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Dennis Plenker Photo by Bob Giglione, 2020/ CSHL

By Daniel Dunaief

If the job is too easy, Dennis Plenker isn’t interested.

He’s found the right place, as the research investigator in Cold Spring Harbor Laboratory Cancer Center Director Dave Tuveson’s lab is tackling pancreatic cancer, one of the more intractable forms of cancer.

Plenker joined Tuveson’s lab in 2017 and is the technical manager of a new organoid facility.

Organoids offer hope for a type of cancer that often carries a poor prognosis. Researchers can use them to find better and more effective treatments or to develop molecular signatures that can be used as a biomarker towards a specific treatment.

Scientists can take cells from an organoid, put them in miniature dishes and treat them with a range of drugs to see how they respond.

The drugs that work on the organoids offer potential promise for patients. When some of these treatments don’t work, doctors and researchers can continue to search for other medical solutions without running the risk of making patients ill from potentially unnecessary side effects.

“Challenges are important and there is a sweet spot to step out of my comfort zone,” Plenker explained in an email.

Dennis Plenker Photo by Bob Giglione, 2020/ CSHL

In an email, Tuveson described Plenker as a “pioneer” who “likes seemingly impossible challenges and we are all counting on him to make breakthroughs.”

Specifically, Tuveson would like Plenker to develop a one-week organoid test, where tissue is processed into organoids and tested in this time frame.

Organoids present a cutting edge way to take the modern approach to personalized medicine into the realm of cancer treatments designed to offer specific guidance to doctors and researchers about the likely effectiveness of remedies before patients try them.

Plenker and others in Tuveson’s lab have trained researchers from more than 50 institutions worldwide on how to produce and use organoids.

“It’s complicated compared to conventional tissue culture,” said Plenker, who indicated that considerably more experience, resource and time is involved in organoid work. “We put a lot of effort into training people.”

Tuveson explained that the current focus with organoids is on cancer, but that they may be useful for other conditions including neurological and infectious diseases.

The way organoids are created, scientists such as Plenker receive a biopsy or a surgical specimen. These researchers digest the cells with enzymes into singular cells or clumps of single cells and are embedded. Once inside the matrix, they form organoids.

When they “have enough cells, we can break these down and put them into multi-well plates,” Plenker explained. In these plates, the scientists test different concentrations and types of drugs for the same patient.

It’s a version of trial and error, deploying a range of potential medical solutions against cells to see what weakens or kills cells.

“If you do that exercise 100 times, you can see how many times compound A scores vs. C, E and F. You get a sense of what the options are versus what is not working,” Plenker said.

While scientists like Plenker and Tuveson use targeted drugs to weaken, cripple or kill cancer, they recognize that cancer cells themselves represent something of a molecular moving target.

“There is a very dynamic shift that can happen between these subtypes” of cancer, Plenker said. “That can happen during treatment. If you start with what’s considered a good prognosis, you can end up with a higher fraction of basal cancer cells” which are more problematic and have a worse prognosis. “We and others have shown that you have a mixture of cell types in your tumor all the time.”

Part of what Plenker hopes to discover as the director of the organoid center is the best combination of ingredients to foster the growth of these versatile and useful out-of-body cancer models.

The gel that helps the cells grow is something Plenker can buy that is an extracellular matrix rich matter that is of murine, or rodent, origin. He hopes to develop a better understanding of some of these proprietary products so he can modify protocols to boost the efficiency of the experiments.

Plenker is “trying to innovate the organoids, and so he may need to adjust conditions and that would include inventing his own recipes,” Tuveson explained.

The facility, which received support from the Lustgarten Foundation, will engage in future clinical trials.

The type of treatments for pancreatic cancer patients typically fall into two arenas. In the first, a patient who is doing well would get an aggressive dose of chemotherapy. In the second, a patient who is already sick would get a milder dose. Determining which regimen is based on the current diagnostic techniques.

Plenker and his wife Juliane Dassler-Plenker, who works as a post-doctoral fellow in the lab of Mikala Egeblad at Cold Spring Harbor Laboratory, live in Huntington. The pair met in Germany and moved to the United States together.

Plenker calls himself a “foodie” and appreciates the hard work that goes into creating specific dishes.

In his career, Plenker always “wanted to help people.” He has appreciated the latest technology and has disassembled and put back together devices to understand how they work.

