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Power of 3

Paolo Boffetta. Photo by Jeanne Neville/Stony Brook Medicine

By Daniel Dunaief

Screening for cancer can help people take steps to head off the development of a disease that could threaten the quantity and quality of their lives.

During the start of the pandemic, people around the world stopped screening for cervical, breast and colorectal cancer, according to a recent study led by Paolo Boffetta, Associate Director for Population Sciences at Stony Brook University’s  Cancer Center.

The results of the study were recently published in the journal JAMA Oncology.

Compared to 2019, screenings for breast cancer dropped in the first few months after the start of the pandemic by 35.6 percent for breast cancer, 41.8 percent for colorectal cancer, and 54.1 percent for cervical cancer compared to the same period in 2019.

Paolo Boffetta. Photo by Jeanne Neville/Stony Brook Medicine

Boffetta chose these three cancers because they are the ones public health authorities recommend for the population at large. Screenings can improve patient outcomes. 

“For some/ most cancer, the earlier the better for detection,” explained Stony Brook Cancer Center Director Yusuf Hannun.

Boffetta, who is also Adjunct Professor at the Icahn School of Medicine at Mount Sinai in New York City, suggested that the longer-term impact of a reduction in screenings in the early part of the pandemic won’t be clear to doctors or patients in the short term.

“It will take a little bit of time to have a full understanding of this,” said Boffetta. Depending on the specific type, cancers “that are detected by screenings would not otherwise appear for a few years.”

Boffetta suggested that the pandemic, apart from the illnesses and symptoms that threatened the health of people who were battling the virus itself, affected public health services. He believes several factors likely contributed to the decrease in screenings. Patients around the world were reluctant or restricted in their ability to leave their homes amid lockdowns.

Additionally, some cancer centers likely reduce the number of people they monitored to cut back on the density of patients in health care facilities, although Boffetta did not gather any data on the reduction in the number of screenings at health care centers.

The positive news amid this study, which surveyed cancer screening data in PubMed and other medical journals from 19 countries from January 2020 through December 2021, was that the number of patients screened returned to a more normal level within several months of the start of the pandemic.

“An important finding is that by the summer of 2020, the decrease in screenings for breast cancer and cervical cancer seem to have disappeared,” Boffetta said by phone from Italy, where he is a part-time professor at the University of Bologna. “For colorectal cancer [the decrease in screenings] lasted longer,” through the end of 2020.

Boffetta described the reduction in screenings and then a return to normal as a U-shaped curve, with an initial decline followed by a recovery. Doctors typically screen for colorectal cancers by using a colonoscopy. This technique requires several hours in the hospital. Patients may have been “more reluctant to go back to such a complex procedure, compared to the mammography or pap smear” which screen for breast and cervical cancers, respectively.

Boffetta is conducting a broad study of the cancer literature from early findings to clinical diagnosis to treatment. At this point, he has finished a paper on the frequency and types of clinical diagnoses amid the pandemic. He is collecting data for another study that will examine cancer treatment.

“We are interested in how the pandemic affected each of these stages,” he said.

Hannun suggested that Boffetta’s work expertise help address important health care questions related to the pandemic and other threats to public health, adding, “Epidemiology is essential for understanding the pandemic and many chronic diseases, especially cancer with exposure issues.

A lab update

Boffetta joined Stony Brook University in April of 2020, soon after the start of the pandemic.

Also a Professor in the Department of Family, Population and Preventive medicine at the Renaissance School of Medicine at Stony Brook University, Boffetta will return to the United States in a few weeks from Italy.

Boffetta has added Research Coordinator Germana Giupponi and postdoctoral fellow Malak Khalifeh to his research efforts at Stony Brook. 

Germana Giupponi

A native of Italy, Giupponi, who started working with Boffetta in July of 2020 and provides administrative support and coordination with Boffetta’s collaborators, earned her master’s degree from the University of Milan.

Khalifeh joined Boffetta’s lab in March, is originally from Lebanon and conducted her PhD research in France at the University of Bordeaux. She is studying the link between the exposure people have to various chemicals in drinking water and bladder cancer. The bladder is especially susceptible to toxins from the environment.

Boffetta, meanwhile, has started teaching some graduate level classes at Stony Brook on cancer epidemiology for master’s and PhD students. He will teach one class this fall.

He is also continuing his studies with survivors of the World Trade Center attacks.

He has been comparing the survival of these first responders to the overall population in New York, comparing how the risk of cancer changed over the course of the 21 years since the attacks.

Boffetta has been working with Ben Luft, Director of the Stony Brook WTC Wellness Program at the Renaissance School of Medicine. Luft has provided clinical and research support for WTC responders.

Boffetta continues to have academic affiliations with other academic institutions, including Harvard University and Vanderbilt University.

Boffetta and his wife Antonella Greco, who have been living in New York City, plan to move to the Stony Brook area. Their three daughters live in Brooklyn, Italy and Argentina. Now that pandemic restrictions have lifted, Boffetta has been able to return to the opera and museums and has done some skiing and hiking.

As for this study, Boffetta suggested that the findings about screenings were consistent with what he might have expected during the beginning of the pandemic.Delaying screenings could mean that some people discover cancers at a more advanced state by the time they diagnose them, he said.

Markus Seeliger, third from left, with members of his lab, from left, Terrence Jiang. Aziz Rangwala, Ian Outhwaite, Victoria Mingione,YiTing Paung, and Hannah Philipose. Photo from Markus Seeliger

By Daniel Dunaief

When a dart hits the center of a target, the contestant often gets excited and adds points to a score. But what if that well-placed dart slipped off the board before someone could count the points, rendering such an accurate throw ineffective?

With some cases of cancer treatments, that’s what may be happening, particularly when a disease develops a mutation that causes a relapse. Indeed, people who have chronic myeloid leukemia typically receive a treatment called Imatinib, or Gleevac.

The drug works, hitting a target called a kinase, which this white blood cell cancer needs to cause its cells to continue to divide uncontrollably. Patients, however, develop a mutation called N368S, which reduces the effectiveness of the drug.

While mutations typically make it more difficult for a drug to bind to its target, that’s not what’s happening with this specific mutation. Like the dart hitting the center of a board, the drug continues to reach its target.

Instead, in a model of drug resistance several scientists have developed, the mutation causes the drug to decouple.

