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Daniel Dunaief

Freddie Freeman of the Atlanta Braves. Wikipedia photo

By Daniel Dunaief

Daniel Dunaief

Before I get to the current difficulty of deciding which of the four remaining baseball teams to support, if any, I’d like to offer the following observations on a bipolar Yankees season, in which a 13-game winning stream seemed as unlikely as a 70 loss season.

The team had the talent, sort of. They are, as the saying goes, what their record says they are. In many ways, it’s remarkable that they even made the one-game wildcard playoff. They weren’t exactly world beaters against the Baltimore Orioles, who almost single handedly made it possible for the other four teams in the division to finish with over 90 wins.

They also gave away games that they seemed a lock to win, coughing up leads late, and losing key games to a Mets team that struggled to find its identity and mojo after the best pitcher on the planet, Jacob deGrom, was injured.

But this isn’t about the Mets. So, for what it’s worth, here are my Yankees thoughts. Stop worrying about how much money you’re paying players. Go with the players that helped you win. That means, if defensively-gifted shortstop Andrew Velazquez played a key role in big games with his range and defense, give him a chance.

If that also means Greg Allen needs a few at bats and a chance to race around the bases, give him a shot, too. Oh, and Tyler Wade? I know he’s not going to hit 400-foot home runs too often, but he is a versatile gamer with an ability to play numerous positions and, on occasion, to have a high contact hot streak.

Stock photo

If I were managing my favorite team, I’d stick with whatever is working and not try to race injured and under performing players back. Sure, Gleyber Torres and Gio Urshela have been valuable pieces in the past, but that’s not a reason to put them back on the field in the hopes that they’ll be something they weren’t before each of them got injured.

As for the current playoff conundrum, what should Yankees fans who are still paying attention to baseball root for during the last three series?

Come on, it’s almost impossible to root for the Red Sox because, well, they’re the Red Sox. Then again, the Astros are not just a baseball villain, but are also Yankee killers. Jose Altuve, who used to be a beloved versoin of the little engine that could, hits a huge home run in 2019 off of Aroldis Chapman then covers up his uniform so no one can rip it off and show a tattoo he didn’t like? Yeah, I’m sure that’s what happened because these players are so modest about their body ink.

One of those two teams will represent the American League in the World Series. If I had to choose one, I think, gulp, I’d go with the Red Sox. Part of the reason for that is that I have so many friends and professional colleagues who love the team that I’d be happy for them.

In the National League, the Braves are a feel good team. I saw Freddie Freeman at the All Star Game a few years ago and he seemed like a genuinely good father. I know that’s not a critical criteria for rooting for someone, but he held his kids and smiled at almost anyone who talked to him.

The Dodgers are the beasts of baseball in the last few years. Just when you think they couldn’t get any better, they add Max Scherzer (seriously?) and Trea Turner, two incredible deadline acquisitions for a team that was already a powerhouse. Mookie Betts is otherworldly in one way or another, with his speed, incredible and accurate arm and his ability to put the ball in play and, at times, over the wall.

I’m going to root for the underdog in the national league here, pulling for the Braves to make a Cinderella journey into the World Series and beat the deep and talented Dodgers.

Now, if I get my way and it’s the Braves against the Red Sox? I’m going to root for the Braves because it’s still the Red Sox. No matter who wins, though, I’m hoping for a seven-game series because that’s good for baseball and for the baseball fan. I know the season is long enough, but those last few games are like the final number in a Broadway musical. The energy is high, the fans are on their feet, and no one wants to leave.

David Thanassi. Photo by Jeanne Neville
*Please note: This article was updated on Oct. 15 to include a reference to former President Bill Clinton (D) in the fifth paragraph.

By Daniel Dunaief

David Thanassi wants to give dangerous bacteria in the kidney a haircut.

No, not exactly, but Thanassi, Zhang Family Professor and Chair of the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University, has studied how hair-like structures called P pili in the bacteria Escherichia coli are assembled on the bacterial surface. 

These pili allow bacteria to hang on to the walls of the kidney, where urine would otherwise flush them out.

Learning about pili at different stages of development could provide a way to keep them from attaching themselves to the kidney and from entering the bloodstream, which could lead to the potentially lethal problem of bacterial sepsis. Indeed, this week, former President Bill Clinton (D) checked into the intensive care unit at the University of California Irvine Medical Center after a urinary tract infection spread to his bloodstream.

“We have been looking at this as a really important aspect of initiating infection from a bacteria’s point of view,” Thanassi said. “How do they build these structures” that lead to infection and illness?

Recently, Thanassi published the structure of these pili in the journal Nature Communication.

The current work builds on previous efforts from Thanassi to determine the structure of these pili in the bladder. He has been exploring how the thousands of proteins that make up the pili get transported and assembled in the correct order. “If we can understand that aspect, we can disrupt their assembly or function,” he said.

Urinary tract infections are a major infectious disease, particularly for women. Indeed, about half of all women will have at least one urinary tract infection, which can be uncomfortable and can require some form of medication. 

In some cases, the infections can be recurrent, leading to frequent infections and the repeated need for antibiotics.

