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Daniel Dunaief

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By Daniel Dunaief

Daniel Dunaief

Fear sells. It’s as true when companies are urging people to buy products to protect themselves, families, homes and cars as it is when politicians are trying to scare you  into voting for them or, just as importantly, voting against their opponent.

Sure, they make some effort to suggest that their policies will help you, but they spend considerably more time showing unnerving images of what might happen if you vote for the other team.

One side suggests that a vote for the other candidate could mean the end of democracy, elections and a host of freedoms, while the other suggests that a vote for the other side could mean an end to the world.

Whatever you believe, we have clearly reached an extreme of brinkmanship. 

On top of that, the news is filled with stories and images of murder and mayhem.

These days, all you need to do is turn on your phone and someone, somewhere, is struggling, threatened, or dying.

On top of that, people are sharing concerns about existential threats to the future, with global warming and declines in the food and water necessary to sustain the population.

Regardless of where people check in with the information of the day, threats lurk around every corner.

It’s no wonder that mental health has declined. The world is a place with dark shadows and horrifying possibilities.

Happily ever after has become the launching pad for fractured fairy tales, where couples can’t find affordable homes and, even if they did, couldn’t carry the mortgage.

This mental health strain and the difficulty of disconnecting from a phone that shares these bad news bulletins in constant alerts may be contributing to the record low fertility rate for the country reported this spring in the National Center for Health Statistics at the CDC. 

Specifically, the rates declined for women aged 20 to 39, hitting a record low for women between 20 and 24.

There are numerous other reasons people are foregoing the spectacularly rewarding and challenging decision to have children. Yes, men and women are pursuing careers.

And, yes, people may be more confident and comfortable having children later, putting off the life-altering decision until after a set of vacations, a work milestone or other goals.

But to know exactly why any one or group of people are making the decisions they do requires more than statistics or even surveys. When people answer questions in a survey, they sometimes offer the kinds of replies that look good or that the questioner expects.

I spoke anecdotally with a few 50’ish parents and some children around 30 and got a range of responses about the decision to have or not have children.

Both sides suggested that developing careers made it tougher to start a family. Parents, some of whom seemed eager to have grandchildren, expressed some frustration and, perhaps, judgement, about the decisions of their children and step-children.

Some of the younger crowd said their friends didn’t receive much parenting help from their partners, making the task of raising children more difficult and exhausting and dissuading them and their friends.

They also shared concerns about the high cost of raising children.

One of the younger set added that her mother had been dealing with a lifelong illness and that she had caretaking responsibilities from the time she was young. Her mother continues to need medical and family attention, which she said has made caring for a child less appealing.

One of the younger set asked me what I thought about being a parent. It has filled me with unbelievable joy, affection, love, and laughter and has helped me understand my own parents and grandparents better. Of course, we’ve had our share of challenges interspersed with stomach dropping moments.

Not to blame the media entirely, as I work and live inside that profession, but I feel like the nonstop stream of information, stories, videos, and social media shaming has left people feeling vulnerable and exhausted.

Parenting requires energy and optimism. When people lose sleep, they don’t have much energy and, if they look at their phones, they risk losing their hold on optimism. 

If we want to encourage this generation to continue the chain, we should let them know when they’re ready and when they ask, about the amazing and fulfilling moments, large and small, that make parenting the role of a lifetime.

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Hiro Furukawa Photo courtesy of CSHL

By Daniel Dunaief

Following a relentless drive to succeed, scientists have a great deal in common with athletes.

In addition to putting in long hours and dedicating considerable energy to improving their results, these talented professionals also enjoy moments of success — large and small — as opportunities to appreciate the victories and then build to greater challenges.

And so it is for Hiro Furukawa, a Professor at Cold Spring Harbor Laboratory.

Hiro Furukawa. Photo courtesy of JMSA

Working with a team of scientists including at Emory University, Furukawa recently published a paper in the prestigious journal Nature in which he demonstrated the long-sought structural process that leads to the opening of an important channel in the brain, called the NMDAR receptor.

When this cellular channel doesn’t function correctly, it can lead to numerous diseases, including Alzheimer’s and depression. Understanding the structural details of this channel could, at some point in future research, lead to breakthrough treatments.

“Each moment of discovery is exciting and priceless,” Furukawa explained. “When I finally see what I have sought for many years — in this case, the mechanism of NMDAR channel opening — it fills me with immense euphoria, followed by a sense of satisfaction.”

That sounds like the kind of mountaintop moment that star athletes whose achievements people applaud share once they’ve reached a long-desire milestone, like, perhaps, winning a gold medal in the Olympics.

The thirst for more for Furukawa, as it is for those with a passion for success in other fields beyond science and athletics, is unquenchable and unrelenting.

“This feeling is fleeting,” he added. “Within a few hours, a flurry of new questions arising from the discovery begins to occupy my mind.”

Indeed, Furukawa suggested that he expects that many other scientists share this experience.

