legislator Sarah Anker (D-Mount Sinai) is working on several projects, from bike trails to erosion education programs and more. Photo courtesy Anker’s office

Suffolk County Legislator Sarah Anker (D-Mount Sinai) is at the forefront of several initiatives at the county level. In an exclusive interview with Anker, she opened up about her positions on public campaign finance, the North Shore Rail Trail, coastal erosion and more.

For those who do not know you, can you describe your background?

My background is that I’m a mother of three children and have been a Mount Sinai resident for 25 years. I’ve lived in Middle Island and in Coram, and I’m very familiar with this area and my legislative district. I worked at different ad agencies, did some independent contracting work and at some of the local shops in Patchogue. Then I took off for a handful of years to raise my kids. 

When my youngest was born, the New York State Health Department put out a cancer map showing that our area had a high frequency of cancer, particularly breast cancer, and my grandmother had just passed away from breast cancer. I decided to start a non-for-profit, the Community Health and Environment Coalition, around 2003. And this was basically to advocate to the state to come and do an investigation, tell us what we need to know, why we had these numbers and where these numbers were coming from. 

Eventually, they came back to the community and did testing, but unfortunately, they left more questions than answers. We continue to investigate and try to understand the causes of cancer.

I got a job working as the chief of staff for [Councilwoman] Connie Kepert [D-Middle Island] at the Town of Brookhaven. She pulled me in and then they got a $4.5 million grant for solar programs. Working with Connie, we started the programs and then I was promoted to be in charge of creating an energy department at the Town of Brookhaven. I left that position to run for this position.

I ran for office and have been elected seven times. I’m term limited, so I can’t run anymore. I’m a Democrat but fairly conservative — moderate and in the middle. I find the common denominator and I focus on that. I don’t go too far left or too far right, and I’m here to represent my constituents and to kind of settle the storm when there are issues out there. My top priority is public safety and the safety of my residents. I did that for my kids and my family. I do that now for my constituents.

How did your most recent project, the North Shore Rail Trail, come to fruition?

That one was very challenging. I had to overcome some major obstacles and challenges along the way. 

The three main challenges were getting the county exec on board. The former one was not supportive; the current one, Steve Bellone [D], supported it. I also had to get the energy folks from LIPA on board. I had worked a lot with them while running the energy program at the Town of Brookhaven and we had a good professional relationship. 

That worked because they were open to the idea of LIPA having this as a wonderful public relations project. The third one was getting the community on board. The ability to see this through stemmed from the fact that there had been fatalities related to people attempting to ride their bikes, jog or run along our local highways. Because all of those concerns and challenges were in place, it was time to move forward.

Hopefully, and I stress this, people need to use common sense and they need to take responsibility for their safety when they cross the intersections. But this provides a safe place for people to be able to recreate. 

Can you discuss the work you are doing related to coastal erosion?

Erosion is a huge issue. I was meeting constituents and I was on Culross Drive in Rocky Point and as I walked up to a house, I noticed that their neighbor’s house had fallen off the cliff — literally, it was down the cliff. This was 10 or 11 years ago.

I found that a lot of constituents in my area are part of beach associations. Miller Place, Sound Beach, Rocky Point — these are private beach communities, so they don’t qualify for federal funding. I’m using the resources we do have to educate them on certain seagrasses, different brick structures, just give them ideas to try to address it. 

Unfortunately, if one addresses it and this person doesn’t and this person doesn’t, then it creates issues for the people that do. So I’m trying to see if we can get everyone on board to address the erosion issue. We’ll do what we can.

Public campaign finance has been an ongoing dispute between the county executive and the Legislature. Can you elaborate on your stance regarding the public campaign finance program that was repealed last week?

I support funding campaign finance reform. I support it. It’s a program that was started last year. We put money into it and it’s a shame that we couldn’t try it out. We do pilot programs all the time and I would have hoped that they could have at least done that. 

It was a project that the former presiding officer, Rob Calarco [D-Patchogue], had advocated for. He worked for a long time on it. I respect him and the amount of effort that he put into that. I would have preferred to at least give it a shot and see where it was going.