Pratyush Tiwary with this year’s US top 20 students who are going to the international chemistry olympiad. Photo from Toward

A team of experimental and computational researchers including Markus Seeliger, Associate Professor of Pharmacological Sciences at Stony Brook University, and Pratyush Tiwary, Associate Professor in the Department of Chemistry & Biochemistry at the University of Maryland, published two research papers explaining a process that may also affect the way mutations enable resistance to other drugs.

Seeliger described how different disease-associated mutations bind to Gleevac in a paper published in the Proceedings of the National Academy of Sciences. 

Working with scientists at Memorial Sloan Kettering Cancer Center and Goethe University in Frankfurt, Germany, Seeliger used nuclear magnetic resonance spectroscopy, or NMR. The researchers showed how the drug bound to its target and then released.

Understanding the way diseases like cancer develop such resistance could affect drug discovery, giving pharmaceutical companies another way to prepare for changes diseases make that reduce the effectiveness of treatments.

A ‘hot paper’

Tiwary published research in which Seeliger was a coauthor in late April in the journal Angewandte Chemie that the publication labeled a “hot paper” for its implications in the field. Tiwary developed a way to simulate the kinetic processes that enable the mutated kinases to release the drug.

Tiwary created an artificial intelligence model that extended the time he analyzed the drug-protein interaction from milliseconds all the way out to thousands of seconds.

“Even within the simulation world, if you can quantitatively predict a binding affinity, that’s amazing,” Seeliger said. “It’s extremely hard to calculate kinetics, and he got that right.”

Tiwary, who started talking with Seeliger about five years ago and has been actively collaborating for about three years, uses experimental data to inform the dynamics that affect his simulations.

Seeliger “had done the experiments of the dissociation rates beforehand, but did not have a way to explain why they were what they were,” Tiwary explained in an email. “Our simulations gave him insights into why this was the case and … insight into how to think about drugs that might dissociate further.”

Drug discovery

Tiwary hopes the work enables researchers to look at structural and kinetic intermediates in reactions, which could provide clues about drug design and delivery. While he worked with a single mutation, he said he could conduct such an analysis on alterations that affect drug interactions in other diseases.

He wrote that the computations, while expensive, were not prohibitive. He used the equivalent of 16 independent 64 CPUs for one to two weeks. He suggested that computing advances could cut this down by a factor of 10, which would enable the exploration of different mutations.

“The methods are now so easy to automate that we could run many, many simulations in parallel,” Tiwary explained. Machine learning makes the automation possible.

Given what he’s learned, Tiwary hopes to contribute to future drug begin that addresses mutation or resistance to treatment in other cancers. He also plans to continue to work with Seeliger to address other questions.

Next steps

Seeliger said he plans to extend this work beyond the realm of this specific type of cancer.

He will explore “how common these kinetic mutations are in other systems, other diseases and other kinases,” Seeliger said.

He would also like to understand whether other proteins in the cell help with the release of drugs or, alternatively, prevent the release of drugs from their target. The cell could have “other accessory proteins that help kick out the drug from the receptor,” Seeliger said.

The concept of drug resistance time comes from infectious disease, where microbes develop numerous mutations.

Seeliger, who is originally from Hanover, Germany, said he enjoys seeing details in any scene, even outside work, that others might not notice. 

He described how he was driving with postdoctoral fellows in Colorado when he spotted a moose. While the group stopped to take a picture, he noticed that the moose had an ear tag, which is something others didn’t immediately notice.

As for the research collaboration, Seeliger is pleased with the findings and the potential of the ongoing collaboration between experimental and computational biologists.

“The computational paper, aside from using interesting new methodology, describes why things are happening the way they are on a molecular level,” he said.

Members of the CanCan team, from left,Oliver Maddocks, David Lewis, Johan Vande Voorde, Bette Caan, Marcus Goncalves, Eileen White, Mariam Jamal-Hanjani, Tobias Janowitz, Karen Mustian, Janelle Ayres andToni Hui

By Daniel Dunaief

If a team Cold Spring Harbor Laboratory Assistant Professor Tobias Janowitz co-leads succeeds, researchers will know more about the end stage of numerous types of cancer that involves the loss of tissue and muscle mass.

Tobias Janowitz

Recently, lead scientists Janowitz; Eileen White, Rutgers Cancer Institute of New Jersey Deputy Director and Chief Scientific Officer; and Dr. Marcus DaSilva Goncalves, Assistant Professor of Medicine at Weill Cornell Medicine received $25 million in funding as a part of a Cancer Grand Challenge, which is a combined trans-Atlantic funding effort between Cancer Research UK and the National Cancer Institute in the United States.

The cachexia group was one of four teams to receive funding among 11 finalists.

Bruce Stillman, president of Cold Spring Harbor Laboratory, described cachexia as “one of the most difficult clinical problems with late stage cancer.”

Stillman added that the collaboration is promising because it brings together a group of “remarkable” scientists, including White, who was a postdoctoral fellow in Stillman’s lab. “It has great potential for making a difference in the lives of patients.”

Stillman believes Janowitz is an ideal co leader for this challenging project because he has an MD and a PhD and is clinically certified as an oncologist.

CanCan team

For his part, Janowitz is looking forward to the opportunity to team up with other ambitious research efforts to create a virtual institute.

Eileen White

“It’s incredibly exciting to get the chance to do something you think is higher risk with a large group of people who have come together around this problem,” said Janowitz. “We often talked about how it would be nice to bring team members from other disciplines into this area.”

Indeed, the cachexia team, which White named CanCan for Cancer Cachexia Action Network believes cachexia is a tumor-driven metabolic imbalance. The group is pursuing different areas of research, including metabolism, neuroendocrinology, clinical research, and immunology, among others, to define clinical subtypes with the hopes of creating individualized therapies.

While the effort brings together a range of scientists with different expertise and technological skills, researchers don’t expect an immediate therapeutic solution within that time frame. Rather, they anticipate that their experiments and clinical data will help inform future approaches that could enhance efforts to prevent and treat a wasting disease that causes severe declines in a patient’s quality of life.

“What we would deem as a success is, if in five years time, we have maybe one to three strong lead hypotheses that comes out of our shared work on how we can either prevent or treat cachexia as it emerges,” Janowitz said.

The complexity of cachexia

Dr. Marcus DaSilva Goncalves

As a complex process that involves an understanding of numerous interconnected dynamics, cachexia has been a challenging field for researchers and a difficult one for funding agencies looking for discrete problems with definable results and solutions.

