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Ramana Davuluri

By Daniel Dunaief

Ramana Davuluri feels like he’s returning home.

Davuluri first arrived in the United States from his native India in 1999, when he worked at Cold Spring Harbor Laboratory. After numerous other jobs throughout the United States, including as Assistant Professor at Ohio State University and Associate Professor and Director of Computational Biology at The Wistar Institute in Philadelphia, Davuluri has come back to Long Island. 

As of the fall of 2020, he became a Professor in the Department of Biomedical Informatics and Director of Bioinformatics Shared Resource at Stony Brook Cancer Center.

“After coming from India, this is where we landed and where we established our life. This feels like our home town,” said Davuluri, who purchased a home in East Setauket with his wife Lakshmi and their six-year-old daughter Roopavi.

Although Davuluri’s formal training in biology ended in high school, he has applied his foundations in statistics, computer programming and, more recently, the application of machine learning and deep algorithms to the problems of cancer data science, particularly for analyses of genomic and other molecular data.

Davuluri likens the process of the work he does to interpreting language based on the context and order in which the words appear.

The word “fly,” for example, could be a noun, as in an insect at a picnic, or a verb, as in to hop on an airplane and visit family for the first time in several years.

Interpreting the meaning of genetic sentences requires an understanding not only of the order of a genetic code, but also of the context in which that code builds the equivalent of molecular biological sentences.

A critical point for genetic sequences starts with a promoter, which is where genes become active. As it turns out, these areas have considerable variability, which affects the genetic information they produce.

“Most of the genetic variability we have so far observed in population-level genomic data is present near the promoter regions, with the highest density overlapping with the transcription start site,” he explained in an email.

Most of the work he does involves understanding the non-coding portion of genomes. The long-term goal is to understand the complex puzzle of gene-gene interactions at isoform levels, which means how the interactions change if one splice variant is replaced by another of the same gene.

“We are trying to prioritize variants by computational predictions so the experimentalists can focus on a few candidates rather than millions,” Davuluri added.

Most of Davuluri’s work depends on the novel application of machine learning. Recently, he has used deep learning methods on large volumes of data. A recent example includes building a classifier based on a set of transcripts’ expression to predict a subtype of brain cancer or ovarian cancer.

In his work on glioblastoma and high grade ovarian cancer subtyping, he has applied machine learning algorithms on isoform level gene expression data.

Davuluri hopes to turn his ability to interpret specific genetic coding regions into a better understanding not only of cancer, but also of the specific drugs researchers use to treat it.

He recently developed an informatics pipeline for evaluating the differences in interaction profiles between a drug and its target protein isoforms.

In research he recently published in Scientific Reports, he found that over three quarters of drugs either missed a potential target isoform or target other isoforms with varied expression in multiple normal tissues.

Research into drug discovery is often done “as if one gene is making one protein,” Davuluri said. He believes the biggest reason for the failure of early stage drug discovery resides in picking a candidate that is not specific enough.

Ramana Davuluri with his daughter Roopavi. Photo by Laskshmi Davuluri

Davuluri is trying to make an impact by searching more specifically for the type of protein or drug target, which could, prior to use in a clinical trial, enhance the specificity and effectiveness of any treatment.

Hiring Davuluri expands the bioinformatics department, in which Joel Saltz is chairman, as well as the overall cancer effort. 

Davuluri had worked with Saltz years ago when both scientists conducted research at Ohio State University.

“I was impressed with him,” Saltz said. “I was delighted to hear that he was available and potentially interested. People who are senior and highly accomplished bioinfomaticians are rare and difficult to recruit.”

Saltz cited the “tremendous progress” Davuluri has made in the field of transcription factors and cancer.

Bioinformatic analysis generally doesn’t take into account the way genes can be interpreted in different ways in different kinds of cancer. Davuluri’s work, however, does, Saltz said.

Developing ways to understand how tumors interact with non-tumor areas, how metastases develop, and how immune cells interact with a tumor can provide key advances in the field of cancer research, Saltz said. “If you can look at how this plays out over space and time, you can get more insights as to how a cancer develops and the different part of cancer that interact,” he said.

When he was younger, Davuluri dreamt of being a doctor. In 10th grade, he went on a field trip to a nearby teaching hospital, which changed his mind after watching a doctor perform surgery on a patient.

Later in college, he realized he was better in mathematics than many other subjects.

Davuluri and Lakshmi are thrilled to be raising their daughter, whose name is a combination of the words for “beautiful” and “brave” in their native Telugu.

As for Davuluri’s work, within the next year he would like to understand variants. 

“Genetic variants can explain not only how we are different from one another, but also our susceptibility to complex diseases,” he explained. With increasing population level genomic data, he hopes to uncover variants in different ethnic groups that might provide better biomarkers.

Pexels photo

By Daniel Dunaief

Daniel Dunaief

He was a part of my wife’s family’s inner circle for years. He appeared at summer gatherings and at significant family events and celebrations.