Forming a winning team

Furukawa and Stephen Traynelis, Professor and Director in the Department of Pharmacology and Chemical Biology at Emory University School of Medicine in Atlanta, started to work together on a series of modulators for the NMDAR protein about eight years ago.

Hiro Furukawa. Photo courtesy of JMSA

This particular protein binds to the neurotransmitter glutamate and to glycine, which is another compound. Once bound to both, the channel, as if responding to the correct combination in a garage door, opens, creating electrical signals that contribute to brain functions.

To study the way the binding of these molecules opened the channel, the researchers needed to figure out how to keep the receptor in the open position.

That’s where a combination of work in the labs of Traynelis and Dennis Liotta, also a Professor at Emory, came in. Liotta’s lab made over 400 analogs that Traynelis ran in his lab.

Liotta created a compound called EU-1622-A, which is now known as EU-1622-240, that upregulates NMDAR activity, Furukawa explained.

“We used cryo-EM [electron microscopy] to capture the NMDAR structure with the compound, validated its conformation through electrophysiology and elucidated the activation mechanism,” he said.

Incorporating EU-1622-240 along with glycine and glutamate into the GluN1-2B NMDAR sample, which is a specific subtype and is the easiest to work with, enabled a visualization of the open channel.

Furukawa described the compound Traynelis created at Emory as the “key factor in capturing the open channel conformation.”

Determining the structure of a functioning protein can provide clues about how to alter those that may be contributing to the onset or progression of a disease.

To be sure, Furukawa recognizes the work as one step in what’s likely to involve an extensive research journey.

“We still have a long way to go, but we’ve made progress,” Furukawa said. “In this study, a compound bound to NMDAR gave us a clue on how to control the frequency of ion channel openings. Both hyperactive and hypoactive functions of NMDAR ion channels have been implicated in Alzheimer’s disease, so being able to regulate NMDAR activity would be significant.”

Furukawa can’t say for sure if this compound could alleviate the symptoms of certain diseases, but it serves as a new series of potentially clinically relevant options to test.

The researchers are developing a method to purify NMDAR proteins from animal tissues. Once they accomplish that task, they should be able to isolate NMDAR from Alzheimer’s brains to compare them to a normally functioning protein.

Furukawa suggested that it’s probable that specific NMDAR conformations are stabilized to different extents in various diseases compared to normal brains.

The researchers have not yet presented this work at meetings. First author Tsung-Han Chou, who is a postdoctoral fellow in Furukawa’s lab, plans to present the work at upcoming conferences, such as the Biophysical Society Meeting.

The review process for the research proceeded quickly, as the team submitted the paper in February of this year. 

Next steps

As for what’s next, Furukawa suggested that the team planned to solidify their findings.

“We must determine if the channel opening mechanism applies to other types of NMDARs,” he said. “Although we observed that EU1622-A compound binds to NMDAR, its structure was not sufficient resolved.”

To facilitate the re-design of EU1622-240, the scientists will need to improve the cryo-EM map resolution.

Traynelis, meanwhile, said that he and Liotta are synthesizing new modulators in this class and related classes and are working on mechanisms of action for this series at all NMDA receptors as well as actions in neuronal systems.

“We have a robust synthetic program with our collaborator [Liotta], whose laboratory is synthesizing many new modulators in this class and related classes,” Traynelis explained.

Traynelis added that his goal is to “develop new medicines to address unmet clinical needs. We want to find new and effective therapeutic treatments that help patients.”

The Emory professor is excited about the “potential development of positive NMDA receptor allosteric modulators that could enhance NMDA receptor function.”

Broader perspective

Furukawa, who lives in Cold Spring Harbor and whose sons Ryoma, 16 and Rin, 13, attend senior and junior high school, respectively, was interested in international politics and economics when he attended Tufts University as an undergraduate.

These non-science topics provide additional perspective that enrich his life.

“I remain very interested in understanding history and the reasons behind current events in Europe, the Middle East, and the U.S.,” he said. “This endeavor is far more challenging than decoding NMDAR structures and functions.”

As for his collaborations, Furukawa suggested that the findings from this research inspire him to continue to search for more answers and greater scientific achievements.

“We will continue to unravel these mysteries in future studies,” Furukawa said. “The best is yet to come.”

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Photo courtesy of Wikimedia Commons

By Daniel Dunaief

Daniel Dunaief

Sports resides somewhere near the center of the currency of communication in our house.

In fact, recently our daughter, who is a gifted back row volleyball player despite just clearing five feet tall, and her brother, who is a lifelong baseball player, exchanged amusing anecdotes.

Our daughter attended a minor league baseball game with her friends. In the middle of a close game, she wondered aloud whether, with runners on first and second base and no outs, the batter would bunt.

“Huh?” one of her friends responded. “Why? What are you talking about?”

She tried to explain the strategy, but gave up after it was clear that her friends were more excited to go out together than they were to inhale the drama of a baseball game.

Her brother was watching Olympic volleyball with his friends. They didn’t understand much about back row hitting or trying to spike the ball on the second hit.

Our family enjoyed the parts of the Olympics we watched and, of course, discussed some of our favorite events.

