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Daniel Dunaief

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From left, K. Barry Sharpless and John Moses. Photo from CSHL

By Daniel Dunaief

K. Barry Sharpless changed John Moses’s life. And that’s before Moses even started working as a postdoctoral researcher in Sharpless’s lab.

When Moses, who is the first chemist to work at Cold Spring Harbor Laboratory in its 132-year history, was earning his PhD in chemistry at Oxford, he read an article that Sharpless co-authored that rocked his world.

Nicknamed the “click manifesto” for introducing a new kind of chemistry, the article, which was published in Angewandte Chemie in 2001, was “one of the greatest I’ve ever read,” Moses said, and led him to alter the direction of his research.

Moses walked into the office of the late chemist Sir Jack Baldwin at Oxford, who was Moses’s PhD advisor, and announced that Sharpless, a colleague of Baldwin’s at the Massachusetts Institute of Technology, was the only chemist he wanted to work with in the next phase of his career.

Baldwin looked at Moses and said, in a “very old-fashioned gangster English, ‘That shows you’ve got some brains,’” recalled Moses.

Sharpless was important not only to Moses’s career, but also to the world.

Recently, Sharpless, who is the W.M. Kepp Professor of Chemistry at Scripps Research, became only the fifth two-time recipient of the Nobel Prize.

Sharpless will share the most recent award, which includes a $900,000 prize, with Carolyn R. Bertozzi, the Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences at Stanford University, and Morten P. Meldal, professor at the University of Copenhagen, for the invention of a type of chemistry that has implications and applications from drug discovery and delivery, to making polymers, to developing anti cancer treatments.

The way click chemistry works is that chemists bring together catalysts and reagents, often attached to sulfur or carbon, that have a high level of specific attraction for each other. The click is like the sound a seat belt makes when secured, or the click a bike helmet lock makes when the two units are connected.

Scientists have often described the click reaction as being akin to LEGO blocks coming together, with an exact and durable chemical fit.

Natural product synthesis is generally challenging and often requires complex chemistries that are not always selective. This type of chemistry can produce side reactions that create unwanted byproducts and require purification.

Click reactions, by contrast, are selective and reliable and the products are generally easy to purify. Sometimes, purification is as simple as a water wash.

“It’s a democratization of synthetic chemistry,” Moses said.

Moses said biologists have performed click reactions. Chemists have developed click tablets that can be added to a reaction to create a plug and play system.

Moses described the reactions in click chemistry as “unstoppable” and suggested that they are part of a “domino rally” in which a latent build up of reactivity can create desired products with beneficial properties.

Moses, who arrived at CSHL in 2020, has collaborated with several researchers at the famed lab. He is submitting his first collaborative paper soon with Dr. Michael Lukey, who also started in 2020 and performed his PhD at Oxford, and Dr. Scott Lyons. He is also working on a New York State Biodefense funded project to create shape shifting antibiotics that can keep up with drug resistance pathogens. 

He has collaborated with Cancer Center Director David Tuveson to develop a new ligand to target a protein important in pancreatic cancer. Moses said they have a “very exciting” lead compound.

Early resistance

While the Nobel Prize committee recognized the important contribution of this approach, the concept met with some resistance when Sharpless introduced it.

“When [Sharpless] submitted this, the editor called colleagues and asked, ‘Has Barry gone crazy?’” Moses said.

Some others in the field urged the editor to publish the paper by Sharpless, who had already won a Nobel Prize for his work with chirally catalyzed oxidation reactions.

Still, despite his bona fides and a distinguished career, Sharpless encountered “significant resistance” from some researchers. “People were almost offended by it” with some calling it “old wine in new bottles,” Moses said.

In 2007, Moses attended a faculty interview at a “reasonably good” university in England,. where one of his hosts told him that click chemistry is “just bulls$#t!”

Moses recognized that he was taking a risk when he joined Sharpless’s lab. Some senior faculty advised him to continue to work with natural product synthesis.

In the ensuing years, as click chemistry produced more products, “everyone was using it and the risks diminished quickly,” Moses added.

Unique thought process

So, what is it about Sharpless that distinguishes him?

Moses said Sharpless’s wife Janet Dueser described her husband as someone who “thinks like a molecule,” Moses said.

For Moses, Sharpless developed his understanding of chemistry in a “way that I’ve never seen anyone else” do.

Moses credits Dueser, who he described as “super smart,” with coining the term “click chemistry” and suggested that their partnership has brought together his depth of knowledge with her ability to provide context.

Moses believes Sharpless “would admit that without [Dueser], his career would have been very different! In my opinion, [Dueser] contributed immeasurably to click chemistry in so many ways.”

Indeed, click chemistry won a team prize from the Royal Society of Chemistry last year in which Dueser was a co-recipient.

As for what he learned from working with a now two-time Nobel Prize winner, Moses said “relinquishing control is very powerful.”

Moses tells his research team that he will never say “no” to an innovative idea because, as with click chemistry, “you never know what’s around the corner.”

Moses said Sharpless is a fan of the book “Out of Control” by Kevin Kelly, the co-founder of Wired Magazine. The book is about the new biology of machines, social systems and the economic world. Sharpless calls Kelly “Saint Kevin.”

On a personal level, Sharpless is “humble and a nice person to talk to” and is someone he would “want to go to a pub with.”