If it wasn’t doing well or there were some issues or problems with it, we could have always changed it. I voted to have another way to finance campaigns. Any large organization that has a lot of money can create very, very challenging campaigns for any individual — and I’ve been there personally. 

What is it about the communities that you represent that makes them so distinctive and unique?

I think that we have a lot of folks who understand how important it is to take an active role in their community. We have a lot of folks that participate in projects and events and activities that continue to inspire the people around them. Like the butterfly effect or a ripple in a stream, it just keeps going and I see that in my community.

Right now, in this complicated political climate, we need to understand that we all have something in common and we can all be part of addressing issues and accomplishing our goals by working together collaboratively. I’ve seen that and I do that, and I think that — whether it’s unique to us or not — it’s something that’s important that is happening in our district. 

We get what we put into our community. And right now, the people that have contributed to and who have improved our community, I’m really honored and privileged to work with those folks. 

Whether it’s Bobby Woods with the North Shore Youth Council or Bea Ruberto from the Sound Beach Civic Association, you really see who the true heroes are within your community when you work with them. And I feel very honored to have the ability to be part of what they are trying to create, which is a place that we can call home.

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Eszter Boros. Photo from SBU

By Daniel Dunaief

And the winner is … Eszter Boros. An Assistant Professor in the Department of Chemistry at Stony Brook University, Boros recently won the 2021 Stony Brook Discovery Prize, which includes $200,000 in new funding.

The prize, which was established in 2013, is designed to fund higher-risk research for scientists who are no more than five years beyond tenure and promotion at the Associate Professor level or who are on a tenure track as an Assistant Professor. The research might not otherwise receive financial support from agencies like the National Institutes of Health.

Eszter Boros. Photo from SBU

Stony Brook awards the prize to a faculty member who is considered a rising star.

Boros’s proposal suggests using a radioactive light switch to activate anticancer molecules.

The goal behind Boros’s work is to target cancer cells in particular, while avoiding the kinds of painful side effects that typically accompany chemotherapy, which can lead to gastrointestinal discomfort and hair loss, among others.

Boros, who has been at Stony Brook since 2017, was pleased to win the award. “It’s really exciting,” she said. “I’m kind of in disbelief. I thought all the finalists had convincing and exciting projects.”

The four finalists, who included Eric Brouzes in biomedical engineering, Gregory Henkes in geosciences and Kevin Reed in climate modeling, went through three rounds of screening, culminating in a Zoom-based 10-minute presentation in front of four judges.

Bruce Beutler, the Director of the Center for the Genetics of Host Defense at the University of Texas Southwestern Medical Center, served as one of the four judges.

In an email, Beutler wrote that Boros’s work had an “inventive approach” and was “high risk, but potentially high impact.”

Beutler, who won the 2011 Nobel Prize in Physiology and Medicine, suggested that the Discovery Prize may give a start to “a bright person with relatively little track record and a risky but well reasoned proposal.”

The success from such a distinction “does build on itself,” Beutler wrote. “Other scientists hear of such awards or read about them when evaluating future proposals. This may influence decisions about funding, or other awards, in the future.”

Boros said she would use the prize money to fund work from graduate students and post doctoral fellows, who will tackle the complexities of the work she proposed. She will also purchase supplies, including radioactive isotopes. She hopes to stretch the funds for two and a half or three years, depending on the progress she and the members of her lab make with the work.

The idea behind her research is to send radioactive materials that emit a light as they decay and that bind to the cancer cell. The light makes the chemotherapy toxic. Without that light, the chemotherapy would move around the body without damaging non-cancerous cells, reducing the drug’s side effects.

She is thinking of two ways to couple the radioactive light-emitting signal with an activated form of treatment. In the first, the two parts would not be selectively bound together.

The chemotherapy would diffuse into tissues around the body and would only become activated at the target site. This may affect healthy neighbors, but it wouldn’t cause as many side effects as conventional chemotherapy. This could take advantage of already clinically used agents that she can combine.

In the second strategy, she is taking what she described as a “next level” approach, in which she’d make the radioactive agent and the chemotherapy react with one another selectively. Once they saw one another, they would become chemically linked, searching to find and destroy cancer cells. This approach would require new chemistry which her lab would have to develop. 