One of mine was the 1,500 meter men’s race. All of the build up described the fierce on-the-track rivalry and off-the-track trash talking between Norwegian Jakob Ingebrigtsen and Brit Josh Kerr.

The spotlight followed them from the moments before the race through the starter’s gun. While this one competition might not settle who is the fairest of them all, I mean, the better runner, it would give one of them a gold medal, presumably, and, perhaps more importantly, bragging rights.

Ingebrigtsen dashed off to the front of the pack, setting a blistering pace while maintaining what looked like a business-like attitude.

But then, a funny thing happened on the way to the expected finish. American Cole Hocker snuck around Ingebrigtsen’s left side, finding a higher gear and accelerating towards the finish. Kerr pushed towards the line as well, even as American Yared Nuguse closed the gap. At the end, it was Hocker first, Kerr second and Nuguse third, a mere hundredth of a second behind Kerr.

Oh, and Ingebrigtsen came in fourth.

It was such a delightful unscripted moment, particularly after humility seemed to be in such short supply between the favorites.

There are a few things we will not miss. We didn’t need extreme close ups of athletes who are doing as much in their chairs waiting to compete as we are watching them. At one point, Simone Biles, whose name you might have heard a few thousand times over the fortnight, took off her warm up jacket, which we all saw on TV. The announcer, lacking any other detail to share and exhausted from overusing the word “redemption,” decided to announce that she was taking off her jacket. You stuck the landing on that insightful observation, buddy boy.

So, now, here we are. The Olympics are over, the flame is out, the days of trying to avoid sports headlines until after watching the prime time replay are over.

We can go back to reading the important news of the day, assuming we can find some. 

What’s changed in our house? Well, our dog is much happier. He probably has nothing against the Olympics, but we shouted at the TV much more often than we typically do during a baseball or basketball game.

We can consider the what ifs in our own lives. These Olympians train every day, eat the right foods, try to stay on a sleep regimen and forego other id-driven moments.

And then, on that day, they might win by a hundredth of a second or less. 

At their best, they can inspire us, the way a new year sends people into a list making frenzy. If they can be so amazing, maybe we can, too.

Or, perhaps, we can figure out what else to watch or binge watch on TV. Oh, and there’ll be a winter games, assuming there’ll be a winter, in Italy in two years. Those athletes are undoubtedly doing everything they can to shave another hundredth of a second off their times.

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Student falling asleep at his desk. Courtesy MetroCreative Connection

By Daniel Dunaief

Imagine a typical school classroom filled with adults, listening as intently as they can to a detailed lecture about the finer points of tax law or multivariable calculus.

The adults in the room who weren’t particularly interested in the topic might struggle to concentrate, and several of them might try — perhaps unsuccessfully — to stay awake.

Now, bring a group of 8-year-olds into the same room, with the same instructor, and the same material. The likelihood that any of those younger students would fall asleep in their chair is far lower.

One reason for that difference is that the younger set, consistently, gets more sleep, while the older generation, from high school students on up the chain, typically, are not as well-rested.

“We think it’s normal, if you’re bored, to fall asleep, but it’s not,” said Dr. Steven Feinsilver, director of the Center for Sleep Medicine at Northwell Lenox Hill Hospital. “Falling asleep in a lecture that doesn’t interest you means that you either have a sleep [problem] or, more likely, are sleep deprived.”

Indeed, the percentage of the population that is sleep deprived is estimated at around 50% or more, a staggering number, which means that at least half the population needs more restorative sleep.

With the start of another academic year just under a month away, sleep experts are urging students to start shifting back to their respective school sleep schedule in the coming weeks.

These sleep experts suggest that students who may sleep until 9 a.m. or later during the summer, but will soon get up for school at, say, 6 a.m., are experiencing a type of jet lag people often feel when they travel across the Atlantic.

Sleep experts say that changing an adolescent’s schedule to an earlier waking routine, a week or more before school starts, can ease that school-year transition, while others recommend shifting up wake-up time, by an hour earlier per day during the September lead-up.

“If you know you’re going to have to be waking up at 6 a.m. for the first day of high school, you should be starting to wake up within that hour, within three days or so, before that so your body gets used to it,” said Lauren Hale, professor of preventive medicine and sleep behavior expert at Stony Brook Medicine.

Routines, including getting enough sleep, are important in preparing for the mental effort required to meet daily learning challenges.

“Our brains like a consistent schedule,” said Brendan Duffy, director of Sleep Services at Catholic Health, which includes Port Jefferson-based St. Charles Hospital and Smithtown-based St. Catherine of Siena. “It’s important to get up at the same time,” even on weekends.

Teenagers need more sleep

The academic age group that needs the most sleep is the one that is often getting the least.

High schools often start just after 7 a.m., in part because after-school activities such as athletic practices and events, as well as other extra-curricular activities, take up the hours between the end of school and the onset of darkness.

“Between 15 and 25, everybody’s clock tends to run slow,” Feinsilver said.