Moses believes Sharpless isn’t done contributing to chemistry and the world and anticipates that Sharpless, who is currently 81 years old, could win another Nobel Prize in another 20 years.

An inspirational scientist, Sharpless ” is “that kind of person,” Moses said.

WTC responders at Ground Zero, working on the pile in the aftermath of 911. Photo by John Bombace

As the medical challenges to first responders at the World Trade Center site after the 9/11 attacks increase, Stony Brook University’s treatment program has increased the number of people it helps and, recently, also the federal funds to support efforts to treat people.

Dr. Benjamin Luft at the Stony Brook WTC Wellness Program, where he serves as director. File photo

Recently, the National Institute for Occupational Safety and Health, which is part of the Centers for Disease Control and Prevention, awarded the Stony Brook World Trade Center Health and Wellness Program $147 million over an eight-year period to expand patient care and support infrastructure needs.

The SB World Trade Center Health and Wellness program now sees up to 13,000 patients, which is more than double the 6,000 patients it used to see.

“Patients are getting sicker and their diseases are much more complex with a variety of different systems being involved, both psychologically as well as physically,” said Dr. Benjamin Luft, director of the WTC Wellness Program.

Through the work the SB WTC group has conducted, doctors and researchers have demonstrated that diseases and physical and cognitive challenges associated with aging have occurred more rapidly in the WTC population.

At the same time, COVID-19 has also exacerbated conditions related to exposure to the site, with over 20% of this population experiencing lingering symptoms due to the pandemic.

The WTC first responders have developed chronic sinusitis and a variety of gastrointestinal disorders, such as gastroesophageal reflux disease (or GERD).

While these diseases occur in the general population, “the chronicity is unique,” Luft added.

The SB WTC Wellness program will use the funds to hire additional staff with specialties in pulmonology and psychiatry, among other areas, Luft said.

The majority of the work occurs at the Wellness Center’s main facility and clinic in Commack. SB also runs a site in Mineola. The funds will help revamp the Mineola site as well.

The two sites will use updated technologies and will deploy emerging capabilities in telehealth and artificial intelligence to communicate, diagnose and monitor cases.

Federal funds have supported the effort for 18 years, as NIOSH has funded clinical services for WTC patients treated at Stony Brook.

Medical conditions for this population have included post-traumatic stress disorder and respiratory illnesses.

The funding more than doubles the $60 million, five-year award the WTC Wellness Program received in 2017 from NIOSH that had provided support until the end of March of this year. NIOSH had extended the grant for six months until the current funding started at the end of September, Luft said.

Patients have developed a range of cancers, as well as lung issues such as asthma and chronic obstructive pulmonary disorder.

Additionally, patients are struggling with a variety of mental processing challenges.

“We see a lot of patients who have a variety of cognitive and memory problems,” Luft said. 

Luft emphasized that many of the thousands of patients he treats have several health issues simultaneously. By using new technologies, these efforts will enhance the quality of life for people who were on site after the attack.

Luft added that the connection and support from NIOSH have helped support health care for this population.

“The various people at NIOSH are really involved in the program,” he said. “It’s been very satisfying.”

Stony Brook University faculty in public health, psychiatry, pulmonary care, cardiovascular care and neuroscience all take part in ongoing research related to the health issues of WTC responders.

Luft emphasized that the care first responders at the WTC receive tries to be “proactive” with an extensive effort to screen for various diseases, including cancer.

The research and treatment efforts for the WTC population extends to other health care initiatives for people exposed to carcinogens in wars or from other unintentional exposures.

The exposure from 911 is similar to those from burn pits, Camp Lejuene and other hazards.

“The toxins are similar,” Luft said.

 

 

Fish kills in Long Island have increased from about five per year to 50 this summer. Photo by Laurie Vetere

Fish kills in waterways around Long Island climbed to over 50 this summer from about five per year in earlier years, driven by increasing water temperatures, algal blooms and increased nitrogen in local waters.

With temperatures climbing more than 2 degrees Celsius over the last two decades, waters around Long Island don’t have as much oxygen, particularly at night when photosynthetic plants are no longer able to catch sunlight and turn it into oxygen.

The fish kills represent a “pretty big number,” said Christopher Gobler, endowed chair of Coastal Ecology and Conservation at the School of Marine and Atmospheric Sciences at Stony Brook University.

Members of Gobler’s lab sample Long Island waters routinely as a part of their research. While his team was out gathering data, Gobler asked them to report any fish kills that included 10 or more fish. The area between Hempstead Harbor and Northport Harbor routinely included observations of fish kills.

Warmer water holds less dissolved oxygen than colder water, because oxygen can escape more easily from water in higher heat.

With temperature as the primary driver, a combination of factors robs the water of oxygen.

“The warmer the water gets, the quicker the bacteria take oxygen out, the faster the fish are respiring” Gobler said. 

He added the fish kills often included menhaden, or bunker, fish. These fish have returned in larger numbers in recent years to the waters around Long Island amid other conservation efforts. More menhaden this summer also brought sharks to the area, as these apex predators hunt bunker fish.

While global warming likely had a significant impact on the number of fish kills, Gobler said, an increase in nitrogen in local waterways also contributed to anoxic conditions and is something residents can control locally.

With more nitrogen, typically from onsite wastewater, algae have more nutrients to grow.