The bacteria that cause these infections can become resistant to antibiotics, increasing the importance of finding alternative approaches to these infections, such as interfering with pili.

To be sure, the solution to reducing the bacteria’s ability to colonize the kidney or urinary tract would likely require other steps, as these invaders have additional ways beyond the pili to colonize these organs. Nonetheless, disrupting the way they adhere to the kidney could be a constructive advance that could lead to improved infection prevention and treatment.

One likely strategy could involve using an anti-pilus treatment in combination with other antibiotics, Thanassi explained.

For people who have recurrent infections, anti-pilus therapeutics could offer a solution without resorting to long-term antibiotics.

In his lab, Thanassi is interested in small molecules or chemicals that would disrupt the early stage in pili assembly. “We think of these as protein-protein interactions that are required to build these” pili, he said.

By using a fluorescence reporter, Thanassi and his colleagues can screen libraries of chemicals to determine what might inhibit the process.

As with many biological systems, numerous compounds may seem appropriate for the job, but might not work, as medicine often requires a specific molecule that functions within the context of the dynamic of a living system.

For the helpful bacteria in the gut, pili are not as important as they are for the harmful ones in the kidney, which could mean that an approach that blocked the formation of these structures may not have the same intestinal and stomach side effects as some antibiotics.

To determine the way these pili develop structurally, Thanassi and his lab used molecular and biochemical techniques to stop the assembly of pili at specific stages.

Bacteria assemble these pili during the course of about 30 minutes. An usher proteins serves as the pilus assembly site and pilus secretion channel in the bacterial outer membrane. The usher acts as a nanomachine, putting the pilus proteins into their proper order. A chaperone protein brings the pilus subunits to the usher protein.

In their development, the pili require a protein channel, which is an assembly site.

Thanassi started by working on the usher protein in isolation. The usher proteins function to assemble the thousands of pilus subunits that make up each pilus fiber. The process also involves chaperone proteins, which bind to nascent subunit proteins and help the subunits fold. The chaperone then delivers the subunit proteins to the usher for assembly into the pilus fiber. He used molecular and biochemical methods to express and purify the usher protein.

The assembly process involves interactions between chaperone-subunit complexes and the usher. Over the years, Thanassi has determined how the different proteins work together to build and secrete a pilus.

He was able to force the bacteria to express only one version of the assembly step and then isolate that developmental process.

The majority of the pilus is like a spring or a coil, which can stretch and become longer and straighter to act as a shock absorber, allowing the bacteria to grab on to the kidney cells rather than breaking.

Other researchers are studying how they might make the pili more brittle, preventing that spring-like action from working and compromising its ability to function.

“We’re trying to prevent the pili from assembling in the first place,” Thanassi explained. “Our approach is to try and get molecules that prevent the interaction from occurring.” He is looking at the specific function of one molecule that prevents the usher assembly platform from developing properly, which would wipe out the assembly site.

Thanassi credits former Stony Brook Professor Huilin Li, who is now Chair in the Department of Structural Biology at the Van Andel Institute in Grand Rapids, Michigan, with providing structural insights from his work with the cryo-electron microscoipe. The technology has “revolutionized the work we do,” said Thanassi.

Residents of Smithtown, Thanassi and his wife Kate Kaming, who is Senior Director of Cancer Development at Northwell Health Foundation, have two children. Joseph, 22, attends Northeastern University. Miles, 20, is studying at the Massachusetts Institute of Technology.

Thanassi grew up in South Burlington, Vermont and is an avid skier. He also enjoys mountain biking, walking and music.

Thanassi hopes this latest structural work may one day offer help either with the prevention of infections or with their treatment.

Pixabay photo

By Daniel Dunaief

Daniel Dunaief

What do you name after the man who’s already named everything after himself?

That is the question people will grapple with when they consider how to deploy the name of the 45th president.

Did you know, apart from edifices and casinos, the Trump name has been added to a species of small moth with yellowish-white scales on its head, called the Neopalpa donaltrumpi? Additionally, a sea urchin fossil is called Tetragramma donaldtrumpi.

What should be in the running to honor the legacy of a man who may extend his presidential legacy in 2024?

Here are a few suggestions that, hopefully, will delight and alienate people on both sides of the aisle equally.

— A pizza slicer. Called the Trump, this great divider will cut a pie into two pieces, elevating the one on the right while crushing the one on the left into a mess of tomato sauce and crumbled cheese that wants to tax the rich.

— A board game. With a rotating cast of characters, the object of the Trump Cabinet Shuffle will be for each player to hold onto as many cabinet members for as long as possible, even as many of them either want to leave or write books about their experience.

— A remote control. The former president clearly found TV a relevant and important medium. People around the country could search their couches for the “Trump,” so they can change the channel to watch Fox News, which will provide the names for the Trump Cabinet Shuffle.

— The Trump label maker. Borrowing from an episode of “Seinfeld,” people could develop a label maker named after someone who was fond of naming people and objects. The Trump label maker would default to the most common words in the Trump vernacular, including “disgrace,” “beautiful,” and “fake.”