Prior to the pandemic, Plenker had gone on short trips to Germany to visit with friends and relatives. He is grateful for that time, especially now that he is much more limited in where he can go. He appreciates his landlord and a second American family which helps the couple feel welcomed and grateful.

In 2017, Plenker recalls attending a talk Tuveson gave in Washington, D.C. in which he invited anyone in the audience who wanted to improve a test to come and talk to him after the presentation.

“I was the only one in that regard who talked to him” after that lecture, Plenker said.

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Arkarup Banerjee. Photo from CSHL

By Daniel Dunaief

Arkarup Banerjee is coming back home to Cold Spring Harbor Laboratory. This time, instead of working on the olfactory system, the way he did in Associate Professor Dinu Florin Albeanu’s lab from 2010 to 2016, he is studying vocalizations in the Alston’s singing mouse, a Central American rodent.

Banerjee rejoined Cold Spring Harbor Laboratory in November after almost four years of post-doctoral work at NYU Langone Medical Center. He hopes to use the study of the way these mice react to songs and the way they formulate them to understand how signals from the brain lead to vocalizations.

Singing Mouse

“The reason I decided to come back to Cold Spring Harbor Laboratory is not just because I did my PhD here,” said Banerjee, who is an assistant professor. “Neuroscience [at the lab] is amazing. I have fantastic colleagues. I expect to have lots of collaborations.” CSHL is one of his “top choices” in part because of the ability to interact with other researchers and to attend meetings and courses, he said.

To hear Albeanu tell it, CSHL’s colleagues appreciate the skill and determination Banerjee, whom Albeanu described as a “rare catch,” brings to the site.

“There was pretty much unanimous excitement about his vision for his research,” Albeanu said. “Pretty much everyone was in agreement that [hiring Banerjee] is a must.”

Fundamentally, Banerjee is interested in understanding how the brain computes information. In his new lab at CSHL, he wanted to study the natural behaviors that animals produce without having to teach them anything.

“That’s why my fascination arose in singing mice,” he said. “Nobody has to train them to vocalize.” He hopes to understand the neural circuits in the context of a natural behavior.

In the longer term, Banerjee is interested in contributing to the field of human communication. While numerous other creatures, such as birds, interact with each other vocally, singing from trees as they establish territorial dominance and soliciting mates through their songs, mice, which have cerebral cortexes, have brain architecture that is more similar to humans.

The Alston’s singing mice, which is found in the cloud forests of Costa Rica and Panama, is also different from numerous other species of mice. Many rodents produce vocalizations in the ultrasonic range. These animals can hear calls that are outside the range of human capacity to pick up such sounds.

The singing mice Banerjee is studying produces a stereotyped song that is audible to people. “These mice seem to specialize in this behavior,” he said. In neuroscience, scientists seek animals that are specialists with the hope that understanding that species will reveal how they work, he said.

Audible communications are important for male mice in attracting mates and in guarding their locations against other males. These lower-frequency sounds travel across greater distances.

Specifically, Banerjee would like to know the anatomical differences between the brains of typical rodents and the singing mice. He plans to probe “what kind of changes does it require for a new behavior to emerge during evolution.”

The songs have some value to the males who sing them. Females prefer males who sing more notes per unit time in a 10-second period.

In his experiments, Banerjee has demonstrated that the conventional view about one of the differences between humans and other vocalizing animals may not be accurate. Scientists had previously believed that other animals didn’t use their cortex to produce songs. Banerjee, however, showed that the motor cortex was important for vocal behaviors. Specifically, animals with temporarily inactivated cortexes could not participate in vocal interactions.

As a long term goal, Banerjee is also interested in the genetic sequence that makes the development of any anatomical or behavioral feature different in these singing mice. By using the gene editing tool CRISPR, which CSHL scientists employ regularly, Banerjee hopes to find specific genetic regions that lead to these unique behaviors.

Arkarup Banerjee with Honggoo Chae, a post-doctoral fellow at CSHL, from a Society of Neuroscience Meeting in 2018.

An extension of this research could apply to people with various communication challenges. Through studies of mice with different genetic sequences, Banerjee and other researchers can try to find genes that are necessary for more typical vocalizations. By figuring out the genetic differences, the CSHL scientist may one day discover what researchers could do to minimize these differences.

A resident of Mineola, Banerjee lives with his wife Sanchari Ghosh, who works at Cold Spring Harbor Laboratory press for the preprint service bioRxiv. The couple, who met in India, spend considerable time discussing their shared interest in neuroscience. Banerjee said his wife is a “much better writer” than he and has helped edit his manuscripts.