Cachexia research had “never reached this critical mass that people were seeing where we can say, ‘Okay, there’s enough work going on to really unravel this,’” Janowitz said.

The CanCan team has several scientific themes. Janowitz will be involved with metabolic dysregulation. He would like to understand the behavioral changes around appetite and food intake.

Additionally, the group will explore the interaction of normal cells and cancer cells by looking at the tumor micro environment. This research will explore how cancer cells can reprogram healthy host cells.

“We’ve got a really exciting axis of research” within the network, Janowitz said.

Searching for signaling molecules

Janowitz said Norbert Perrimon, James Stillman Professor of Developmental Biology at Harvard Medical School is one of the leading experts in fly genetics and fly biology. Perrimon has created a model of cachexia in the fruit fly. While that sounds far from patients, Perrimon can use single molecule resolution of the entire organism to get an insight and understanding of candidate molecules.

“We are hoping to search for new signaling molecules that might get involved” in cachexia, Janowitz said. Once the research finds new candidates, he and others can validate whether they also work in mouse models of cancer and cancer cachexia.

With numerous clinical groups, Janowitz hopes to contribute to the design and execution of experimental medicine studies.

The Cancer Grand Challenge will distribute the funds based on what members need. Janowitz described the allocation of funds as “roughly equitable.” He will use that funding to support a postdoctoral researcher, a PhD student and a technician, who can help with specific projects he’s merging in his lab to combine with the team effort.

The funds will also support his salary so he can supervise the work in his lab and help with the coordination of this effort.

The funding agencies have an additional budget to organize conferences and meetings, where researchers can discuss ideas in person and can ensure that any clinical and laboratory work is standardized and reproducible in different facilities.

Cold Spring Harbor Laboratory will host the first full gathering of the cachexia team in November.

Challenging beginnings

When he was a doctor in the United Kingdom, Janowitz was fascinated and confounded by cachexia. In the early years of his training, he saw patients who had a small tumor burden, but were so sick that they died. Those experiences made “such a strong imprint” that he wanted to help unravel this process as a junior oncologist, he said.

Getting funding was challenging because cachexia was complex and didn’t involve a finely defined project that linked a receptor protein to a cell type that led to a diseased condition.

Janowitz, among others in this field, felt passionate enough about this area to continue to search for information about cachexia. After he restructured his research into a narrower focus, he secured more funding.

An unsolved mystery

With enough researchers continuing along this path, Janowitz said the group developed an awareness that this is “one of the big, unsolved mysteries of cancer progression.”

Janowitz appreciates the opportunity to work with a team that has accomplished researchers who work in fields that are related or synergistic, but aren’t necessarily considered part of the cachexia field.

The significant funding comes with expectations.

“The grant is both a great joy, but also, essentially, a mandate of duty,” he said. “Now, you have to utilize this grant to make significant contributions to understand and hopefully treat this debilitating condition.”

A view of Shinnecock Bay. Photo by Christopher Paparo/Fish Guy Photos

By Daniel Dunaief

The Galapagos Islands, the Great Barrier Reef, Little Cayman and … Shinnecock Bay? Yes, that’s correct, the 40 square kilometer bay located on the southern end of Long Island recently joined a distinguished list of celebrated marine locations identified by Mission Blue, a non-profit international organization led by famed marine biologist Sylvia Earle.

Mission Blue named Shinnecock Bay a Hope Spot, one of 132 such locations in the world that it considers critical to the health of the ocean.

Shinnecock Bay has the distinction of being the only Hope Spot in New York State, the only one near a major city and one of three on the Eastern Seaboard.

“The idea that you could have a Hope Spot so close to a major metropolitan area is pretty significant,” said Ellen Pikitch, Endowed Professor of Ocean Conservation Science at Stony Brook University and the School of Marine and Atmospheric Sciences and Director of the Institute for Ocean Conservation Science.

The designation by Mission Blue not only puts Shinnecock Bay in elite environmental company, but it also completes a comeback story driven by scientists, their students, numerous volunteers, and other supportive groups.

“The point of Mission Blue designating this place a Hope Spot isn’t only to bring more people and attention to Shinnecock Bay,” said Pikitch, but is also to “send the message of hope that we can turn things around.”

Pikitch, Christopher Gobler, Endowed Chair of Coastal Ecology and Conservation at the School of Marine and Atmospheric Sciences, and Bradley Peterson, Associate Professor at Somas, led the efforts at the bay.

The scientists created clam sanctuaries in the Western Shinnecock Bay with strict no take rules for people, which helped jump start the restoration. The clams helped meet natural filtration goals.

The researchers also helped restore eelgrass, also called seagrass, which is a more effective natural way to sequester carbon per square inch than the rainforest.

Between 1930 and the start of the project in 2012, New York State had lost about 90 percent of its eelgrass. A task force projected that eelgrass would be extinct in the Empire State by 2030. The bay now has about 100 more acres of eelgrass than it had in 2012.

These efforts have created a “huge leap in the number of forage fish” including bay anchovies and menhaden, said Pikitch, who studies forage fish. “The bay is in a much healthier place now that it was when we started,” she added.

Tough beginnings

Indeed, in 2012, parts or all of the bay had to close because of brown or red tides. The tides sometimes “looked like coffee spilled across the entire bay,” Pikitch said.

The steps the researchers took to improve water quality took some time. “Harmful algal blooms didn’t disappear right away,” Pikitch said. “As the study progressed, the amount of time brown tides occurred got shorter and shorter. Ultimately we stopped seeing brown tides several years ago.”

Red tides, which can cause paralytic shellfish poisoning that could be fatal to people, had also been a problem in Shinnecock Bay. Nearly half the bay was closed to shellfishing in 2011, 2014, and 2015. In 2017 and 2028, about 1/4 of the bay was closed due to red tides. Since 2019, however, red tides haven’t threatened the bay.

On the water

Throughout the restoration process, scientists in training and volunteers contributed to various efforts. Konstantine Rountos, Associate Professor of Biology at St. Joseph’s University in New York, earned his Master’s and PhD and conducted his post doctoral research at Stony Brook University. He also served as the lead research scientist for the Shinnecock Bay Restoration Program trawl survey from 2012 to 2016. 

Rountos called the designation “remarkable and extremely exciting.” When he started working on the bay in 2005 as a Master’s candidate, he saw stressors such as eelgrass declines.

