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Cancer

A Jamaican fruit bat, one of two bat species Scheben studied as a part of his comparative genomic work. Photo by Brock & Sherri Fenton

By Daniel Dunaief

Popular in late October as Halloween props and the answer to trivia questions about the only flying mammals, bats may also provide clues about something far more significant.

Despite their long lives and a lifestyle that includes living in close social groups, bats tend to be resistant to viruses and cancer, which is a disease that can and does affect other mammals with a longer life span.

Armin Scheben

In recent work published in the journal Genome Biology and Evolution, scientists including postdoctoral researcher at Cold Spring Harbor Laboratory and first author Armin Scheben, CSHL Professor and Chair of the Simons Center for Quantitative Biology Adam Siepel, and CSHL Professor W. Richard McCombie explored the genetics of the Jamaican fruit bat and the Mesoamerican mustached bat.

By comparing the complete genomes for these bats and 13 others to other mammals, including mice, dogs, horses, pigs and humans, these scientists discovered key differences in several genes.

The lower copy number of interferon alpha and higher number of interferon omega, which are inflammatory protein-coding genes, may explain a bat’s resistance to viruses. As for cancer, they discovered that bat genomes have six DNA repair and 33 tumor suppressor genes that show signs of genetic changes.

These differences offer potential future targets for research and, down the road, therapeutic work.

“In the case of bats, we were really interested in the immune system and cancer resistance traits,” said Scheben. “We lined up those genomes with other mammals that didn’t have these traits” to compare them.

Scheben described the work as a “jumping off point for experimental validation that can test whether what we think is true: that having more omega than alpha will develop a more potent anti-viral response.”

Follow up studies

This study provides valuable potential targets that could help explain a bat’s immunological superpowers that will require further studies.

“This work gives us strong hints as to which genes are involved, but fully understanding the molecular biology will require more work” explained Siepel.

In Siepel’s lab, where Scheben has been conducting his postdoctoral research since 2019, he is using human cell lines to see whether adding genetic bat elements makes them more effective in fighting off viral infections and cancer. He plans to do more of this work with mice, testing whether these bat variants help convey the same advantages in live mice.

Armin Scheben won the German Academic International Network Science Slam competition with his presentation on bat genomics.

Siepel and Scheben have discussed improving the comparative analysis by collecting information across bats and other mammals of tissue-specific gene expression and epigenetic marks which would help reveal changes not only in the content of DNA, but also in how genes are being turned on and off in different cell types and tissues. That could allow them to focus more directly on key genes to test in mice or other systems.

Scheben has been collaborating with CSHL Professor Alea Mills, whose lab has “excellent capabilities for doing genome editing in mice,” Scheben said.

Scheben’s PhD thesis advisor at the University of Western Australia, Dave Edwards described his former lab member’s work as “exciting.”

Edwards, who is Director of the UWA Centre for Applied Bioinformatics in the School of Biological Sciences, suggested that Scheben stood out for his “ability to strike up successful collaborations” as well as his willingness to mentor other trainees.

Other possible explanations

While these genetic differences could reveal a molecular biological mechanism that explains the bat’s enviable ability to stave off infections and cancer, researchers have proposed other ways the bat might have developed these virus and cancer fighting assets.

When a bat flies, it raises its body temperature. Viruses likely prefer a normal body temperature to operate optimally. 

Bats are “getting fevers without getting infections,” Scheben said.

Additionally, flight increases the creation of reactive oxygen species, which the bat needs to control on an ongoing basis.

At the same time, bats produce fewer inflammatory cytokines, which helps prevent them from having a runaway immune reaction. Some researchers have hypothesized that bats clear reactive oxygen species more effectively than humans.

A ‘eureka’ moment

The process of puzzling together all the pieces of DNA into individual chromosomes took considerable time and effort.

A Mesoamerican mustached bat, one of two bat species Scheben studied as a part of his comparative genomic work. Photo by Brock & Sherri Fenton

Scheben spent over 280,000 CPU hours chewing through thousands of genes in dozens of species on the CSHL supercomputer called Elzar, named for the chef from the cartoon “Futurama.” Such an effort would have taken eight years on a modern day personal computer.