The school districts that have pushed high school start times back have seen their test scores go up, added Feinsilver.

He acknowledged that it’s challenging for parents who are managing their own work schedules to balance their children’s academic hours. Parents and schools can and should try to compromise, he urged.

Benefits on the athletic field

Boy chases a soccer ball. Pixabay photo

A return to school also means the restarting of athletic programs, some of which begin before the first day of the new academic calendar.

Student-athletes are pushing their minds and bodies, as they juggle demanding academic requirements with training and competition.

Sleeping the estimated optimum of seven to nine hours per night not only helps improve an athlete’s competitive skills but also helps prevent physical problems.

Sleeping enough is a “way to avoid injuries,” said Duffy, who has been talking to students in a range of ages all the way through college.

Duffy added that professional teams are also encouraging athletes to budget for the sleep their minds and bodies need.

Additionally, he suggests sleep is a form of prehab, as sufficient rest can prevent injuries that would require rehabilitation.

Duffy has spoken with several area teams about the importance of sleep, including the Stony Brook women’s soccer team.

“For 90% of the players, this is the first time” they hear about the importance of sleep athletically, said Tobias Bischof, the head coach of SBU women’s soccer team. “My players are 18-to-22 years old and it’s not on their radar yet how important sleep is.”

He describes sleep as “probably the greatest recovery tool we have” and believes it’s “super important for injury prevention.”

As a coach, Bischof has started journaling his sleep patterns and believes he and others can be better coaches with enough rest.

He suggested that coaches are under tremendous pressure and sleep helps him become more patient.

Numerous factors contribute to success on and off the field with these student athletes, including nutrition, hydration, self-care and relationships with their families, as well as sleep, Bischof added.

The soccer coach doesn’t ask about sleep when he’s speaking with high school players who might join the SBU team, but it comes up when athletes ask about ways the school works with athletes beyond training.

He describes mental health support as well as sleep education.

“You always want to make them a better version of themselves,” Bischof said.

Jim Taylor, who specializes in the psychology of sports and parenting and who has been a consultant to the U.S. and Japanese ski teams, met Duffy when they were on a podcast panel related to sport psychology in 2022. Taylor suggested that sleep is much more than a physical process, as it has psychological and emotional implications.

“One of the most powerful tools that athletes have is sleep, which impacts them in so many ways,” he explained in an email.

Taylor, who competes in triathlons, has seen his results improve from top 20 in his age group to two national championship titles and three world championship podiums.

“Of course, I’m sure other factors contributed to my improved results, but I know that improved sleep was a key contributor,” he explained.

Mental health

Sleep can also be a sign of, or a contributing factor to, mental health issues.

In a Sleep-to-Rise campaign, the Sun Belt Conference suggests that talking about sleep is a gateway to discussing mental health.

Not getting enough sleep or poor sleep quality can increase the risk for mental health issues, while poor sleep itself can reflect mental health challenges.

In its sleep-to-rise online effort, the conference urges athletes to consider sleep a “competitive advantage.”

“With student-athletes, we emphasized the importance of prioritizing your sleep,” Lauren Shear, assistant commissioner of Championships & Sports Administration at the Sun Belt Conference, explained in an email. “This meant highlighting how sleep affects both mental health and physical health.”

Shear added that the conference tries to provide educational resources on mental health, nutrition, sleep and other factors to equip the student-athletes with the information they need to succeed in and outside competition.

She tries to get seven to eight hours of sleep per night and has noticed that when she gets six or less, she’s more irritable and lethargic. She’s also more likely to get sick.

Stony Brook’s Hale added that sleep, unlike diet or other life changes, can provide a noticeable benefit.

“People can see immediate results quicker than other behaviors,” Hale said. “If you choose not to have dessert, you might feel like you lost something and you don’t see a benefit the next day. If you actually got a full night of sleep, you might feel the benefits that day.”

Sleep tips from SBU’s Hale

•  Prioritize your sleep health

• Try to have regular sleep times, even on

weekends

• Make sure you get morning light

• Avoid substance use, like caffeine late in

the afternoon

• Put screens away before bedtime

• Sleep in a cool, dark, quiet place

• Pay attention to your body. Figure out when you get restorative rest compared with when you don’t.

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METRO photo

By Daniel Dunaief

Daniel Dunaief

I’m tired, crabby, angry, annoyed, frustrated, disappointed, appalled and short tempered. 

Sleep, as a feature in TBR News Media this week suggests, will cure some of that.

But I’m just so fed up with the nonstop negativity in the country. Half the country not only wants to win, but seems thrilled with the prospect that the other half will lose. The worse the losers feel, the happier they are.

We’ve become a society of stomping toddlers, eager to crush the careful creations and ideas of those we oppose under our feet. Cut it out! This isn’t helping.

Okay, let’s take a step back from politicians and discuss us, you know, John and Joan Q. Public.

We are generally sleep deprived, according to statistics and people who pinch themselves not out of sheer joy but out of the necessity of staying awake each day.