“Not only was the ecosystem showing signs of collapse (decreased seagrass, decreased hard clams, increased harmful algal blooms), but the Bay was supporting fewer and fewer baymen,” he said. The Long Island “cultural identity of ‘living off the bay’ was in serious danger.”

Rountos believes people often overlook the significant ecological importance of this area, driving past these environmental and ecological treasures without appreciating their importance. 

Amid his many Bay memories, he recalls catching a seven-foot long roughtail stingray. “It was very surprising to pull that up by hand in our trawl net,” he said.

A veteran of the bay since 2016, Maria Grima spent time on Shinnecok as an undergraduate at Stony Brook and more recently for her Master’s training, which she hopes to complete this August.

Grima has been studying the invasive European green crab that shreds eelgrass and consumes shellfish such as clams, oysters and mussels. In a preliminary analysis, the population of this crab has declined. Grima noted that it’s difficult to prove cause and effect for the reduction in the number of these crabs.

Rather than pursue a potential career in medicine, which was her initial focus when she arrived at Stony Brook, Grima decided to focus on “fixing the environmental issues that cause human health problems.”

She is “really proud that Shinnecock Bay” achieved the Hope Spot designation. 

One of her favorite Bay memories involves seeing an ocean sunfish, which is a distinctive and large fish that propels itself through water with its dorsal and ventral fins and is the world’s largest bony fish. Seeing the biodiversity on a bay that has had historically poor water quality “gives you hope when you’re on the boat,” Grima said.

When friends and volunteers have joined her on the Bay, she has delighted in watching them interact with seahorses, which “wrap their little tail around your finger.”

Looking toward the future

While Pikitch is pleased with the designation, she said the work of maintaining it continues.

“We can’t rest on our laurels,” she said. “Continued construction on Long Island’s East End and the growing threat of climate change may require additional restoration work. We need to keep a close eye on what is happening in Shinnecock Bay and be ready to take action if necessary.”

In left photo, Zhiyang Zhai, on the right, with John Shanklin and Jantana Keereetaweep; in right photo, Zhiyang Zhai with Hui Liu. Photos courtesy of BNL

By Daniel Dunaief

In a highly competitive national award process, the Department of Energy provides $2.5 million to promising researchers through Early Career Research Funding.

Recently, the DOE announced that Zhiyang Zhai, an associate biologist at Brookhaven National Laboratory, was one of 83 scientists from around the country to receive this funding.

“Supporting talented researchers early in their career is key to fostering scientific creativity and ingenuity within the national research community,” DOE Office of Science Director Asmeret Asefaw Berhe, said in a statement.

Zhai, who has worked at BNL for 11 years, is studying a signaling protein called Target Of Rapamycin (TOR) kinase, which is important in the plant and animal kingdom.

He hopes to develop a basic understanding of the way this kinase reacts to different conditions, such as the presence of carbon, to trigger reactions in a plant, including producing oils through photosynthesis or making seeds.

Zhiyang Zhai. Photo from BNL

“Ancient systems like this evolve in different lineages (like plants and animals) to work differently and [Zhai] wants to find out the details of how it works in plants,” John Shanklin, chair of BNL’s Biology Department, explained in an email. 

Zhai is trying to define which upstream signals interact with TOR and what the effects of those interactions are on TOR to learn how the kinase works.

He is hoping to get a clear idea of how different nodes interact and how signaling through carbon, nutrients and sunlight affects TOR kinase levels and its configuration.

Researchers may eventually use the knowledge of upstream regulators to reprogram responses by introducing enzymes that would cause the synthesis, or degradation, of upstream regulatory metabolites, Shanklin suggested.

This could be a way to “tune” the sensor kinase activity to increase the synthesis of storage compounds like oil and starch.

In the bigger picture, this type of research could have implications and applications in basic science that could enhance the production of renewable resources that are part of a net-zero carbon fuel strategy.

The DOE sponsors “basic science programs to discover how plants and other organisms convert and store carbon that will enable a transition towards a net zero carbon economy to reduce the use of fossil fuels,” Shanklin said.

In applying for the award, Zhai paid “tremendous attention” to what the DOE’s mission is in this area, Shanklin said. Zhai picked out a project that, if successful, will directly contribute to some of the goals of the DOE.

Through an understanding of the way TOR kinase works, Zhai hopes to provide more details about metabolism.

Structure and function

Jen Sheen, Professor in the Department of Genetics at the Harvard Medical School, conducted pioneering work on how TOR kinase regulates cell growth in plants in 2013. Since then, TOR has attracted attention from an increasing number of biologists and has become “a hot and rapidly-developing research direction in plant biology,” Zhai explained.

He hopes to study the structure of TOR using BNL’s Laboratory of Biomolecular Structure at the National Synchrotron Lightsource II.

Zhai, who hopes to purify the plant version of TOR, plans to study how upstream signaling molecules interact with and modify the structure of the enzyme.

He will also use the cryo-electron microscope to get a structure. He is looking at molecular changes in TOR in the presence or absence of molecules or compounds that biochemically bind to it.

Through this funded research, Zhai hopes to explain how signals such as carbon supply, nutrients and sunlight regulates cell growth.

Once he’s conducted his studies on TOR, Zhai plans to make mutants of TOR and test them experimentally to see if a new version, which Zhai described as “TOR 2.0,” has the anticipated effects.

Zhai is building on his experience with another regulatory kinase, called SnRK1, which is involved in energy signaling.

“His expertise in defining SnRK1’s mechanism ideally positions him to perform this work,” Shanklin said.

At this point, Zhai is focused on basic science. Other researchers will apply what he learns to the development of plants for commercial use.

A seminal moment and a call home

Zhai described the award as “very significant” for him. He plans to continue with his passionate research to explore the unknown.

He will use the funds to hire new postdoctoral researchers to build up his research team. He also hopes this award gives him increased visibility and an opportunity to add collaborators at BNL and elsewhere.

The funding will support part of Zhai’s salary as well as that of his staff. He will also purchase some new lab instruments and tap into the award to attend conferences and publish papers.

When he learned he had won the award, Zhai called his mother Ruiming, who lives in his native China. “She is so proud of me and immediately spread the good news to my other relatives in China,” Zhai recalled.

When Shanklin spoke with Zhai after the two had learned of the award, he said he had “never seen Zhai look happier.”Shanklin suggested that this is a “seminal moment” in a career that he expects will have other such milestones in the future.

