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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!”

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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.

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Babak Andi holds a 3-D model of the coronavirus responsible for the COVID-19 pandemic. Photo courtesy of BNL

By Daniel Dunaief

For close to two and a half years, the world has had a microbial enemy. The SARS-CoV2 virus, which causes Covid-19, has resulted in close to 6.5 million deaths, caused lockdowns, restricted travel, closed businesses, and sickened millions. The key to fighting such a dangerous enemy lies in learning more about it and defeating its battle plan.

Working with principal investigator Daniel Keedy, Assistant Professor at the City University of New York and Diamond Light Source in the United Kingdom, Babak Andi, who is a beamline scientist from the structural biology group at Brookhaven National Laboratory, spent over two years studying a key viral enzyme.

Recently, the researchers revealed the structure at five temperatures of an enzyme called Mpro, for main protease. This enzyme, which separates proteins the virus makes, is critical for the maturation of the SARS-CoV-2 virus particles. They published their work in the Journal of the International Union of Crystallography (IUCrJ).

Using the Frontier Macromolecular Crystallography (FMX) beamline at the National Synchrotron Light Source II at BNL, Andi collected data on the structure of the enzyme at temperatures ranging from 100 degrees Kelvin, which is about negative 280 degrees Fahrenheit, all the way up to 310 degrees Kelvin, which is normal body temperature. “Nobody had done that, specifically for this protein,” said Andi.

Keedy, who guided the data collection, processed the information and wrote most of the paper, described the effort as a “great collaboration.” The gradual change in the conformation of the enzyme helped the scientists learn how it may move or shape-shift in general, he explained.

Keedy had worked with BNL in the past and pursued research at the FMX beamline because the scientists at BNL had “been working with Mpro on site, and were very approachable and open to the idea.”

Finding the specific structure of important proteins like Mpro can help researchers, pharmaceutical companies and doctors search for inhibitors or small molecules that could be specific to these proteins and that might interfere with their function.

Andi and other scientists at this beamline worked through the pandemic shutdown because of the potential practical application of what they were doing.

“We almost had all the infrastructures in place to allow other scientists to connect and operate the beamlines remotely, enabling them to collect data on Covid-19 virus proteins,” said Andi. “In my opinion, being able to support all the academic and industrial scientists to collect data for Covid-19 research was our greatest achievement during the worst period of the pandemic.”

While coming into the lab in those early months raised concerns about their own health, Andi and his colleagues, who developed safety protocols, felt an urgency to conduct this research.

“When Covid hit, we had a sense that this is our duty, this is our job to contribute to this field, to make sure that every scientist who works on Covid-19 had easy access to our beamlines, facilities and all the tools [necessary] to make new drugs,” said Andi. 

How they solved the structure

The technology for the beamline enables Andi and other scientists to collect data quickly and even remotely. Speed helps because the longer x-rays hit a protein, the more likely they are to cause the kind of damage that makes determining the structure difficult, particularly at higher temperatures.

The first step in this research was in producing this protein, which Andi’s collaborators at BNL in the biology department provided. The biology department also helped with crystallization.

Andi prepared the beamline and aligned the x-ray beam, which are necessary to collect data.

The scientists rotated and moved the crystal through the x-ray, distributing the beam over the length of the crystal to minimize radiation damage.

The small size of the x-ray beam made it possible to keep the beam focused on the smallest dimension of the structure. The researchers studied the crystal at five different temperatures, starting at cryogenic all the way up to physiological.

Of the 195,000 structures listed in the Protein Data Bank, or PDB, only five had been determined at body temperature. That includes two from the group of collaborators who participated in this study.

Andi collected three or four data sets at each temperature.

“The different conformations we saw may inspire a new twist on antiviral drug development that targets a different place in the protein, but with a similar or better effect,” Keedy explained.

The researchers did not include other factors that might affect the conformation of the protein, such as pH, pressure, the number of ions or salts in the environment, among others. For the Mpro protease to work, it has to bond to another similar protein, forming a dimer.

Andi said the Pfizer treatment Paxlovid binds to the active site of this enzyme, inactivating it.

The drugs he is looking for are similar, although he is also searching for other places on the enzyme besides its active site.

Keedy hopes to try to make a monomeric form of the enzyme through a mutation. He could then find drug-like small molecules that target the exposed interface between the two copies.

BNL origins

After he completed his PhD and post doctoral work at the University of Oklahoma, Andi started his career at BNL 11 years ago as a post doctoral researcher.

During his childhood, Andi was initially interested in astronomy. When he enrolled at a university outside the United States, he took an entrance exam.

“Based on your score, it tells you which discipline of science you can go into,” he said. His score directed him to the field of cell and molecular biology.

“I’m happy this happened,” he said. “I find that I’m actually more interested in molecular biology than in astronomy.”

Outside of work, Andi enjoys do-it-yourself projects. Astronomy also continues to appeal to him, as he is fascinated with astrophotography and reads astronomy articles.

As for the work with a Covid enzyme, Andi hopes he has other opportunities to contribute. 