More than one out of two people in the cars next to us may not only be texting and/or talking on the phone, but is also likely struggling to stay awake. That’s not good for them or for us.

Think about it: when you go to a store for stuff, call a company to send someone to fix your air conditioners in overbearing heat, or need someone to provide a skill set that you don’t possess, you don’t ask a long list of questions to make sure they were on the winning political team or that they believe everything you believe or even that they got enough sleep the previous night.

But, wait, what if the help we need is part of the other political team or, even going outside the realm of politics, is a devoted fan of the Red Sox, believes in red herrings, or is a fan of the color red?

You might privately enjoy the victory of your team or your would-be political leader, but are you really eager for them — you know, the “others” who are a part of our lives — to be miserable?

Their misery could become your misery.

It might tickle you to watch them cry and to ponder the existential threat that the person you support won and the person they supported lost, but you still need them even if you have no use for their political leaders.

If they lose sleep and are worse at their jobs, you might have to wait longer in line, deal with an incorrect bill you have to keep fighting, or suffer through the consequences of getting a meal that contains an allergen you told the waitress you couldn’t eat.

Even if you feel a momentary satisfaction that people who are supporting the wrong candidates  lost, you shouldn’t be too eager to push their head in the mud or to throw tomatoes at them. You might need those people and your tomatoes.

What happened to agreeing to disagree, to the art of compromise or even just to listening?

If whichever side loses feels like they still have a seat at the table, an ability to affect policies, an opportunity to help our children learn — is anyone on this campaign talking about education, ever? — and confidence that someone will listen to their ideas, the political and cultural temperature wouldn’t be so high and we the people would sleep and work better.

Yes, the extremes on each side can be absurd and frustrating, but even those people with the most ridiculous signs can be agreeable and helpful outside the context of political ideology.

So, just to recap, we might want to consider this great experiment in democracy as a team effort. We don’t always say and do the right things and we don’t always back the right horses, but, together, we can be greater than any one election or one would-be leader.

Unless we’re ready to live on a farm and eat our own food, educate our children, provide our own energy and entertainment and perform necessary surgeries on ourselves, we need each other. Once we remember that, we might have a better chance of sleeping well at night, which will make us better at our many roles, from parenting, to working, to contributing to our communities.

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Qingtao Sun, postdoctoral researcher at CSHL, presents a poster of the cachexia research taken at a Society for Neuroscience meeting in 2023 in Washington, DC. Photo by Dr. Wenqiang Zheng

By Daniel Dunaief

Cancer acts as a thief, robbing people of time, energy, and quality of life. In the end, cancer can trigger the painful wasting condition known as cachexia, in which a beloved relative, friend or neighbor loses far too much weight, leaving them in an emaciated, weakened condition.

A team of researchers at Cold Spring Harbor Laboratory has been studying various triggers and mechanisms involved in cachexia, hoping to find the signals that enable this process.

Recently, CSHL scientists collaborated on a discovery published in the journal Nature Communications that connected a molecule called interleukin-6, or IL-6, to the area postrema in the brain, triggering cachexia.

By deleting the receptors in this part of the brain for IL-6, “we can prevent animals from developing cachexia,” said Qingtao Sun, a postdoctoral researcher in the laboratory of Professor Bo Li.

Through additional experiments, scientists hope to build on this discovery to develop new therapeutic treatments when doctors have no current remedy for a condition that is often the cause of death for people who develop cancer.

To be sure, the promising research results at this point have been in an animal model. Any new treatment for people would not only require additional research, but would also need to minimize the potential side effects of reducing IL-6.

Like so many other molecules in the body, IL-6 plays an important role in a healthy system, promoting anti- and pro-inflammatory responses among immune cells, which can help fight off infections and even prevent cancer.

“Our study suggests we need to specifically target IL-6 or its receptors only in the area prostrema,” explained Li in an email.

Tobias Janowitz, Associate Professor at CSHL and a collaborator on this project, recognized that balancing therapeutic effects with potential side effects is a “big challenge in general and also is here.”

Additionally, Li added that it is possible that the progression of cachexia could involve other mechanistic steps in humans, which could mean reducing IL-6 alone might not be sufficient to slow or stop this process.

“Cachexia is the consequence of multi-organ interactions and progressive changes, so the underlying mechanisms have to be multifactorial, too,” Miriam Ferrer Gonzalez, a co-first author and former PhD student in Janowitz’s lab, explained in an email.

Nonetheless, this research result offers a promising potential target to develop future stand alone or cocktail treatments.

The power of collaborations

Working in a neuroscience lab, Sun explained that this discovery depended on several collaborations throughout Cold Spring Harbor Laboratory. 

“This progress wouldn’t be possible if it’s only done in our own lab,” said Sun. “We are a neuroscience lab. Before this study, we mainly focused on how the brain works. We have no experience in studying cachexia.”

This paper is the first in Li’s lab that studied cachexia. Before Li’s postdoc started this project, Sun had focused on how the brain works and had no experience with cachexia.

When Sun first joined Li’s lab three years ago, Li asked his postdoctoral researcher to conduct an experiment to see whether circulating IL-6 could enter the brain and, if so where.