A resident of Mt. Sinai, Zhai lives with his wife Hui Liu, who is a Research Associate in Shanklin’s group specializing in plant transformation, fatty acids and lipidomics analysis.The couple has two sons, nine-year-old Terence and three-year-old Steven.

As for his work, Zhai hopes it has broader implications.

“The knowledge of TOR signaling will provide us [with] tools to achieve hyperaccumulation of lipids in plant vegetative tissues, which is a promising source for renewable energy,” he said.

By Daniel Dunaief

Kelp, and other seaweed, may prove to be an oyster’s best friend. And, no, this isn’t a script for a new episode of SpongeBob SquarePants.

A thick, heavy leafy seaweed, kelp provides an environmentally friendly solution to several problems. Amid higher levels of carbon dioxide, the air has become warmer and oceans, including coastal regions, are more acidic. That’s because carbon dioxide mixes with water, producing negative hydrogen ions that lower the pH of the water.

Enter kelp.

A rapidly growing seaweed, kelp, which is endemic to the area, uses that carbon dioxide in the same way trees do, as a part of photosynthesis. By removing carbon dioxide, kelp raises the pH, which is helpful for the area’s shellfish.

The above graph shows pH scale measurements with and without kelp. The graph shows continuous pH (NBS scale) bubbling, and the addition of 4 x 104 cells mL-1 Isochrysis galbana added daily to simulate daily feedings of bivalves.  Image provided by Chris Gobler

That’s the conclusion of a recent study published in Frontiers in Marine Science by Stony Brook University Professor Christopher Gobler, Endowed Chair of Coastal Ecology and Conservation at the School of Marine and Atmospheric Sciences, and Mike Doall, Associate Director of Shellfish Restoration and Aquaculture at Stony Brook University.

In a series of five laboratory experiments and a field study, Gobler and Doall showed that kelp lowered acidification, enabling better growth for shellfish like oysters. “There was better oyster growth inside the kelp than 50 meters away” Doall said, in what he and Gobler describe as the “halo” effect.

Gobler was especially pleased with the implications of the field experiment.“While showing that  [result] in the lab was exciting, being able to improve the growth of oysters on an oyster farm experiencing coastal acidification proves this approach can have very broad implications,” Gobler said in a statement.

Doall estimates that kelp farmers can grow 72,000 pounds per acre of kelp in just six months, during the prime growing season from December through May.

Doall, whose primary role in the study was to grow the kelp and set up the field experiment, said he grew kelp at the Great Gun oyster farm in Moriches Bay that were up to 12 feet long. Over the last four years, he has grown kelp in 16 locations around Long Island, from the East River to Fishers Island.

This year, the team conducted kelp studies in nine locations. The best growth occurred in the East River and in Moriches Bay, Doall said. He harvested about 2,000 pounds each from those two sites this year and is primarily using the kelp in a host of fertilizer studies.

Gobler explained that using seaweed like kelp could enhance aquaculture.

“The intensification of ocean acidification now threatens bivalve aquaculture and has necessitated a solution,” Gobler said in a statement. “We believe our work is foundational to a solution.”

Above, Mike Doall during a recent kelp harvest in Moriches Bay. Photo by Cameron Provost

One of the challenges of using kelp to improve the local conditions for shellfish is that it grows during the winter through May, while the growing season for shellfish occurs during the summer.

“That is why we are now working on summer seaweeds,” Gobler explained in an email.

Gobler and Doall are looking for similar potential localized benefits from Ulva, a green sea lettuce, and Gracilaria, which is a red, branchy seaweed.

“Most water quality issues occur during summer, so it’s important to grow seaweed year round,” Doall said.

The Stony Brook scientists, who have worked together since the early 1990s when they were graduate students, are also exploring varieties of kelp that might be more heat tolerant and will try to use some of those on Long Island.

Woods Hole Oceanographic Institution is leading a project to hybridize these heartier strains of kelp, Doall said. GreenWave, which supports regenerative ocean farming, is also participating in that effort.

Gobler explained that they also plan to start earlier, which will extend the growing season.

While the different growing seasons for kelp and oysters may make kelp only part of the solution for reducing ocean acidification for shellfish, the different growing seasons makes the seaweed a complementary companion crop for commercial shellfish diggers.

Summer laborers who work on oysters can transition to kelp harvesting in the fall and winter.

A resident of Rocky Point, Doall lives with his wife Nancy, who teaches at North Coleman Road Elementary School in the Middle Country School District.

The Doall’s 23-year old daughter Deanna, who is a graduate of the University of Tampa, is currently traveling in Guatemala, while their 20-year old daughter Annie is attending Florida Gulf Coast University.

Doall grew up in Massapequa Park. As a 12-year old, he pooled his lawn mowing money with a friend’s paper route funds to buy a small boat with a 1967 10-horsepower Evinrude engine. The pair went out on bays to fish and, periodically, to clam.

Doall, who loves gardening and being in the ocean, described the two of them as being “notorious” for needing tows back to the shore regularly when their engine died.

The former owner of an oyster farm, Doall also enjoys eating them. He particularly enjoys eating oysters in the winter and early spring, when they are plump. His favorite way to eat them is raw on the half shell, but he also appreciates his wife’s “killer Oysters Rockefeller,” as he described it.

As for kelp, the current supply in the area exceeds the demand. The excess kelp, which farmers harvest to prevent the release of carbon dioxide and nitrogen that the seaweed removed from the water, can be composted or used for fertilizer, explained Gobler.

This map shows of the status of marine protected areas in the United States. Credit: Sullivan-Stack et al., Frontiers in Marine Science 2022

By Daniel Dunaief

Time is not on our side.

That’s one of the messages, among others, from a recent paper in Frontiers in Marine Conservation that explored Marine Protected Areas around the United States.

In a study involving scientists at universities across the country, the researchers concluded that the current uneven distribution of MPAs do not offer sufficient protection for marine environments.

Left, Ellen Pikitch holds gooseneck barnacles in The Olympic Coast National Marine Sanctuary, an MPA in Washington State.

 

“The mainland of the United States is not well protected” with no region reaching the 10 percent target for 2020, said Ellen Pikitch, Endowed Professor of Ocean Conservation Sciences at the School of Marine and Atmospheric Sciences at Stony Brook University and a co-author on the study. “The mid-Atlantic is one of the worst of the worst in that regard. We’re not well positioned and we have no time to waste.”