During this effort, Scheben saw this “stark effect,” he said. “We had known that bats had lost some interferon alpha. What astounded me was that some bats had lost all alpha” while they had also raised interferon omega. That was the moment when he realized he found something novel and bat specific.

Scheben recognized that this finding could be one of many that lead to a better understanding of the processes that lead to cancer.

“We know that it’s unlikely that a single set of genes or a small set of genes such as we identified can fully explain the diversity of outcomes when it comes to a complex disease like cancer,” said Scheben.

A long journey

A resident of Northport, Scheben grew up in Frankfurt, Germany. He moved to London for several years, which explains his use of words like “chuffed” to describe the excitement he felt when he received a postdoctoral research offer at Cold Spring Harbor Laboratory.

When he was young, Scheben was interested in science despite the fact that classes were challenging for him.

“I was pretty poor in math and biology, but I liked doing it,” he said.

Outside of work, Scheben enjoys baking dense, whole wheat German-style bread, which he consumes with cheese or with apple, pear and nuts, and also hiking.

As for his work, which includes collaborating with CSHL Professor Rob Martienssen to study the genomes of plants like maize that make them resilient amid challenging environmental conditions, Scheben suggested it was the “best time to be alive and be a biologist” because of the combination of new data and the computational ability to study and analyze it.

Scheben recognized that graduate students in the future may scoff at this study, as they might be able to compare a wider range of mammalian genomes in a shorter amount of time.

Such a study could include mammals like naked mole rats, whales and elephants, which also have low cancer incidence and long lifespans.

Getting a good night's rest helps keep your mind and body healthy. METRO image
Sleep apnea may increase your risks of cardiovascular disease and cancer

By David Dunaief, M.D.

Dr. David Dunaief

Our physical and mental wellbeing depends on getting quality, restful sleep; however, many of us struggle to achieve this. For those with obstructive sleep apnea (OSA), quality sleep is particularly elusive.

Sleep apnea is an abnormal pause in breathing that occurs at least five times an hour while sleeping. It can have an array of causes, the most common of which is airway obstruction. Some estimates suggest that about 30 million people suffer from sleep apnea in the United States (1).

OSA diagnoses are classified as either mild, moderate or severe. It’s estimated that roughly 80 percent of moderate and severe OSA sufferers are undiagnosed.

After family history, most risk factors for OSA are modifiable. They include chronic nasal congestion, excess weight or obesity, alcohol use and smoking (2).

Symptoms of OSA include daytime fatigue, loud snoring, breathing cessation observed by another, impaired concentration, and morning headaches. While these are significant quality of life issues, OSA is also associated with an array of more serious health consequences, such as cardiovascular disease, high blood pressure and depression.

Fortunately, we have an arsenal of treatment options, including continuous positive airway pressure (CPAP) devices; oral appliances; lifestyle modifications, such as diet, exercise, smoking cessation and reduced alcohol intake; and some medications.

How does sleep apnea affect cardiovascular disease risk?

In an observational study of 1,116 women over a six-year duration, the risk of cardiovascular mortality increased in a linear fashion with the severity of OSA (3). For those with mild-to-moderate untreated sleep apnea, there was a 60 percent increased risk of death; for those in the severe group, this risk jumped considerably to 250 percent. However, the good news is that treating patients with CPAP considerably decreased their risk by 81 percent for mild-to-moderate patients and 45 percent for severe OSA patients.

Another observational study of 1,500 men with a 10-year follow-up showed similar risks of cardiovascular disease with sleep apnea and benefits from CPAP treatment (4). The authors concluded that severe sleep apnea increases the risk of nonfatal and fatal cardiovascular events, and CPAP was effective in curbing these occurrences.

In a third study, this time involving the elderly, OSA increased the risk of cardiovascular death in mild-to-moderate patients and in those with severe OSA by 38 and 125 percent, respectively (5). But, as in the previous studies, CPAP decreased the risk in both groups significantly. In the elderly, an increased risk of falls, cognitive decline and difficult-to-control high blood pressure may be signs of OSA.