Beutler suggested that Boros’s work might have other applications, even if cancer might currently be the best one. Some focal but infectious diseases can be treated with antimicrobial therapy which, like cancer directed chemotherapy, is toxic, he explained.

The same principle of using a drug activated by light that is connected to a site-specific marker “could be used in such cases,” he said.

While the potential bench-to-bedside process for any single treatment or approach can seem lengthy and filled with unexpected obstacles, Beutler said he has seen certain cancers that were formerly fatal yield to innovation. “People who are battling cancer can at least be hopeful that their cancer might fall into this category,” he said.

Boros appreciated the opportunity to apply for the award, to bond with her fellow finalists and to benefit from a process that included several sessions with experts at the Alan Alda Center for Communicating Science, who helped prepare her for the presentation in front of the judges. She developed her full proposal during the course of a week, over the December holiday, when her lab had some down time.

In the final stage, she met weekly for an hour with Louisa Johnson, an Improvisation Lecturer at the Alda Center and Radha Ganesan, an Assistant Professor of Medicine, to hone her presentation.

Boros said she appreciated how the Alda Center guides helped her focus on the obsession she and other scientists sometimes have of putting too much text in her slides. “I put text and conclusions on every slide,” she said. Ganesan and Johnson urged her to focus on what she wants to say, while letting go of this urge to clutter her presentation with the same words she planned to use in her presentation. “That was a huge shift in mindset that I had to make,” she said.

As for the work this prize will help fund, Boros said she’ll start with targets she knows based on some research she’s already done with prostate, breast and ovarian cancers.

Boros, who was born and raised in Switzerland, described herself as a chemist at heart.

Outside of work, she enjoys spending time with her husband Labros Meimetis, Assistant Professor of Radiology at the Renaissance School of Medicine at Stony Brook, and their nine-month-old son.

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Tobias Janowitz with research technician Ya Gao at Cold Spring Harbor Lab Photo by ©Gina Motisi, 2019/CSHL

By Daniel Dunaief

It’s a low-tech setting with high stakes. Scientists present their findings, often without slides and pictures, to future colleagues and collaborators in a chalk talk, hoping faculty at other institutions see the potential benefit of offering them an employment opportunity.

For Tobias Janowitz, this discussion convinced him that Cold Spring Harbor Laboratory was worth uprooting his wife and three young children from across the Atlantic Ocean to join.

Chalk talks in most places encourage people to “defend their thinking. Here, it was completely different. They moved on from my chalk talk quickly,” said Janowitz in a recent interview.

Research technician Ya Gao and Tobias Janowitz at Cold Spring Harbor Lab. Photo by ©Gina Motisi, 2019/CSHL

Janowitz recalled how CSHL CEO Bruce Stillman asked him “what else will you do that’s important and high risk. He moved me on from that discussion within five minutes and essentially skipped a step I’d usually spend at another institution. It’s a very special place.”

Janowitz, who earned a medical degree and a doctorate from the University of Cambridge, came to the lab to work in a field where he’s distinguished himself with cancer research that points to the role of a glycoprotein called interleukin 6, or IL-6, in a specific step in the progression of the disease, and as a medical oncologist. He will work as a clinician scientist, dedicated to research and discovery and advancing clinical care, rather than delivering standard care.

As CSHL continues to develop its ongoing relationship with Northwell Health, Janowitz said he expects to be “one of the intellectual bridges between the two institutions.”

In his research, the scientist specializes in understanding the reciprocal interaction between a tumor and the body. Rather than focusing on one type of cancer, he explores the insidious steps that affect an organ or system and then wants to understand the progression of signals and interactions that lead to conditions like cachexia, in which a person with cancer loses weight and his or her appetite declines, depriving the body of necessary nutrition.

CSHL Cancer Center Director David Tuveson appreciates Janowitz’s approach to cancer.

“Few scientists are ready to embrace the macro scale of cancer, the multiple organ systems and body functions which are impaired,” Tuveson said. Janowitz is “trying to understand the essential details [of cachexia and other cancer conditions] so he can interrupt parts of it and give patients a better chance to go on clinical trials that would fight their cancer cells.”