Indeed, the United States, through the administration of President Joe Biden (D), has committed to protecting 30 percent of the oceans by 2030. At this point, 26 percent of the oceans are in at least one kind of MPA. That, however, doesn’t reflect the uneven distribution of marine protection, Pikitch and the other authors suggested.

As much as 96 percent of the protection is in the Central Pacific Ocean, Pikitch explained. That compares with 1.9 percent of the mainland United States and 0.3 percent of the mid-Atlantic.

“We are denying the benefits of ocean protection to a huge portion of the U.S. population,” Pikitch said. “This needs to change if we want the full spectrum of marine life in U.S. ocean waters and to obtain the many benefits to human well-being that this would provide.”

The researchers in the study used a new science-based framework called “The MPA Guide,” which Pikitch helped create. This study represents the first application of this guide to the quantity and quality of marine protection around the United States.

The Guide, which was published in September in the journal Science, rates areas as fully, highly, lightly or minimally protected and is designed to bridge the gap between scientific research and government policies.

Jenna Sullivan-Stack, a research associate at Oregon State University and lead author on the paper, credits Pikitch with helping to create the guide.

Pikitch made “key contributions to this work, especially putting it in context relative to international work and also thinking about how it can be useful on a regional scale for the mid-Atlantic,” Sullivan-Stack explained in an email.

“These findings highlight an urgent need to improve the quality, quantity and representativeness of MPA protection across U.S. waters to bring benefits to human and marine communities,” Sullivan-Stack said in a statement.

Pikitch said MPAs enhance resilience to climate change, providing buffers along shorelines. Seagrasses, which Long Island has in its estuaries, are one of the “most powerful carbon sequesters” on the planet, she explained.

Pikitch suggested there was abundant evidence of the benefits of MPAs. This includes having fish that live longer, grow to a larger size and reproduce more. Some published, peer-reviewed papers also indicate the benefit for nearby waterways.

“I have seen the spillover effect in several MPAs I have studied,” Pikitch said.

To be sure, these benefits may not accrue in nearby waters. That depends on factors including if the area where fishing is allowed is downstream of the protected area and on the dispersal properties of the fished organism, among other things, Pikitch explained.

Lauren Wenzel, Director of NOAA’s Marine Protected Areas Center, said the government recognizes that the ocean is changing rapidly due to climate change and that MPAs are affected by warmer and more acidic water, intense storms and other impacts.

“We are now working to ensure that existing and new MPAs can help buffer climate impacts by protecting habitats that store carbon and by providing effective protection to areas important for climate resilience,” Wenzel said.

The researchers made several recommendations in the paper. They urged the creation of more, and more effective, MPAs, urging a reevaluation of areas with weak protection and an active management of these regions to generate desired results.

They also suggested establishment of new, networked MPAS with better representation of biodiversity, regions and habitats. The researchers urged policy makers to track areas that provide conservation benefits, such as military closed regions.

The paper calls for the reinstatement and empowerment of the MPA Federal Advisory Committee, which was canceled in 2019.

While the National Oceanographic and Atmospheric Administration has no plans to reinstate this committee, is it “considering ways to expand the dialogue and seek advice from outside the government on area-based management,” Wenzel said.

The paper also urges the country to revisit and update the National Ocean Policy and National Ocean Policy Committee, which were repealed in 2018 before plans were implemented.

Wenzel said that the United States recently joined the High-Level Panel for a Sustainable Ocean Economy, a multi-national effort to ensure the country commits to developing a national plan within five years to manage the ocean under national jurisdiction sustainably.

In terms of enforcing MPAs, the Office of National Marine Sanctuaries supports enforcement that fosters voluntary compliance through educating sanctuary users and promoting a sense of stewardship toward the living and cultural resources of the sanctuary, Wenzel added.

“The sanctuary system’s goal is to provide a law enforcement presence in order to deter and detect violations,” she said.

The Office of National Marine Sanctuaries works with the U.S. Coast Guard and the Department of the Interior.

In terms of the impact of the paper, Pikitch said she hopes the paper affects policies and ignites change.

“We need to ramp up the amount and quality of protection in U.S. ocean waters, particularly adjacent to the mainland U.S. and the mid-Atlantic region,” she said.

Corina Amor ©Len Marks Photography, 2022/CSHL

By Daniel Dunaief

What if scientists could train the immune system to recognize something specific on the outside of unwanted cells?

That’s what new Cold Spring Harbor Laboratory fellow Corina Amor is doing, as she found an antigen on the surface of senescent cells. She hopes to train a patient’s T-cells to search for these cells, much like providing a police dog with the scent of a missing person or escaped convict.

Amor, who joined Cold Spring Harbor Laboratory in January after earning her medical degree in  at Universidad Complutense de Madrid in Spain and her PhD in the lab of CSHL Adjunct Professor Scott Lowe, recently found a surface molecule called uPAR that is upregulated on senescent, or aging, cells.

If senescent cells excessively accumulate, it can lead to tissue decline and disease like lung and liver fibrosis, Lowe, who is the Cancer Biology Chair at Memorial Sloan Kettering Cancer Center, explained in an email. Senescent cells also contribute to tissue decline as people age.

Studies suggest eliminating these senescent cells could provide therapeutic benefit, she added.

Using artificial T-cells, called CAR-T, for Chimeric Antigen Receptor, Amor looks to use specific antigens to find these senescent cells and eliminate them.

“It was sort of a crazy idea, but it worked and, while much more preclinical and clinical work needs to be done, the concept could lead to better treatments for lung and liver fibrosis, and other diseases that increase as we age,” Lowe wrote.

The combination of an inflamed environment and an ineffective immune system can create conditions that favor the growth and development of cancer.

Amor, who currently has one technician and is planning to add a graduate student this summer at her lab at CSHL, is building on her PhD research.

“My doctoral work was the development of the first CAR-T cells that are able to target senescent cells,” she said. “We were the first in the world to do this.”

Amor, who was recently named to the 2022 Forbes 30 under 30 Europe list, describes this approach as a new frontier for treating senescent cells and one in which researchers would need to clear numerous hurdles before developing clinical therapies.

She is searching for other antigens on the surface of cancerous and fibrous cells that would increase the specificity of these synthetic immune cells.

Combining antigens could be the key to avoiding off target effects that might cause the immune system to attack healthy cells.

Amor plans to tap into CSHL’s affiliation with Northwell Health to analyze clinical samples that might provide a better understanding of various potential markers.