Banerjee is passionate about teaching and hopes he has a chance to educate more students once the pandemic recedes. Outside the lab, Banerjee shares an important quality with the mice he studies: he sings. He trained as a vocalist when he was growing up in India, and listens to a range of music.

Albeanu, who was teaching a course in Bangalore, India in 2009 when he met Banerjee, said it is a “pleasure to listen to [Banerjee] singing.”

Albeanu recalls how Banerjee stood out for many reasons when he first met him, including developing a way to modify a microscope.

As for his work, Banerjee hopes to understand behaviors like vocalizations from numerous perspectives. “We can seek explanations for all of these levels,” he said.

A neuroscientist by training, Banerjee would like to determine the connection between neural circuitry and the behavior it produces. “The understanding would be incomplete if I didn’t understand why this behavior is being generated.”

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Tobias Janowitz. Photo from CSHL

By Daniel Dunaief

The body’s savior in its battle against disease, immune cells respond to a collection of signals which tell them to dial up or down their patrolling efforts.

Scientists and doctors are constantly trying to determine what combination of beneficial or detrimental signals can lead to different outcomes.

Recently, Assistant Professor Tobias Janowitz and Professor Douglas Fearon of Cold Spring Harbor Laboratory, working with Duncan Jodrell at the University of Cambridge Cancer Research Institute, used an inhibitor developed and tested for the treatment of the human immunodeficiency virus (HIV), the virus that causes AIDS, in patients with colorectal and pancreatic cancer for a week.

Douglas Fearon. Photo from CSHL

The study was done on 24 patients and is a phase 0 effort, in which scientists and doctors test the pharmacokinetics and pharmacodynamics of the treatment.

In the study, which was published in the prestigious journal Proceedings of the National Academy of Sciences of the United States of America, the researchers showed that the treatment got into the blood, that the patients tolerated it, and that it enabled immune treatments to reach the tumors.

While this is an encouraging step, Janowitz cautioned that any such studies are far from a potentially viable treatment for either type of cancer. Indeed, the Food and Drug Administration requires a lengthy and rigorous scientific process for any possible therapy, in part because numerous promising efforts haven’t led to viable therapies for a host of reasons.

Still, this study offers a promising beginning for a potential approach to treating various forms of cancer.

Janowitz said patients “tolerated the treatment by and large very well,” and that “no new toxicities were observed compared to the ones that were known.” Some people developed slight disturbances in their sleep, which were immediately resolved after they discontinued using the treatment.

The history of the possible treatment for HIV showed similar side effects years ago. “We anticipated it would have a favorable toxicity profile,” said Janowitz.

The link between this early candidate for HIV treatment and cancer came from an analysis of the receptor that is expressed on immune cells, called CXCR4.

This receptor is targeted by the drug plerixafor. Most of the work linking the inhibited receptor to potential cancer treatment came from Fearon’s lab, Janowitz explained.

Fearon found that blocking the receptor enabled immune cells to migrate to cancer in a mouse study. Along with Janowitz and CSHL Cancer Director David Tuveson, he published a paper on the preclinical study in a mouse model in PNAS in 2013.

This inhibitor also has been used to release stem cells from bone marrow that can be used in a hematological context for treatment and transplantation. During their cancer study, the scientists found these stem cells circulating in the blood. It’s unclear from this first study how the combination of cancer therapy and releasing stem cells from bone marrow affects patients.

“We are not able to say that that has a relevancy to the cancer patient,” Janowitz said.

While some drug treatments work for a period of time until a cancer returns, immunotherapy may have a longer term benefit than chemotherapeutics, as some studies suggest.

“By giving this drug, our hope is that we enable an influx of immune cells into the tumor and have an across the board integrated immune response,” Janowitz said.

Down the road, Janowitz said the group hopes that this treatment will be a part of a combination of treatments that treat cancer.

By enabling immune cells to access cancer where the mutation rate is lower, these treatments could provide a sustained treatment.

The researchers chose pancreatic and colorectal cancer because those cancers don’t respond to current immunotherapy. “It’s really important to uncover why that is,” said Janowitz. The scientists had evidence from pre-clinical models that the pathway and the biochemistry that this drug activates can be effective.

In his lab, Janowitz performed some of the mechanistic work to understand why this drug might function. A medical doctor who is awaiting his license to practice in New York, Janowitz was also involved in the trial management group and in analyzing the multiplicity of data that came together.