A successful and driven scientist and medical doctor, Janowitz “is very talented and could be anywhere,” Tuveson said, and was pleased his new colleague decided to join CSHL.

Janowitz suggested that the combination of weight loss and loss of appetite in advancing cancer is “paradoxical. Why would you not be ravenously hungry if you’re losing weight? What is going on that drives this biologically seemingly paradoxical phenomenon? Is it reversible or modifiable?”

At this point, his research has shown that tumors can reprogram the host metabolism in a way that it “profoundly affects immunity and can affect therapy.” Reversing cachexia may require an anti-IL-6 treatment, with nutritional support.

As he looks for clinical cases that could reveal the role of this protein in cachexia, Janowitz has seen that patients with IL-6-producing tumors may have a worse outcome, a finding he is now seeking to validate.

At this point, treatment for other conditions with anti-IL-6 drugs has produced few side effects, although patients with advanced cancer haven’t received such treatment. Researchers know how to dose antibodies to IL-6 in the human body and treatment intervals would last for a few weeks.

Scientists have long thought of cancer as being like a wound that doesn’t heal. IL-6 is important in infections and inflammation.

Ultimately, Janowitz hopes to extend his research findings to other diseases and conditions. To do that, he would need to take small steps with one disease before expanding an effective approach to other conditions. “Are disease processes enacting parts of the biological response that are interchangeable?” he asked. “I think that’s the case.”

Eventually, Janowitz hopes to engage in patient care, but he first needs to obtain a license to practice medicine in the United States. He hopes to take the steps to achieve certification in the next year.

He plans to gather samples from patients on Long Island to study cancer and its metabolic consequences, including cachexia.

Several years down the road, the scientist hopes the collaborations he has with neuroscientists can reveal basic properties of cancer.

Tuveson believes Janowitz has “the potential of having a big impact individually as well as on everyone around him,” at Cold Spring Harbor Laboratory. “We are lucky to recruit him and want him to succeed and solve vexing problems so patients get better.”

Janowitz lives in Cold Spring Harbor Laboratory housing with his wife Clary and their three children, Viola, 6, Arthur, 4, and Albert, 2.

Clary is a radiation oncologist who hopes to start working soon at Northwell Health.

The Janowitz family has found Long Island “very welcoming” and appreciates the area’s “openness and willingness to support people who have come here,” he said. The family enjoys exploring nature.

The couple met at a production of “A Midsummer Night’s Dream,” which was performed by a traveling cast of the Globe in Emmanuel College Gardens in Cambridge, England.

As with many others, Janowitz has had family members who are living with cancer, including both of his parents. His mother has had cancer for more than a decade and struggles with loss of appetite and weight. He has met many patients and their relatives over the years who struggle with these phenomena, which is part of the motivation for his dedication to this work.

Most cancer patients, Janowitz said, are “remarkable individuals. They adjust the way that they interact with the world and themselves when they get life changing diagnoses.” Patients have a “very reflected and engaged attitude” with the disease, which makes looking after them “incredibly rewarding.”

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Above, Mikala Egeblad works with graduate student Emilis Bružas in the Watson School of Biological Sciences. Photo from Pershing Square Soon Cancer Research Alliance

By Daniel Dunaief

For some people, cancer goes into remission and remains inactive. For others, the cancer that’s in remission returns. While doctors can look for risk factors or genetic mutations, they don’t know why a cancer may come back at the individual level.

In a mouse model of breast and prostate cancers, Mikala Egeblad, an associate professor at Cold Spring Harbor Laboratory, has found an important driver of cancer activation and metastasis: inflammation. When mice with cancer also have inflammation, their cancer is likely to become more active. Those who don’t have inflammation, or whose inflammation is treated quickly, can keep the dreaded disease in check. Cancer cells “may be dormant or hibernating and not doing any harm at all,” she said. “We speculated what might be driving them from harmless to overt metastasis.”

Egeblad cautioned that this research, which was recently published in the journal Science, is on mice and that humans may have different processes and mechanisms.