With his white hair, his signature smile and a Polish accent that seemed as fresh in each conversation as it likely was the first time he arrived in the United States, Carl wandered in and out of conversations and rooms, often smiling and always listening.

He seemed as comfortable in his own skin as anyone I’d ever met, paying close attention to his wife, interacting with his children and grandchildren and soaking up life the way everyone around him soaked up the warm rays of the sun.

Carl watched one day almost 20 years ago when my daughter got too close to the pool’s edge, falling in before she could swim. I immediately jumped off the diving board and brought her back up, where, as I dried her off, she protested that it took too long for me to get her.

When my daughter felt comfortable and confident enough to walk away from me, Carl waited for me to make eye contact.

“That’s what you do when you’re a father,” he smiled.

I nodded and sighed while my blood pressure and pulse returned to normal.

Several times over the years, Carl and I sat next to each other, sharing buffet-style meals of chicken kebobs, pasta, and filets.

Carl didn’t have the numbers tattooed on his arm, but I knew some of the story of his life. I didn’t want to bother him or upset him with a discussion of what was a painful and difficult period.

Once, when we were alone inside a screened-in area, I raised the topic.

“Hey, Carl, I understand you survived the holocaust,” I said.

When he looked me in the eyes, he narrowed his lids slightly, processing what I said and, likely, trying to figure out whether he wanted to talk.

“It’s okay,” I said, immediately backing off. As a journalist, I have a tendency to ask questions. I recognize, however, the boundaries that exist during social interactions and with family and friends. I wanted to speak with him to hear about what had been an unspoken part of his life.

“Yes, I survived,” I said.

“How? Where?”

“In the woods,” he said. “I lived in the woods when the Nazis came.”

He described how he was so hungry that he ate leaves, bugs and bark. That, however, was far preferable to being caught by the Nazis, who had murdered the rest of his family. Carl had been a teenager when he escaped to the woods, avoiding Nazi guards who were always searching for people they deemed enemies and who they readily killed.

Surrounded by a collection of other people who might, at any given time, vanish forever, Carl survived for several years, emerging at the end of the war to try to restart a life shattered by violence and cruelty.

After a brief description of his experience, he told me how important he felt it was that people study the specifics of World War II and understand what really happened to him, his family and people in so many other countries. It angered him that people tried to ignore a history that took so much from him.

All those years later, Carl seemed so easy going and relaxed, so prepared to laugh and smile and to enjoy another bite of lunch or dinner.

Carl recently died. I’m sorry for the loss to his family. I’m glad to have known him and to have shared a few meals, a few smiles and a few stories. All those days, months and years of life, like initials carved into a tree, showed that he was, indeed, here and, having seen his family react and interact with him, that his life had meaning.

Stock photo

The Greek letter versions of the variants are beating up on Suffolk County, just as families prepare to gather during the holidays and New Year.

Suffolk County reported a 13.6% positive testing rate on Dec. 20, which is the highest rate in over a year, according to County Executive Steve Bellone (D).

“The omicron variant is, without question, powering a surge in cases here,” Bellone said on a conference call with reporters. “We are seeing that play out in long lines for testing as the holiday season continues and as Christmas and New Year’s approach.”

Indeed, Bellone announced that he is using his emergency powers to create three new testing sites on Long Island. The county will open a site at Gabreski Airport in Westhampton Beach on Dec. 27, in West Sayville on Dec. 27, and in the Sound Beach area on Jan. 4.

Bellone said he chose these sites near locations where the positivity rate is higher.

Bellone encourages residents to visit the county’s website, at suffolkcountyny.gov/covid19 to get details about signing up for tests at these new locations.

As for holiday preparations, Bellone and Dr. Gregson Pigott, commissioner of the Suffolk County Department of Health Services, suggested residents could continue with their holiday gathering plans as long as they take adequate precautions.

“It’s important to be vaccinated with Pfizer or Moderna,” Pigott said. “It’s more important to get that third shot, that booster shot, that’ll give you the maximum protection.”

Infectious disease experts urged residents to remain vigilant about the virus during the current surge and as people prepare to visit families.

“I would suggest making sure that everyone test for COVID and receive a negative test result” before family gatherings, Sean Clouston, associate professor in the Department of Family, Population and Preventive Medicine, explained in an email. “This is especially true for those in which there are individuals who are either unvaccinated, or those where attendees either are vaccinated but aged 60 and older.” Hospitals in the area have seen a dramatic increase in emergency room visits from residents who contracted COVID.

“The number of COVID hospitalizations has tripled in the last three weeks,” Dr. Adrian Popp, chair of Infection Control at Huntington Hospital/Northwell Health, wrote in an email.

Popp explained that patients who have been vaccinated have a milder form of COVID, while unvaccinated patients have suffered more severe symptoms. About two thirds of hospitalized patients are unvaccinated at Huntington Hospital, while several patients are in the intensive care unit.

With the increase in omicron cases, Popp explained that “we are all concerned that we may be overwhelmed if too many sick patients will show up all at once in the emergency room.”