Fellowship route

Cold Spring Harbor Laboratory is one of several programs in the country that provides talented researchers with the opportunity to go directly from finishing their PhD to leading their own lab.

Amor is following in the footsteps of her MSKCC mentor Lowe, who also had been an independent fellow at CSHL.

Lowe saw some similarities in their career paths, as they both made “unexpected discoveries during our Ph.D. research that were not only important, but clearly set a path for future research,” he explained in an email.

Lowe describes Amor as an “intense and driven scientist” who has an “extraordinary bandwidth to get things done, and a mental organization that allows her to execute science efficiently.” He believes her work is game changing at many levels and opens up numerous new directions for scientific study.

Lowe is “extraordinarily proud of [Amor] for becoming a CSHL fellow – and I hope she both contributes and benefits from the lab as I did,” he wrote in an email.

Amor said CSHL provided an ideal balance between finding collaborators who worked in similar areas, without competing for the same resources and conducting similar research.

“The last thing you want is to go somewhere and be completely isolated,” she said. “You also don’t want to be at a place where there’s three other people doing the same thing and you’re not adding anything.”

She feels like she had a “nice synergy” with CSHL, which is trying to expand its immunology research. 

As the first person to bring cellular therapy to CSHL, she has already started collaborating with several groups. 

Amor recognizes the challenges ahead in training scientists who often have their own ideas about the questions they’d like to ask.

“The science is the easy part” and it comes naturally, but there is a “learning curve in how to manage people,” she said.

She appreciates the opportunity to talk with senior researchers at Cold Spring Harbor Laboratory and plans to attend courses and seminars for principal investigators who are starting out.

When she was in graduate school, Amor said she rotated through different labs. When everything didn’t work as she might have hoped during those rotations, she said she had the opportunity to learn from those experiences.

“When training people in the lab, I try to be really specific about what I want to do” while also ensuring that the researchers understand and appreciate the bigger picture and context for individual experiments, she said.

Originally from Madrid, Amor felt comfortable during her five years in Manhattan and is enjoying the open space and fresh air of Long Island in her role at CSHL. She also appreciates the chance to kayak in the waters around Long Island.

When she was around seven years old, Amor said her mother Esperanza Vegas was diagnosed with breast cancer. By participating in a clinical trial for a new drug, her mother fought off the disease.

“That made me realize how important science and research is,” Amor said.

During her educational training, Amor went directly from high school into a six-year program in which she earned a bachelor’s degree and a medical degree.

By the time she finished her PhD, she was hooked on research.

She appreciates the advice she received from Lowe, who encouraged her to conduct experiments despite the risks.

“Don’t get paralyzed at the beginning by fear,” she said. “Do the experiment and see what happens.”

Paul Freimuth and co-author Feiyue Teng, a scientist in Brookhaven Lab’s Center for Functional Nanomaterials (CFN), at the light microscope used to image bacteria in this study. Photo from BNL

By Daniel Dunaief

Researchers regularly say they go wherever the science takes them. Sometimes, however, the results of their work puts them on a different path, addressing new questions.

So it was for Paul Freimuth, a biologist at Brookhaven National Laboratory. Freimuth was studying plant proteins of unknown function that he thought might play a role in the synthesis or modification of plant cell walls. The goal was to produce these proteins in bacteria or yeast to facilitate an understanding of the protein structures.

When he inserted plant genes into bacteria, however, one of those genes experienced a phase shift, producing a misfolded protein that, when produced in high enough quantities, killed the bacteria.

Working with several interns over the course of five years, as well as a few other principal investigators, Freimuth discovered that this protein had the same effect as antibiotics called aminoglycosides, which are the current treatment for some bacterial infections. He recently published the results of these studies in the journal Plos One.

Aminoglycosides enter the cell and cause ribosomes to create proteins in an error-prone mode, which kill the bacterial cells. The way these proteins kill the cells, however, remains a mystery. Antibiotic-treated cells produce numerous proteins, which makes determining the mechanism of action difficult.

The protein Freimuth studied mirrors the effect of treating cells with aminogylcosides. Researchers now have a protein they can study to determine the mechanism of cell killing.

To be sure, Freimuth said the current research is at an early stage, and is a long way from any application. He hopes this model will advance an understanding of how aberrant proteins kill cells. That information can enable the design of small molecule drugs that mimic the protein’s toxic effect. He believes it’s likely that this protein would be toxic if expressed in other bacteria and in higher cells, but he has not tested it yet.

With antibiotic resistance continuing to spread, including for aminoglycosides, Freimuth said the urgency to find novel ways to kill or inhibit bacterial growth selectively without harmful side effects has increased.

Aminoglycosides cause the ribosome to shift coding phases or to make other errors. The model toxic protein he studied resulted from the bacteria starting to translate amino acids at an internal position, which produced a new, and, as it turns out, toxic sequence of amino acids.

The phase-shifted gene contained a stop codon located just 49 codons from the start site, which means that the toxic protein only contained 48 amino acids, which is much shorter than the average of 250 to 300 amino acids in an E. coli protein.

Since the model toxic protein was gene-encoded rather than produced by an antibiotic-induced error in translation, Freimuth’s team were able to study the sequence basis for toxicity. The acutely toxic effect was dependent on an internal region 10 amino acids in length.

Narrowing down the toxic factor to such a small region could help facilitate future studies of the mechanism of action for this protein’s toxic effect.

Misread signal

Freimuth and his team discovered that the bacteria misread the genetic plant sequence the researchers introduced. The bacteria have a quality control mechanism that searches for these gibberish proteins, breaking them down and eliminating them before they waste resources from the bacteria or damage the cell.

When Freimuth raised the number of such misfolded proteins high enough, he and his colleagues overwhelmed the quality control system, which he believes happened because the misfolded protein affected the permeability of the cell membrane, opening up channels to allow ions to flood in and kill the cell.

He said it’s an open question whether the protein jams open existing channels or becomes directly incorporated into the membrane, compromising membrane stability.

He showed that cells become salt-sensitive, indicating that sodium ion concentration increases. At the same time, it is likely that essential metabolites are leaking out, depriving the cell of compounds it needs to survive.

Now that the bacteria has produced this protein, Freimuth can use various tools and techniques at BNL, including the X-ray beamlines for protein crystallography and the cryo electron microscope, which would provide ways to study the interaction of the protein with cell components. High resolution structures such as the ones he hopes to determine could be used to guide drug design.