CSHL’s Mikala Egeblad. Photo from Pershing Square Soon Cancer Research Alliance

“It is critical to verify whether the process happens in humans,” Egeblad suggested in an email, which she will address in her ongoing research. Still, the results offer a window into the way cancer can become active and then spread from the lungs. She believes this is because the lungs are exposed to so many external stimuli. She is also looking into the relevance for bone, liver and brain metastases. The results of this research have made waves in the scientific community.

“This study is fantastic,” declared Zena Werb, a professor of anatomy and associate director for basic science at the Helen Diller Family Comprehensive Cancer Center at the University of California in San Francisco. “When [Egeblad] first presented it at a meeting six months ago, the audience was agog. It was clearly the best presentation of the meeting!”

Werb, who oversaw Egeblad’s research when Egeblad was a postdoctoral scientist, suggested in an email that this is the first significant mechanism that could explain how cancer cells awaken and will “change the way the field thinks.”

Egeblad credits a team of researchers in her lab for contributing to this effort, including first author Jean Albrengues, who is a postdoctoral fellow. This group showed that there’s a tipping point for mice — mice with inflammation that lasts six days develop metastasis.

Egeblad has been studying a part of the immune system called neutrophil extracellular traps, which trap and kill bacteria and yeast. Egeblad and other researchers have shown that some cancers trick these NETs to aid the cancer in metastasizing.

In the new study, inflammation causes cancer cells that are not aggressive to develop NETs, which leads to metastasis. The traps and enzymes on it “change the scaffold that signals that cancer should divide and proliferate instead of sitting there dormant,” Egeblad said.

To test out her theory about the role of enzymes and the NETs, Egeblad blocked the cascade in six different ways, including obstructing the altered tissue scaffold with antibodies. When mice have the antibody, their ability to activate cancer cells after inflammation is prevented or greatly reduced, she explained.

The numbers from her lab are striking: in 100 mice with inflammation, 94 developed metastatic cancer. When she treated these mice with any of the approaches to block the inflammation pathway, 60 percent of them survived, while the remaining 40 percent had a reduced metastatic cancer burden in the lungs.

If inflammation is a key part of determining the cancer prognosis, it would help cancer patients to know, and potentially treat, inflammation even when they don’t show any clinical signs of such a reaction.

In mice, these NETs spill into the blood. Egeblad is testing whether these altered NETs are also detectable in humans. She could envision this becoming a critical marker for inflammation to track in cancer survivors.

The epidemiological data for humans is not as clear cut as the mouse results in Egeblad’s lab. Some of these epidemiological studies, however, may not have identified the correct factor.

Egeblad thinks she needs to look specifically at NETs and not inflammation in general to find out if these altered structures play a role for humans. “We would like to measure levels of NETs and other inflammatory markers in the blood over time and determine if there is a correlation between high levels and risk of recurrence,” she explained, adding that she is starting a study with the University of Kansas.

Werb suggested that inflammation can be pro-tumor or anti-tumor, possibly in the same individual, which could make the net effect difficult to determine.

“By pulling the different mechanisms apart, highly significant effects may be there,” Werb wrote in an email. Other factors including mutation and chromosomal instability and other aspects of the microenvironment interact with inflammation in a “vicious cycle.”

In humans, inflammation may be a part of the cancer dynamic, which may involve other molecular signals or pathways, Egeblad said.

She has been discussing a collaboration with Cold Spring Harbor Laboratory’s Doug Fearon, whose lab is close to hers.

Fearon has been exploring how T-cells could keep metastasis under control. Combining their approaches, she said, cancer might need a go signal, which could come from inflammation, while it also might need the ability to alter the ability of T-cells from stopping metastasis.

In her ongoing efforts to understand the process of metastasis, Egeblad is also looking at creating an antibody that works in humans and plans to continue to build on these results. “We now have a model for how inflammation might cause cancer recurrence,” she said. 

“We are working very actively on multiple different avenues to understand the human implications, and how best to target NETs to prevent cancer metastasis.”