To be sure, even with the increase in hospitalizations from the fall, the number of people batting the disease in the hospital remains well below peak levels. As of a year ago, 526 people battled COVID in the hospital. This week, that number stood at 326.

“The numbers are increasing, but they are still less than they were,” Bellone said.

Dr. Sunil Dhuper, chief medical officer at Port Jefferson’s St. Charles Hospital, suggested a three-pronged approach to defending against the next phase in the spread of COVID.

Getting vaccines and boosters is the first and most important step. Treating vulnerable residents with monoclonal antibodies is the second, and testing and wearing masks is the third step.

GlaxoSmithKline’s monoclonal treatment, called sotrovimab, works the best against omicron, Dhuper said.

At this point, the supply of that treatment, however, is limited. Dhuper hopes to get the supply issue resolved this Monday.

Until that is resolved, however, only people who are unvaccinated and who are vaccinated and immunocompromised or over 65 are eligible for this treatment, which is what the National Institutes of Health and Department of Health have recommended, Dhuper said.

The shortage of monoclonal antibodies is “an issue that needs to be addressed at the state and federal levels,” Bellone said. “I’m encouraged by what we’ve seen happening there. It’s an issue that we’ve heard from hospitals. With this surge, we’re seeing all of the capacity tested once again.”

Indeed, hospitals remain prepared to increase their staffing levels, particularly in January when people return from traveling and visiting family members.

“Everybody is aware that we may call upon any employee at any time, even if they are on vacation if we begin to see that the system is getting overwhelmed,” Dhuper said.

Pixabay photo

By Daniel Dunaief

While wind is nice and effective, moving water is even more promising, especially in the future of alternative energies.

Ali Khosronejad. Photo from SBU

That’s because water is almost 1,000 times more dense than air, which means that the movement of the wet stuff due to tides or storms could produce a considerable amount of energy.

Indeed, “if we can effectively harness the energy from moving waters in our national waterways alone, it could provide enough energy to power the whole country,” said Ali Khosronejad, Assistant Professor in the Department of Civil Engineering at Stony Brook University.

Khosronejad recently received $2 million as part of a $9.7 million four-year Department of Energy grant to study and develop ways to turn the movement of water into usable energy.

“I’m very optimistic about the future of this” approach, he said.

The DOE funds, which will involve a collaboration with East Carolina University, the University of New Hampshire, and Lehigh University, is a part of the new Atlantic Marine Energy Center, for which Khosronejad is a co-director.

The funds at Stony Brook will support hiring researchers at numerous levels, from post doctoral scientists, to graduate students and undergraduates. The money will also support adding new computer modules and expanding storage at the supercomputer. 

Stony Brook will also tap into these funds to enable travel for these new hires, to help them interact in person with their collaborators from other universities.

The combined effort at these academic centers will be dedicated to researching ocean energy technology, education and outreach. 

Researchers will work in the field, the laboratory and with computers on these ocean energy projects. They will seek to use wave energy and tidal energy conversion through such efforts as wave energy converters and tidal turbine farms.

This image depicts simulated turbulence in a waterway where a virtual tidal farm can be installed. The Stony Brook research team will use such simulations to investigate potential renewable ocean energy options. Image from Ali Khosronejad

The wave-energy converter floats on the seawater surface and uses the energy from the up and down motion of the water surface to produce electrical energy.

Researchers around the world are working to improve the efficiency of tidal turbine farms. Khosronejad described the effort as being in its infancy.

A good portion of the current project involves finding ways to optimize the positioning and layout of turbines in tidal farms. In his team, Khosronejad will work on the development of new artificial intelligence approaches to optimize the positioning and layout of turbines in tidal farms.

Stony Brook’s role in this project will involve working with computers.

In his research group, Khosronejad will work with supercomputers. His effort involves working to develop high-fidelity mathematical models that can address sediment transport and sediment-laden flows in tidal farms. 

Scientists at the University of New Hampshire and ECU are involved in addressing environmental concerns.

In the Department of Electrical Engineering at Stony Brook, co-principal investigators Fang Luo, Associate Professor and Peng Zhang, Professor in the Department of Electrical Engineering will work with computers and laboratories for micro-grid software and hardware research, respectively.

Ali Khosronejad, right, with former graduate student Kevin Flora, who earned his PhD in 2021

Working with Lehigh University, Khosronejad is doing high fidelity simulations, to replicate what researchers in the field at the University of New Hampshire and the Coastal Studies Institute at ECU are studying.

“We validate and develop artificial intelligence for design optimization of these tidal farms,” Khosronejad explained. The goal is to optimize the design of hydrokinetic turbines in estuaries and coastal areas that can create tidal farms.

The collaboration will coordinate with the National Renewable Energy Laboratory, Sandia National Laboratories, Pacific Northwest National Laboratory, European Marine Energy Centre and Old Dominion University.

The first year of the project involves hiring, training graduates and undergraduates, setting up the foundation, and beginning the infrastructure upgrade.