“I am interested [in continuing] the research in this field,” he explained. “That depends on time, resources and current or future priorities.”

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From left, Chang Kee Jung, Barry Barish and Carl Lejuez. Photo by John Griffin/Stony Brook University

By Daniel Dunaief

Albert Einstein predicted gravitational waves existed, but figured interference on the Earth would make them impossible to observe. He was right on the first count. On the second, it took close to a century to create an instrument capable of detecting gravitational waves. The first confirmed detection, which was generated 1.3 billion light years away when two black holes collided, occurred in September of 2015.

For his pioneering work with gravitational waves, which now include numerous other such observations, Barry Barish shared the Nobel Prize in 2017 with physicists Rainer Weiss and Kip Thorne.

In the fall of 2023, Barish is bringing his physics background and knowledge to Stony Brook University, where he will be the inaugural President’s Distinguished Endowed Chair in Physics. Barish will teach graduate students and serve as an advisor to Chang Kee Jung, Chair of the Department of Physics and Astronomy and Distinguished Professor.

From left, Barry Barish and Chang Kee Jung. Photo by John Griffin/Stony Brook University

“I’m really happy,” said Jung in an interview. “Nobel Prize winning work is not all the same. This work [Barish] has done with LIGO [the Laser Interferometer Gravitational-Wave Observatory] is incredible.”

Jung suggested the discovery of these two merging black holes “opened up a completely new field of astronomy using gravitational waves.” The finding is a “once-in-a-generation discovery.”

Gravitational waves disrupt the fabric of spacetime, a four-dimensional concept Einstein envisioned that combines the three dimensions of space with time. These waves are created when a neutron star with an imperfect spherical shape spins, and during the merger of two black holes, the merger of two neutron stars, or the merger of a neutron star and a black hole.

Jung suggested a way to picture a gravitational wave. “Imagine you have a bathtub with a little rubber ducky,” he said. In the corner of the bathtub, “you slam your hand into the water” which will create a ripple that will move the duck. In the case of the gravitational wave Barish helped detect, two black holes slamming into each other over 1.2 billion light years ago, when life on Earth was transitioning from single celled to multi celled organisms, started that ripple.

While Barish, 86, retired after a lengthy and distinguished career at CalTech in 2005, Stony Brook has no plans to create a team of physicists who specialize in this area. “The most important thing is that people together exchange ideas and figure out what to do next that’s interesting,” Barish said in an interview. “I’ll keep doing gravitational waves.”

Instead of encouraging graduate students and even undergraduates to follow in his footsteps, Barish hopes to “help stimulate the future here and help educate students,” he said.

An important call

Jung, who became chair of the department in the fall of 2021, has known Barish for over three decades. On a periodic informal zoom call, Jung reached out to Barish to tell him Stony Brook had offered Jung the opportunity to become chair. Barish suggested he turn it down. As Jung recalled, Barish said, “Why do you want to do that?”

On another informal call later on, Jung told Barish he decided to become chair, explaining that he wanted to serve the university and the department. Barish asked him what he would do as chair. Jung replied, “‘I would like guys like you to come to Stony Brook. It took [Barish] about 10 seconds to think about it and then he said, ‘That’s possible.’”

That, Jung said, is how a Nobel Prize winning scientist took the first steps towards joining Stony Brook.

Last week, Barish came to Stony Brook to deliver an inaugural lecture as a part of the newly created C.N. Yang Colloquium series in the Department of Physics and Astronomy.

Stony Brook officials were thrilled with Barish’s appointment and the opportunity to learn from his well-attended on-site lecture.

In remarks before Barish’s packed talk at the Simons Center Della Pietra Family Auditorium, Carl Lejuez, Executive Vice President and Provost, said he hears the name C.N. Yang “all the time,” which reflects Yang’s foundational contribution to Stony Brook University. “It’s fitting that we honor his legacy with a speaker of Dr. Barish’s character who, like Yang, is also a Nobel Prize winner. It’s a really nice synergy.”

Indeed, Yang, who won his Nobel Prize in 1957, coming to Stony Brook “instantaneously raised the university profile,” said Jung, whose department is the largest on campus with 75 faculty.

Surrounded by a dedicated team of scientists, and with the addition of another Nobel Prize winner to the fold, Jung believes the team will continue to thrive. 

“If you put together great minds, great things will happen,” he said.

Seeing the bigger picture

Barish is eager to encourage undergraduates and graduate students to consider the bigger picture in the realm of physics.

“[In general] we train graduate students to do something really important by making them narrower and narrower and narrower, so they can concentrate on doing something that’s worthy of getting a thesis and is as important as possible,” Barish said. “That works against creating a scientist who can look beyond something narrow. That’s bothered me for a long time.”

The problem, Barish continued, is that once researchers earn their degree, they continue on the same path. “Why should you happen to have had a supervisor in graduate school determine what you do for the rest of your life?” he asked.

Once students have the tools of physics, whether they are experimental or theoretical, they shouldn’t be so locked in, he urged. “It’s possible to use these same tools to do almost any problem in physics,” Barish added.

