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Daniel Dunaief

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0 2018
File photo

By Daniel Dunaief

Daniel Dunaief

Three years and a different world ago, I attended a scientific conference at Cold Spring Harbor Laboratory on a gene editing technique called CRISPR, or more technically CRISPR-cas9.

I rubbed elbows with some of the many talented scientists at an internationally renowned institution. In a casual atmosphere filled with high-powered talks from people who speak the language of science with accents from all over the world, the grounds at CSHL, with its winding roads and personalized parking spaces, offers a tree-lined backdrop for new collaborations and discoveries.

Back then, I invited one of the conference organizers, Jennifer Doudna (pronounced Dowd nuh), who is a Professor of Chemistry and Molecular and Cell Biology at the University of California, to lunch.

After a talk she gave to a packed Grace Auditorium, she and I strolled to the cafeteria to discuss a gene editing tool that has the potential to change the world.

Indeed, even today, labs around the world are using a technique based on the way bacteria recognize and fight off viruses to combat the effect of SARS-CoV-2, or the virus that causes COVID-19.

During that sunny July day in 2017, however, we were blissfully unaware of the challenges to come in 2020. We sat down at a central table outside, with people passing, nodding and acknowledging my tall and talented lunch guest.

While she responded to an appreciative crowd of casually dressed researchers, she was present and focused on the many questions I’d prepared for an upcoming Power of 3 column (see page B9 for another look at that column).

Like many revolutionary technologies and inventions such as splitting the atom, CRISPR is neither all good nor all bad. Editing genes creates opportunities to cure or prevent diseases and to disarm a range of miniature invaders.

At the same time, gene editing puts the power of Mary Shelley’s Frankenstein into the hands of scientists or doctors, offering the kind of tool that requires careful ethical considerations.

Indeed, just last year, a Chinese court sentenced a researcher to three years in prison for using gene editing in unborn babies.

Doudna, who moved to Hawaii when she was seven and is a passionate gardener, is in the third year of a four-year $65 million grant from the Defense Advanced Research Projects Agency, which monitors security concerns for the intentional or accidental misuse of the technology.

Eating with Doudna on a breezy, bright summer day, I appreciated how ready she was to tailor the conversation to my level of understanding of this technology, offering details about gene editing and making sure I understood her.

While she was impressive and articulate, she certainly didn’t seem as if she were speaking to me from on high. She shared a deliberate and directed intelligence, blending a combination of an explanation of what she’d done and thoughts on the next scientific steps.

Doudna, who lives with her husband Jamie Cate, who is also a Berkeley scientist, and their high school senior son Andrew, shared an appreciation for the history of Cold Spring Harbor Laboratory, where she’d visited at different points in her career.

Back in 1987, she spotted a woman walking towards her. Nobel prize winner Barbara McClintock, whose name still comes up regularly in conversations with scientists at the site, strolled by, giving Doudna a thrill.

The next time someone spots or interacts with the Berkeley Professor at CSHL, they will likely feel the same excitement, as Doudna was recently named a recipient of the Nobel Prize.

Then again, it was clear from the way the attendees at the conference reacted to Doudna three years ago that, Nobel prize or not, she was already a rock star in the scientific community whose foundational work may, one day, lead to the kind of breakthroughs that extend and improve life.

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Christina Joselevitch

By Daniel Dunaief

Children knock on the door of 1313 Gluto Lane, a favorite house for Halloween. The resident, known for providing coveted confections at a rapid rate, immediately comes to the door, asks no questions about the Halloween costumes that might slow the process down and, with almost super-human speed, dumps candy into open bags and closes the door.

Word spreads about the house on Gluto Lane. Soon, the doorbell rings at a furious pace, with children eager to get the best candy of this difficult year and move on to the next house.

At first, with Trick or Treaters coming at a regular pace, the process works, but then, something goes awry, creepy music begins and the door doesn’t open.

That’s what’s happening in bipolar retinal cells in the goldfish Christina Joselevitch, a Postdoctoral Associate in the Neurobiology and Behavior Department at Stony Brook University’s Renaissance School of Medicine, is studying.

Known for their incredible speed at releasing neurotransmitters stored in circular vesicles, these bipolar retinal cells go through a depression in which they can’t release the neurotransmitter glutamate despite repeated signals for the release of the neurotransmitter.