“The training part is important,” Khosronejad said. “This will be the next workforce. The infrastructure will stay there for the next 10 years” so the university can use it in a host of other projects.

Khosronejad is encouraged by the financial commitment from the Department of Energy. “They understand how important it is, which is why they are investing a lot in this,” he said. Some of these tidal farms are already working in the East River, between Manhattan and Roosevelt Island.

Wind turbines

At the same time, Khosronejad is continuing a wind turbine project he started with Fotis Sotiropoulos, the former dean of the College of Engineering and Applied Sciences at Stony Brook who is now Provost at Virginia Commonwealth University.

Khosronejad is now the principal investigator on that $1.1 million project and is continuing to work with Sotiropoulos, who officially left the project but is still volunteering to participate in its research activities. The scientists are working on how to use artificial intelligence to enhance the design of wind turbines.

Computer programs can alter the angle of the blades for the offshore wind farms where they attempt to use a control system to pitch the blades automatically to reduce the wind load during highly turbulent wind flows.

Changing the angle of attack of the blade can lower the loads and save money that would otherwise go to repairing blades that cracked or developed weaknesses amid strong winds, Khosronejad said.

The researchers presented their results at the American Physical Society meeting in Phoenix just before Thanksgiving. 

The researchers are trying to balance between using the turbine to generate energy and preventing the force of the winds from damaging the system.

When wind speeds are up to 25 miles per hour, the system uses the full power of the wind to maximize energy production. At speeds above that, the turbulent wind can damage the rotor and gearbox. The blades are pitched to reduce the angular velocity, which is known as self-preservation mode. At speeds over 55 miles per hour, the turbine stops working to produce no energy and avoid significant damage to the rotors and gearbox.

Generally, such federal research projects involve sharing results publicly and with the industry sector. The goal is to share science that enables the production of reliable energy.

 

 

Pixabay photo

By Daniel Dunaief

Daniel Dunaief

Dogs need to go outside, regardless of the temperature. My dog, who has a thick coat of hair, loves the winter and is perfectly happy to linger outside, especially when it’s close to freezing. When the grass is covered with frost, he slowly lowers his right cheek and does a lawn dive, bringing the rest of his body piece by piece down onto the cold, wet surface.

Once he’s completely on the ground, he rolls onto his back, using the blades of grass and the water and ice to scratch his back, while snorting with delight. With the eye that isn’t pressed into the ground, he stares at me, waiting for me to give up the ghost on getting some exercise or coming back inside quickly. When I reach down to pet him, I can almost see him smirk as he wags his tail triumphantly.

This month, he and I have seen some unusual sights. When I see something unusual, I try to take out my phone, but my reaction time, and all the extra material in my pocket, makes that a largely ineffective effort.

Even when I do manage to take out the camera and point it in the general direction of something interesting, the pictures typically disappoint, because my dog who hates to move suddenly gets the urge to pull just as I’m snapping the photo, leaving me with a blurry image of the road.

A few days ago, we were at the top of our street at dusk, near one of my dog’s favorite places to poop. In fact, I can take him on a four-mile walk and, within a tenth of a mile of our home, he finds his favorite blades of grass, takes his usual tentative steps, turns away from me — he needs privacy — and does his business.

This time, though, just as he was approaching his familiar spot, a hawk passed by only a few feet from my head, giving me a chance to look him, and the object he was carrying, squarely in the eyes.

The hawk was holding a squirrel, which seemed especially odd to me given the relative size of the two animals. The squirrel wasn’t moving but was clearly alive. When I told my family about it, they were sympathetic to the squirrel.

A few days later, walking toward the other end of the block, my dog and I observed a blow-up Frosty on one end of a lawn and a blow-up Santa on the other rise slowly from the ground as air flowed slowly into them.

My dog, whose fear of unusual inanimate objects builds around Halloween and the December holidays, stood at attention and considered announcing his presence with authority to objects that can’t, and don’t, react to his deep bark.

Fortunately, he only pulled his lips back slightly and lifted his tail, allowing the neighbors to enjoy their dark, quiet evening without the sound of a panicked pooch on a poop walk.

A few minutes later, I studied the stars at a distance when a light appeared in the sky, flashed toward the horizon and disappeared. Never having seen a shooting star before, I was mesmerized.

When I returned and shared the story, my son, who doesn’t seem too keen on superstition but is clearly aware of pop culture, asked if I made a wish. Not wanting to pass up the opportunity for help from anywhere, I did. Maybe by next December, I’ll let you know if it came true!

By Daniel Dunaief

Daniel Dunaief

Before each game, the Stony Brook University women’s basketball team meditates.

The pre-game ritual, among other changes and additions first-year Coach Ashley Langford instituted, has worked, as the team has a 7-1 record and sits first in the America East division.

Meditating “calms us and helps us visualize what we want to see in a game,” said India Pagan, a starter for Stony Brook and a graduate student with an extra year of eligibility because of the COVID pandemic.

A standout guard for Tulane University who finished her college career first in assists, Langford appreciates how hard the team has worked and how well they’ve come together.