— A fast-food franchise. Given the former president’s predilection for the fast food he served to college football players, it’s surprising no one has come up with Trump World Burgers. Each restaurant could have a game of darts, where patrons could sling darts at the faces or names of their least favorite democrats. Every wall would have a TV tuned to Fox News and every place setting would sit on top of the New York Post.

—A magic wand. Can’t you picture it? Let’s get out the Trump wand and make everything unpleasant — impeachments, investigations, and distasteful stories- disappear.

— A fertilizer company. Yeah, okay, this might seem especially harsh, but fertilizer, while it’s made from feces, is necessary for the growth of many of the foods we eat, whether we’re vegetarians and eat only greens, or carnivores and eat the meat that eats the greens.

— Oversized boxing gloves. With pictures of the former president on each hand, a boxer could put his small, medium or large hands into red Trumps to fight against the forces of evil.

— An especially tall straw pole next to a smaller pole. The taller Trump pole could show how, even at a distance, he’s leading his closest competitor. “Trump is always ahead at the polls.”

— A distorted mirror. Like the side view mirrors on cars, these Trump mirrors could accent certain features while minimizing others, creating whatever reality the viewer prefers.

— Stiff-legged pants. With material that stiffens during the playing of the National Anthem, the Trump pants would make it impossible to kneel.

— A huggable flag. Given his preference for hugging flags, someone should design a flag with arms that hug back, as in, “the Trump flag is ready for its hug.”

— A “yes” puppy. You know how people have little puppies whose heads pop up and down when you touch them on their dashboard? Someone could add a sound effect to that, like “yes, yes, yes, yes,” each time the Trump head moved.

Pixabay photo

By Daniel Dunaief

Daniel Dunaief

This time of year, my dog walks with relief and trepidation.

The relief comes from temperatures that have cooled off enough that his heavy fur doesn’t exacerbate the humidity and discomfort from stifling heat.

The trepidation arises out of the emergence of ominous additions to the neighborhood that change the world he knows.

The spiderwebs along fences and hanging on bushes and trees don’t bother him, but the ghosts planted in the ground, the green glow-in-the-dark skeletons and the hanging vampires terrify him, as he prefers to scamper toward the street and passing cars rather than walk near an inexplicable figure swaying in the wind, hovering over him like some supernatural predator.

And so it was, recently, that we took an early October walk through our neighborhood.

While these figures create anxiety for him, I was mulling the numerous global threats to the future for which we Americans and we humans are grappling. Global warming, debt limits, infrastructure bills, gun violence, the pandemic, partisanship, educational deficiencies, a destructive oil spill in California and everything else ricocheted around my head as I thought of the many looming crises.

A sight on the horizon snapped me out of my anxiety labyrinth. There, around the corner, appeared to be roadkill.

In the distance, I couldn’t recognize it, but I was sure that, once we got closer, my dog would pull desperately to inspect the flesh and innards of a former living creature.

Generally, when I try to pull away from decaying matter on the road, my dog seems eager to get as close as he can, like a forensic photographer or a police inspector from Law & Order, trying to figure out who might be at fault for the end of a life, whether the driver tried to maneuver away from the animal based on any skid marks nearby, or, perhaps, whether the animal contributed to its own untimely end.

I try to distract him, whistling, calling his name, tugging ever so slightly on his leash to redirect him away from these sites, hoping to keep far enough away that the flies feasting on rotting animal flesh don’t land on us.

Usually, such maneuvers have the same effect as making suggestions to my kids about what to do, like studying the bassoon because every band needs a bassoon player and many schools are lucky to have one or two such double-reeded wonders: they cause an equal and opposite reaction.

I’m sure Newton’s third law wasn’t referring to parenting, but it seems that when we say “here” they want to go “there,” and when we say “there,” they want to go “here.” My dog seems to have studied the same playbook in response to any such guidance or direction.

As we walked, I pulled left, trying to figure out what was on the road, which seemed broken into four parts. This could be a particularly unappealing mess, I thought, trying not to make a subconscious suggestion through the leash that he head straight for it.

I held my breath as a slight wind picked up from the other side of the detritus, hoping I wouldn’t smell something awful and that, somehow, neither would my dog.

As we got closer, I used my peripheral vision. That’s when I noticed something unusual. Amid the odd red and brown colors was a mixture of an orange and blue mess. What kind of animal’s innards are orange and blue? Was this a Halloween roadkill? 

I deciphered letters on the ground. That was definitely not blood. It was a Burger King wrapper, with obliterated fries, a flattened Whopper and a crushed cup.

Perhaps too focused on the Halloween decorations, the dog wasn’t at all interested or enticed by the fast food roadkill.

A TRACER site similar to this one in Argentina is being constructed in Pearland, Texas. Photo courtesy of ARM

By Daniel Dunaief

Before they could look to the skies to figure out how aerosols affected rainclouds and storms around Houston, they had to be sure of the safety of the environment on the ground.

Researchers from several institutions, including Brookhaven National Laboratory, originally planned to begin collecting data that could one day improve weather and even climate models on April 15th of this year.

The pandemic, however, altered that plan twice, with the new start date for the one-year, intensive cloud, study called TRACER, for Tracking Aerosol Convection Interactions, beginning on Oct. 1st.