His goal in a course he plans to teach to advanced graduate students (that’s also open to undergraduates) is to provide exposure to the frontiers of science.

A few years ago, Barish recalled how the New York Times ran a picture of a black hole above the fold. He taught a class how scientists from around the world combined radio telescopes to make it act like one radio telescope the size of the Earth.

Helping students understand how that happened “pays off in the long run in making our physics students that we turn out be broader and more interesting and more interested in physics,” Barish said.

When Barish arrives next September, Jung said he plans to have some assignments for interactions with undergraduates. “Undergraduate research is critically important,” Jung said. Barish will also interact with various student groups, as well as the community outside the university.

“We will create those opportunities,” Jung said.

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A baby gelada foraging in Simien Mountains National Park in Ethiopia. Their early-life gut microbiome, from infancy through first years of life, are shown to be influenced by bacteria likely passed down from mom. Photo by Sharmi Sen

The bacteria that reside in the human gut (“the gut microbiome”) are known to play beneficial and harmful roles in human health. Because these bacteria are transmitted through milk, mothers can directly impact the composition of bacteria that their offspring harbor, potentially giving moms another pathway to influence their infant’s future development and health. A study of wild geladas (a non-human primate that lives in Ethiopia) provides the first evidence of clear and significant maternal effects on the gut microbiome both before and after weaning in a wild mammal. This finding, published in Current Biology, suggests the impact of mothers on the offspring gut microbiome community extends far beyond when the infant has stopped nursing.

A research team co-led by Stony Brook University anthropologist Dr. Amy Lu, and biologists Dr. Alice Baniel and Dr. Noah Snyder-Mackler at Arizona State University, came to this conclusion by analyzing one of the largest datasets on gut microbiome  development in a wild mammal.

“Early life gut microbial development is known to have a large impact on later life health in humans and other model organisms,” said Lu, Associate Professor in the Department of Anthropology in the College of Arts and Sciences at Stony Brook University. “Now we have solid evidence that mothers can influence this process, both before and weaning. Although we’re not 100% certain how mothers do this, one possible explanation is that they transfer specific bacteria to their offspring.”

The research team used high throughput DNA sequencing to identify and characterize the bacteria residing in the guts of young geladas, and identified 3,784 different genetic strains of bacteria belonging to 19 phyla and 76 families. However, this diversity was not equally distributed across the developmental spectrum: similar to what is seen in humans, younger infants had the least diverse microbial communities that gradually became more diverse as they got older. These changes reflected what the infant was eating, specifically when they switched from consuming milk to consuming more solid foods. These diet-focused bacteria actually help infants process foods – for instance, milk glycans, which cannot be digested without the help of bacteria.

However, it was the team’s findings of strong maternal effects on the infant gut microbiome both before and after weaning that was the most groundbreaking.

“Infants of first-time moms showed slower development of their gut microbiota, meaning that their guts were specialized toward milk digestion for longer compared to kids from other moms. This may put offspring of newer moms at a slight developmental disadvantage,” said Baniel. “In addition, even after infants were weaned, their microbiome community was more similar to mom’s than to other adult females in the population, suggesting that mom’s may be sharing microbes with their offspring.”

According to Snyder-Mackler, “these early life changes might have far-reaching consequences–impacting the health and survival of these offspring once they become adults.”

Future work from this research team will focus on examining how differences in the gut microbiome during infancy influence other aspects of development, such as growth, the maturation of the immune system, or the pace of reproductive maturation. Because they are continuing to study the same infants as they age, they expect to eventually be able to link the infant gut microbiome and the early-life maternal effects to health, reproduction, and survival in adulthood.

The research was funded by several grants from the National Science Foundation, the National Geographic Society, the Leakey Foundation, and from the University of Michigan, Stony Brook University, and Arizona State University.

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Aleida Perez during BNL's virtual teaching sessions this summer

By Daniel Dunaief

For well over two years, herd immunity, vaccination status, social distancing, masking and airborne particles became regular topics of conversation. 

People have a range of understanding of these terms and how to apply them to understanding the fluid conditions that are an evolving part of the pandemic.

Aleida Perez

This summer, with funding from the National Science Foundation, a group of scientists and doctors from Brookhaven National Laboratory, Stony Brook University, New York University and MoMath, the National Museum of Mathematics, worked together with middle school and high school teachers around Long Island to prepare lesson plans on how to use and understand the application of statistics to the pandemic.

“It was a wildly successful summer,” said Dr. Sharon Nachman, Chief of the Division of Pediatric Infectious Diseases at Stony Brook Children’s Hospital. “We spent hours and hours of time” working with teachers who developed lessons that addressed a host of issues related to COVID-19.

It was “an amazing experience” and the teachers “were the best part,” said Dr. Nachman.

Allen Mincer, Professor of Physics at New York University, has been working on and off with BNL for over two decades on various educational programs. He has been more actively engaged in the last four years.