“When you stimulate those cells very strongly, with two stimuli close apart, they suffer depression,” Joselevitch said. “Nobody knew why, if they’re able to signal constantly, they should suffer from depression.

To be sure, Joselevitch was working with extreme stimulation to probe the limits of the system and understand its underpinnings. This is not necessarily how these cells work. She said the researchers don’t know if retinal neurons experience synaptic depression under normal conditions and what function depression would have in bipolar cell physiology, in vision or in signaling processing in general.

In a recent publication in the Journal of Neuroscience, Joselevitch described at least two processes that contribute to this slowdown, which she describes as the rate limiting steps. The vesicles need to get to the membrane and they need to get ready to mature before they are release. Once vesicles move towards the cell membrane, they don’t immediately fuse and send their neurotransmitter into the synapse between cells. In some cells, such as the retinal photoreceptors and bipolar cells and in hair cells of the ear and lateral line in fish and in cells of the pineal gland, they gather in a ribbon close to calcium entry points.

Scientists have two theories of the ribbon function. The first is that it could act as a conveyor belt and speed up vesicle priming and delivery to the membrane and the second is that it could set a constant pace for vesicle delivery.

Joselevitch’s results suggest that the vesicles attach to the ribbon, where they go through a maturation process. These paired-pulse depressions don’t just occur in fish: they also affect the ability of mammalian cells to respond to a second stimulus.

These cellular phenomena show the limits of the system. Indeed, Joselevitch likened the process to a car that has reached its maximum speed. Pushing down harder or more on the accelerator won’t enable further acceleration.

The impact of this work is “broad,” she said. Studying this process could enable a stronger awareness of the steps in fast-acting processes in the nervous system. Such research could also provide an understanding about processes that go awry in various neurological diseases.

In an email, Professor Lonnie Wollmuth, who is the principal investigator for the Stony Brook lab in which Joselevitch works, described Joselevitch as “invaluable to our on-going efforts to study presynaptic mechanisms in the retina.” He wrote that she was an “outstanding and very careful scientist” who is “passionate” about her research and has served as a mentor for others in the lab.  Joselevitch has been working in Wollmuth’s lab for about 16 months.

Synaptic transmission is fundamental to all brain function, Wollmuth explained. “Changes in the strength of synaptic transmission underlie basic higher order brain functions like learning and memory,” the Stony Brook Professor wrote. Joselevitch’s experiments “reveal mechanisms of presynaptic vesicle release at all synapses and provide novel insights into the processing of vesicles at ribbon synapses.”

Based on Joselevitch’s work, Wollmuth’s lab has submitted a large National Institutes of Health grant to the National Eye Institute to study the molecular components of presynaptic release in the retina. She has also started to integrate her work with Alzheimer’s Disease, as proteins found in that disease disrupt the molecular machinery involved in presynaptic release.

A native of Brazil, Joselevitch has been at Stony Brook University since last July. She is on sabbatical with the University of São Paulo. She is hoping to participate in these studies in New York for a few more years.

She said she was “always a nerd,” and liked to study languages. With varying levels of proficiency, she speaks five languages: Portuguese, English, German, Dutch, and Spanish. At one point, she wanted to be an astronaut, but her mother Carmen dissuaded her from pursuing that interest.

Joselevitch had planned to return to Brazil to see her family in April, but had to cancel that plan because of a travel ban from the COVID-19 pandemic. She said her parents have been “good sports” and her father has bought a smartphone so he can talk through Skype or WhatsApp with his scientist daughter.

Joselevitch enjoys biking, hiking, singing and playing guitar and has been productive during the pandemic, writing papers and proposals. Stony Brook is nominating her work for consideration for the Warren Alpert Distinguished Scholar Award.

Wollmuth wrote that Joselevitch’s research forms “the foundation for future experiments to address the molecular components of vesicle dynamics.” Once they are identified, researchers can modulate and protect them in brain diseases.

Citing author James Joyce, Joselevitch explained her focus on neurons in the fish eye, which, she hopes, may lead to a broader understanding of neurology and disease. When asked why he wrote about Dublin when he could describe other places he’s visited, Joyce responded, “In the particular is contained the universal.”

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METRO photo

By Daniel Dunaief

Daniel Dunaief

We are one of the loudest families on the block, and there are only four of us when we’re all home. Well, five, if you count the dog, and you should definitely count the dog.

Every so often, my dog gets on one of his benders where the entire neighborhood has to hear him. He races into the backyard and barks at shadows that my eyes, and the eyes of my son, who runs to the back door and turns on the light, can’t see either.