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Kids get their heads shaved at the annual St. Baldrick's event at Centereach Fire Department March 16. Photo by Doug Dickerson

By Kyle Barr

On the night before St. Patrick’s Day, hair rained down onto the floor of Centereach Fire Department. People clapped and cheered as blonde, brown and even green-dyed hair fell from amused faces before being swept away during the annual St. Baldrick’s charity event to raise money for childhood cancer research March 16.

Area local Aimee Jackson watched her teenage son Zachary get shaved, the first head of the night to go bald. It was his fourth time participating, and every year the duo has tried to raise more and more money.

“The first time he did it he was little — 5 years old — we both did it,” she said. “He’s shaving in honor of his twin brother, Kendall, who passed away just before their fifth birthday.”

Zachary Jackson has his head shaved in honor of his twin brother, Kendall, who died of cancer at age 4. Photo by Kyle Barr

The Middle Country Youth Civic Association and Centereach Fire Department joined with local sponsors to host the fourth annual event. Before the buzzer even started sounding, the team of brave bald-headed
community members raised close to $30,000. By Monday, the event had raised over $47,000, close to twice the original $25,000 goal, according to event organizer Doug Dickson. The largest donor was 12-year-old Austin Vero, who raised over $15,000 alone.

“Thank God for our barbers — with all the hair on the ground, they bring their own guys, they’re sweeping all the time,” Dickson said, laughingly.

The night was full of Irish flavor with the inclusion of FDNY Emerald Society bagpipers and Irish step dancers from Mulvihill-Lynch Studio of Irish Dance in Lake Ronkonkoma. Attendees were decked in green from head to toe, including Rob “Squid” Wilson, who was one of many prospective head-shavers to dye their hair green.

Wilson has been hosting local St. Baldrick’s events for 16 years. This year, he dressed in a bright green shamrock coat and a green tiara.

“My team is the Squid and the Squires,” Wilson said. “Each team is a bunch of clowns like us who are doing it for the right reasons.”

He and his friend Tom Duffy have been involved and shaved their heads every year since their first rodeo.

“It’s important to show kids it’s not a big deal to get their heads shaved,” Duffy said. “My big thing is I feel if [scientists] can cure cancer with kids — they can cure cancer.”

Members of the Suffolk County Police
Department shave their heads at the event. Photo by Doug Dickerson

Several staff members at the fire department joined in the shaving spirit, including Assistant Chief Joseph Feola.

“It’s a huge event — one of the bigger events we have,” Feola said. “It’s great to see all this support from the community.”

Nine barbers and hairdressers volunteered their time to shave heads, including the owner of Rockabilly Barbers of Stony Brook’s Vinnie Ferrara. He and his crew of barbers have also been involved in the event for 16 years.

“The greatest thing about it is that we’ve been doing it for so long and seen so much money raised,” Ferrara said. “It just goes to a great cause.”

“The people are so into it,” owner of Centereach-based Blondie’s Creations Inc. Mary Beth Mastando said. She and her team have been shaving heads at the event for three years.

“The community gets together, and everybody helps,” Mastando said. “They’re excited to be shaving their head, and I’m the one doing it, so that’s pretty cool.”

The Centereach St. Baldrick’s organizers are accepting donations until next year’s event. To join in the cause, visit www.stbaldricks.org/events/mypage/10953/2018.

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Joel Saltz. Photo from SBU

By Daniel Dunaief

In the battle against cancer, doctors and scientists use targeted drugs to treat the disease. They also employ radiation, starve it of the nutrients it might need to grow, block key metabolic pathways in its development and encourage the immune system to attack these genetically misdirected cells that grow out of control. A developing field in this battle includes the use of computers, artificial intelligence and math.

Joel Saltz, the Cherith Chair of Biomedical Informatics at Stony Brook University, recently teamed up with researchers from Emory University and the University of Arkansas and won an $8 million grant from the National Cancer Institute to coordinate radiology and pathology information in the battle against cancer.

“By gathering more information, researchers can understand better what’s happening, what might happen and how best to treat cancer,” Saltz said. The grant will be divided equally among the three institutions over the course of five years. Saltz will be collaborating with Ashish Sharma at Emory and Fred Prior at the University of Arkansas.