Does OSA increase your risk of cancer?

In sleep apnea patients under age 65, a study showed an increased risk of cancer (6). The greater the percentage of time patients spend in hypoxia (low oxygen) at night, the greater the risk of cancer. The authors believe that intermittent low levels of oxygen, caused by the many frequent short bouts of breathing cessation, may be responsible for the development of tumors and their subsequent growth.

Does OSA affect male sexual function?

Erectile dysfunction (ED) may also be associated with OSA and, like other outcomes, CPAP may decrease this incidence. This was demonstrated in a small study involving 92 men with ED (7). The surprising aspects of this study were that, at baseline, the participants were overweight, not obese, on average and were only 45 years old. 

In those with mild OSA, the CPAP had a beneficial effect in over half of the men. For those with moderate and severe OSA, the effect was still significant, though not as robust, at 29 and 27 percent, respectively.

An array of other studies on the association between OSA and ED have varying results, depending on the age and existing health challenges of the participants. Some study authors have postulated that other underlying health problems may be the cause in some patient populations.

Can diet help address OSA?

For some of my patients, their goal is to discontinue their CPAP. Diet may be an alternative to CPAP, or it may be used in combination with CPAP to improve results.

In a small study of those with moderate-to-severe OSA levels, a low-energy diet showed positive results. A low-energy diet implies a low-calorie approach, such as a diet that is plant-based and nutrient-rich. It makes sense, since this can help with weight loss. In the study, almost 50 percent of those who followed this type of diet were able to discontinue CPAP (8). The results endured for at least one year.

If you think you are suffering from sleep apnea, you should be evaluated at a sleep lab and then follow up with your doctor. Don’t let obstructive sleep apnea cause severe complications, possibly robbing you of more than sleep. There are many effective treatments.

References:

(1) sleepapnea.org. (2) JAMA. 2004;291(16):2013. (3) Ann Intern Med. 2012 Jan 17;156(2):115-122. (4) Lancet. 2005 Mar 19-25;365(9464):1046-1053. (5) Am J Respir Crit Care Med. 2012;186(9):909-916. (6) Am J Respir Crit Care Med. 2012 Nov. 15. (7) Sleep. 2012;35:A0574. (8) BMJ. 2011;342:d3017.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

Represented in this illustration is the authors’ finding that DNA hypermethylation disrupts CCCTC-binding factor (CTCF) mediated boundaries which in turn lead to aberrant interactions between an oncogene and an enhancer, driving hyperproliferation and subsequently tumorigenesis from normal OPCs. Photo by William Scavone/Kestrel Studio

Study in Cell led by Stony Brook researcher provides unique analysis in a glioma model

Gliomas are incurable brain tumors. Researchers are trying to unlock the mysteries of how they originate from normal cells, which may lead to better treatments. A new study published in the journal Cell centers on epigenetic rather than genetic changes that drive normal cells to form tumors. The work reveals the precise genes that are regulated epigenetically and lead to cancer.

Genes make us who we are in many ways and are central to defining our health. Cancer is often viewed as a disease caused by changes in our genes, thus our DNA. Epigenetics is the study of how behavior, environment, or metabolic changes can cause alterations to the way genes work. Unlike genetic changes, epigenetic changes do not change one’s DNA, and they can be reversed.

“We used tumor samples and mouse modeling to discover and functionally demonstrate the role of epigenetic alterations in gliomas,” says Gilbert J. Rahme, PhD, first author and Assistant Professor in the Department of Pharmacological Sciences at the Renaissance School of Medicine, and formerly a postdoctoral fellow at the Dana-Farber Cancer Institute in Boston. “By doing this, we discovered genes regulated epigenetically in gliomas, including potent tumor suppressor genes and oncogenes, that drive the tumor growth.”

In the paper, titled “Modeling epigenetic lesions that cause gliomas,” the research team show in the model that epigenetic alterations of tumor suppressor and oncogenes collaborate together to drive the genesis of this brain tumor.