The delay meant that the “intensive observational period was moved from summer 2021 to summer 2022,” Michael Jensen, the Principal Investigator on Tracer and a meteorologist at Brookhaven National Laboratory, explained in an email.

Scientists and ARM staff pose during planning for TRACER (left to right): Iosif “Andrei” Lindenmaier, ARM’s radar systems engineering lead; James Flynn, University of Houston; Michael Jensen, TRACER’s principal investigator from Brookhaven National Laboratory; Stephen Springston, ARM’s Aerosol Observing System lead mentor (formerly Brookhaven Lab, now retired); Chongai Kuang, Brookhaven Lab; and Heath Powers, site manager for the ARM Mobile Facility that will collect measurements during TRACER. (Courtesy of ARM)

At the same time, the extension enabled a broader scientific scope, adding more measurements for the description of aerosol lifecycle and aerosol regional variability. It also allowed the researchers to include air quality data, funded by the National Aeronautics and Space Administration and urban meteorology, funded by the National Science Foundation.

The primary motivation for the project is to “understand how aerosols impact storms,” Jensen explained in a presentation designed to introduce the TRACER project to the public.

Some scientists believe aerosols, which are tiny particles that can occur naturally from trees, dust and other sources or from man-made activities like the burning of fossil fuels, can make storms stronger and larger, causing more rain.

“There’s a lot of debate in the literature” about the link between aerosols and storms, Jensen said.

Indeed, there may be a “sweet spot” in which a certain number or concentration of aerosols causes an invigoration of rainstorms, while a super abundance beyond that number reverses the trend, Jensen added.

“We don’t know the answers to those questions,” the BNL scientist said. “That’s why we need to go out there and take detailed measurements of what’s going on inside clouds, how precipitation particles are freezing or melting.”

Even though aerosols are invisible to the naked eye, they could have significant impacts on how mass and energy are distributed in clouds, as well as on broader atmospheric processes that affect weather patterns.

The TRACER study, which is a part of the Department of Energy’s Atmospheric Radiation Measurement, or ARM, user facility, could “help forecast heavy rains that can cause flash flooding,’ said Chongai Kuang, atmospheric scientist and TRACER co-investigator at BNL.

The TRACER study will explore the way sea and bay breeze circulations affect the evolution of deep convective storms as well as examining the influence of urban environments on clouds and precipitation.

Several additional funding agencies have stepped in to address basic scientific questions, including the National Aeronautics and Space Administration’s efforts to address air quality issues in Houston and the Texas Commission on Environmental Quality, which funded a study on ozone and low-level atmospheric mixing.

“Our original TRACER field campaign provided a seed for what is now a major, multi-agency field campaign with a significantly expanded scientific scope,” Jensen explained in an email.

A joint team from BNL and Stony Brook University is developing new software to scan the precipitation radar system to select and track storm clouds to observe the rapid development of these storms. Additionally, aerosol instrumentation will help provide updated information on the precursor gases and the smallest aerosol particles at the earliest stages of the aerosol cycle, Jensen explained.

Ultimately, the data that these scientists gather could improve the ability to forecast storms in a range of areas, including on Long Island.

“Understanding sea breezes and the coastal environment is a very important aspect of TRACER,” Jensen said. “Even though it’s not the preliminary focus, there’s an opportunity to learn new science, to improve weather forecasting and storm forecasting for those coastal environments.”

Researchers chose Houston because of their desire to study a more densely populated urban area and to understand the way numerous factors influence developing clouds, weather patterns and, ultimately, the climate.

“We know the urban environment is where most people live,” Jensen said. “This is taking us in new directions, with new opportunities to influence the science” in these cities.

Researchers plan to collect information about clouds, aerosols and storms everywhere from ground-based instruments stationed at four fixed sites, as well as through mobile facilities, to satellite images.

The program operates a tethered balloon which is “like a big blimp that goes up half a mile into the atmosphere,” said Heath Powers, the Atmospheric Radiation Measurement facility site manager for Tracer from Los Alamos National Laboratory.

The tethered balloon is located at Smith Point, Texas, on the eastern shore of Galveston Bay and will do low-level profiling of aerosols, winds, thermodynamics and ozone as it is influenced by bay breeze circulation, Jensen explained.

The National Science Foundation is planning to bring a C-130 plane to conduct overflights, while the group will also likely use drones, Powers added.

The TRACER study will launch around 1,500 weather balloons to gather information at different altitudes. The research will use over four dozen instruments to analyze meteorology, the amount of energy in the atmosphere and the air chemistry.

“Clouds are the big question,” Powers said. “Where they form, why they form … do they rain or not rain. We are well-positioned to get at the core of a lot of this” through the information these scientists gather.

Dave Tuveson. Photo by Gina Motisi/CSHL

By Daniel Dunaief

While one bad apple might spoil the bunch, the same might be true of one bad cancer gene.

Cold Spring Harbor Laboratory’s Cancer Director Dave Tuveson and Derek Cheng, who earned his PhD from Stony Brook University while conducting research in Tuveson’s lab, recently explored how some mutant forms of genes in pancreatic cancer can involve other proteins that also promote cancer.