Freimuth is in the process of applying for National Institutes of Health funding for additional research, which could help the NIH’s efforts to counter the increasing spread of antibiotic resistance.

Freimuth has worked at BNL since 1991. He and his wife Mia Jacob, who recently retired from her role in graphic design in Stony Brook University’s Office of Marketing and Communication, reside in East Setauket.

The couple’s daughter Erika, who lives in Princeton and recently got married, works at Climate Central as an editor and writer. Their son Andrew works in Port Jefferson at an investment firm called FQS Capital Partners.

When Freimuth is not working at the lab, he enjoys sailing, kayaking and canoeing. During the pandemic, he said he purchased a small sailboat, with which he has been dodging the ferry in Port Jefferson Harbor.

Originally from Middletown, Connecticut, Freimuth was interested in science from an early age. He particularly enjoyed a mycology class as an undergraduate at the University of Connecticut.

As for his unexpected research with this protein, the biologist is pleased with the support he received from Brookhaven National Laboratory.

He said BNL enabled him to address the biofuel problem from protein quality control, which is a new angle. “BNL appreciates that valuable ideas sometimes bubble up unexpectedly and the lab has ways to assist investigators in developing promising ideas,” he said.

Pallavi Tatapudy with her husband Nishank Mehta.

By Daniel Dunaief

Bringing together people from a range of experiences and perspectives, Stony Brook University is preparing to complete the first year of its LEND training program, which is designed to help provide support and services for people with autism and neurodevelopmental disabilities.

Over 100 trainees will complete the course this month, as the leaders of LEND, which stands for Leadership Education in Neurodevelopmental and other related Disabilities, prepare to educate a second year of participants that is expected to exceed 300 people.

Top row: Dr. Matthew Lerner, Dr. Michelle Ballan (co-director and director)
2nd row: Pallavi Tatapudy, Isaac Rodriguez, Morgan McNair
3rd row: Sarah Grosser, Anjolie Nagarwalla, Jenny Andersson
Bottom row: Christopher Rosa, Ava Gurba

Matthew Lerner, LEND Center Co-Director, Research Director of the Autism Initiative, and Associate Professor of Psychology, Psychiatry & Pediatrics, and Michelle Ballan, LEND Program and Center Director, Professor, and Associate Dean for Research in the School of Social Welfare and Professor of Family, Population and Preventive Medicine, run the program, which is the first on Long Island to receive a federal grant that supports training students, families, professionals and self-advocates.

Lerner described three key takeaways for the $2.2 million, five-year grant. 

First, “if we want to be effective in supporting individuals with neurodevelopmental disorders we have to be interdisciplinary,” he said.

Second, the group, which includes trainees at three different levels depending on their time commitment to the program, needs to “listen to the voices of autistic people,” Lerner added. For too long, “they’ve been an afterthought at the table of care.”

Third, the work is a “process and not an outcome,” he said.

Many of the participants in the program appreciated the opportunity to engage in an interdisciplinary effort.

Self-advocate

Ava Gurba, a self-advocate and master’s student at Stony Brook University who has autism and cerebral palsy, said she saw LEND as her chance to “reframe the professional discipline” and inform people in a range of fields about what life is “really like” for her and others.

Many professionals in health care have limited experience working with self-advocates.

“They have only interacted with disabled people as clients in a therapeutic setting or as research subjects,” Gurba said.

Researchers and service providers don’t often know how to incorporate the lived experience for the family and from self- advocates, she added.

Gurba suggested that some professionals need to “unlearn” practices that don’t incorporate the values and needs of people with disabilities.

The medical community is often looking for cures, while Gurba said she and others with disabilities are more often looking for ways to be integrated into the community, through social, employment, or educational opportunities.

Clinical training

For Alan Gerber, a doctoral student in the Department of Psychology at Stony Brook, LEND provided autism-specific clinical training, including planning treatment and reviewing the progress for specific patients.

“It gives me an opportunity to get together with an inter-disciplinary cohort and see things from a different lens,” Gerber said.

Gerber plans to be a clinical researcher and will conduct post doctoral research at the Yale Child Study Center.

LEND “made me think very deeply about what is clinically meaningful research,” Gerber said. When he speaks with families, pediatricians and social workers, he wants to do the kind of research that is “really going to change a family’s life.”

Gerber hopes to remain in contact with other members of the LEND community, where he felt he was part of a team.

Paradigm shift

As a high school bilingual speech language pathologist who works closely with individualized education plans, Jenn Solomon wanted to understand more about the lives and challenges of people with developmental disabilities.

LEND provided a paradigm shift for Solomon in helping her understand disability. “I can listen to what people with disabilities have to say, and I can reflect and learn,” Solomon said.

One of Solomon’s broader goals is to advocate on behalf of students who have obstacles to overcome.

Jenny Andersson, who works for the New York State Department of Education Office of Special Education funded project called the Educational Partnership, suggested that LEND “exceeded what I had imagined.”

Like other trainees, Andersson, who is Director of the Early Childhood Family and Community Engagement Center, appreciated the participation of self-advocates.

“I approach everything in my work now and ask, ‘Did we invite all stakeholders to the discussion?’”

Ripple effects

Andersson is excited to see the ripple effect of the program, where other professionals benefit from what trainees learn and discuss and change their practices.

Indeed, Dr. Pallavi Tatapudy, a second-year psychiatry resident at Stony Brook, said her husband Nishank Mehta, who is a first-year orthopedic surgery resident at Stony Brook, has learned about advocacy from some of the discussions she had through LEND.

“This experience of working together and hearing all of these personal insights, you cannot get from a textbook,” Tatapudy said. 

Tatapudy understands the value of consulting with people who have disabilities and with their families. “The patient is the expert,” she said.

When she worked in the inpatient psychiatric unit on the 12th floor of Stony Brook Hospital, Tatapudy said she spoke to a family who was admitting a child with a neurodevelopmental disability. She asked parents for an idea of ways to comfort their child that de-escalate emotionally charged moments at home. His parents said a particular blanket from home provided comfort, which they brought to the hospital.

Tatapudy is “proud” that Stony Brook is a LEND center, joining 60 others throughout the country.

For Lerner, who was a LEND trainee about a dozen years ago and continues to stay in touch with his LEND cohort, the effort helps experts learn from each other and from self-advocates who can share their perspectives. “None of us has enough expertise to do this alone,” he said.