Every neighbor presents his or her unique challenges to a block where we continue to spend a large percentage of our time. There’s the guy who drives too fast. We all glare at him, but he doesn’t seem to notice. He probably can’t see us because he’s moving too quickly and exists in a different space-time continuum. Don’t you love a word like continuum that dares to have two “u’s” in a row?

Then there’s the neighbor whose house is under constant construction. No matter what season, time of the month, or time of day, construction people are always there, digging, pulling, pushing, installing, removing, re-laying, resurfacing, ripping up, putting back down.

Who needs all that continuous fixing? I don’t even live in their house and I’m exhausted by the constant change. Sure, it’d be nice if that bulb above my wife’s head in our bedroom actually worked, but my arms are too short on the ladder and the bed is in the wrong place. I put my son on my shoulders and he reached up and turned, but the bulb and the fixture kept spinning.

On the other side, we have a lovely neighbor who is so nice that even the people who frown at the bunnies and deer, which prance through our neighborhood as if they were responding to a cue from a Disney director, smile at her. Her smile and laughter seem like a starter’s gun, waiting for a small cue to explode to the surface.

Anyway, the rest of her family is friendly enough, but doesn’t share her ebullience. They do, however, love their cars. The louder the sound, the more impressive the car, or so it seems. Their driveway hosts regular revving contests. Okay, how many columns have words with two consecutive “u’s” and two consecutive “v’s” in them? Revving continuum, anyone?

Somehow, despite the constant cacophony from the driveway, their house attracts an abundance of magnificent birds, even when they use the leaf blower to keep their immaculate backyard free of the few leaves with the temerity to fall on their property.

Then there is the talker. She’s incredibly sweet, insightful and intelligent. The two challenges are that the polite banter doesn’t seem to have a natural end, and she is so soft spoken that I find myself nodding and raising my eyebrows, hoping I’m offering the proper response to questions I can’t hear. I can’t move closer to her because we react to people as if they were porcupines, with six foot quills.

Then there are the adorables. These are the families that have young children who giggle, laugh and play, blissfully unfocused on the pandemic and thrilled that they are out on a bike or that they can identify a bird that passed overhead. They race each other on tiny bikes, ask me why I’m wearing the same sweatshirt again, and skip to the sound of music I can’t hear. They also see the nonstop trucks delivering materials to the construction house as a source of entertainment. One of our young neighbors was on her way to school on a recent morning. Her mother stopped her car and rolled down the window so she could tell me about Mrs. Cathy and Ms. Mary. Those happy adorables are the block winners.

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Jeremy Borniger. Photo from CSHL

By Daniel Dunaief

Much as New Yorkers might want to minimize sleep, even during the pandemic when the need to be active and succeed is hampered by limited options, the body needs rest not only for concentration and focus, but also for the immune system.

Recently, Assistant Professor Jeremy Borniger, who joined Cold Spring Harbor Laboratory in January, collaborated with his former colleagues at Stanford University to publish research in the journal Science Advances that sheds light on the mechanism involved in this linkage.

Doctors and researchers had known for a long time that the release of glucocorticoids like cortisol, a stress hormone, can suppress the ability to fight off an infection. “That happens in people that are chronically stressed, even after surgery,” said Borniger in a recent interview.

A comprehensive understanding of the link between neuronal cells that are active during stress and a compromised immune system could help develop new ways to combat infections. The Stanford-led study provides evidence in a mouse model of the neuronal link between stress-induced insomnia and a weakened immune system.

Ideally, scientists would like to understand the neural pathways involved, which could help them design more targeted approaches for controlling the immune system using natural circuitry, according to Borniger.

Scientists could take similar approaches to the therapies involved with Parkinson’s, depression and obesity to increase or decrease the activity of the immune system in various disease states, instead of relying on a broader drug that hits other targets throughout the body.

In theory, by controlling these neurons, their gene products or their downstream partners, researchers could offer a way to fight off infections caused by stress.

While their studies didn’t look at how to gauge the effect of various types of sleep, such as napping or even higher or lower quality rest, their efforts suggest that sleep can help protect against stress-triggered infections.

The total amount and the structure of sleep play roles in this feedback loop. The variability among people makes any broad categorization about sleep needs difficult, as some people function well with six hours of sleep, while others need closer to eight or nine hours per day.