“Our chemistry has been really good early on, to the point where, sometimes, [I wonder] is it November or is it March?” she said.

With five players averaging double digits in scoring, Stony Brook becomes harder to guard.

“On any given night, we’re moving and sharing the ball,” Langford said. “They are selfless. They don’t care who has the most points.”

While earning a spot in March Madness this year for just the second time in the program’s history would be rewarding, Langford focuses on each game.

“I’m a person that stays in the moment,” Langford said. “As long as we’re getting better, that puts us in a position to win the next game.

To that end, Langford would like the team to continue to improve in its transition defense.

She would like to see the team, which includes starters Earlette Scott, Gigi Gonzalez, Leighah-Amori Wool, Anastasia Warren and Pagan, continue to collect more offensive rebounds.

Langford’s assistant coaches, which includes recruiting coordinator Shireyll Moore, have been searching for players who might join the program as student-athletes.

“We’re in the position we are today because we have pretty good players,” Langford said. “My staff does a lot of this. They are more actively involved in the recruiting” each day.

Stony Brook has signed three current high school seniors and is focusing on juniors.

Before each game, Langford’s assistant coaches watch film of their opponents. They give her a cheat sheet before she watches film as well.

While Langford plans to stick to the team’s strengths, she will add a few wrinkles depending on the insights she gains about her opponents.

In the team’s first loss, Pagan and Warren were unavailable to play for medical reasons.

The team could have gone to Fordham feeling defeated, but the players fought to the end in a game they lost, 71-59.

“They don’t like losing, we don’t like losing,” Langford said. “They have responded well this week.”

The start of a season as head coach has taught Langford several lessons, including pacing herself and, in particular, protecting her voice. She drinks tea all day long and tells her staff to remind her not to yell in practice, because she shouts over the band at games.

In practice, Langford grabs a ball periodically to demonstrate what she’d like to see from her players.

As for her activity during the game, Langford sits only for about the first 30 seconds and then works the sidelines.

Pagan appreciates the work Langford puts in and the way her new coach has improved her game. While she used to get three or four rebounds a game, she’s often snagging 10 or more.

Pagan also sees herself hustling more, particularly after Langford created a drill where the players dive for loose balls.

“Before, I wouldn’t think of diving for a ball. Now, it’s ingrained into my head,” Pagan said. “The hustle doesn’t stop until the whistle blows. You play until you can’t play any more.”

From left, Daniele Rosado and Ullas Pedmale examine a sample of the model plant Arabidopsis. Photo courtesy of Ullas Pedmale

By Daniel Dunaief

Many plants are in an arms race akin to the developers of skyscrapers eager to get the most light for their prized penthouse apartments. Only, instead of trying to collect rent from well-heeled humans, these plants are trying to get the most sun, from which they create energy through photosynthesis.

Plants are so eager to get to the coveted sunlight that the part growing towards the light sends a distress signal to the roots when they are in the shade. While that might help an individual plant in the short term, it can create such shallow and ineffective roots that the plant becomes vulnerable to unfavorable weather. They also can’t get as many nutrients and water from the ground.

This is problematic for farmers, who want plants that grow in the sun, but that don’t sacrifice the development of their roots in the shade. Ullas Pedmale, Assistant Professor at Cold Spring Harbor Laboratory, is working to lend a hand.

Pedmale, who recently published research in the journal Plant Physiology, is studying the signals the shoots, or the parts of the plants either in the sunlight or the shade, send to the roots.

Pedmale and postdoctoral researcher Daniele Rosado, who is the first author on the recent paper, explored the genes that turned on in the roots of the model plant Arabidopsis and tomato plants when these plants were in the shade.

When plants are in the shade, they “prioritize shoot growth and try to outcompete the neighboring plants,” said Rosado. “That’s when root development is compromised.”

Among the genes that are active when plants are in the shade is a family of genes called WRKYs, which affect gene expression and cause stunted growth in the roots.

WRKY genes respond to stress. Keeping WRKY genes on all the time, even when a plant is in the sun, caused stunted growth of the roots. WRKY proteins turn on or off other genes.

This can be problematic for farmers, who tend to try to increase yield by putting more plants in an area. At that point, the plants shade each other, which is “bad for the root system. If we can find a way to get the roots to grow normally, we can potentially increase yield,” Rosado said.

This could also remove more carbon dioxide from the air and store it in the developing roots, helping to mitigate the effect of global warming. “Our study can give a roadmap on how to make longer, deeper roots,” Pedmale said.

At this point, researchers still don’t know how the plant transfers information about the amount of sunlight it receives in the green chloroplasts where photosynthesis occurs to the WRKY genes, which are in the nucleus.

Researchers have been studying the shade response in the shoots of plants for over five decades. They have not, however, focused as much attention on the effect of less sunlight on the roots.

“We want to tackle this problem,” Pedmale said.

WRKY genes are a generalized stress signal, which is not just involved when a plant isn’t getting enough light. They are also turned on during pathogen attacks, stress and amid developmental signals.