At the same time, when more abundant algae dies, the bacteria that break down the algae consume oxygen.

An additional emerging perspective suggests that the more abundant algae at night are respiring, removing oxygen from the water.

Gobler said people can reduce the release of nitrogen into local waterways, which can also affect groundwater, by upgrading their sewage treatment systems. Suffolk County has created rules, including a Reclaim our Water Septic Improvement Program, which protects the environment by reducing nitrogen emissions.

Gobler remains concerned not only for the fish that wash up in numbers along the shore, but for the marine organisms that aren’t as mobile, such as the invertebrates at the bottom of the waterways.

The fish kills are a flag that “these water bodies are impaired and are not capable of sustaining marine life in a way we’d like them to,” Gobler said.

As for the future, Gobler said it’s difficult to predict how the combination of factors, from global warming to nitrogen runoff, will affect marine life.

“Maybe next year, we go back to five [fish kills] in the summer,” he said. This year was “unlike anything we’ve seen” with a combination of high temperatures and numerous fish kills.

Peter Westcott, on right, in the lab with technicians Zakeria Aminzada, on left and Colin McLaughlin, center. Photo by Steven Lewis

By Daniel Dunaief

When Peter Westcott was growing up in Lewiston/Auburn, Maine, his father Johnathan Harris put the book “Human Genome” on his bed. That is where Westcott, who has a self-described “obsessive attention to detail,” first developed his interest in biology.

Westcott recently brought that attention to detail to Cold Spring Harbor Laboratory, where he is an assistant professor and Cancer Center member. He, his wife Kathleen Tai and their young children Myles and Raeya moved from Somerville, Massachusetts, where Westcott had been a postdoctoral fellow at the Koch Institute of Integrative Cancer Research at the Massachusetts Institute of Technology.

Westcott will take the passion and scientific hunger he developed and honed to the famed lab, where he plans to continue studies on colon cancer and the immune system.

“A lot of things attracted me to Cold Spring Harbor Laboratory,” said Westcott who had been to the lab during conferences, joining three Mechanisms and Models of Cancer meetings, and appreciated that the small size of the lab encourages collaboration and the sharing of ideas across disparate fields.

At this point, Westcott, who purchased a home in Dix Hills and started on campus on September 1st, has two technicians, Zakeria Aminzada and Colin McLaughlin working with him. He will be taking on a graduate rotation student from Stony Brook University soon and would also like to add a postdoctoral researcher within about six months. He plans to post ads for that position soon. 

Research directions

Westcott said his research has two major research directions.

The first, which is more translatable, involves looking at how T cells, which he described as the “major soldiers” of the immune system, become dysfunctional in cancer. These T cells balance between attacking unwanted and unwelcome cells relentlessly, disabling and destroying them, and ignoring cells that the body considers part of its own healthy system. When the T cells are too active, people develop autoimmunity. When they aren’t active enough, people can get cancer.

“Most cancers, particularly the aggressive and metastatic ones, have disabled the immune response in one way or another, and it is our focus to understand how so we can intervene and reawaken or reinvigorate it,” he explained.

During cancer development, T cells may recognize that something on a tumor is not healthy or normal, but they sometimes don’t attack. Depending on the type of genetic program within the T cells that makes them tolerant and dysfunctional, Westcott thinks he can reverse that.

A big push in the field right now is to understand what the genetic programs are that underlie different flavors of dysfunction and what cell surface receptors researchers can use as markers to define T cells that would allow them to identify them in patients to guide treatment.

Westcott is taking approaches to ablate or remove genes called nrf4a 1, 2 and 3. He is attacking these genes individually and collectively to determine what role they play in reducing the effectiveness of the body’s immune response to cancer.

“If we knock [some of these genes] out in T cells, we get a better response and tumors grow more poorly,” he said.

Westcott is exploring whether he can remove these genes in an existing T cell response to cause a regression of tumor development. He may also couple this effort with other immunotherapies, such as vaccines and agonistic anti-CD40 antibody treatment.

As a second research direction, Westcott is also looking more broadly at how tumors evolve through critical transitions. Taking an evolutionary biology perspective, he hopes to understand how the tumors start out as more benign adenoma, then become malignant adenocarcinoma and then develop into metastatic cancer. He is focusing in particular on the patterns of mutations and potential neoantigens they give rise to across the genome, while concentrating on the immune response against these neoantigens.

Each tumor cell is competing with tumor cells with other mutations, as well as with normal cells. “When they acquire new mutations that convey a selective advantage” those cells dominate and drive the growth of a tumor that can spread to the rest of the body, Westcott said.

Using a mouse model, he can study tumors with various mutations and track their T cell response.

T cells tend to be more effective in combating tumors with a high degree of mutations. These more mutated tumors are also more responsive to immunotherapy. Westcott plans to study events that select for specific clones and that might shift the prevalence, or architecture, of a tumor.

Some of the work Westcott has done has shown that it is not enough to have numerous mutations. It is also important to know what fraction of the cancer cells contain these mutations. For neoantigens that occur in only a small fraction of the total cells in the tumor, the T cell responses aren’t as effective and checkpoint blockade therapy doesn’t work.