“Scientists are still working out how the brain keeps track of how much sleep it needs to rest and recover,” Borniger explained. “If we can figure this out, then, in principle, we could mess with the amount of sleep one needs without jeopardizing health.”

Researchers don’t know much about the circuitry controlling sleep amount. Borniger recognizes that the conclusions from this study are consistent with what doctors and parents have known for years, which is that sleep is important to overall health. The research also identifies a brain circuit that may be responsible for the way sleep buffers stress and immune responses.

People who have trouble sleeping because of elevated stress from an upcoming deadline often have a flare up of diseases they might have had under control previously, such as herpes viruses or psoriasis. These diseases opportunistically reemerge when the immune system is weakened.

The major finding in this study is not that the connection exists, but that the researchers, including principal investigator Luis de Lecea and first author Shi-Bin Li at Stanford, found the neural components.

While the studies of these linkages in the hypothalamus of mice were consistent across individuals, the same can’t be said for anecdotal and epidemiological evidence in humans, in part because the mice in the study were genetically identical.

For humans, age, sex, prior experiences, diet, family history and other factors make the linkage harder to track.

Even though researchers can’t control for as many variables with humans as they can with mice, however, several other studies have shown that stress promotes insomnia and poor immune function.

Borniger emphasized that he is the second author on the paper, behind Li and was involved in tracking the immune system component of the work.

Borniger and de Lecea are continuing to collaborate to see if drugs that target the insomnia neurons block the effect of stress on the immune system.

Now that he has moved into the refurbished Demerec Laboratory at CSHL, Borniger plans to work on projects to investigate how to use the nervous system to control anti-tumor immunity in models of breast and colorectal cancer, among others.

By understanding this process, Borniger can contribute to ways to manipulate these cells and the immune system to combat cancer and other inflammatory diseases.

Ideally, he’d like to be a part of collaborations that explore the combination of manipulating nervous and immune systems to combat cancer.

Borniger came to Cold Spring Harbor Laboratory because he was eager to collaborate with fellow scientists on site, including those who look at the immune system and metabolism. He appreciates how researchers at the famed research center look at how bodies and the brain respond to a growing tumor and would like to explore how tumors “influence nerves and then, reciprocally, how nerves influence tumor progression.”

The first few steps towards working at CSHL started in 2018, when Tobias Janowitz, Assistant Professor at CSHL, saw a paper Borniger published on breast cancer and asked him to give a 15-minute talk as a part of a young scholars symposium.

Borniger grew up in Washington, DC, attended college at Indiana University, went to graduate school at Ohio State and conducted his post-doctoral work at Stanford. Coming to CSHL brings him back to the East Coast.

Borniger and his fiancée Natalie Navarez, Associate Director of Faculty Diversity at Columbia University, met when they were in the same lab at Stanford. The couple had planned to get married this year. During the pandemic, they have put those plans on hold and may get married at City Hall.

Borniger and Navarez, who live on campus at Hooper House at CSHL, look forward to exploring opportunities to run, hike and swim on Long Island.

The new CSHL researcher appreciates the new opportunities on Long Island.

“This sort of collaborative atmosphere is what I would have in my Utopian dream,” Borniger said.

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Bear

By Daniel Dunaief

Daniel Dunaief

My dog is delightfully imperfect. In fact, as I type this at my home computer, he is staring at me, hoping that I have succumbed to the snack urge and I will either intentionally toss a few morsels his way or that gravity will help him out, causing a carrot to slip off my desk.

Yes, he eats carrots, which isn’t terribly surprising because he also eats cat poop whenever he can get to it. I’m not sure he has taste buds or that he pays attention to them.

I love my imperfect dog and would like to share some of his quirks.

For starters, walking in a straight line is clearly against his religion. As soon as he’s on one part of a sidewalk, he needs to cross in front of me to the other side. He is a canine windshield wiper, swishing back and forth in case there is a scent, a scurrying insect, or a frog hopping nearby that he needs to see or smell.

When he’s not sitting during our walks, because he seems to have the words “walk” and “sit” confused, he turns around every few seconds to see what’s behind us. If he is a reincarnated person, he must have been in the rear guard of a military unit, making sure no one was following him.

When we turn around to go back in the direction he was staring, he then stops to look over his shoulder in the direction we had been walking.

It’s not about what’s out there, but what’s back there that concerns him.