As he and his collaborators were discussing possible educational outreach topics, they focused on the disruptive disease that changed the world over the last few years.

“This year, we were talking about it and, instead of doing random applications of statistics, we figured, why not do something that’s very practical in everyone’s mind,” Mincer said.

The projects and discussions, which were all conducted virtually, centered on numerous misconceptions people have about the pandemic. Teachers focused on questions including: what is the “efficiency” of a vaccine and how is it determined, what does a positive virus test result mean, if I am vaccinated, why do I care if others are, why take a vaccine when there are side effects, and I have to go to school and mix with people, so why shouldn’t I also let down my guard in other ways, among others.

“The challenges that this virus brings concerning topics like herd immunity was very interesting,” said Scott Bronson, manager of outreach to K-12 teachers and student for BNL’s Office of Educational Programs.

Scott Bronson during the BNL virtual teaching sessions this summer.

For teachers and their students, the realities of the pandemic were the backdrop against which these teachers were seeking to provide guidance. “It was happening live,” said Bronson. “What is herd immunity? That’s where the work of [Dr. Nachman and Mincer] came together beautifully.”

Bronson added that students will have a chance to explore the kinds of questions pharmaceutical companies are addressing, such as “What would you want the next vaccine to do” and “What would you do to make the vaccine better at preventing infection.”

The organizers put together teams of three to four high school and middle school teachers who created statistics lessons plans for the group.

“The way we worked it out, we put teachers in groups,” said Aleida Perez, supervisor of student research and citizen science programs for Brookhaven National Laboratory’s Office of Educational Programs. “We wanted to have different teachers with different courses and different perspectives on how to do things.”

One of the overarching goals was to help students understand such lessons as what it means to have a negative result on a virus test or what it meant when scientists and pharmaceutical companies described a vaccine’s efficacy.

The teachers explored the probability of side effects like myocarditis and whether the “benefit outweighs the risk of taking the vaccine,” Perez said.

For many of the teachers, the discussion expanded beyond COVID to an analysis of any infectious agent. Indeed, one of the groups of teachers described a zombie apocalypse.

The teachers provided a “nice overview to look at the education of public students,” said Perez.

The group hopes to make these lessons available for other teachers, although they haven’t determined where or how to post them.

The scientific team also hasn’t determined yet how to measure the long term impact or effectiveness of these lessons.

ATLAS project

As a part of the team involved in the ATLAS physics program at the Large Hadron Collider in Geneva, Switzerland, Mincer uses statistics to design, test and implement the tools to pick and choose from numerous reactions and then to study the data collected.

“We actually keep about a billion events out of the 100 trillion or so interactions the LHC produces in a year,” Mincer explained.

In previous years, Mincer has taught about statistics in general and its use in ATLAS. This year, he focused on statistics and its application to pandemic questions.

Several years ago, Mincer taught a freshman seminar called “Great science, fabulous science and voodoo science,” in which he described what students could learn from statistics, how the media covers science, science and government policy and how lawyers use science in the courtroom.

“After explaining statistics [and sharing] why we can only say we have evidence down to this level, I had a student tell me he’s dropping out of science as a major because he wanted certainty and I disillusioned him,” Mincer said.

As for the work with the high school teachers, Mincer said it was “great what they have been able to do” in preparing lessons for their students and sharing information about statistics.

Mincer has received some additional funds from the NSF to support two more such educational outreach programs, one of which will tentatively cover climate change.

“Statistics can be used to quantify the likelihood of events in the absence of climate change,” he explained.

Statistics provide a tool to document subtle but potentially significant changes in climate.

While Bronson wouldn’t commit to a discussion of climate change for the next group of teachers, he said he “wouldn’t be surprised if we look at climate change” and that “there’s a lot of interesting areas to explore in this field.”

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Arjun Venkatesan is testing an enhanced coagulation approach to treat contaminated water. Photo by John Griffin/Stony Brook University

By Daniel Dunaief

One person’s toilet flush is another’s pool of information.

Arjun Venkatesan, Associate Director for the New York State Center for Clean Water Technology at Stony Brook University, has gathered information from wastewater plants to search for traces of opioids and other chemicals.

Such monitoring is a “great tool” and relies on the sensitivity of the method, Venkatesan said.

Indeed, other scientists, including Professor Christopher Gobler, Endowed Chair of Coastal Ecology and Conservation at the School of Marine and Atmospheric Sciences at Stony Brook, have used wastewater monitoring to collect information about the prevalence of Covid-19 in a community.

Gobler explained that such monitoring has proven to be an “ideal way to track community infections. Through early to mid 2022, positive test rates and wastewater virus levels tracked perfectly. Since then, people began home testing and now, wastewater epidemiology is probably our best sign of community infection rates.”

In a joint effort through the Center for Cleanwater Technology, Venkatesan’s team monitors for chemicals, including opioids and other drugs. Such tracking, which college campuses and local governments have done, does not involve gathering information from any specific home. Instead, the scientists take anonymous samples from a larger dorm or a neighborhood, hoping to track changes in the presence of chemicals or a virus to enable health care mitigation efforts.