A gene well-researched in Tuveson’s lab, mutated KRAS promotes cell division. Mutant versions of this gene continue to produce copies of themselves, contributing to cancer.

Derek Cheng

Turning off or blocking this gene, however, doesn’t solve the problem, at least not in the laboratory models that track a cancer cell’s response.

In laboratory models of pancreatic cancer, a disease for which the prognosis is often challenging, other proteins play a role, creating what researchers call an “adaptive resistance” to chemotherapy.

In a paper published in the journal Proceedings of the National Academy of Sciences, Cheng, who is the first author and is currently in his final year of medical school at the Stony Brook Renaissance School of Medicine, and Tuveson showed that a protein called RSK1 interacts at the membrane with mutated KRAS. When KRAS is inhibited, the RSK1 protein, which normally keeps RAS proteins dormant, becomes more active.

“If you antagonize KRAS, you would get a rebound” as the cancer cells develop a resistance to the original drug, Tuveson said. “We found a feedback loop.”

The research “focused on identifying protein complexes with oncogenic KRAS that would potentially be relevant in pancreatic cancer,” Cheng explained in an email. “My work suggests that an RSK1/NF1 complex exists in the vicinity of oncogenic KRAS.”

While Cheng was able to show that the role of membrane-localized RSK1 provided negative regulation of wild-type RAS, it “remains to be studied what the role of the RSK1 at the membrane [is] in the context of oncogenic KRAS.”

KRAS is a molecular switch that turns on and off with the help of other proteins. With certain mutations, the switch doesn’t turn off, continuing to signal for copying and dividing, which are hallmarks of cancer cells. With specific activating mutations, the switch can lose its ability to turn off and constitutively signal for proliferation, metabolic reprogramming, and other behaviors characteristic of cancer cells, Cheng explained.

A cell with an oncogenic KRAS has the tendency to be more fit than a normal cell without one. Such cells will likely grow at a faster rate under stressful conditions, which, over time, can enable them to outcompete normal cells, Cheng continued.

When KRAS is in an oncogenic state, another protein, called RSK1 is hanging around the membrane. RSK1 has several functions and can participate in numerous cellular signaling pathways.

KRAS cytoplasm

While RSK1 is involved in protein translation by phosphorylating S6 kinase, it also has other functions at the plasma membrane, where it shuts down wild type RAS proteins.

Other researchers have suggested a negative feedback for RSK1 and NF1.

“Our contribution demonstrated some relevance of this interaction in pancreatic cancer cells,” Cheng explained in an email.

Cheng said RSK is known to have various effects, depending on the context. In the paper, the scientists showed that RSK has a “negative feedback properties, such as that, upon the removal of mutant KRAS, it has this negative regulatory role.”

Graduate student Sun Kim and post doctoral researchers Hsiu-Chi Ting and Jonathan Kastan are currently exploring whether RSK has a pro-oncogenic function on the membrane in the tumor cell.

So far, these studies suggest that while a direct inhibitor against oncogenic KRAS would likely be the greatest target for an effective therapy, cancer cells may still be able to use signals from other RAS isoforms.

“A combination of targeting KRAS and modulating regulators of RAS such as RSK1/NF1 and SOS1 may enhance therapeutic efficacy,” Cheng suggested.

Cheng is grateful for the opportunity to learn from numerous Tuveson lab members on ways cancer cells differ from healthy cells.

The discovery of the potential roles of RSK1 in cancer provides some possible explanation for the potential resistance mechanisms of mutant KRAS inhibitors.

While he was encouraged that a prestigious journal published the research, Tuveson said he hopes this type of observation “will lead to something that will be useful for a pancreatic cancer patient and not just” provide compelling ideas.

Cheng attended medical school for two years before joining Tuveon’s lab for the next six years.

Cheng defended his thesis in 2020 during the pandemic on a zoom call.

“I was one of the first people to defend with this format for both CSHL and SBU,” Cheng explained. “I was able to invite many friends and family that probably would not have been able to make the trip.”

Cheng’s family has battled cancer, which contributed to his research interests.

When he was an undergraduate, he had an uncle develop glioblastoma, while another uncle and his grandfather developed colon cancer.

“I knew I wasn’t going to be able to do much about their medical condition, but I wanted to work on something that people cared about,” Cheng explained.

Outside of the lab, Cheng enjoys working on his car and his motorcycles. He feels a sense of autonomy working on his own projects.

He’s most proud of a motorcycle for which he rebuilt the front end with parts from another model to outfit a larger brake system.

A native of St. Louis, Cheng is a fan of the hockey team, the Blues. He owns a game-worn jersey from almost every member of the 2019 cinderella team that won the Stanley cup, with some of those jerseys coming from Stanley Cup final games.

Cheng plans to apply to residency in internal medicine this year because he wants to continue applying what he learned in his scientific and medical training.

The clinical work reminds him to treat patients and not just the tumors, while scientific research trained him to loo at evidence and literature carefully to find clinical gaps, he explained.