Saltz has been working with Sharma for several years, when the two were at Ohio State and then moved together to Emory. This is Saltz’s first major grant with Prior, although the two have also known each other for years and have been working in the same NCI program.

Prior has considerable expertise in radiology, while Saltz is adding his pathology background to the mix. Radiology has used digital imaging for a long time and, until recently, pathology data was collected on glass slides. Saltz is helping bring digital pathology to this effort.

“We had been on panels for many years with NCI saying we need to do this sort of” collaboration, Saltz added, and now the trio is putting that idea to work.

Yusuf Hannun, the director of the Cancer Center at Stony Brook, sees the potential for this type of collaboration. “This is a very important effort that builds on several areas of outstanding strength” at the Cancer Center, the director explained in an email.

Exploring information from digitized radiology and pathology samples will “allow us to understand individual cancers at a much higher level. It should improve accuracy in diagnosis [and offer an] ability to provide better informed prognosis” and individual therapy, Hannun continued.

Researchers on the current grant, which is part of the Information Technology for Cancer Research, plan to expand resources for integrative imaging studies, build on the capacity to acquire high-quality data collections, dedicate resources to support reproducible research and increase community engagement.

Saltz will use the portion of the Stony Brook funds to develop new software integration tools and curation and work with researchers to analyze and understand their patient data. Over time, he will also hire additional staff to build out this expertise. He has collaborated with Kenneth Shroyer, chair of the Department of Pathology at Stony Brook, on pancreatic and ovarian cancer and on breast cancer with pathology professor Patricia Thompson, who is also director of basic science at the Cancer Center. Shroyer “plays an important role” in all his research, Saltz said.

“Digital pathology will supplement that art of surgical pathology with quantitative data, to improve diagnostic accuracy,” Shroyer wrote in an email, which will “inform decisions on how to optimize therapeutic intervention for the treatment of cancer and many other diseases.”

Shroyer interviewed Saltz before Stony Brook hired its first bioinformatics chair. “Based on his research focus, including his pioneering efforts in digital pathology, he clearly stood out as my top choice.”

Saltz and Shroyer have generated maps of patterns for immune cells in tumors. “We and others have shown that these are related to how patients respond to treatment,” Saltz said. He described his work with these scientists as “basic clinical cancer research,” in which he develops and enhances technology to understand various types of cancer.

This particular grant is “more about technology and curation,” Saltz said. “People are developing new algorithms, in artificial intelligence and machine learning.” By making this information available, scientists from around the world who have insights into the specific types of cancer can use it to predict responses to treatment and develop and refine the algorithms that underlie the computer analysis.

Using specific cancers from radiology and pathology studies is akin to sitting in a football stadium and examining a blade of grass from the bleachers, Saltz suggested, borrowing from a phrase he’d heard at a recent panel discussion with Liron Pantanowitz from the Department of Pathology at the University of Pittsburgh Medical Center.

“What we do is we create catalogs of every blade of grass and every worm and weed,” Saltz added. “It’s a huge database problem” in which he is integrating software development.

Hannun, who has been working to help Stony Brook University earn a National Cancer Institute designation, suggested that this bioinformatics work is “a critical component of our plans” and represents an area of exceptional strength.”

Cancer bioinformatics is “one of the main pillars of our research program and it integrates well with our efforts in imaging, metabolomics, improved diagnostics and improved therapeutics,” Hannun explained.

As for his department, Saltz said Stony Brook will have its first biomedical informatics Ph.D. graduate at the end of 2017. Yanhui Liang joined Stony Brook when Assistant Professor Fusheng Wang came to Long Island from Emory. Xin Chen will graduate in May of 2018.

The doctoral program, which launched last year, has five current students and “we’re hoping to get a bigger class this year,” Saltz said. “Informatics involves making techniques for better health care,” Saltz said. People with medical degrees can do fellowship training in clinical informatics.

A resident of Manhasset, Saltz lives with his wife Mary, who is an assistant clinical professor of radiology at Stony Brook University. Over the course of the next five years, Saltz said he believes this grant will continue to allow him and his collaborators to develop tools that will help provide insights into cancer research and, down the road, into personalized cancer treatment.

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