The authors explain that “epigenetic activation of a growth factor receptor, the platelet-derived growth factor receptor A (PDGFRA) occurs by epigenetic disruption of insulator sites, which act as stop signs in the genome to prevent aberrant activation of genes. The activation of PDGFRA works in concert with the epigenetic silencing of the tumor suppressor Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) to transform a specific cell type in the brain, the oligodendrocyte progenitor cell (OPC), driving the formation of brain tumors.”

Rahme says the next step is to test whether therapies that can reverse the epigenetic changes observed in brain tumors can be helpful as a treatment.

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.

 

Ke Jian Liu

By Daniel Dunaief

Ke Jian “Jim” Liu, who arrived at Stony Brook University in late July, plans to help build effective, interdisciplinary research teams.

Ke Jian Liu

Most recently at the University of New Mexico, Liu joins Stony Brook as a Professor in the Renaissance School of Medicine’s Department of Pathology and Associate Director of Basic Science at the Stony Brook Cancer Center.

“In my mind, Stony Brook, research wise, is outstanding,” Liu said in an interview. “The quality of the faculty is excellent.”

Liu will rely on the team building experience he honed while serving as Distinguished Professor in the Department of Pharmaceutical Sciences and Associate Dean for Research in the College of Pharmacy at the University of New Mexico. He also worked for eight years at Dartmouth Medical School, where he focused on developing larger collaborations.

“I really enjoy working with people and building teams,” Liu said.

In a note announcing Liu’s arrival, Kenneth Shroyer, chair in the Department of Pathology, recognized Liu’s multidisciplinary approaches in his research. Shroyer explained that Liu has used techniques ranging from chemical to biochemical to biophysical, and from the molecular and cellular level to animal models, to answer specific biological questions.

Shroyer wrote that Liu would focus on opportunities for grant development within several programs. 

At the Cancer Center, Liu said he plans to continue the effort to help Stony Brook earn National Cancer Institute designation.

To achieve that designation, Stony Brook will need to continue to provide outstanding medical care, demonstrate community engagement and highlight what makes Stony Brook different from everyone else, he said.

“It takes a village to do that,” Liu said.

He praised the efforts of current Cancer Center Director Yusuf Hannun, who recently announced his plans to step down as head of the center, triggering a nationwide search for a replacement.

Liu said an ideal candidate for that position would have clinical experience.

Player coach

With a busy research effort and lofty leadership goals, Liu explained that he’s able to tackle numerous challenges at once.

“I consider myself a player coach,” he said. “I enjoy research. I have my own research grant and am working with my students and post docs.”

Liu typically maintains a lab with five to six people at different levels. His research has two branches, cancer and stroke, that most people likely consider unrelated, but for which he has found connections.

“People always think, ‘Cancer is cancer and stroke is stroke and they are two entirely different diseases,” Liu  said. As a basic researcher, however, he looks at the cells and the molecules involved in both conditions.

“At a molecular level, a molecule doesn’t care where it is,” he said. “When a disease develops, the biological fundamental process is the same. For me, it’s interesting to look at [whether] certain processes that occur in the brain also occur in cancer.”

Liu’s cancer research focuses specifically on the molecular processes that become carcinogenic when metals like arsenic enter people’s bodies. A well-described poison in numerous murder mysteries, arsenic can contaminate drinking water, get incorporated into crops like rice, or can appear in fruit juices.

When metal enters the body, it doesn’t just cause damage everywhere. It has to find a certain molecular target with which to interact.

What Liu and researchers in his lab have discovered is that the target for arsenic is often the same pathways the body uses in zinc. A transition metal, zinc provides an important element as a part of transcription factors that are critical in biological processes.

Arsenic, however, replaces zinc, which is “one of the major mechanisms for carcinogenesis,” Liu said.

Fortunately for residents of Long Island, arsenic isn’t as prevalent as it is in the midwest and the southwest.