His breath is an absolute mystery. He consumes a bowl of chicken and rice formula twice a day. And yet, somehow, his breath smells like fish. You know how they say you can hear the ocean in a conch shell? Well, you can smell the ocean, and not the good, salty crisp air parts, but the rotting-seaweed-and-dead-crabs-on-an-airless, overheated-beach parts, on my dog’s breath.

Then, there are the neighbors. They are so appealing to my dog that he pulls to go see them whenever they are outside. I’m sure it has nothing to do with the fact that they drop a treat in front of him each time he appears.

Yes, I know I could train him, but I could also go running more often, go to bed earlier, read better books and make better choices for myself, so I haven’t trained either of us particularly well.

You know that delightful foot thing dogs do when you pet them behind the ear, on their stomach or on their chests? It’s the one where they shake their leg as you scratch them. Well, he does that once a month, as if he wants to confirm that he actually is a dog, but that he’s a conscientious objector to flailing his feet in the air regularly.

He treats the doorbell as if it were the starting gun at a race. He jumps up from the floor, ready to greet refrigerator repair people or HVAC workers as if they had come to see him, refusing to let them pass without an ear rub.

Food is the ultimate motivator. He may not particularly want to lie down at my feet and have me pet him while shaking his paws, but he does go back and forth with me to the grill. He always seems to be on the wrong side of our patio door. If he’s outside, he barks to come in. As soon as he’s inside, he barks to go out.

Maybe he’s not actually a dog, but a metaphor.

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U.S. Rep. Lee Zeldin said Suffolk County’s federal assistance is going to come down to closing the gap between each party’s proposed bills. File photo by Alex Petroski

U.S. Rep. Lee Zeldin (R-NY1) has been in the thick of federal discussions about another program to support state and local governments.

He said the federal government is having “active talks with respect to there being a next coronavirus response bill … I have been advocating directly to the president and his chief of staff [Mark Meadows] and leaders in Congress about Suffolk County and our local towns and villages.”

The local congressman, whose district covers the North Fork and South Fork all the way west to most of Smithtown, said President Donald Trump (R) called his house last Sunday night and that he used the opportunity to talk about getting funding for local government. Zeldin brought up the MTA with the president.

“I’m trying to get top line numbers for our county, towns, villages, the MTA and Port Authority,” he said.

Zeldin suggested three factors affected a national funding bill. The first is that the Nov. 3 election is rapidly approaching.

“You have to have a willingness to allow your political opposition to also have a win when you have a government that’s divided between parties,” he said. “The only way for a next coronavirus response bill to become law is similarly to the way the past coronavirus response bill became law,” by Republicans and Democrats working together.

Passing another bill would give everyone, including U.S. Senate Minority Leader Chuck Schumer (D-NY), Speaker of the House Nancy Pelosi (D-CA) and Trump a win, the congressman said.

“That’s a problem for some, because there are people who really don’t want the president to get reelected,” Zeldin said. “If anyone wants to suggest that that’s not a factor, a political calculation and electioneering, they are incredibly naive to that absolute factor to these talks.”

Additionally, the Republicans and Democrats have been far apart in the amount of funding. The Democrats initially had passed a bill in the House for approximately $900 billion for state and local governments out of a $3.4 trillion total aid bill, but the congressman claimed Democrats are sticking to their highball number. According to Axios, Pelosi is now aiming for a new total aid package hovering around $2.2 trillion with local assistance reduced to $436 billion.

Meadows and Treasury Secretary Steven Mnuchin have offered a $150 billion package for state and local governments.

“You can’t stick to a state and local government funding number as high as $900 billion,” Zeldin said. “That’s far more than state and local governments are asking for. If you insist on $900 billion or bust, there’s not going to be any additional state and local funding.”

The additional dynamic that comes into play is that some Democrats who were elected for the first time in Republican districts have been putting pressure on Pelosi in the last few weeks, Zeldin said.

“They want there to actually be negotiations and compromise to get it over the finish line,” he said.

With talks restarted between congressional Democratic leadership and the Trump administration, Zeldin said he was “hopeful” that the discussions would result in a new bill.

He said the amount of money the states and local governments are asking for has also declined since the original request. Indeed, New York State has cut its request to $30 billion from $60 billion.

Any bill that passed wouldn’t likely indicate how county and local governments should spend the money, the congressman said.