Venkatesan has been looking at common over-the-counter drugs and anti-viral treatments that residents used to treat Covid-19 infection, particularly before the development and distribution of several vaccines. He noticed an increase in over the counter use that matched the increase of Covid cases, which suggested that the infected people took these pain medicines for their symptoms first.

Venkatesan’s group monitored the use of these drugs over the last two years to confirm the trends. This baseline allowed him to “see increasing trends” in usage, he said. The increase “clearly indicates something more than what the drugs are regularly used for.”

Opioids

Venkatesan’s group has been working with the Department of Health to develop standard protocols to measure drugs at these sewage treatment plants. The testing needs to be updated to account for changes in consumption of new drugs that are being synthesized.

Each sample Venkatesan and his colleagues collect typically has hundreds of thousands of people in it, because the treatment plants process sewage for a large collection of communities. “This keeps anonymity,” he said. “We don’t want to dig up [information] from a single family home.”

The method is also cost effective when a single sample represents a larger population. This kind of information, however, could help public health professionals monitor the presence of drugs broadly in a community, providing them with a way to track the prevalence of addictive and potentially harmful drugs.

Venkatesan is developing methods to track fentanyl, a highly addictive drug linked to numerous deaths throughout the country and the world. Studies in other regions have demonstrated elevated levels of this drug.

Venkatesan said New York State responded to the pandemic by developing surveillance over the last few years. The approach was not well known and was limited mostly to illicit drugs. The pandemic made a significant impact, which helped officials appreciate the value of such a tool.

The state could also theoretically monitor for any chemicals that are stable enough in sewage.

While Venkatesan hasn’t measured traces of alcohol at sewage treatment plants, researchers and public health officials could create a screen to measure it. He was involved in a study that monitored for alcohol and nicotine consumption in many cities. “We could get interesting trends and understand community and population health in a better way,” he said. The pandemic has “helped establish the importance of this network.”

Surveys in which people call and ask about the consumption of drugs or alcohol can contain self-reporting error, as respondents may not know exactly how much they drink or may be reluctant to share those details.

Wastewater monitoring could capture trends, including whether communities have a spike in the use of drugs or alcohol on Friday nights or on weekends.

The Centers for Disease Control and Prevention created standardized methods for monitoring Covid-19 in the wastewater of cities and states.

Wastewater monitoring techniques are different for detecting viruses compared to chemicals. Venkatesan’s group is developing different method to screen for opioids. “We are excited about it,” he said. “Hopefully, next year, we should be able to monitor communities.”

As long as the sampling doesn’t cross any predetermined ethical line, monitoring could provide an effective way of looking at the trends and data, he said.

With so much water flowing through pipes and treatment plants, one of the biggest challenges in these efforts is to understand variables that affect what the scientists are monitoring.

The time between when a toilet is flushed in an apartment to the time when it reaches a plant can vary, depending on numerous variables, which creates uncertainty in the data.

To reduce this variability, scientists could do some sampling in manholes, between treatment plants.

Scientific roots

Venkatesan took an elective at the end of college in environmental science when he attended Anna University in Chennai, India. It was the first time he observed a wastewater treatment plant.

Fascinated by the process, he earned a Master’s in Environmental Engineering at the University of Nevada, Las Vegas and then went on to get a PhD at Arizona State. He also did his post doctoral research in Arizona.

Stony Brook was looking for a scientist to screen for contaminants in drinking water, including PFAS chemicals, which is a group of chemicals that are stable, hard to break down and are linked to thyroid cancer, among others.

PFAS chemicals are used in cleaners, textiles, fire-fighting foam and other applications.

Venkatesan leads drinking water efforts, while waste water epidemiology remains an ongoing project of interest.

Gobler hired Venkatesan five years ago to help run and then to exclusively run the drinking water initiative at Stony Brook.

Through the process, Venkatesan has “brought new insights and research programs related to wastewater epidemiology, bisolids and many other topics,” Gobler explained. Venkatesan has “exceeded expectations,” as he transitioned from a postdoctoral researcher to become Associate Director for Drinking Water Initiatives.”

Gobler called his colleague a “complete professional” who is “very positive and a good person to work with.”

In his research, Venkatesan develops technologies to remove these PFAS chemicals, while monitoring is also a part of that effort. Activated carbon filters can remove these chemicals from groundwater. These filters, however, require frequent replacement. Venkatesan is exploring ways to improve the life of the carbon filter.

PFAS chemicals make rain water unsafe to drink. Removing PFAS chemicals is an “important research topic locally and globally.”