He wants to understand how the T cell responses against these neoantigens change when they go from being subclonal “to being present in most or all of the tumor cells,” he explained. That can occur when a single or few tumor cells acquire a selective advantage. His hypothesis is that these selective events in tumor progression is inherently immunogenic. \

By exploring the fundamental architecture of a tumor, Westcott hopes to learn the mechanisms the tumor uses to evade the immune system.

Ocean breeze

As Westcott settles in at CSHL, he is excited by the overlap between what he sees around the lab and the Maine environment in which he was raised.

“Looking out the window to the harbor feels like New England and Maine,” he said. “It’s really nostalgic for me. Being near the ocean breeze is where I feel my heart is.”

Before his father shared the “Human Genome” book with him, Westcott was interested in rocks and frogs. In high school, his AP biology teacher helped drive his interest in the subject by encouraging discussions and participation without requiring her students to repeat memorized facts. The discussions “brought to life” the subject, he said.

As for his work, Westcott chose to study colon cancer because of its prevalence in the population. He also believes colon cancer could be a model disease to study all cancers. By understanding what differentiates the 12 percent of cases that are responses to immunotherapy from the remainder that don’t respond as well to such approaches, he hopes to apply these lessons to all cancer.

“There is a huge, unmet need,” he said.

Recently, 1,150 members of the LGBTQ+ community participated in including Micah Schneider, from Ronkonkoma, above. Photo rom Lisa Czulinski

In a first of its kind survey of 1,150 members of the LGBTQ+ community on Long Island, Stony Brook Medicine found that people in this group struggle with numerous health care challenges.

Stony Brook Medicine’s Dr. Alison Eliscu was the principal investigator of the study that 1,150 members of the LGBTQ+ community recently participated in. Photo from Stony Brook Medicine

Over two in five people responding to an online survey between June and September of 2021 said they were in fair to poor mental health. Additionally, about one in three people had thoughts of self harm, while 23.9% had seriously considered suicide within the past three years.

People in the LGBTQ+ community are struggling with mental health and access to care, while they also have had negative experiences with health care providers, who may have been making incorrect assumptions about their lives or who haven’t respected them, said Dr. Allison Eliscu, principal investigator of the study and medical director of the Adolescent LGBTQ+ Care Program at Stony Brook Medicine.

Partnering with 30 Long Island-based community leaders and community organizations, including Planned Parenthood, Stony Brook Medicine created the survey to gather the kinds of data that could inform better health care decisions, could provide a baseline for understanding the needs of the LGBTQ+ community in the area, and could shed light on the disparity in health care for this community.

“The idea [for the survey] came out when we were creating the Edie Windsor Healthcare Center” in Hampton Bays, Eliscu said, which opened its doors in 2021 and is the first such center for the LGBTQ+ population on Long Island. “We were trying to think about what we want [the center] to provide and what does the community need.”

Without local data, it was difficult to understand what residents of Long Island, specifically, might need.

The data suggests a disparity between the mental health of the LGBTQ+ community in the area and the overall health of the population in the country. 

Over half of the people who took the survey indicated that they had symptoms of chronic depression, compared with 30.3% for the nation, based on a 2020 PRC National Health Survey. Additionally, 23.9% of the LGBTQ+ community described a typical day as “extremely or very stressful” compared with 16.1% for the nation.

To be sure, the national data sampling occurred just prior to the start of the COVID-19 pandemic, in February of 2020, while the Stony Brook Medicine survey polled residents during the second year of COVID.

Nonetheless, Eliscu suggested that her anecdotal experience with her patients indicates that the LGBTQ+ community likely suffered even more during the pandemic, as some people lived at home with relatives who may not have been supportive or with whom they didn’t share their identity.

Additionally, the isolation removed some LGBTQ+ residents from an in-person support network.

Stony Brook Medicine has taken steps to provide specific services to residents who are LGBTQ+. People who are transitioning and have a cervix continue to need a pap smear.

Some members of the transgender community may not be comfortable going to a gynecologist’s office. Stony Brook Medicine has put in place extended hours to meet their needs.

Micah Schneider, a social worker who lives in Ronkonkoma, served as a survey participant and also as a guide for some of the wording in the survey.

Schneider, who identifies as nonbinary and transgender and prefers the pronoun “they,” said the survey can help people “recognize that we’re not alone.”

When Schneider was growing up, “I had a sense that I was the only person in the entire world dealing with this,” which included a struggle with identity and mental illness.

“We as a community have each other and we can lean on each other,” Schneider said.

As for medical providers, Schneider suggested that this kind of survey can alert these professionals to the need to honor names, pronouns and identities and not make blanket assumptions.

Despite some improvements, the local and national LGBTQ+ community remains at risk, Schneider said.

“There are any number of people who are actively considering suicide,” Schneider added. “It’s a very real crisis in our community.”

On a conference call announcing the results of the survey, Dr. Gregson Pigott, Suffolk County Commissioner of Health, described the survey, which Stony Brook plans to repeat in a couple of years, as “groundbreaking. What you have here is hard data based on the survey.”

Metro photo

By Daniel Dunaief

Daniel Dunaief

I have never been as happy to hear a Madonna song as I was this weekend.

Let me back up. My family and I attended our second familial wedding of the last three months. This one was a destination wedding in Ithaca, New York.

Stepping out of the rental car at the hotel on campus, I realized I wasn’t in Kansas anymore, as shorts, a T-shirt and a sweatshirt weren’t sufficient for the cooler upstate air.