Pixabay photo

By Daniel Dunaief

Daniel Dunaief

If you’ve ever watched the show “The Voice,” which teenage sensation Carter Rubin from Shoreham won last year, you know the format involves celebrity judges making blind choices during a prolonged audition process.

With their backs to the performers, the judges listen to the contestants sing several bars of familiar songs, sometimes swaying, sometimes mouthing the words, until they hear something in the voices that clicks or that they think they can improve to lead these aspiring artists to the promised land of a music contract, fame and fortune.

The process is imperfect, as are most decisions we make.

The judges don’t get to rate everyone, listening to the entire array of singers before rank ordering or assembling their team. As they go, they add aspiring musicians to their teams, competing against the other judges to encourage performers to work with them.

This process is akin to so many others in so many contexts.

Many years ago, I attended a spectacular and extravagant holiday party for Bloomberg News at the Museum of Natural History. The organization had rented the entire museum during after hours. Fortunately, I brought my then-girlfriend, who is now my wife, to that event, which has given us a party to remember over two decades later.

Anyway, each room had a performer and a collection of tables with mouth-watering food. Hungry and maneuvering slowly through each room, we probably ate more than we should have in the first few rooms, until we understood the spectacular assortment of foods, culminating with sushi under the blue whale in the main room.

Pixabay photo

Having eaten more than I should prior to reaching the whale, I could only sample a few pieces of sushi before shutting down the food consumption. Well, that was true until we waited for the one person in the coatroom who was matching tickets to coats. At that point, servers brought trays of dark and white chocolate-covered strawberries up and down the line.

The point, however, is that the imperfect choices my wife and I made earlier in the evening affected how much we could eat as the night wore on.

In the last few months, I spoke with several researchers in Stony Brook University’s Department of Geosciences, including Joel Hurowitz and Scott McLennan. They are working with a rover on Mars that is choosing rocks in the Jezero crater, putting together a collection of samples that will, one day, return with a round trip mission to the Red Planet.

They can’t sample every rock that might reveal something about Mars, indicating whether life could have existed on the planet billions of years ago.

The decision to choose something in the present, like the rock in front of the rover on Mars, the current singer who is living out his or her dream on “The Voice,” or the morsel of food in a buffet that stretches throughout a museum, can limit the ones those same people have in the future.

Hopefully, along the way, we learn from the decisions we’ve made, the ones that work out and the ones that don’t, that enable us to improve our ability to make informed choices.

And, even if whatever we chose may not be exactly what we thought it was, we, like the judges on “The Voice,” might be able to mold the raw materials of our lives into something even better than we’d initially imagined.

Semir Beyaz (center) with research assistant Onur Eskiocak, left, and graduate student Ilgin Ergin. Photo by Gina Motisi/CSHL

By Daniel Dunaief

High fat diets present numerous health problems for humans and mice, which are often used as a model organism to understand disease.

In a recent multi-disciplinary study with mice, Cold Spring Harbor Laboratory Fellow Semir Beyaz and 32 colleagues from 15 other institutions explored how a high fat diet affects the development of intestinal tumors.

Semir Beyaz. Photo by Gina Motisi/CSHL

The diverse team of scientists brought together a range of expertise to discover the way a high fat diet disrupts the cross talk among the microbiome, stem cells and immune cells, triggering tumors through the reduction in the expression of an important gene, called major histocompatibility complex II, or MSC-II.

“This work nicely integrates efforts in stem cell biology, immunology, microbiology and metabolism in the context of understanding how diet is linked to cancer,” Beyaz explained in an email. With such interdisciplinary studies, “we hope to improve our understanding” of the mechanisms that link nutrition to diseases.

The paper, published in Cell Stem Cell, for which Beyaz is the first and corresponding author, shows how a high fat diet leads to immune evasion of tumor initiation stem cells due to the suppression of the immune recognition molecule MHC-II.

At the center of this study, the MHC-II gene encodes a protein that presents antigens, or foreign substances, to the immune system. When a cell is infected or cancerous, immune cells detect the unwelcome agents through their surveillance of MHC molecules, Beyaz said.

A high fat diet also results in the alteration of immune cells in the micro environment and the signals that they produce, called cytokines.

“The novel finding of our study is that the crosstalk between stem cells, microbes and immune cells is critical for eliminating tumor initiating cells and this cross talk is dampened in response to a high fat diet, demonstrating a mechanistic basis for how high fat diets may promote cancer,” said Beyaz.

A current hypothesis, which has some supporting evidence in Beyaz’s study, suggests that diet-related factors might facilitate early onset colorectal cancer.

To be sure, researchers need to conduct more work to understand the environmental factors that facilitate early onset colorectal cancer, Beyaz explained. “The knowledge of what causes early onset colorectal cancer in young adults is very limited,” he added.

Semir Beyaz with visiting clinical researcher Aaron Nizam (left) and research tech Katherine Papciak. Photo by Gina Motisi/CSHL

Beyaz believes diet is one of the most important environmental factors that contribute to cancer risk. Diet could affect sleep, stress and other factors.

“There are so many things we don’t know about how diet affects our body,” he said. “That’s why I’m very excited to work on understanding these mechanisms.”

Beyaz said the mice in his study consumed a lard-based pro-obesity diet that was high in carbohydrates.