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This rendered image of the brain via a technique called diffusion tractography reveals parts of the brain’s white matter in a compilation of WTC responders experiencing cognitive impairment (CT). These areas depicted by various colors illustrate where the brain is more vulnerable to neurodegenerative processes. The different colors represent differences in the heath of various parts of the brain including the limbic system. Credit: Chuan Huang
Stony Brook-led imaging study sheds light on PTSD-associated mental decline

A study that assessed the brains of 99 World Trade Center (WTC) responders by using diffusion tractography, a 3-D imaging technique, showed that WTC responders with cognitive impairment (CI), a possible sign of dementia, and post-traumatic stress disorder (PTSD), have a different presentation of the white matter in their brains compared to responders with CI without PTSD. Led by researchers at Stony Brook University affiliated with the Stony Brook WTC Health and Wellness Program, the study suggests a specific form of dementia could be affecting WTC responders who also have PTSD. The findings are published early online in the Journal of Alzheimer’s Disease.

According to the authors, this is the first study to examine white matter alterations using connectometry in a sample of WTC responders in mid-life (average age: 56) with and without concurrent PTSD. The goal of the study was to examine and elucidate the extent to which white matter tract integrity might be impaired in WTC responders with CI and/or PTSD. Previously, the researchers had identified changes in white matter diffusivity in small numbers of responder patients.

“Our findings are by no means conclusive in terms of defining CI or dementia in WTC responders, and if this study provides evidence of a new form of dementia emerging,” says Sean Clouston, PhD, lead author and Associate Professor in the Program in Public Health, and in the Department of Family, Population, and Preventive Medicine at Stony Brook University.

“Overall, the study supports the view that responders with CI have neurological changes consistent with neurodegenerative disease, but they are inconclusive as to the type of disease,” he adds. “Our findings do show that dementia due to PTSD is clearly different from non-PTSD dementia in this responder population.”

Subjects in the study were matched by age, gender, occupation, race and education. Cognitive status was determined by using the Montreal Cognitive Assessment, and PTSD status was determined by using the Diagnostics and Statistics Manual-IV. The researchers used diffusion tensor imaging via a mMR scanner, and they used connectometry to examine whole-brain tract level differences in white matter integrity as reflected by fractional anistrophy (FA) values.

In summary, the team found that FA was negatively correlated with CI and PTSD status in the fornix, cingulum, forceps minor of the corpus callosum, and the right uncinate fasciculus. Additionally, FA was negatively correlated with PTSD status, regardless of the CI status in the superior thalamic radiation and the cerebellum.

The authors conclude that the brain imaging results “suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.”

The technique and other findings

Clouston and colleagues used the imaging technique diffusion tractography to examine how healthy axons are in the brain’s white matter. The technique helped to determine that responders with CI had signatures in their white matter that did not match patterns seen in old-age Alzheimer’s disease and other related dementias.

By using the imaging technique, they also compared responders with PTSD and dementia to those with dementia but without PTSD. The imaging revealed a lot of similarities between the groups but also showed a remarkable difference in the white matter of those with PTSD and dementia – showing evidence of cerebellar atrophy, a finding that is inconsistent with other studies of dementia.

The research for the study was supported in part by the National Institutes of Health’s National Institute on Aging (grant # R01AG049953), and the Centers for Disease Control and Prevention (grant # U010H011314) and the National Institute for Occupational Safety and Health, NIOSH, (grant # 200-2011-39361).

 

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Joanna Wysocka

By Daniel Dunaief

This is part one of a two-part series featuring Cold Spring Harbor Laboratory alums Joanna Wysocka, Robert Tjian, Victoria Bautch, Rasika Harshey and Eileen White. Part two will be in the issue of Aug. 25.

Often working seven days a week as they build their careers, scientists plan, conduct and interpret experiments that don’t always work or provide clear cut results.

Driven by their passion for discovery, they tap into a reservoir of ambition and persistence, eager for that moment when they might find something no one else has discovered, adding information that may lead to a new technology, that could possibly save lives, or that leads to a basic understanding of how or why something works.

Nestled between the shoreline of an inner harbor along the Long Island Sound and deciduous trees that celebrate the passage of seasons with technicolor fall foliage, Cold Spring Harbor Laboratory has been a career-defining training ground for future award-winning scientists.

Five alumni of Cold Spring Harbor Laboratory recently shared their thoughts, experiences, and reflections on the private lab that was founded in 1890.

While they shared their enthusiasm, positive experiences and amusing anecdotes, they are not, to borrow from scientific terminology, a statistically significant sample size. They are also a self-selecting group who responded to email requests for interviews. Still, despite their excitement about an important time in their lives and their glowing description of the opportunities they had to hone their craft, they acknowledged that this shining lab on the Sound may not be paradise for everyone.

Cold Spring Harbor Laboratory is considerably smaller than some of the research universities around the country. Additionally, scientists with a thin skin — read on for more about this — may find their peers’ readiness to offer a range of feedback challenging. Still, the lab can and has been a launching pad.

A suitcase and a dream

Joanna Wysocka’s story mirrors that of other immigrants who came to the United States from their home countries. Wysocka arrived from Poland in 1998 with one suitcase that included mementos from her family, a Polish edition of her favorite book, One Hundred Years of Solitude, and a dream of developing her scientific career.

She was also chasing something else: her boyfriend Tomek Swigut, who had come to Cold Spring Harbor Laboratory. “I was fresh off the boat without any fancy resume or anything,” Wysocka recalls. “They really took a chance on me.”