Indeed, plants in the shade that have turned on these signals are especially vulnerable to attacks. Caterpillars, for example, can eat most of a shaded plant because the plant is so focused on growing its shoot that its defenses are down.

When that same plant is in the sunlight, it is more effective at defending itself against caterpillars.

At this point, Pedmale doesn’t know whether these genes and signals occur across a broad species of plants beyond tomatoes and Arabidopsis. He and others are hoping to look for these genes in grasses and grains.

Pedmale is also searching for other signals between the shoot and the root. “Plants are masters of adaptation,” he said. “They might have redundant systems” that signal for roots to slow their growth while the shoots tap into the available energy to grow.

Plants may also have natural molecules that serve as brakes for the WRKY signal, preventing the shoot from taking all the available energy and rendering the plant structurally fragile.

A scientist at CSHL for five years, Pedmale came to the lab because of the talent of his colleagues, the reputation and opportunity at CSHL and the location.

Born and raised in Bangalore, India, Pedmale enjoys reading fiction and autobiographies and wood working when he’s not in the lab. He recently made a book shelf, which provides him with a chance to “switch off” from science, which, he said, is a 24-hour job. He has taken wood pieces from his workshop and brought them to PhD classes at CSHL, where he can show them plant biology and genetics at work.

Pedmale and his wife Priya Sridevi, who also works at CSHL, have a mini golden doodle named Henry.

A native of São Paulo, Brazil, Rosado is married to plant biologist Paula Elbl, who is the co-founder of a start up called GALY, which is trying to produce cotton in a lab instead of in a field.

Rosado is the first in her family to attend a public university. She has been working in Pedmale’s lab for two years and plans to continue her research on Long Island for at least another year.

Rosado knew Pedmale had worked as a post doctoral researcher in the lab of celebrated plant biologist Joanne Chory at the Salk Institute for Biological Studies. She met Pedmale at a plant conference, where she expressed an interest in his research.

Longer term, Rosado hopes her research has a broader impact.

“If I’m lucky, I’ll be able to see the fruits of my work being applied to make a difference and help feed people,” she said.

As for his work, Pedmale is eager to understand and use the signals from one part of a plant to another, given that the plant lacks a nervous system. “Once we can understand their language,” he said, “we can manipulate it to increase yield.”

Jessica Tollkuhn Photo courtesy of CSHL

By Daniel Dunaief

They are like directors in a carefully choreographed production, instructing certain groups that become active, while giving others a five-minute break.

In the case of the human body, directors take many forms, including hormones; the same hormones that can transform adorable, sweet and well-behaved children into smelly, strong-willed teenagers.

Hormones like estrogen, testosterone and progesterone affect people at various ages and in different ways.

Recently, Cold Spring Harbor Laboratory Assistant Professor Jessica Tollkuhn and her graduate student Bruno Gegenhuber teamed up with University of California at San Francisco Herzstein Professor of Molecular Physiology Holly Ingraham to link the way estrogen in a specific area of the brain turns on particular genes.

For mice that are representative of post-menopausal women, the lower activity of a gene called melanocortin-4, or MC4R causes these mice to become less active.

By activating MC4R neurons in the ventrolateral ventromedial hypothalamic nucleus of the brain in the absence of estrogen, researchers caused a dramatic increase in physical activity and 10 percent body weight loss after one day.

Additionally, turning up the MC4R gene increased their bone density over time.

Linking the gene activated by estrogen in a part of the brain that affects how adult females use energy, the scientists provided a causative link that explains lower energy in this population.

Tollkuhn said her contribution showed that the estrogen receptor binds DNA in the presence of hormones.

The scientists published their research in the journal Nature.

“If anything, this paper is a study of how just one gene can show this exquisite behavioral response,” Tollkuhn added.

The MC4R gene is also found in the male brain, although not in the same area. Experimentally, turning up the gene also increases physical activity in males.

Numerous drugs currently target this gene in connection with increasing libido in post-menopausal women. Using these treatments for other issues, like weight gain and activity level, would require additional study.

Estrogen affects numerous other areas of the body, including some that may cause other problems. Hormone replacement therapy has contributed to the development or worsening of other cancers, such as breast cancer, although it is not clear why or how this happens.

“There’s evidence that there can be positive benefits [like bone and mental health], but also evidence that it can increase the risk of cancers,” Tollkuhn said.

Ingraham knew Tollkuhn from their overlapping research experiences at the University of California at San Diego and, later at UCSF.

Ingraham had reached out to Tollkuhn to see if the experiments in Tollkuhn’s lab could determine the link between the hormone and the MC4R gene.

“It’s always a challenge in biology to get a direct causality” because numerous factors in a living system could contribute to the development of a condition or a behavior, Tollkuhn said.

Tollkuhn suggested that the bulk of the experiments were done in Ingraham’s lab.

Ingraham recognized early on the benefit of finding these direct binding sites.