“Long Island doesn’t have too much arsenic in drinking water,” Liu said, although people are still exposed to it through fruit juices, rice and other products.

Arsenic also causes vascular disease issues and anemia. People who develop these other conditions in response to arsenic are also at higher risk to develop cancer. The specific types of cancers arsenic causes are lung, skin and bladder cancer.

“Arsenic is the dirty bomb” in the body as it creates multiple problems, Liu said. “Arsenic interacts with those key zinc molecules.” 

Overlap between stroke and cancer

In highlighting the overlaps between the two fields of research, Liu related how the brain has one of the highest concentrations of zinc in the body.

When people have strokes, their brain cells have oxidative stress, which causes a flood of zinc into the brain tissue that also damages cells.

“We are trying to understand how zinc is released and how zinc causes damage to the brain,” Liu said.

Stroke and cancer also have molecular overlaps regarding oxygen. In a stroke, a blood clot causes a blockage of blood flow. Without oxygen, a situation called hypoxia, neurons start to die.

By contrast, a tumor grows in a hypoxic environment, using energy from sugars like glucose, rather than relying on oxygen for its growth.

Liu emphasized the importance of continuing to provide oxygen to brain regions around a clot even before trying to remove the clot or restore blood flow.

A goal for his 100th year

Originally from Beijing, China, Liu and his wife Jiao Ding enjoy traveling. Their daughter Sarah Liu is a resident at Vermont Medical Center and their son Evan Liu is a PhD student at Stanford.

An avid tennis player who plays the sport at least twice a week, Liu is looking forward to attending his first U.S. Open next year.

He and his former tennis partner in New Mexico joked that their goal is to be in the top 20 in the United States when they are 100 years old.

Liu chose the American name “Jim” because it sounds similar to the second syllable of his given name, Ke Jian.

“If people can’t pronounce your name, they shy away,” he said. He believes it’s important to “make yourself adaptable.”

METRO photo

By Matthew Kearns, DVM

Dr. Matthew Kearns

Working in a general practice for many years now, I am commonly asked the question of whether or not a growth under the skin is something to worry about or not. The good news is the majority of subcutaneous (under the skin) lumps are benign, or non-cancerous. They are usually lipomas (benign tumors made up of fat cells), or cysts. Some, however, can be cancerous and are better off being removed before they get too big or invade the surrounding tissues making it more difficult or impossible to remove completely. How are we to tell?

It is always good to bring any new growths to your veterinarian’s attention as soon as possible. When I evaluate any new subcutaneous growths I was taught to look for three characteristics:

Is it hard or is it soft? A growth that is hard is not always malignant, and a growth that is soft is not always benign. However, in my book, a growth that is hard is more concerning than a growth that is soft.

Is it freely movable or well attached to underlying tissues? Growths that are soft and freely movable are more likely to be benign than growths that are hard and well attached.

Is it painful, or non-painful? subcutaneous growths that are non-painful to palpation are less likely to be malignant.

I like to have the three criteria in combination to feel confident in telling a pet owner that the growth is something just to be monitored. Therefore soft, freely movable, non-painful is good, and firm, well-attached, and painful is concerning. 

I also like to recommend owners monitor these growths closely for change. The two changes I look for is a rapid change in size, and/or a change in character. If a growth doubles in size in a month or less, or a change in character (soft to hard, freely movable to well attached, non-painful to painful) then please have your pet seen again immediately.

There are different ways to test these growths. My favorite first test is a fine needle aspirate and cytology. This test involves inserting a needle into the growth and aspirating a sample of cells. The sample is then sprayed onto a microscope slide, allowed to dry and sent to the lab for evaluation by a pathologist. 

Cytology is the evaluation of individual cells so it is not as accurate as a biopsy but one can get a lot of information from individual cells. A fine needle aspirate is something that is well tolerated by most patients so sedation or anesthesia is not usually required to perform this procedure. 

There are cases where the fine needle aspirate and cytology are inconclusive and a biopsy is needed. However, I feel a fine needle aspirate and cytology is an excellent first step. I hope this information helps.