“I’m not looking for Congress to break up every dollar being appropriated for Suffolk County,” Zeldin said. “The best thing to do would be to provide flexibility, so that county level elected officials can determine the best use of additional funding.”

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Rocky Point VFW during a 2019 Veterans Day Event. The Rocky Point VFW has donated to the Joseph P. Dwyer project, but that same initiative may be losing funds without federal aid. Photo by Kyle Barr

County officials said the Joseph P. Dwyer program, which provides veterans with peer to peer counseling for post traumatic stress disorder and traumatic brain injury, is under financial pressure amid the economic collapse caused by the pandemic.

Though at the same time, a local congressman who helped start the program has questioned whether the program could truly be defunded, even as local officials are facing a grim financial outlook.

U.S. Rep. Lee Zeldin said there is not much risk of the Dwyer program being defunded any time soon. File photo by Kevin Redding

A loss of the Dwyer program is especially problematic this year, as the need for these services on Long Island has more than doubled in the last six months, according to Marcelle Leis, program director of the Joseph P. Dwyer Veterans Peer Support Project.

Suffolk County Executive Steve Bellone (D) led a group of people focused on veterans affairs in the county, which has the largest population of veterans in the state, to ask for federal disaster relief.

The Dwyer program is “at risk because of tough budgets in the state,” Bellone said on a conference call with reporters. It is “critical that the federal government provide disaster aid to state and local governments so we can continue to function and provide critical services during the pandemic.”

Veterans commit about 20 suicides per day, which is a “national shame,” Bellone said. The county executive cited a recent report in Newsday that estimates that veteran suicides are up by 20 percent since the pandemic began.

“All of the challenges people have faced” have been exacerbated by the “unprecedented natural disaster that we are all living through,” Bellone added.

Domestic violence, mental health and addiction issues have all become more prevalent amid the threat to public health and the economic uncertainty caused by COVID-19, officials said.

Thomas Ronayne, Director of the Suffolk County Veterans Service Agency, said resources for veterans in Suffolk County were “stretched to near the breaking point.”

Ronayne suggested the virus that has changed the world during this challenging year has been no less an enemy than any combatant veterans faced on a battle field, in a jungle or in a desert city.

Veterans have struggled with the isolation created by calls for them to avoid social interactions, when agencies like Ronayne’s would normally encourage them to socialize and interact with the community and their peers.

Indeed, Joe Cognitore, Commander of the Rocky Point VFW Post 6249, who received the Bronze Star and the Combat Infantry Badge for his service during Vietnam from 1969 to 1971, said he has typically felt relief going out and feels much more pent up by being indoors.

“Staying in and [staring at] the four walls of your home takes a toll on you,” Cognitore said.

Cognitore said the Rocky Point VFW recently donated $2,500 to the Dwyer Program.

Leis said the Dwyer Program receives $185,000 in Suffolk County each year in state funding. Cutting or eliminating that funding would reduce the services veterans can access.

“We do save lives,” Leis said. “We cannot do it alone.”

Ronayne said veterans can reach out to the Agency by calling (631) 853-8387, adding that they are always available to support veterans, but that people who need help immediately should call 911.

Bellone said U.S. Rep. Lee Zeldin (R-NY1) has a “close, working relationship with the president and the White House,” Bellone said. “That’s a critical thing. We need the president to weigh in with [Senate Majority Leader Mitch McConnell (R-KY).] We need all parties to come to an agreement on disaster aid.”

Zeldin was a state senator when the Dwyer Program started and said in a phone interview Tuesday that he has continued to provide support.

While Zeldin has spoken with President Donald Trump (R) this Sunday by phone about the need for funding for Suffolk County, he has not heard about any imminent threat to state-sponsored support for a program he helped create.

The Dwyer Program is funded through the end of the first quarter of 2021, Zeldin said, adding he wasn’t aware of anyone inside the state executive or legislative branch who is planning to cut funding for this program.

Zeldin doesn’t anticipate that this particular program will be cut at the state level either.

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File photo

Suffolk County Police said a man was seriously injured in a single vehicle crash early Sunday morning.

Police said Joseph Aiello, 43 of Port Jefferson Station was driving a 2001 Nissan Maxima southbound on Jayne Boulevard Sept. 27 when his vehicle left the roadway and struck a tree at the intersection with Roe Avenue at around 5:30 a.m.

Aiello, who was alone in the vehicle, was transported to Stony Brook University Hospital where he was admitted in critical condition.