The researchers in this study came from fields including bioinformatics, clinical medicine, pharmacology, and immunology. Fearon explained in an email that Jodrell wrote the grant to Stand Up to Cancer, or SU2C, in 2014 to obtain funding for the trial. Jodrell oversaw the clinical trial and Fearon directed the evaluation of the immunology findings.

Janowitz had a “major role in putting together the clinical data for the write-up,” and Daniele Biasci, a computational biologist at Cambridge, developed the analysis of the transcriptional data of the tumor biopsies, said Fearon.

As for the next stages in this work, physicians at Johns Hopkins Medicine International and Dana Farber Cancer Institute will soon start a phase 2 trial that is already registered and that combines this inhibitor with anti-PD-1.

Fearon said his continued pre-clinical research has shown that this immune suppressive pathway may be relevant to multiple human carcinomas, and has identified new potential targets for more effective immunotherapy.

Janowitz, meanwhile, will explore the systemic immune competence of the body as he continues to take a top down, broad-based approach to cancer.

He would like to know the degree to which the body can mount an effective immune response, while also exploring the factors that diminish that ability.

Separately, with three young children at home, Janowitz and his wife Clary, who is a radiation oncologist, have been balancing between their busy careers and the demands of parenting during the pandemic. Their extended families are both in Europe.

“We can’t visit them and they can’t visit us,” he said adding that he appreciated the way CSHL has offered day care to young children on campus.

As for this study, Janowitz said he’s encouraged by the early results.

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Veronica Sanders. Photo from BNL

By Daniel Dunaief

If doctors could somehow stick numerous miniature flashlights in human bodies and see beneficial or harmful reactions, they would be able to diagnose and treat people who came into their offices.

That’s what Vanessa Sanders, Assistant Scientist at Brookhaven National Laboratory, is working to develop, although instead of using a flashlight, she and her colleagues are using radioisotopes of elements like arsenic. Yes, arsenic, the same element at the center of numerous murder mysteries, has helpful properties and, at low enough concentrations, doesn’t present health threats or problems.

Arsenic 72 is useful in the field of theranostics, which, as the name suggests, is a combination of therapeutics and diagnostics.

Isotopes “allow us to observe visual defects and through using these radioactive agents, we can also observe the functionality of organs,” Sanders explained in an email. These agents can assist in diagnosing people, which can inform the treatment for patients.

What makes arsenic 72 and other radioisotopes helpful is that they have a longer half-life than other isotopes, like fluorine 18, which only lasts for several minutes before it decays. Arsenic-72 has a half life of 26 hours, which matches with the life of an antibody, which circulates through bodies, searching for targets for the immune system. The combination of arsenic-72 and arsenic-77 allows the former to act as a diagnostic agent and the later as a therapeutic partner.

By attaching this radioisotope to antibodies of interest, scientists and doctors can use the decay of the element as a homing device. Using Positron Emission Tomography, agents allow for the reconstruction of images based on the location of detected events.

“When you want to use an antibody as a target for imaging, you want an isotope that will be able to ride with the antibody and accumulate at an area of interest,” Sanders said.

A radiochemist, Sanders is working to develop systems that help researchers and doctors diagnose the extent of problems, while also tracking progress in fighting against diseases. She is working to produce arsenic-72 through the decay of selenium-72.

Using the Brookhaven Linac Isotope Producer, scientists produce selenium-72. They then create a generator system where the selenium 72 is absorbed onto a solid substrate. As it decays, the solid substrate is washed to obtain arsenic-72.

Sanders is hoping to create a device that researchers could ship to clinical institutions where institutions could use arsenic-72 in further applications.

The system BNL is creating is a research and development project. Sanders and her colleagues are working to optimize the process of producing selenium-72 and evaluating how well the selenium, which has a half life of eight days, is retained and how much they can load onto generators.

“We want [arsenic 72] in a form that can easily go into future formulations,” Sanders said. “When we rinse it off that column, we hope to quickly use it and attach it to biomolecules, antibodies or proteins and use it in a biological system.”

With the increasing prevalence of personalized approaches to diseases, Sanders explained that the goal with these diagnostic tools is to differentiate the specific subtype.

A person with pancreatic cancer, for example, might present a specific target in high yield, while another patient might have the same stage cancer without the same high yield target.