 Dr. Kearns practices veterinary medicine from his Port Jefferson office and is pictured with his son Matthew and his dog Jasmine. 

Concerns about students with health problems prompted the temporary closing of Northport Middle School in 2020 and was one of the reasons the state Department of Health conducted a study of cancer cases in the district. File photo by Lina Weingarten

Residents of the Northport-East Northport school district have waited anxiously for the recent report by the New York State Department
of Health.

According to a NYSDOH study, the investigation of cancer incidents in the school district between 1999 and 2018 was initiated by the department “in response to an inquiry from members of the community who shared information about leukemias and other cancers diagnosed among members of the Northport High School graduating class of 2016 since their graduation and among other children and young adults in the Northport area.” The report also mentioned health concerns cited about Northport Middle School students.

In January 2020, the district decided to close the middle school for a few months after the consulting firm hired by the district, P.W. Grosser Consulting, tested the soil on the grounds and found elevated levels of benzene in two separate septic systems on site. Before a cleanup, three science classrooms in the middle school’s G-wing were closed out of an abundance of caution. During the investigation, it was found science rooms had sinks that drain into the leaching pool, where the mercury and silver were found. While odorless fumes could have potentially migrated through the piping into classrooms, the drain systems rely on P traps that prevent that from occurring, according to the district at the time. Air quality results in the G-wing classrooms were later found to be normal.

The DOH’s primary source of data was the New York State Cancer Registry. For the years after 2018, registry data was not official at the time of analyses, according to the DOH report. 

“We identified 4,593 cases of cancer among district residents, compared with 4,454 that would be expected,” the report read. “This 3% excess was statistically significant, meaning it was unlikely to occur by chance.”

An increase in pancreatic cancer, malignant melanoma of the skin, uterine (corpus) cancer and prostate cancer made up the excess. The report went on to say, “There were significantly fewer than expected numbers of cases of stomach cancer and lung cancer. Numbers of cases of leukemia, other blood cancers (Hodgkin and non-Hodgkin lymphomas and multiple myeloma), and 13 other types of cancer examined separately were not significantly different from expected.”

While the community around East Northport Middle School had about the expected cases, the area around Northport Middle School had 7% higher-than-expected levels of cancer.

Regarding the number of 2016 high school graduates who came down with leukemia, the study concluded, “It is possible that the elevated occurrence of leukemia among 2016 graduates could be related to factors not possible to uncover, including environmental exposures.” 

Robert Banzer, district superintendent of schools, sent out a letter June 23 to community members to notify them that the study was completed. In the letter, he said, “The district fully cooperated with the NYSDOH during this process.”

After summarizing the findings in the letter, he said, “We appreciate the hard work of the NYSDOH in this endeavor and look forward to continuing to provide our students and staff with a safe learning environment.”

Lawsuits and disappointment in health study

Attorney Lilia Factor, of Melville-based Napoli Shkolnik PLLC, said her law firm has filed three lawsuits for nine plaintiffs so far against the Northport-East Northport school district. One of them is a proposed class-action lawsuit on behalf of all Northport Middle School students. The others are on behalf of individuals who have become sick. She is aware of at least five other lawsuits in total as other law firms have filed lawsuits against the district in the Suffolk County Supreme Court.

On July 12, according to Factor, the court consolidated lawsuits for the purposes of exchanging documents and depositions. A most recently filed case from Napoli Shkolnik was not included as a judge has not been assigned yet.

Tara Mackey is one of the plaintiffs in the class-action lawsuit. She said her daughter suffered from migraine headaches while studying at Northport Middle School and developed asthma. When Mackey brought her daughter to the doctor for her headaches, carbon monoxide was found in her blood.

“She had to get blood tests every four to six weeks for the remainder of time that she was in the school, and it just showed a pattern of when they would test her blood after, say, five days a week of school, she would have very high levels of carbon monoxide in her blood and then when they tested it during holidays or summer break, it was perfectly normal,” Mackey said.