A diet that is lower in carbohydrates and higher in fat is more similar to a ketogenic diet, which could have other outcomes. His ongoing studies are trying to tease apart some of these differences.

To counteract the effect of diet on the development of cancer, Beyaz plans to activate the altered pathways by using either microbes or small molecule drugs.

“We believe if we promote immune surveillance by activating these pathways, we can elicit preventative and therapeutic strategies against cancer,” he explained.

Additionally, in his ongoing research, Beyaz plans to address numerous other questions that link diet to disease.

An increasing number of studies are exploring how diet and microbes affect cancer, which he described as a “hot topic.”

Beyaz believes a high fat diet might turn on or off some genetic sequences, enabling the latent development of cancer.

His unique niche involves searching for a connection between diet and perturbations that affect cross talk among cells. While this field has numerous challenges, Beyaz suggested he was “drawn” to that difficulty.

Beyaz’s expertise is in stem cell biology and immunology. He appreciates and enjoys the opportunity to interact with researchers from other disciplines that could lead to actionable progress.

Hannah Meyer. Photo from CSHL

While science has to be reductionistic and focused on one molecule or cells at times, new conceptual and technical advances have made it possible for the lines between disciplines in biology to disappear slowly, he explained.

Beyaz and his colleagues are looking forward to taking some of the next steps in this effort.

For starters, he is excited to expand this study, to understand whether there is a threshold for a high fat diet that favors the growth of tumors. Diets that fall below a potential threshold might not promote the growth or development of tumors.

Such a threshold could become clinically relevant, providing health care workers with a pre-cancerous marker that could signal the need for lifestyle changes and medical vigilance that could stave off or avoid the formation of disease-bearing and life-threatening tumors.

“We have some ongoing work to delineate such thresholds and proxies,” Beyaz said. Additionally, they would like to see whether this effect is reversible, to determine whether an altered microbiome might promote the expression of MHC-II, which could derail the tumor forming process.

Pawan Kumar. Photo from SBU

Beyaz’s collaborators on this work include Hannah Meyer, who is a fellow at Cold Spring Harbor Laboratory Fellow, and Pawan Kumar, who is an Assistant Professor in the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University.

In his life outside the lab, Beyaz, who enjoys fishing, gardening, and hiking, avoids excessive sugar and fat consumption. He doesn’t eat fast food or consume sugary drinks.

Originally from the town of Samandag which is near the Mediterranean Sea in the southeastern part of Turkey, Beyaz enjoys cooking and is fond of making lamb, beef, chicken and eggplant kebabs.

When he was growing up, Beyaz said science was a passion for him.

“It is not a job or a career,” he explained. “It is the way I find meaning in life, by learning how to ask and (sometimes) answer questions at the edge of cumulative human knowledge.”

Pixabay photo

By Daniel Dunaief

Daniel Dunaief

In a fractured and uncertain world, the skill sets that make us marketable to potential friends, employers and neighbors have shifted.

Sure, competence, professionalism and experience can and do come in handy in the context of numerous environments. These days, though, getting along with others and navigating through the cacophony of frustration beamed into our living rooms and phones on an hourly basis seems to have elevated what otherwise might seem like trivial skill sets in another time.

I have come up with a list of skills or, perhaps more appropriately, qualities that might be helpful in the modern world.

I don’t overuse the word “literally.” To emphasize a point, people often literally throw the word “literally” into phrases, as in “I literally hate tofu.” I’m not sure you can figuratively hate tofu, but I don’t overuse that word.

I keep a straight face: even when confronted with outrageous claims in which others hold fast to ideas, to heroes or to patterns I find questionable or even objectionable, I don’t wince, roll my eyes or shout them down until I’m in the safe space of my home with my wife.

I know how to write a handwritten note. Electronic communication has become so ubiquitous that sharing a personal touch that comes from writing something by hand has scarcity value.

I have trained my dog to do exactly what he wants. Sure, other people have trained their dogs to sit, roll over, fetch the newspaper and come to them when they call, but my dog does exactly what he wants. That means when he wags at me, he’s genuinely excited to see me and he’s not just wagging because he’s expecting some immediate reward or punishment.

I can find almost anything in a supermarket. Having spent an embarrassing amount of time searching the supermarket for foods that satisfy four diets and that take the place of in-person dining and social interactions, I can find most items sooner than supermarket employees.  

Through a hard-target search of every bed sheet, blanket and pillowcase, I can find the remote control. While that may seem trivial, it shows a willingness to go the extra mile to avoid having to take a few extra steps to change the channel.

I speak teenager. Yes, they are wonderful people who not only have a shorthand way of speaking, but also have a tendency to multitask while they are talking, looking at their phones or speaking through a mouthful of food. I can interpret much of what they say even when they appear to be offering disconnected sounds in a guttural and frustrated language.

I can finish an entire chapter in a non James Patterson book without checking email or texts. That means I can concentrate for longer periods of time. Patterson is excluded because the chapters in his violent novels are often shorter than this column.

I can make myself laugh. Every week, I enter the New Yorker cartoon contest. The captions I write never win, but they make me laugh.