Sun discovered that it could only enter one area, which took Li’s research “in an exciting direction,” Li said.

CSHL Collaborators included Janowitz, Ferrer Gonzalez, Associate Professor Jessica Tolkhun, and Cancer Center Director David Tuveson and former CSHL Professor and current Principal Investigator in Neurobiology at Duke University School of Medicine Z. Josh Huang.

Tollkuhn’s lab provided the genetic tool to help delete the IL-6 receptor.

The combination of expertise is “what made this collaboration a success,” Ferrer Gonzalez, who is now Program Manager for the Weill Cornell Medicine partnership with the Parker Institute for Cancer Immunotherapy, explained in an email.

Tuveson added that pancreatic cancer is often accompanied by severe cachexia.

“Identifying a specific area in the brain that participates in sensing IL-6 levels is fascinating as it suggests new ways to understand physiological responses to elevated inflammation and to intervene to blunt this response,” Tuveson explained. “Work in the field supports the concept that slowing or reversing cachexia would improve the fitness of cancer patients to thereby improve the quality and quantity of life and enable therapeutic interventions to proceed.”

Tuveson described his lab’s role as “modest” in promoting this research program by providing cancer model systems and advising senior authors Li and Janowitz.

Co-leading an effort to develop new treatments for cachexia that received a $25 million grant from the Cancer Grand Challenge, Janowitz helped Sun understand the processes involved in the wasting disease. 

Connecting the tumor biology to the brain is an “important step” for cachexia research, Janowitz added. He believes this step is likely not the only causative process for cachexia.

Cutting the signal

After discovering that IL-6 affected the brain in the area postrema, Sun sought to determine its relevance in the context of cachexia.

After he deleted receptors for this molecule, the survival period for the test animals was double that for those who had interleukin 6 receptors in this part of the brain. Some of the test animals still died of cachexia, which Sun suggested may be due to technical issues. The virus they used may not have affected enough neurons in the area postrema.

In the Nature Communications research, Sun studied cachexia for colon cancer, lung cancer and pancreatic cancer.

Sun expects that he will look at cancer models for other types of the disease as well.

“In the future, we will probably focus on different types” of cancer, he added.

Long journey

Born and raised in Henan province in the town of Weihui, China, Sun currently lives in Syosset. When he’s not in the lab, he enjoyed playing basketball and fishing for flounder.

When he was growing up, he showed a particular interest in science.

As for the next steps in the research, Sun is collaborating with other labs to develop new strategies to treat cancer cachexia.

He is eager to contribute to efforts that will lead to future remedies for cachexia.

“We are trying to develop some therapeutic treatment,” Sun said.

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Students are asked to craft a story inspired by the above sea glass fragment.

By Daniel Dunaief

Daniel Dunaief

Once a piece of glass falls in the ocean, the magic begins.

Given an opportunity to enter the Whaling Museum & Educational Center of Cold Spring Harbor’s sea glass fiction writing contest, students from around Long Island accepted the challenge, offering a dynamic, exciting and inspiring range of stories.

Students from third grade through high school looked at the same piece of glass and developed stories filled with literary devices like onomatopoeia (where a word, like “whack” comes from a sound), personification and more.

The narratives ran the gamut from tales of mermaids to creations of new mythology to a search for meaning and identity. 

Along the way, the writers seized on the opportunity to share the journey sea glass takes as it transitions from a sharp piece of glass into a smoother, colorful object.

Some of the stories offered vivid descriptions of the world beneath the waves, taking readers into a magnificent aquatic seascape.

Amid narratives about pirates and mermaids, some writers chose to address dramatic and challenging themes, weaving emotionally resonant stories that tackled broken families, alcoholism and infidelity.

As a judge for the contest, I was not only surprised by the directions these stories took, but was also appreciative of the combination of realism and fantasy that suffused the writing, the willingness to take chances, and the pieces of the writers I could hear through their imaginations.

The writers imagined the glass either as the centerpiece of an important story or as a passenger, observing the dynamics that define the way people interact.

Judging writing and fiction is a subjective process, with each judge bringing his or her own ideas to the process.

I’m glad I wasn’t the only judge and enjoyed the opportunity to consider why the readers at the Whaling Museum & Education Center of Cold Spring Harbor chose to rank the submissions in a particular order.

I invite TBR readers to immerse themselves in these entries and to enjoy the worlds these writers have created or, in some cases, reflected. You can see some of the entries in the Arts & Lifestyles section of this week’s papers.

As for the writers, I want to thank them for finding time in their lives to share their ideas and to create their own stories.

In a contest in which third through fifth graders could write up to 500 words, sixth through eighth graders, 750 words, and high schoolers, 1,000 words, they developed stories, backdrops and themes that offered complete narratives and that carried readers off the page.

I particularly appreciate how these writers found the time to prepare and submit an entry. Student lives are filled with activities and assignments. Homework, required reading, chores, and sports and theater practices, to name a few, fill busy schedules that rarely leave them time to add an extra assignment or challenge to their calendars.