Factor said while Mackey’s daughter was fortunate not to get cancer, she and other students are at a higher risk of developing illness later in life due to latency periods, a fact she said the NYSDOH report acknowledges. If the class-action suit is successful, anyone who becomes sick in later years would be covered. In cases such as this, a fund is established where people can be tested or a protocol would be distributed to local doctors to know what to look for if a patient attended Northport Middle School 

“We want there to be a medical monitoring program established for everyone so that they can screen people and watch them, and if they develop any symptoms of a serious illness that’s associated with these contaminants to try to catch it early,” Factor said.

Mackey said the health issues can weigh heavily on families, and many of them faced criticism in Northport when they brought the problems to the district. She and her family moved to South Carolina after they were harassed by community members creating uncomfortable situations.

“We endured a lot of harassment, along with a lot of other parents, from people in the community that didn’t want bad press about any potential environmental issues that could lead to health problems for people in the school and the community, because people feared for their property values,” she said. “It just made a very uncomfortable situation for many of us, and we moved because we couldn’t keep our kids safe.”

She added, coincidentally, two other families, who she didn’t know while living in Northport, moved near her.

Factor said while it is good that the DOH conducted the report, the study didn’t look at other factors such as families who have moved away and may have been diagnosed with an illness.

“They would not be part of those statistics, which were in themselves pretty disturbing,” Factor said.

She added the DOH didn’t talk to or survey community members and medical providers.

“It’s good that they did something, but it really needs to be a lot more comprehensive if they really want to understand cancer incidence in this community.” Factor said.

The attorney and Mackey added there have been other illnesses that have surfaced such as scleroderma and aplastic anemia. Mackey said that she was also disappointed that the study was cut off at the year 2018 as she has heard of more cases of cancer that have been diagnosed recently and therefore not counted.

“I just think all of the families and the parents, children themselves, they at least deserve the facts and the full facts,” the mother said. “Nothing can change at this point. We can’t change what happened to our children, but at least we can take charge and be observant and try to keep them in the best health possible and at least know what to look for.”

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.”

David McCandlish, center, with postdoctoral researchers Anna Posfai and Juannan Zhou. Photo by Gina Motisi, 2020/ CSHL

By Daniel Dunaief

If cancer were simple, scientists would have solved the riddle and moved on to other challenges.

Often, each type of the disease involves a combination of changes that, taken together, not only lead to the progression of cancer, but also to the potential resistance to specific types of treatment.

Using math, David McCandlish, Assistant Professor at Cold Spring Harbor Laboratory, is studying how the combination of various disruptions to the genome contribute to the development of cancer.

McCandlish recently published a study with colleagues at Cold Spring Harbor Laboratory in the journal Proceedings of the National Academy of Sciences.

David McCandlish. Photo by Gina Motisi, 2020/CSHL

The research didn’t explore any single type of cancer, but, rather applied the method looking for patterns across a range of types of cancers. The notion of understanding the way these genetic alterations affect cancer is a “key motivating idea behind this work,” McCandlish said.

So far, the method has identified several candidates that need further work to confirm.

“Cancer would be a lot easier to treat if it was just one gene,” said Justin Kinney, Associate Professor at CSHL and a collaborator on the work. “It’s the combination that makes it so hard to understand.”

Ultimately, this kind of research could lead researchers and, eventually, health care professionals, to search for genetic biomarkers that indicate the likely effect of the cancer on the body. This disease playbook could help doctors anticipate and head off the next moves with various types of treatments.

“This could potentially lead to a more fundamental understanding of what makes cancer progress and that understanding would very likely open up new possibilities in cancer treatments,” Kinney said.

To be sure, at this point, the approach thus far informs basic research, which, in future years, could lead to clinical improvements.

“We are working on this method, which is very general and applicable to many different types of data,” McCandlish said. “Applications to making decisions about patients are really down the road.”

McCandlish described how he is trying to map out the space that cancer evolves in by understanding the shape of that space and integrating that with other information, such as drug susceptibility or survival time.

“We are trying to ask: how do these variables behave in different regions of this space of possibilities?” he said.