“We are saying, ‘Here is a hormone and it is acting through this molecule and it’s causing this change … that we know is really important for eliciting this behavior,” Ingraham said.

Ingraham, who worked with Tollkuhn when she was a post doctoral researcher and Tollkuhn was a graduate student in Geoffrey Rosenfeld’s lab at UC San Diego, called her colleague “really talented” and said she “spent years working this whole system out. It’s heroic and nobody else has done it.”

Ingraham sent Rosenfeld a message after the journal Nature accepted their paper, indicating his trainees had “hit pay dirt on this one.”

Ingraham hopes the paper motivates other researchers to think about entering this area and tackling this challenge, which is so important for women’s health.

“The only way we’re going to move forward for women’s health is to understand all these different facets of what estrogen is doing in the brain,” she added.

In press coverage of the research, Ingraham described the comments as falling into two categories. In the first, women suggest that they’re past menopause and have never been more active. In the second, women indicate that getting hormone replacement therapy genuinely helped them, including with brain fog.

Other scientists have sent Ingraham congratulatory emails about the paper. They have “appreciated that this had such a great molecular story,” she said.

In a broader research context, Tollkuhn is interested in determining how hormones affect the brain during sexual differentiation.

She is now focused on identifying a new repertoire that she and others can explore in future studies.

Tollkuhn’s lab is also investigating how estrogen influences brain development. She has found dozens of genes she would like to understand in the kind of detail with which she explored MC4R. Estrogen receptors also are connected to HTR1A and HTR1D, which are genes for serotonin receptors and may connect estrogen to mood.

Studies in scientific literature have shown that numerous psychiatric and neurological conditions have sex differences in terms of their impacts on men and women.

“We have these pieces and we can try to put together this puzzle,” Tollkuhn said. “We can try to understand why this would be the case. The long term goal is to figure out why there is a greater increase in [certain diseases] in men or women, which could lead to the development of better treatment.”

Tollkuhn is also interested in understanding the progression of neurodegenerative conditions like Alzheimer’s, which is twice as likely in women as in men. The symptoms for this disease develops more rapidly in post menopausal women, who typically have a more precipitous decline in estrogen than older men do in their levels of testosterone.

“I’m interested in what hormone receptors are doing in the brain,” she said.

Pixabay photo

By Daniel Dunaief

Daniel Dunaief

When she was little, my daughter loved to build sand castles. She’d put wet sand in a bucket, gently pull the bucket back and marvel at the details in the castles that came out.

My son wasn’t as interested in building castles. He derived special pleasure out of stomping on the castles she made. It wasn’t just that it gave him power over the sand: he also felt power over his older sister, who was furious with him for crushing her castles.

While I tried to reason with him, which is almost as effective today as it was when he was two, I came up with an alternative plan that required additional energy from me, but that created peace on the beach. I’d quickly put together a ring of 15 castles, grabbing wet sand and dumping it several feet from where my daughter was working on her creation.

Like a young Olympic sprinter, my son would race over to the collection of castles and stomp all over them, while my daughter slowly built her own city of sand.

These days, it seems, we are surrounded by people eager to stomp on everyone else’s sandcastles.

Sure, it’s satisfying to feel the figurative sand in our toes and to revel in tearing down what other people have created.

But, really, given all the challenges of the world, I think we should ask a few questions of all those people who are so eager to belittle, attack and undermine others. What’s your solution? What are you doing better? How would you fix the problem?

Insulting others for their efforts, their awkwardness or their perceived flaws often seems like a form of ladderism. No one wants to be on the bottom rung of a ladder, so people try to push others down or to shout to anyone who will listen about how much better they are than the people below them. That seems to be a sign of weakness or insecurity, reflecting the notion that other people are below them.

In addition to dumping on others, we live in a society of people for whom hearing views that differ from their own somehow turns them into victims. Surely we have more choices than simply, “I’m right and you’re wrong.” If someone doesn’t agree with you, maybe it’s worth finding out why.

Anger, frustration and hatred, while they may make us feel slightly better in the moment, aren’t solutions and they don’t improve our world. They are a form of destructive energy, like stomping on sand castles.

We should ask more of ourselves and from our leaders. I’m tired of hearing about politicians who will fight for me. I don’t want to send people into office to fight against others who are trying to do the best they can for the country. I want leaders who will learn, listen and, gasp, reach across the aisle in the search for solutions.

While platforms aren’t as sizzling as slogans or take downs, they include ideas and potential solutions.

Civility makes it possible for us to hear and learn.

We have enough threats to our lives without needing to turn against other people or to give in to the urge to crush other people’s sandcastles to feel better. We don’t all have to be best friends, but it’d be nice to look forward to a holiday season and the start of a new year that focused on a shared sense of purpose. We need better ideas, not better ways to attack.

Families opened their doors to each other during Thanksgiving, eager for a long-awaited reunion and hoping to keep out COVID-19. Stock photo

Despite the desire to relax, remove masks and go on with life, the pandemic, even prior to the emergence of a new, mutation-laden variant, has become a central concern among government and health care officials.