Joanna Wysocka

While she learned how to conduct scientific experiments, she also recognized early on that she was a part of something bigger than herself. Early on, she found that people didn’t hold back in their thoughts on her work. “You always got critical feedback,” she said. “People felt very comfortable picking apart each other’s data.”

The positive and negative feedback were all a part of doing the best science, she explained.

Wysocka felt the inspiration and exhilaration that comes from a novel discovery several times during her five-year PhD program.

“It’s 11 p.m. in the evening, you’re in the dark room, developing a film, you get this result and you realize you’re a person who knows a little secret that nobody else in the world knows just yet,” she recalled. “That is really wonderful.”

For special occasions, the lab celebrated such moments with margaritas. Winship Herr, her advisor, made particularly strongest ones. 

In one of her biggest projects, Wysocka was working with a viral host cell factor, or HCF. This factor is critical for transcription for the Herpes simplex virus. What wasn’t clear, however, was what the factor was doing. She discovered that this factor worked with proteins including chromatin modifiers. “From this moment, it set me up for a lifetime passion of working on gene regulation and chromatin,” she said.

As for the scientific process, Wysocka said Herr offered her critical lessons about science. When she started, Herr expected two things: that she’d work hard and that she’d learn from her mistakes. During the course of her work, she also realized that any work she did that depended on the result of earlier experiments required her own validation, no matter who did the work or where it was published. “You need to repeat the results in your own hands, before you move on,” she explained.

Despite the distance from the lab to New York City and the smaller size of the lab compared with large universities, Wysocka never felt isolated. “Because of all the conferences and courses, the saying goes that ‘if you want to meet somebody in science, go to a Cold Spring Harbor bar and sit and wait.’” That, however, is not something she took literally, as she put considerable hours into her research. While she wishes she had this incredible foresight about choosing Cold Spring Harbor Laboratory, she acknowledges that she was following in Swigut’s footsteps.

The choice of CSHL worked out well for her, as her research has won numerous awards, including the Vilcek Prize for Creative Promise in Biomedical Science, which recognizes immigrant scientists who have made a contribution to U.S. society. She now works as Professor at Stanford University and is married to Swigut.

Swinging for the fences

In 1976, Robert Tjian had several choices for the next step in his developing scientific career after he completed his PhD at Harvard University. James Watson, who had shared the Nobel Prize in 1962 for the double helix molecular structure of DNA with Francis Crick and Maurice Wilkins and was director at Cold Spring Harbor Laboratory, convinced him to conduct his postdoctoral research at CSHL.

Robert Tjian

The contact with Watson didn’t end with his recruitment. Tjian, who most people know as “Tij,” talked about science on almost a daily basis with Watson, which he considered an ‘incredible privilege.”

Although he only worked at CSHL for two years, Tjian suggested the experience had a profound impact on a career that has spanned six decades. 

Learning about gene discovery was the main driver of his time at CSHL. An important discovery during his work at CSHL was to “purify a protein that binds to the origin of replication of a tumor virus, which was what [Watson] wanted me to do when he recruited me,” he said. That launched his career in a “positive way.”

Tjian feels fortunate that things worked out and suggested that it’s rare for postdoctoral students to achieve a transformative career experiment in such a short period of time either back then or now. He attributes that to a combination of “being in the right place at the right time,” luck and hard work.

At Berkeley, where he is Professor of Biochemistry, Biophysics and Structural Biology and has been running a lab since 1979, he has observed that the most successful researchers are the ones who are “swinging for the fences. If you don’t swing for the fences and get lucky, you sure as hell aren’t going to hit a home run.”

Tjian learned how to run a lab from his experience at CSHL. He selects for risk takers who are independent and feels the only way to motivate people is to ensure that the work they are pursuing involves questions they want to solve.

One of the most important and hardest lessons he learned during his research career was to “fail quickly and move on.” He tells his student that about 85 percent of their experiments are going to fail, so “get used to it and learn from it.”

Despite his short and effective stay at CSHL, Tjian suggested he made “more than his fair share” of mistakes. Terri Grodzicker, who is currently Dean of Academic Affairs at CSHL, taught Tjian to do cell culture, which he had never done before. He contaminated nearly all the cultures for about a month.

While Tjian described the lab as a “competitive place,” he felt like his colleagues “helped each other.”

When he wasn’t conducting his experiments or contaminating cultures, he spent time on the tennis court, playing regularly with Watson. Watson wasn’t “exactly the most coordinated athlete in the world,” although Tjian respected his “remarkably good, natural forehand.” He was also one of the few people who was able to use the lab boat, which he used to fish for striped bass and bluefish early in the morning. “I would try to drag all kinds of people out there,” he said. 

While his CSHL experience was “the best thing” for him, Tjian explained that the lab might not be the ideal fit for everyone, in part because it’s considerably smaller than larger universities. At Berkeley, he has 40 to 55 PhD students in molecular biology and he can interact with 40,000 undergraduates, which is a “very different scale.”