In the hours before the ceremony on Saturday, my son, brother-in-law, his grown sons and I threw a tiny gift shop Nerf ball around on the baseball field, while surrounded by a visual collage of multi-colored foliage. That tiny football was probably the best $7.50 I’ve ever spent at a wedding.

With the wedding in the hotel, we only had to push an elevator button to get to the correct floor.

The bride and groom exchanged vows that they hadn’t previously shared with each other. Not too surprisingly after dating for close to a decade, the vows included many of the same references to things they each enjoyed about their time together, including dancing in the kitchen while making dinners, watching TV shows together during college, and running to the clock tower and back.

During the cocktail hour, I excused myself from my social circle to go to the bathroom, where I overheard the first of two unusual restroom conversations. The groom and his young cousin were chatting.

“You know the secret to a successful marriage?” the young man asked, eager to share the accelerated wisdom he’d accrued during his short life.

“What’s that?” the groom asked gamely.

“Separate vacations,” the sage young man suggested.

“Hmm, well,” the groom continued, “thanks so much for coming. I appreciate it.”

“My mom said my grandparents would have wanted us to come, so we came,” the unfiltered young man added.

Fortunately, neither of them could hear me inhale sharply.

Listening to the toasts and comments from the parents of the bride and groom, each side seemed to think the new member of the family would help soothe their partner. Perhaps, that says something about the way the bride and groom interact with their parents?

After dinner and before the music started, I returned to the restroom. This time, a man was standing at the sink, washing his hands.

“Out of respect for the gentleman who just walked in, I’m going to end our conversation about poop,” he said to a friend in the stall.

“Oh, uh, I’ll be leaving soon,” I offered, not wanting to interrupt.

“It’s okay,” he added. “We were done.”

Returning to the ballroom, I raced to the dance floor once the music started. My wife, children and I love to dance, with each of us smiling and shimmying as we jump, sway and sing the lyrics of the music. Somehow, our daughter knows the words to just about every song at most of these events, singing and shouting them to her cousin’s girlfriend, who has the same encyclopedic knowledge of modern music. I chime in with the chorus, while our son glides around, often with his arms in the air.

And here’s where Madonna came in. After bending my knees and swaying to numerous rap songs I had never heard before, I was thrilled to hear the familiar intro to a Madonna hit.

Buoyed by throwback sounds from an earlier decade, I threw myself around the floor, crooning for all I was worth.

When the rap songs returned, I scanned the floor and saw the bride, groom and their friends sharing their euphoria for the moment and for their familiar music. While Frank Sinatra never made an appearance, the happy couple were clearly doing it their way.

Caroline Mota Fernandes Photo by Jonas Nascimento Conde

By Daniel Dunaief

Fungal infections represent a significant health risk for some patients, killing about 1.5 million people globally each year. Doctors struggle to provide medical help for some of these patients, especially those whose weakened immune systems offer insufficient protection against developing pathogens.

Invasive fungal infections, which people typically contract by inhaling them as spores, account for about half of all AIDS-related deaths.

Maurizio del Poeta, Distinguished Professor at the Renaissance School of Medicine at Stony Brook University, has been studying ways to boost the body’s defenses against these potentially deadly infections, even among people with weakened immunities.

Recently, Caroline Mota Fernandes, a postdoctoral researcher in del Poeta’s lab, published research in the journal mBIO, a publication of the American Society for Microbiology, that demonstrated that a heat-killed, mutated version of the fungus Aspergillus conveyed protection in an animal model of an immunocompromised individual.

“The biggest news is that we can simply use the ‘autoclaved’ mutated version,” explained del Poeta in an email. “This version cannot be more dead!”

An autoclave is like a scientific oven: it raises the temperature or pressure. In this case, it can kill the mutated fungus, leaving only the mutated signal that primes the immune system.

The mutated and heat-killed version of the fungus, however, still provided full protection in a condition in a model of a weakened immune system.

“That means this formulation is highly stable and resistant to heat degradation,” del Poeta added.

Del Poeta’s lab had conducted similar research with another fungus called Cryptococcus.

By demonstrating that this approach also works with Aspergillus, del Poeta said the result “validates the cryptococcal vaccine (after all, it uses a mutant of the homolog gene, Sg11 in Crypto and SglA in Aspergillus.”

It also shows that protection exists under an additional type of immunodepression that is different from the one used in the cryptococcal vaccine.

The encouraging results, while in the preliminary stages, are relevant not only for immunocompromised people in general, but also for those who have been battling Covid, as Aspergillus was the cause of death for many patients during the worst of the pandemic.

Homologous genes

Del Poeta’s lab has focused on genes that catalyze the breakdown of steryl glucosides, which scientists have also studied in the context of plants. Crops attacked by various fungi become less productive, which increases the need to understand and disrupt these pathways.

“Folks working with plants started observing that these molecules had some kind of immunomodulatory property,” said Fernandes. “That’s where the idea of this steryl glucosides, which also is medicating fungal virulence, came from.”

The mutation Fernandes studied removed the sterylglucosidase gene sglA. Without the enzyme that breaks up the steryl glucose, the fungus had less hypha, which are necessary for the growth of the fungus. The mutation also changed the cell wall polysaccharides. Mice vaccinated with this heat-killed mutation had a one hundred percent survival rate in response to exposure to the live fungus.