“We want to have different varieties or different options of these diagnostic tools to be able to tailor it to the individual patient,” explained Sanders.

Cathy Cutler, Director of the Medical Isotope Program at BNL, said the isotopes Sanders is working on “have a lot of promise” and are “novel.” She described Sanders as “very organized” and “very much a go-getter.”

Cutler said the department feels “very lucky to get her and have her in the program.”

In her group, Sanders explained that she and her colleagues are eager to develop as many radioisotopes as possible to attach them to biomolecules, which will enable them to evaluate disease models under different scenarios. Other researchers are working with arsenic-77, which acts as a therapeutic agent because it emits a different particle.

Scientists are working on a combination of radioisotopes that can incorporate diagnostic and therapeutic particles. When the arsenic 77 destroys the cells by breaking the DNA genetic code, researchers could still observe a reduction in a tumor size. Depending on the disease type and the receptor targeted, scientists could notice a change by observing less signal.

Sanders is working on attaching several radioisotopes to biomolecules and evaluating them to see how well they are produced and separated.

“We make sure [the isotope] attaches to the thing it’s supposed to stick to” such as an antibody, she said.

A resident of Sound Beach, Sanders grew up in Cocoa, which is in central Florida. When she was younger, she wanted to be a trauma surgeon, but she transitioned to radioisotopes when she was in college at Florida Memorial University. “I liked the problem solving aspect of chemistry,” she said. While she works with cancer, she said she would like to investigate neurological diseases as well.

Sanders, who has been living on Long Island since 2017 when she started her post doctoral work at BNL, enjoys the quieter, suburban similarities between the island and her earlier life in Florida.

At six feet, one and a half inches tall, Sanders enjoys playing center on basketball teams and, prior to the pandemic, had been part of several adult leagues in the city and on Long Island, including Ladies Who Hoop and LI Hoops. She is also involved in a sorority, Zeta Phi Beta Sorority Inc, that contributes to community service efforts.

Sanders and her fiancee Joshua Morancie, who works in IT support, had planned to get married in July. They set a new date in the same month next year. If the pandemic continues to derail their party plans next year, the couple plan to wed in a smaller ceremony.

As for radioisotopes, Sanders hopes people become inspired by the opportunities radioisotopes provide for science and medicine.

“There are so many good things that come out of radioisotopes,” Sanders said. “There are so many promising advantages.”

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From left, Kamazima Lwiza aboard the hospital ship Jubilee Hope which is owned by a British NGO known as Vine Trust and provides services to several islands on Lake Victoria with Deogratias Kabogo, Chief Engineer of the ship. Photo by Pascal Ferdinand

By Daniel Dunaief

In tropical and subtropical countries, including Brazil and the Ivory Coast, a parasite moves from snails to humans, causing 220 million illnesses a year and as many as 200,000 annual deaths.

People contract the parasite when they enter shallow, warm waters, where the schistosomiasis larvae known as cercariae enters through the skin, moves through the blood stream and settles near the stomach or bladder.

Once it’s near the bladder, the parasite reproduces, sending its eggs out through urine or feces, which, if directed towards warm, shallow water bodies, can enter the snail and begin the process again.

Schistosomiasis causes anemia, malnutrition and learning difficulties, according to the Centers for Disease Control and Prevention, as the parasite robs humans of zinc and vitamins A and D. Prolonged infection can also cause bladder cancer.

Kamazima Lwiza, Associate Professor at the School of Marine and Atmospheric Sciences at Stony Brook University, is part of a new, five-year study on the effects of climate change on schistosomiasis.

Lwiza’s part of the research, which is lead by Stanford University and involves several institutions, is analyzing the latest Global Climate Models known as Coupled Model Intercomparison Project phase 6 results. Lwiza studies the models under four-kilometer resolution to look for patterns and trends.

By creating a model that predicts temperature changes, Lwiza’s part of the efforts hope to help other collaborators apply those temperature expectations to epidemiological models. The ability of the parasite to survive, reproduce and infect humans depends on the viability of the snails, which are temperature sensitive. The temperature range is between 14 and 35 degrees Celsius, with an optimal temperature of between 30 and 32 degrees Celsius.

A warmer climate would likely increase the prevalence of schistosomiasis in the regions of Brazil and the Ivory Coast that this study is exploring, as well as in newer areas.