Detectives are asking anyone with information on this crash to call the 6th precinct at 631-854-8652.

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Taken around 1890, the photo above includes Lucas Cheadle’s great, great grandparents Martin Van Buren Cheadle and his wife Mary Vera with their children, from left, Overton, Ellis, Lurena and Thomas (who is Cheadle’s great grandfather).

By Daniel Dunaief

In joining Cold Spring Harbor Laboratory, Lucas Cheadle has continued his professional and personal journey far from his birthplace in Ada, Oklahoma.

Then again, his travels, which included graduate work in New Haven at Yale University and, most recently, post doctoral research in Boston at Harvard Medical School, wasn’t nearly as arduous or life threatening as the forced trip his ancestors had to take.

In 1837, Cheadle’s great, great, great grandparents had to travel from Pontotoc, Mississippi to southern Indian Territory, which is now near Tishomingo, Oklahoma as a part of the Trail of Tears. Native American tribes, including members of Cheadle’s family who are Chickasaw, cleared out of their lands to make way for Caucasian settlers.

Lucas Cheadle

Proud of his biracial heritage, which includes Chickasaw, Choctaw, and Cherokee lineages, Cheadle hopes to make his mark professionally in his studies of the development of the brain (see article on page B). At the same time, he hopes to explore ways to encourage other members of the Chickasaw tribe to enter the fields of science, technology, engineering and mathematics.

One of three sons of a mixed Chickasaw father named Robert Cheadle and a Caucasian mother named Cheryl, Cheadle would eventually like to provide the kind of internship opportunities through his own lab that he had during his high school years.

Indeed, during the summer of his junior year, Cheadle did a health care internship, in which he shadowed different types of physicians. He watched active surgeries and observed a psychiatrist during patient visits. After that summer, Cheadle thought he might become a psychiatrist as well because he knew he was interested in the study of the brain.

Down the road, Cheadle envisions having one or two people learn as interns in the lab during the summer. Longer term, Cheadle hopes other investigators might also pitch in to provide additional scientific opportunities for more Native American high school students.

Growing up in Oklahoma, Cheadle never felt he stood out as a member of the Chickasaw tribe or as a biracial student.

His father, Robert, was active with the tribe, serving as a tribal judge and then as a legislative attorney for the Chickasaw. His grandfather, Overton Martin Cheadle, was a legislator.

Through their commitment to the Chickasaw, Cheadle felt a similar responsibility to give back to the tribe. “It was an incredibly important part of their professional lives and it was a passion” to help others, he said. “I’m driven by that spirit.”

His father took people in who had nowhere to go. In a few cases, people he put up robbed the family. Even after they robbed him, Cheadle’s father took them back. When Robert Cheadle died earlier this year, one of the people whom Cheadle supported helped out with his funeral arrangements.

Driven to accomplish his mission as a scientist, Lucas Cheadle feels he can reach out to help high school students and others interested in science during his research journey.

“The better I can do, the more I can help,” Cheadle said. He hopes to “open doors for other people.”

With some of these efforts to encourage STEM participation among Native Americans, Cheadle hopes to collaborate with John Herrington, a Chickasaw astronaut who took a Native American flute into space during one of his missions. “It would be wonderful to discuss this” with Herrington, “if he has time for me,” said Cheadle.

In modern times, the Chickasaw tribe has made “good strides” in being successful. One challenge to that success, however, is that it has included assimilation.“The main goal is to hold onto the heritage as much as we can,” said Cheadle.

As for now, he plans to honor his heritage in his lab by “working hard to create a safe, respectful environment where people’s unique backgrounds and characteristics are supported and embraced. I try to create a space where diversity can thrive.”

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Lucas Cheadle. Photo from CSHL

By Daniel Dunaief

One of the newest additions to Cold Spring Harbor Laboratory’s neuroscience program, Lucas Cheadle, who is an assistant professor, is exploring the early environmental factors at a molecular level that shape the neurological development of the mouse visual system.

While nature and nurture combine to produce the individuals each life form becomes, Cheadle is focused on the ways nurture, specifically, shapes the pathways in the brain that affect the development of sight.

Microglia are an unlikely player in this environmentally-triggered development, as doctors and researchers previously saw these cells primarily as participants in neurinflammation.

That is not the case anymore, with Cheadle and other scientists demonstrating over the past decade or so that microglia play important parts in the healthy brain. Cheadle, specifically, has demonstrated that these cells play a role in experience-dependent circuit development.