And, of course, social media and virtual communication often require regular check-ins and updates. The modern-day student, after all, can’t take too long to answer an urgent text from a friend at the risk of becoming less of a confidant or of sliding down the social hierarchy.

And yet, somehow, even with the importance of staying plugged in, none of the sea glass stories included references to social media and none was told through the prism of a social media world.

I hope the students enjoyed the opportunity to write something outside the context of a graded assignment and that they reveled in the freedom to go in any direction, imagine any characters, and create excitement or drama that appealed to them.

As for what’s next, the museum plans to run the competition next year, giving new entrants the opportunity to unleash their imaginations.

Many of the stories shared similarities with the sea glass itself: they shined in the distance, becoming increasingly interesting on closer inspection.

See pages B13 to B16 for the winning entries.

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Writer and director Brandt Andersen
A scene from 'The Stranger's Case'. Photo courtesy of Philistine Films
A scene from 'A Stranger's Case'. Photo courtesy of Philistine Films

UPDATE: “The Strangers’ Case” won the Jury Award for Best Feature at the Stony Brook Film Festival.

TBR News Media reporter Daniel Dunaief recently spoke with Brandt Andersen, writer and director of the film “The Strangers’ Case,” about five families in four countries who are confronting the refugee crisis. Andersen will attend a screening of his feature film directorial debut at the Stony Brook Film Festival on July 20th at the Staller Center.

Listen to the episode now.

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Mario Shields Photo by David Cardona-Jimenez

By Daniel Dunaief

Friend or foe? The question isn’t as easy in the world of molecular biology as it might be after captains pick players for a team.

An important biomolecule in one context could trigger the growth or spread of cancer, while in another system or organ, that same signal might suppress or stop the development or growth of a disease that can threaten people’s health.

So it is for G-proteins, which, in some tumors, serve as tumorigenic signaling hubs that participate in invasion and metastasis and promote inflammation and immune evasion.

In tumors “there was this notion that it works in a certain way, driving tumor development and progression,” said Mario Shields, Associate Professor of Research Pathology at Stony Brook University. “We had that original hypothesis when we investigated it in pancreatic cancer. We found that it’s the opposite.”

Indeed, when the specific proteins he studies, called G alpha 13, are absent, mouse models develop well-differentiated tumors that reduce their survival.

“My research now is to understand why it’s playing the opposite role that we initially expected,” Shields, who joined Stony Brook in July after six years at Northwestern University.

Having worked at Cold Spring Harbor Laboratory in the lab of Mikala Egeblad from 2012 to 2018, Shields is returning to the Long Island area with a focus on defeating a problematic type of cancer that steals precious time from people and robs families of important members.

“I have come to appreciate the dire situation of people who are diagnosed with pancreatic cancer,” Shields said. “We need to figure out how to lower the curve.”

A recipient of the National Cancer Institute’s Moonshot Award, Shields is one of the first 11 Cancer Moonshot Scholars who received a total of $5.4 million.

The program, which was launched by the Biden administration in the summer of 2023, seeks to advance cancer science while diversifying the pool of early-stage researchers and approaches to research that NCI funds.

The goal of the program is to inspire and support scientists from diverse backgrounds, including those from underrepresented groups in the biomedical sciences.

The NCI award, which Shields brings with him to Stony Brook, will support his efforts.

Egeblad, who is now Bloomberg Distinguished Professor of Tumor Microenvironment, has stayed in contact with Shields since he left her group. The work he’s doing is “very important” in understanding the “basic mechanism of pancreatic cancer progression” as he has been “very successful in making discoveries and raising funds for his research.”

Egeblad appreciates his contribution to her lab. Shields “was responsible for establishing our research program in pancreatic cancer,” she explained. “Before he joined my lab, I had only worked on breast cancer and [Shields] established the various models to also study pancreatic cancer — models that we are still using.”

Building on CSHL work

At CSHL, Shields worked in Egeblad’s lab and received advice and oversight from David Tuveson, Cancer Center Director at CSHL, who developed the mouse model Shields uses.

Shields has been using human and mouse cell lines to interrogate the mechanism of action of these G proteins in suppressing cancer. 

At Stony Brook, he plans to use patient samples to develop patient-derived tumor specimens.

The major hub of what Shields is studying is the mTOR pathway, which stands for mammalian/ mechanistic target of rapamycin. First isolated in a bacteria on Easter Island in the middle of the 20th century, rapamycin is an immunosuppressant drug.

Any defects that activate the mTOR pathway can lead to the growth and development of cancer.

A developing field

Shields explained that the G protein he is studying, G alpha 13, is a “niche” area right now, with few other labs pursuing the same mechanistic pathway. The G proteins are of more interest to molecular pharmacology and drug design.

In his studies, Shields hopes to use the information on the response to changes in the protein to predict how patients respond to therapy that inhibits the mTOR pathway.

Specifically, he is exploring how alterations in the microenvironment can cause the tumor to progress in pancreatic cancer.