“What was a very great achievement of our work was getting 100 percent protection,” said Fernandes. For immunocompromised people for whom a live attenuated fungus might threaten their health, the effectiveness of the heat-killed mutation proved especially promising.

In the experiment, she administered the vaccine 30 days before exposure, while providing boosters as often as every 10 days.

Fernandes, who started her post doctoral research in del Poeta’s lab in 2018, said several questions remain. “After this study, we are going to try to characterize exactly how this strain induces the immunity and protection to a secondary challenge of Aspergillus,” she said. Dr. Veronica Brauer, another post doctoral researcher in del Poeta’s lab, is conducting this research.

At this point, it’s unclear how long protection against a fungal infection might last.

“For us to estimate the duration of the protection, we have to have a more specific understanding of which immune components are involved in the response,” said Fernandes.

As of now, the mice vaccinated with the mutated and heat-killed fungus had no off target effects for up to 75 days after vaccination.

Fernandes is also working to characterize the mechanism of action of a new class of antifungal drugs previously identified by the lab, called acylhydrazones. She hopes to identify a new virulence protein in Cryptococcus as well.

Collaboration origins

Fernandes, who was born and raised in Rio de Janeiro, Brazil, first worked in del Poeta’s lab in 2013, while she was conducting her PhD research at Federal University of Rio de Janeiro. She was studying antifungal peptides and explained to the Brazilian government why coming to Stony Brook would contribute to her research.

Fernandes started studying fungi when she was in her second year of college at Federal University of Rio de Janeiro.

The daughter of two chemists, Fernandes said she grew up in a house in which she had pH strips, which she used to test the acidity of shampoo, water and anything else she could test. She also entered numerous science fairs.

Fernandes met her husband Jonas Conde, who is a virologist at Stony Brook University and who has studied Covid-19, when they were in nearby labs during their PhD research.

Residents of Port Jefferson, Fernandes and Conde have a four-month-old son named Lucas.

Having a child “motivates me to be better in my work and to set an example for him to be committed in doing some good for other people,” Fernandes said.

Del Poeta described Fernandes as being “extremely effective” in managing her time and has “extraordinary motivation.” He appreciates her commitment to her work, which is evident in the extra papers she reads.

Fernandes appreciates being a part of del Poeta’s lab. She described him as an “amazing” researcher and supervisor and said being a part of his group is “an honor.”

Del Poeta said Fernandes will continue to make mutants for additional fungi, including Mucorales and Rhizopous, for which antifungal therapy is not particularly effective.

Del Poeta added that the urgency of this work remains high. With several other Stony Brook faculty, he has submitted grants to study Sgl1 as a vaccine and antifungal target.

“Imagine [making] a drug that not only can treat the primary infection, but, by doing so, can potentially prevent the recurrence of a secondary infection?” he asked rhetorically. “Exciting!”

Cell phone etiquette. METRO photo

By Daniel Dunaief

Daniel Dunaief

You’re meeting with your boss, and you can feel your phone vibrating in your pocket with a new text message, an incoming email or a good old-fashioned phone call.

What do you do?

You’d be on pins and needles if someone you knew, your spouse or partner, perhaps, were expecting a baby. Or, perhaps, someone was traveling a great distance through a storm and you were eager to hear that your friend or family member had arrived safely.

But most of the time, the stakes aren’t quite as high with incoming information. In fact, some of the time, we’re getting spam that seeks our attention.

So, when we are talking to our boss, we generally realize that responding to our demanding electronics probably isn’t a great idea.

But what about when we are talking to a parent, a friend, a child or a neighbor?

Given the frequency with which I have seen the tops of people’s heads as they look down at their phones instead of in their eyes, it seems people have concluded that eye contact is so 20th century.

Since when did people outside the room become so much more important and demanding than the ones with whom we are interacting? If we can’t find people who are as interesting in person as the ones far away, perhaps it is time to move to interact with some of those fascinating folks.

I understand that people online don’t have bad breath and messy hair and aren’t wearing the same clashing outfit that they wore last week, and that continues to threaten to give us a migraine.

Maybe we ought to consider classes in electronic etiquette that teachers can share with students or with people who are receiving their first phone.

We can address not only how to handle an incoming text while in the middle of a conversation, but also how to unplug ourselves and our lives from endless messages, games, movies and TV shows.

If I could go back to the time when we handed phones to our children, ensuring that the phone would eventually replace bedtime stories, dinnertime conversation and eye contact, I would consider establishing our own “Ten Commandments” of phone ownership and usage.

These might be:

10. Limit the time each day when you use your phone, with only extraordinarily limited exceptions. If you need to use your phone for schoolwork for two or three hours, that still counts as phone usage.

9. Leave the phone in another room when you’re not using it.

8. If you can’t say something supportive or pleasant on social media, don’t say anything.

7. No anonymous messages or criticism. If you can’t use your name or stand behind what you write, you shouldn’t have written it in the first place.

6. Don’t take embarrassing pictures of your parents and share them with your friends. Older people don’t tend to look as glamorous in digital pictures as younger people, so be kind.

5. Internet fame is not a life goal.

4. When you become better at using your phone than your parents (which occurs in a surprisingly short time), share your wisdom and skills with them. Think of it as familial community service.