Indeed, the process of circuit refinement in the developing brain, which Cheadle describe as being among the “most complex structures in the known universe,” is akin to a room full of half-full boxes, which represent synaptic connections between neurons.

The brain begins with numerous little boxes that make the room difficult to navigate. As the brain consolidates the important items into a smaller number of larger boxes and removes the smaller boxes, the room becomes more manageable.

This is consistent with what Cheadle has seen during refinement. A smaller number of synapses become stronger and are maintained, while others are removed. This promotes the efficiency and precision of neural processing, he explained.

When the contents of some of those boxes disappear, however, the result can lead to neurodegenerative diseases like Alzheimer’s, in which a person struggles to find memories that may have been unwittingly cleared out.

Cheadle, who most recently was a post doctoral researcher at Harvard Medical School, is exploring the way microglia shape the connections between the eyes and the brain between when a mouse is born and when it reaches one month of age.

His work has shown that microglial cells are required for the sensory-dependent phase of visual circuit development. Disrupting signals between microglia and neurons affects synapse elimination, akin to removing the smaller boxes, which is important for circuit function.

Indeed, prior to work Cheadle and others have done in recent years with these cells in the brain, researchers thought microglia in the brain were quiescent, or inactive, after birth, except for their role in brain injury, disease pathology and neuroinflammation.

Until the first week of life, microglia engulf and then digest synaptic connections between some neurons, in a process called phagocytosis. During the sensory-dependent phase of refinement in the third week after birth, which Cheadle demonstrated in a paper published this month in the journal Neuron, microglia stop phagocytosis and rely on cytokines to break down synapses.

The cytokine pathway Cheadle discovered, called TWEAK, which is a ligand expressed by microglia, and Fn14, a receptor expressed by neurons, becomes active between eye opening, which is around two weeks, and peaks at about four weeks old.

When mice don’t have exposure to important visual stimuli during this critical period, the circuit has too many synaptic connections, which reduces the effectiveness of the developing visual system.

While Cheadle is working on visual development, specifically, he is interested in the broader implications of this work in the context of the environmental signals that affect the development of the brain.

In that broader context, the processes involved in autism and schizophrenia could reflect a period in which individuals have an overabundance of synapses that weren’t sufficiently pruned and refined.

Despite the fact that researchers hypothesized that synaptic pruning may lead to these disorders decades ago, they still have a limited awareness of whether and how this might happen. Studying the way microglia contribute to healthy circuit development could provide important clues about these processes.

Some epidemiological evidence points to the linkage between immune activity and neurodevelopmental disorders. In 1918 and 1919, during the Spanish Flu pandemic, children born during that period had a higher incidence of an autism or schizophrenia later in life.

Other evidence shows an interaction between immune activation and neurodevelopmental dysfunction, including the genetic loci associated with such disorders and increased inflammatory markers in the blood and brains of people with such disorders. “There’s really no question that there is a link,” Cheadle explained. “The nature of the link is still poorly understood.”

While earlier epidemiological data raises questions about the current pandemic, it doesn’t provide a definitive answer because “we still don’t quite understand what the nuanced molecular factors are that link the immune activation to the increase in disease prevalence,” Cheadle suggested.

“There’s a real chance that having COVID during pregnancy may impact the development of the offsprings’ nervous systems as has been seen in other infections,” Cheadle wrote. “While it is not the current priority of COVID research, it certainly warrants studying.”

Cheadle hopes to understand the “underlying principals of disorders” he said.

A resident of Huntington, Cheadle lives five minutes from the lab. He plans to rent for now because he didn’t want to start a new lab and move into a new house at the same time.

Cheadle has hired a technician and is in the process of hiring another. A post doctoral scientist will join his lab in November.

Early on in his life, Cheadle said he was fascinated with the interface between the world and biology. He wanted to understand how human brains interpret the information that comes from our senses. Everything culminated, professionally, in his interest in neurobiological mechanisms.

Currently, Cheadle is also interested in the looming behavior of mice. In the field, when mice see a bird that is flying slowly overhead, they are more likely to make a mad dash for safety, running into weeds or for cover from a tree. When the bird, however, is flying too rapidly, the mice freeze.

“I’m intrigued to find out whether the dichotomy of fight or flight could be shifted by the function of microglia,” he said. “I like to understand something at a functional level and dissect it to a molecular level.”

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