Shields has found some “interesting dependencies” in the mechanism he’s studying. In the first year of work at Stony Brook, he would like to figure out how Ga13 regulates mTOR signaling, as the current context dependency is vague.

The gene that codes for this protein is not heavily mutated. Shields anticipates that a threshold level of the protein may be responsible for conveying its benefit in suppressing cancer, rather than a specific mutational change.

He is eager to explore whether nutrient availability plays a role in cancer progression through the reduction in this G protein. He has exploring that in vitro and is curious how that will translate at the organismal level.

Returning to Long Island

Shields had recently been Research Associate Professor in the Department of Medicine at the Feinberg School of Medicine at Northwestern University.

Having worked at Cold Spring Harbor Laboratory, Shields felt comfortable moving back to the Long Island area.

“Stony Brook is a good place to do research,” said Shields.

Additionally, Shields was impressed with the number of people who had presented their research from Pathology Chair Kenneth Shroyer’s lab at a conference.

“Further discussions [with Shroyer] indicated we have areas of common interest in terms of pancreatic cancer,” Shields added.

Shields appreciates the greenness of Long Island. When he worked at CSHL, he enjoyed walking on trails and enjoyed the variety of fall colors.

Shields brought one person with him from Northwestern and plans to have a lab of about six people.

As for running his lab, Shields plans to “be patient” and to “see where people are coming from and what they are capable of” as he takes on the role of mentor for members of his lab at Stony Brook.

Shields hopes to inspire and encourage under represented groups to pursue careers in science, technology, engineering and math.

Egeblad suggested that Shields is warm and calm, which “helps those entering the field really take to his instruction.” She added she believes he is an inspiration to many young scientists.

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Pixabay photo

By Daniel Dunaief

Daniel Dunaief

When we don’t know how to reprogram our remote control for our garage, search engines like Google can not only offer a written explanation, but can also provide videos with step by step guides that make even the least mechanical people — okay, me —barely competent.

Yes, I can change most light bulbs. Let me rephrase that: I can change most conventional light bulbs. For whatever reason, the fluorescent ones that require turning them at exactly the right angle befuddle me.

Google can also help us find ways to improve our daughter’s softball swing, can explain the Pythagorean Theorem, and can give us quizzes to help us prepare for important exams in school.

When we don’t know the history of an important event, when we want to find some information about someone before we go to a job interview, or when we are curious about what other movies someone who looks vaguely familiar in a streaming show has also been in, we can type their names and find instant answers.

And yet, shockingly, Google and other search engines have their limitations.

Search engines connect the words we’re looking for to the information, or misinformation, available online. These engines don’t have a fact filter, a scientifically proven filter, or an incontrovertible truth filter. It’s up to us to decide whether what we see or read is valid.

In fact, I would advocate for a high school class on information vs. misinformation, giving students a chance to think for themselves to spot online fakes. Most teenagers and 20-somethings, for example, can spot an altered photograph based on the unusual shape of an arm, different shading patterns, or, perhaps, a turn in a shoulder that defies our normal biological range of motion.

When people are in panic mode about a rash, the sudden onset of vague symptoms — a high fever, fatigue and muscle aches, perhaps — they sometimes race to plug those symptoms in to a search engine in the hopes of self diagnosing.

While that might save them the trouble of going to an emergency room in the middle of the night, where they could have to wait hours to see a medical professional, the use of a search engine can also create unnecessary anxiety and frustration or provide a false sense of security.

A search engine diagnosis that indicates you or your loved one might have some horrific disease likely raises your blood pressure and may cause you to drive erratically to a hospital.

A friend of ours once received a horrific call that his daughter was injured at school. During a long and excruciatingly painful drive through the night, he set his cruise control to the speed limit, despite his urge to drive 100 miles per hour. He recognized that he wouldn’t do himself, his family or his daughter any good by getting into a car accident or endangering the lives of others on the road during that painful trip. Fortunately, his daughter made a complete recovery.

Such rational thinking on the part of someone in intense distress, however, may not apply when people make a search engine diagnosis.

Recently, I spoke with Dr. Sharon Nachman, Chief of the Division of Pediatric Infectious Disease at Stony Brook Children’s Hospital, about several different viruses. I suggested to her that the symptoms for different conditions seemed remarkably similar, with the kinds of general physical discomfort, fever, and aches dominating the list, making it difficult to come up with an accurate diagnosis. 

“That’s why Dr. Google is not the right answer,” Dr. Nachman said.

For illnesses or symptoms that rise to the level of genuine concern, people should consult physicians who can test for a range of potential problems, ruling out conditions until they come up with an informed diagnosis.

In some cases, time is of the essence, with drugs like Paxlovid providing effective relief for Covid-19 within a limited time window, or Ttaamiflu offering the most effective benefit for people with the flu within 48 hours of the beginning of symptoms.

And, while Google may help with your science homework, the search engine may prove especially useful in directing you to experts at hospitals or urgent care centers who can interpret your symptoms and offer an informed diagnosis.

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