Tjian has returned many times to CSHL and is planning to visit the lab at the end of August for a meeting he’s organizing on single molecule microscopy.

Each time he comes back, he “always felt like I was coming home,” he said.

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Jim and Jacqueline Olsen

By Daniel Dunaief

When Jacqueline Olsen learned the day before her birthday last November that she needed surgery for lung cancer, she felt anxious about a procedure she knew could be painful and could involve a lengthy recovery.

“It’s not only my birthday, it’s Thanksgiving,” said Olsen, who is a resident of St. James and is an agent for personal insurance such as home, auto and umbrella insurance. “Everybody was real tense. It was not a pleasant holiday.”

Olsen’s father, William Leonard, and father-in-law, James Olsen, had died of lung cancer after having open chest surgeries. The pain of what her father went through 48 years ago and father-in-law over 20 years ago was fresh in her mind as she readied herself for her own procedure.

Dr. Ankit Dhamija

Speaking with doctors at Stony Brook University Hospital, Olsen heard about newer, better options.

Dr. Ankit Dhamija, Cardiothoracic Surgeon and Director of Thoracic Robotic Surgery at Stony Brook Medicine, suggested to Olsen that she was a candidate for a robot-assist surgery called the da Vinci Surgical System. 

Olsen and her family gathered considerable information about the procedure.

“I did some research on it and it said it would be a faster recovery and I would be up and back to my normal self pretty soon afterward,” said Olsen. “It seemed like a less invasive surgery.”

The robotic surgery does not involve turning over the procedure to a machine, Dr. Dhamija explained.

Instead, the process involves making considerably smaller incisions and guiding the robot through the body to remove the cancerous tissue.

“The robot is a machine that is an extension of our hands,” said Dr. Dhamija, who has performed about 500 such procedures with the help of a robot, including around 70 since he arrived at Stony Brook.

The robotic system allows surgeons like Dr. Dhamija and Dr. Henry Tannous, Cardiothoracic Surgeon and Chief of the Cardiothoracic Surgery Division at Stony Brook Medicine, among others, to sit in the operating room with the patient while the robot enters through an incision. The robot provides a three dimensional view of the inside of the body, magnifying cells by ten times.

The robot assist can also improve the ability of surgeons to perform fine operations.

The system “does have a machine algorithm associated with it that actually is known to reduce tremors in surgeons that have tremors,” said Dr. Dhamija. “Someone that may not be able to do a certain portion of the operation due to their technical limitations can subsequently do it with the robot.”

Dr. Henry Tannous

In the procedure, the surgeon can see and maneuver through the body effectively, searching for the specific cells to remove.

An interventional radiologist can inject a dye which under CT guidance allows the surgeon to “see where the lesion is and to verify that you have adequate margins” or the border between cancerous and non-cancerous cells, Dr. Dhamija said. “Having the dye in there to identify [the cancer] is helpful,” he added.

By using the robot instead of creating a large incision, doctors can reduce the time patients spend in a hospital down to as little as one to three days from the four to eight days after an open chest lobectomy.

“There’s so much to be said about someone [recovering] in their own home,” said Dr. Dhamija. They “get to sleep properly, their bowel habits are more normal, and they get to reengage in their daily life functions sooner. I’m a big proponent of a patient taking charge of their own postoperative care.”

Indeed, Stony Brook doctors have become so confident and comfortable with the robot assist that it has become the main platform for thoracic oncology patients at Stony Brook Medicine, explained Dr. Tannous. Tannous estimates that 90 percent of the lobectomies will be performed robotically in 2022, up from 10 to 20 percent in 2021.

In an email, Dr. Tannous wrote that other specialties that have adopted the robotic platform include gynecology, urology, colorectal, bariatrics, and general surgery.

Stony Brook is also expanding robotic surgery to include cardiac procedures in 2023.

Dr. Tannous said robotic procedures that cut down on recovery time means less risk of hospital-acquired infections, lower extremities blood clots, and numerous other benefits.

Some day, theoretically, the robot may enable remote procedures, with surgeons operating the robot with the help of an on-site local medical team. That could be helpful for astronauts who develop a medical problem far from home where they need emergency surgery.

An important caveat with that, Dr. Dhamija said, is that the staff on site would need to be able to complete a procedure if an open chest surgery became necessary.

Olsen, who was out of the hospital less than 24 hours after she had surgery in late May, has become a fan of the technology and of the team at Stony Brook.

Olsen, who has three scars on her back and two on her side, felt pain for about a week. As she recovered, she never felt the need to fill a prescription for a stronger painkiller, choosing to treat the pain with Motrin. She plans to continue to take blood tests every three months and to get CAT scans every six months.

Olsen was thrilled with the quality of care she received and is pleased she can look forward to sharing quality summer time during the family’s annual beach trip. “It’s heaven to me,” she said, where she can “spoil my grandchildren.

As for a perspective on her surgery, she said the difference between 20 years ago and now is “unbelievable. It was such an awful experience” for her father and father in law. “This was a million times better.”

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