I have a wealth of untapped ideas. I look at all the masks around me and think, “Hmm, I could come up with so many new mask products.” For example, how about mood masks, which change color depending on the person’s mood? Or, perhaps, masks with the outline of states, presidents of the United States, or images of abolitionists, important women in history or slogans? Masks could become the equivalent of educational posters hung on the walls of classrooms or, if you prefer, facial bumper stickers, giving someone starting at our covered mouths a chance to read or see something new.

Ellen Pikitch. Photo from Stony Brook University

By Daniel Dunaief

Preserving the oceans of the world will take more than putting labels on sensitive areas or agreeing on an overall figure for how much area needs protection.

It will require consistent definitions, guidelines and enforcement across regions and a willingness to commit to common goals.

A group of 42 scientists including Ellen Pikitch, Endowed Professor of Ocean Conservation Sciences at the School of Marine and Atmospheric Sciences at Stony Brook University, recently published a new framework developed over more than 10 years in the journal Science to understand, plan, establish, evaluate and monitor ocean protection in Marine Protected Areas (MPAs).

“We’ve had MPAs for a long time,” said Pikitch. Some of them are not actively managed, with activities that aren’t allowed, such as fishing or mining, going on in them. “They may not be strongly set up in the first place to protect biodiversity. What this paper does is that it introduces a terminology with a lot of detail on when an MPA qualifies to be at a certain level of establishment and protection.”

These scientists, who work at 38 institutions around the world, created an approach that uses seven factors to derive four designations: fully protected, highly protected, lightly protected, and minimally protected.

If a site includes any mining at all, it is no longer considered a marine protected area.

Fully protected regions have minimal levels of anchoring, infrastructure, aquaculture and non-extractive activities. A minimally protected area, on the other hand, has high levels of anchoring, infrastructure, aquaculture and fishing, with moderate levels of non-extractive activities and dredging and dumping.

Using their own research and evidence from scientific literature, the researchers involved in this broad-based analysis wanted to ensure that MPAs “have quality protection,” Pikitch explained. “The quality is as important, if not moreso, than the quantity.”

The researchers are pleased with the timing of the release of this paper, which comes out just over a month before the United Nations’ Convention on Biological Diversity, which will meet virtually in October. Over 50 countries, including the United States, have already agreed to protect 30 percent of the ocean by 2030.

Pikitch called this a “critical time to get this information in front of decision makers.” The meeting will occur in two parts, with the second one set for an in-person gathering in China in April.

The point of the paper is to “help clarify what is an MPA, how do we distinguish different types and their outcomes,” Pikitch added.

The people who attend the CBD meeting range from high level government officials all the way up to the president of small countries.

About a decade ago, an earlier convention targeted protecting 10 percent of the oceans by 2020. The world fell short of that goal, with the current protection reaching about 7.7 percent, according to Pikitch.

Indeed, amid discussions during the development of this new outcome-based approach to MPAs, some researchers wondered about the logic of creating a target of 30 percent within the next nine years even as the world fell short of the earlier goal.

Some people at the meetings wondered “should we be pushing these things when a lot of them are failing?” Pikitch recalled of a lively debate during a meeting in Borneo. “Part of the answer is in this paper. These [earlier efforts] are failing because they are not doing the things that need to be done to be effective. It definitely helped us inform what we should be thinking about.”

Enabling conditions for marine protected areas go well beyond setting up an area that prevents fishing. The MPA guidelines in the paper have four components, including stages of establishment, levels of protection, enabling conditions and outcomes.

The benefits of ensuring the quality of protecting marine life extends beyond sustaining biodiversity or making sure an area has larger or more plentiful marine life.

“More often than not, it’s the case that MPAs do double duty” by protecting an environment and providing a sustainable resource for people around the area, Pikitch said. Locally, she points to an effort in Shinnecock Bay that provided the same benefits of these ocean protection regions. 

In the western part of the bay, Pikitch said the program planted over 3.5 million hard clams into two areas. In the last decade, those regions have had an increase in the hard clam population of over 1,000 percent, which has provided numerous other benefits.

“It demonstrates the positive impact of having a no-take area,” Pikitch said.

At the same time, the bay hasn’t had any brown tides for four straight years. These brown tides and algal blooms can otherwise pose a danger to human health.

By filtering the water, the clams also make it easier for eel grass to grow, which was struggling to survive in cloudier waters that reduce their access to light. With four times as much eel grass as a decade ago, younger fish have a place to hide, grow and eat, increasing their abundance.

Being aware of the imperiled oceans and the threats humans and others face from a changing planet has sometimes been a struggle for Pikitch.

The marine researcher recalled a time when four hurricanes were churning at the same time in the Atlantic.

“I went to bed and I have to admit, I was really depressed,” Pikitch said.

When she woke up the next morning, she had to teach a class. She regrouped and decided on a strategic message.

“This is reality,” she told her class. “We have to accept this is the world we made. Everything we do that can make a positive difference, we do.”

Pikitch is encouraged by the work done to develop a new MPA framework.

These protected areas “provide a sustainable pathway to ensure a healthy ocean and to provide a home for future biodiversity,” she said.