3. Don’t assume everything you find online is true. In fact, at least once a week, or even once a day, find something on the internet that you think is false. Use trusted sources to contradict what you think an internet provider got wrong.

2. If it looks like everyone else is having a better time than you, put your phone down. They aren’t.

1. If you can tell your parents to wait while you respond to a text or call from a friend, make sure you tell your friends the same thing when your parents reach out to you.

Dr. John Clarke. Photo from BNL

By Daniel Dunaief

Live from Upton, New York, it’s … Dr. John Clarke.

While the arrival of the new Occupational Medicine Director and Chief Medical Officer at Brookhaven National Laboratory doesn’t involve late-night comedy, or a live studio audience, it does bring a medical doctor with a passion for bringing his rap and musical skills to a health care audience.

Dr. John Clarke. Photo from BN

Formerly the director of occupational medicine at Cornell University, Dr. Clarke joined the Department of Energy lab as Occupational Medicine Director and Chief Medical Officer for BNL in June..

“My role is to help maintain safety and wellness among the workers,” said Dr. Clarke. “If we have employees who start coming in for some sort of complaint and we see a pattern, that may help us identify who could be at risk of something we didn’t know about that we are detecting.”

A doctor who served as chief resident at New York Medical College in family residency and Harvard University in occupational & environmental medicine, Dr. Clarke said he plans to support a range of preventive efforts.

“I’m excited about the potential to engage in what’s considered primary prevention,” said Clarke, which he defined as preventing a disease from occurring in the first place.

Through primary prevention, he hopes to help the staff avoid developing chronic illnesses such as cancer, while also ensuring the health and responsiveness of their immune systems.

Through physical fitness, a plant-based diet including fruits and vegetables, adequate sleep and hydration with water, people can use lifestyle choices and habits to reduce their need for various medications and enable them to harness the ability of their immune systems to mount an effective response against any threat.

“Modifying your lifestyle is the therapy,” he said. “If you engage [in those activities] in the right way, that is the treatment.”

Dr. Clarke added that the severity and stage of a disease may impact the effectiveness of such efforts. For any vaccine and for the body’s natural immunity to work, people need a healthy immune system.

When Dr. Clarke practiced family medicine, he saw how patients lost weight through a diet that reduced the need for medication for diabetes and high blood pressure.

“Losing weight and staying active does provide a therapeutic impact, where you could be medication free,” he said.

To be sure, living a healthier lifestyle requires ongoing effort to maintain. After reaching a desired weight or cholesterol level, people can backslide into an unhealthier state or condition, triggering the occurrence or recurrence of a disease.

In the vast majority of cases, Clarke said, “you have to make a permanent lifestyle change” to avoid the need for pharmaceutical remedies that reduce the worst effects of disease.

BNL has an exercise physiologist on staff who “we hope to engage in consultations with employees,” said Clarke. He would like the exercise physiologist to go to the gym with staff to show them how to use equipment properly to get the maximum benefit.

BNL already has some classes and various initiatives that promote wellness. “One of the things we’d like to do is coordinate and try to publicize it enough where employees are aware” of the options available at the lab to live a healthier and balanced life, he added.

BNL also has a dietician on staff. Dr. Clarke has not worked with the dietician yet, but hopes it will be part of an upcoming initiative. As he and his staff respond to the demand, they will consider bringing on other consultants and experts to develop programs. 

Covid concerns

Like others in his position in other large employers around Long Island, Dr. Clarke is focused on protecting workers from any ongoing threat from Covid-19.

“We’re still learning more as [SARS-CoV2, the virus that caused the pandemic] evolves,” he said. BNL does a “great job about monitoring the prevalence and the numbers of cases in Suffolk County and among workers.”

Dr. Clarke said he and others at BNL are following the Department of Energy, New York State and Centers for Disease Control and Prevention guidance on these issues.

If the numbers of infections and hospitalizations increase in the coming months, as people move to more indoor activities, BNL may consider deploying a strategy where the lab provides more opportunities for staff to work remotely.

Prior to his arrival at BNL, Dr. Clarke worked as a consultant for a company that was looking to create numerous permanent jobs that were remote.

He suggested that workers need to remain aware of their remote surroundings and shouldn’t work near a furnace or any heater that might release dangerous gases like carbon monoxide. 

Additionally, people should avoid working in areas that aren’t habitable, such as in an attic. Dr. Clarke urges people to notify and consult their employer if they have concerns about working safely at home or on site.

Music vs. medicine

A native of Queens who spent three years of his childhood in Barbados, Dr. Clarke attended Columbia University, where he majored in sociology and music while he was on a pre-med track.

While he was an undergraduate, Dr. Clarke wrote, produced and performed original music. An independent label was going to help secure a major label deal.

He chose to attend medical school at Icahn School of Medicine at Mount Sinai.

Dr. Clarke has championed a program he calls “health hop,” in which he has used rap to reach various audiences with medical care messages. In 2009, he won a flu prevention video contest sponsored by the Department of Health and Human Services for an “H1N1 rap.”

Train commuters may also recognize him from his work for the Long Island Railroad, for which he created a “gap rap.” The public service announcement was designed to protect children from falling into or tripping over the gap between the train and the platform.

Dr. Clarke has produced music for numerous genres, including for a children’s album and a Christian album.