McCandlish is making this approach available to scientists in a range of fields, from those scientists interpreting and understanding the effects of mutations on the development of cancer to those researchers pursuing a more basic appreciation of how such changes affect the development and functioning of proteins.

“This is accessible to a wide array of biologists who are interested in genetics and, specifically in genetic interactions,” said McCandlish.

The main advance in this research is to take a framework called maximum entropy estimation  and improve its flexibility by using math to capture more of the underlying biological principals at work. Maximum entropy estimation is based on the idea of inferring the most uniform distribution of behaviors or outcomes with the least information that’s compatible with specific aspects of experimental observations.

Using this philosophy, scientists can derive familiar probability distributions like the bell curve and the exponential distribution. By relaxing these estimates, scientists can infer more complicated shapes.

This more subtle approach enhances the predictive value, which captures the distributions of data better, McCandlish explained. “We’re trying to capture and model cancer progression in a new and more expressive way that we hope will be able to tell us more about the underlying biology.”

The idea for this paper started when McCandlish, Kinney and  Jason Sheltzer, a former fellow at Cold Spring Harbor Laboratory and a current Assistant Professor of Surgery at Yale School of Medicine, discussed the possibilities after McCandlish attended a talk by Wei-Chia Chen, a post doctoral researcher in Kinney’s lab.

Chen will continue to pursue questions related to this effort when he starts a faculty position in the physics department at National Chung Cheng University in Taiwan this spring.

Chen will use artificial intelligence to handle higher dimensional data sets, which will allow him “to implement effective approximations” of the effect of specific combinations of genetic alterations, Kinney said.

Kinney believes teamwork made this new approach, which the high-impact, high-profile journal PNAS published, possible.

“This problem was an absolutely collaborative work that none of us individually could have done,” Kinney said. He described the work as having a “new exploratory impact” that provides a way of looking at the combination of genomic changes that “we haven’t had before.”

Working at Cold Spring Harbor Laboratory, which McCandlish has done since 2017, enables collaborations across different disciplines.

“We have this quantitative biology group, we also have people working on neuroscience, cancer, and plant biology,” McCandlish added.

McCandlish is also currently also working with Professor Zachary Lippman and his graduate student Lyndsey Aguirre to understand how multiple mutations interact to influence how the fruit on tomato plants develop.

“The idea is that there are these huge spaces of genetic possibilities where you can combine different mutations in different ways,” McCandlish explained. “We want to find those key places in that space where there’s a tipping point or a fork in the road. We want to be able to identify those places to follow up or to ask what’s special about this set of mutations that makes it such a critical decision point.”

A native of Highland Park, New Jersey, McCandlish was interested in math and science during his formative years. 

As for the work, McCandlish appreciates how it developed from the way these collative researchers interacted.

“This would never have happened if we weren’t going to each other’s talks,” he said.

The Comsewogue boys soccer program hosted its inaugural “Kicks for Cancer” fundraiser at home against Deer Park Oct 12. Bill Landon photo

The Comsewogue boys’ soccer program, both varsity and JV, put on the inaugural “Kicks for Cancer” game — a fundraising event to honor of two former players whose mothers are battling breast cancer. 

The Oct. 12 event was the brainchild of seniors Dan Dein, Matthew Sparhuber, Josh Carroll and Ryan Carnaxide, according to Comsewogue boy’s booster club member Kathy Dein.

“These boys have known both moms all through growing up and decided to hold a Kicks for Cancer fundraiser to benefit the ‘Triple Negative Breast Cancer Foundation’ in their honor,” said Dein, who added that both the JV & Varsity have raised over $1,100 for the cause and still going. 

The team all wore pink jerseys adorned the field with posters to promote the event. 

“I’m tremendously proud that our boys realize that it’s more than just a game it’s bringing the community together and this is their way to give back,” Dein said.

With the game under way the Warriors evened the score late in the game when Ryan Harding to tie the game at 1-1. Despite two overtime periods both teams drew the tie keeping the Warriors atop the league IV leaderboard at 10-1-1.

— All photos by Bill Landon