The stock market has felt the effects of concerns over the Omicron variant, hospitals are sending off some positive tests to check for the new variant, and the federal government is restricting travel from several countries in Africa.

While health care officials anticipate the inevitable presence of confirmed cases of Omicron in the United States and New York, they had already seen an increase in confirmed cases and had increased the need for treatment.

At St. Catherine of Siena Hospital in Smithtown, the hospital provided monoclonal antibody treatment for 32 people the Tuesday before Thanksgiving, according to St. Catherine Chief Medical Officer Dr. Mickel Khlat. That is up from an average of four to five a day just a few weeks earlier.

That increase comes not only from a rise in group activities indoors, but also from a reduction in the immunity conferred by vaccines that are less effective after six months.

Six weeks ago, unvaccinated patients represented 80% of those who received monoclonal antibody treatments, said Dr. Khlat. Recently, the percentage of vaccinated people who receive antibody treatment has risen to 50%.

“If you got the vaccine six or seven or eight months ago, your immunity is waning,” said Dr. Khlat.

Dr. Gregson Pigott explained that monoclonal antibody treatment could be lifesaving.

“The key is to seek treatment soon after a COVID diagnosis,” Dr. Pigott explained in an email.

The percentage of positive tests in Suffolk County has been rising at a rapid pace, mirroring the positive tests for the nation. The percentage of positive tests on a seven-day average reported on Tuesday, Nov. 29, was 5.3%. That is up from a seven-day average of 3.7% just two weeks earlier and 2.4% a month earlier, according to data from the Suffolk County Department of Health.

Dr. Susan Donelan, medical director of the Healthcare Epidemiology Department at Stony Brook Medicine, explained that this is likely a result of variable acceptance of vaccination opportunities, inconsistent or poor mask usage compliance, increased indoor activity, initiation of indoor heating and general pandemic fatigue.

At the same time, hospitals on Long Island and around the state are preparing and monitoring for the potential arrival of the Omicron variant, which the World Health Organization recently deemed a variant of concern in part because of the number of mutations to the spike protein. These mutations could alter the dynamic in the Stéphane Bancel indicated that vaccines may not be as effective against this variant.

Pigott suggested that too little is known to determine how effective the current vaccines would be against the new variant.

“We will learn more from the World Health Organization and the [Centers for Disease Control and Prevention] in the weeks to come,” Pigott explained in an email.

Dr. Adrian Popp, chair of Infection Control at Huntington Hospital/Northwell Health, said numerous mutations don’t necessarily mean this variant is any worse.

“It’s important to see what is the effect of these mutations,” Popp explained in an email. The answers to whether the strain is more virulent or if the vaccines are less effective are still unknown. The next few weeks could provide a clearer picture, Popp said.

Doctors urged residents to become vaccinated and, if eligible, get the booster.

“My message to the public is to still get the vaccine,” said Khlat. “I wouldn’t tell people to wait” until companies like Pfizer, Johnson & Johnson and Moderna develop vaccines or boosters for the latest variant. COVID is a “killer. I want everyone vaccinated as soon as possible.”

At the same time, hospitals are actively monitoring positive cases for the potential spread of the Omicron variant into the area.

Since the emergence of the new variant on Nov. 26, “Stony Brook’s labs have been hard at work in pursuit of an answer” to whether any patients have contracted the variant, Donelan explained in an email.

Stony Brook routinely sends 10 random samples of positive COVID swabs each week to the Wadsworth Virology lab for genomic sequencing. The hospital epidemiologist reviews the available electronic medical record of all positives to identify any patient who may have key characteristics, such as traveling in areas in which Omicron is more prevalent.

“Our lab is working directly with Wadsworth to facilitate rapid sequencing of any samples with high suspicion,” Donelan added.

Scientists are also trying to determine whether this variant has different symptoms and outcomes from the original virus.

The mRNA platforms from Pfizer and Moderna have the ability to pivot rapidly in the manufacturing process in response to changes in the genetic sequences of the virus.

Thanksgiving and holiday effects

With families coming together over Thanksgiving, health care professionals anticipate that the number of cases will rise.

“Thanksgiving gatherings, historically, have provided an annual springboard for cross-transmission of all sorts of respiratory viruses,” Donelan wrote. “This year shouldn’t be expected to be different.”

Pigott added that he would anticipate that the number of positive cases
would rise.

As for travel during the December holidays, Pigott advises people to practice prevention strategies that include washing their hands frequently, wearing masks in public indoor settings, keeping their distance as much as possible in public and when people don’t know the vaccination status of others.

Khlat suggested that people didn’t necessarily need to cancel any holiday travel plans because of the new variant. He urged people to “be smart” and make sure they wear masks on airplanes and remain aware of their surroundings.

“We can’t be prisoners,” he said. He also recommended that people stay home if they have symptoms like sniffles or a cough.

Khlat, who is planning to travel in January, will bring along hand sanitizer and may wear an n95 mask.