As for life outside BNL, Dr. Clarke is married to Elizabeth Clarke, who is a nurse practitioner and is in the doctorate of nursing practice and clinical leadership program at Duke University.

When he’s not spending time with his wife or their children, he enjoys home projects like flooring and tiling.

Dr. Clarke is pleased to be working at the national Department of Energy lab.“BNL is a great place, because the science and the work they do has an impact,” he said.

Dr. Farquharson suggests showing a person experiencing a mental health emergency your hands with the palms open to show you are not a threat to the person. Stock photo

Long Island residents have taken CPR classes and learned lifesaving basics to help others with injuries through programs like “Stop the Bleed.”

But what about mental health emergencies?

Those may be more difficult to diagnose or understand, particularly for people who may not know the person in emotional distress.

While Suffolk County Police Department officers with specialized training, support service organizations like Diagnostics, Assessment and Stabilization Hub (known as DASH) and Family Service League, and mental health care workers are available to help, doctors offered suggestions for people who would like to provide assistance for a friend, coworker or relative while awaiting professional assistance.

Dr. Wilfred Farquharson IV, a licensed psychologist and director of the Child and Adolescent Psychiatry Outpatient Clinic at Stony Brook Medicine, helped create a two-page patient education sheet titled “Mental Health Emergency Response Guidance Sheet — Knowing Your Options.”

The guide provides suggestions on how to respond to a variety of emergencies, starting with lower level crises, which could include a change in mood or side effects from a medication that is not dangerous to a person’s health.

The options in that case are to contact a mental health provider to schedule an appointment, to use a safety plan or to schedule an urgent visit with a primary doctor.

In situations in which a person is destroying property, is threatening physical injury and is not in a position for a safe transport, the guide suggests calling 911.

To ensure effective help from emergency responders, the guide urges people to go to Smart911 to complete a profile for the household.

Additionally, people who call 911 should indicate that there is a mental health emergency. The person making the call should be prepared to offer the person’s name and location, the reason for the call, the person’s diagnosis (if known), things that upset the person, such as yelling at them or getting too close, things that might help soothe the person, and special considerations.

While people are waiting for first responders, they can try to deescalate the situation, using tools similar to the ones professionals practice.

“A lot of what we do is give the person space,” Farquharson said. “We show them our hands, with open palms, and let them know we’re not trying to be a threat. We don’t say too much. We allow the person to talk, as long as they’re being safe. We allow them to yell.”

Neutral tone

Dr. Adnan Sarcevic, chairman of the Psychiatry Department at Huntington Hospital, also urges people to provide “as much privacy as possible” for someone in distress.

Sarcevic recommended that supportive family, friends or community members be empathetic without being judgmental.

“Keep your tone and your body language neutral,” Sarcevic said. He urges people to remain calm and friendly.

People can help deescalate situations by acknowledging that someone else’s feelings are important and indicating that crying or being angry is okay.

Taking a cue from the person in distress can also help. If a person stops talking, “let him or her be there in silence. Let them reflect,” Sarcevic said.

Additionally, the Huntington Hospital doctor urged people to respect the personal space of someone who is struggling.

As far as his list of “don’ts,” Sarcevic said people shouldn’t use judgmental language or wag their fingers.

“Don’t ask, ‘Why’ or ‘How could you do that?’” Sarcevic advised.

Other resources

The Suffolk County Police Department implemented a 911 call diversion pilot program in 2021 which allows Emergency Complaint Operators to divert crisis calls, when considered safe, to the Crisis Hotline at Family Service League.

The SCPD collaborates with Family Service League on a 24-hour crisis hotline as well as a mobile crisis team of mental health professionals that can be deployed 24/7, officials from the SCPD explained in an email.

Additionally, the department said about 20% of SCPD officers are Crisis Intervention Team trained. Someone with that training is always on patrol. 

In addition to 911, people can reach out to DASH, which is the Diagnostic, Assessment and Stabilization Hub. A community crisis program with a Mobile Crisis Team for Suffolk residents, DASH is open every hour of every day and offers services for people who have mental health and substance abuse disorders.

For situations in which there are no safety risks, Stony Brook Medicine suggested that DASH is a good option. Residents can call the hotline at 631-952-3333.

Additionally, residents can call the Suicide and Crisis Hotline at 988 at any time.

Dr. Stacy Eagle, director of Psychiatry at St. Charles Hospital, cautioned that what deescalates one person might be different from what helps someone else.

Offering physical comfort to some people may help, while others might prefer to have their own space.

All three mental health professionals said the pandemic has contributed to higher levels of anxiety and depression among the population.

“The pandemic has increased the level of distress for those patients,” Eagle said. The pandemic could be the “stressful hit” that triggers discomfort or a mental health episode.

Farquharson has noticed an increase in the acuity of symptoms for some residents.

The mental health practitioners said the response to a crisis depends on the person involved and the type of problem he or she
is experiencing.

“You have to use [your] judgment”
when dealing with various circumstances, Sarcevic said.

Mental health professionals urged people to develop a plan that includes having phone numbers nearby, for 911, 988, DASH and the Family Service League, among others.

Additionally, doctors suggested people can help by being supportive and being prepared.

Farquharson said people should learn what to do if someone is not feeling well emotionally or mentally when a doctor’s office might be closed.