Kamazima Lwiza prepared instruments before installation aboard the hospital ship Jubilee Hope, which is owned by a British NGO known as Vine Trust and provides services to several islands on Lake Victoria. Photo by Pascal Ferdinand

Depending on the regional topography, human population and amount of rainfall, the area that is conducive to Schistosomiasis could expand. An area that is relatively flat and where rainfall increases and human population is low but increasing could cause the infection rate to climb.

As waterways that were too cold either reach the minimum temperature threshold for snails, or increase the temperature into the optimal range, snail populations are likely to flourish.

Part of the funding for the SoMAS portion of the study is coming from the National Science Foundation and the National Oceanic and Atmospheric Administration. These national funding agencies recognize that increasing temperature and land use has created an environment that fosters the expansion of snails and increased prevalence of parasites into areas in the southern United States.

“Given the climate change,[some parts of Florida and Georgia] will be falling within that temperature range,” Lwiza said. “The worry is that, if this disease is going to spread, how are we going to be prepared to keep it off.”

Lwiza had originally planned to travel to Brazil this past summer to collect baseline data on water temperatures. The pandemic caused him to cancel his travel. Next year, he hopes to build on data around significant water bodies where the disease is prevalent.

While the portion of the study that includes Lwiza focuses on temperature, the Stony Brook scientist is working with other researchers who are exploring a range of other analytical and mitigation measures.

For starters, in some countries that have battled against this parasite, the use of dams has exacerbated the problem. Dams have kept out prawns, who are natural predators for snails.

Scientists are considering reintroducing prawns. These shellfish, which look somewhat like shrimp, could not only reduce the population of snails and the parasites they carry, but could also become an economic boon, as a part of an aquaculture project.

The goal of that part of the study is to “see if [prawns] can be used as biological control agents,” Lwiza said. “If we can find a way of introducing these back to where they used to be, we can cut down the snail population.”

The third aspect of the study involves the use of artificial intelligence. Researchers are putting together a program that will allow people to take pictures of the parasites they find and upload them to a web site to identify them.

“That way, we are doing crowd sourcing” which will allow “people to contribute to our investigation,” Lwiza said. Researchers will be able to map the location of the parasites.

Lwiza said Schistosomiasis can affect anyone who goes in the water. The illness doesn’t get as much attention as malaria. When people go to a rural clinic, if they have malaria, they can get medicines from 20 vendors. A person with Schistosomiasis, however, may need to go to a district or regional hospital for medication.

Originally from Tanzania, Lwiza grew up on the western shores of Lake Victoria, where strong waves don’t favor the development of snails. He currently lives in East Northport with his wife Catherine Kentuha, who works in the United Nations Development Program. The couple has three children — Philip, Johnathan and Mulokozi.

Lwiza has worked at Stony Brook University for 29 years and has lived in Port Jefferson Village and East Setauket.

When he lived in Port Jefferson Village, he was pleased and surprised by how his neighbors brought him candles during a brown out and made sure he and his family were okay.

“It was like, ‘Wow, this is really great. This is like Africa,’” he recalls thinking.

When he’s not working, Lwiza enjoys riding a bike and listening to Indian, Arab, African and Latin music. He is also interested in computer programming.

As this study of Schistosomiasis progresses, Lwiza hopes the incidence of disease decreases and that the science helps protect the population against a widespread illness.

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At an Oct. 19 press conference announcing a new study to help youth in Paterson, New Jersey, from left, Paterson Mayor André Sayegh; Antoine Lovell; Director of Paterson Youth Services Bureau Christina Barnes Lee; Ijeoma Opara; Program Coordinator at Municipal Alliance Prevention Program Tenee Joyner; Councilman Luis Velez and Chief Operating Officer of OASIS Paterson Jim Walsh. Photo from Ijeoma Opara

By Daniel Dunaief

Stony Brook University’s Ijeoma Opara, a new Assistant Professor in the School of Social Welfare, is starting her promising early scientific career by making history, becoming the first social worker to receive an Early Independence Award from the National Institutes of Health.

Opara, who hopes the award opens doors to other social workers and to other scientists of color, plans to use the funds to create a research study and intervention program that will make a difference.

Opara will study the link between mental heath and substance abuse in Paterson, New Jersey, where she conducted her PhD training while attending Montclair State University and where she hopes to help youth who may not attend school often enough to benefit from programs in academic settings. She also hopes to understand issues that youth may be facing that lead to substance abuse and poor mental health.

Opara plans to use the $1.84 million, five-year grant to conduct venue-based sampling, where she will search for at-risk youth and where she can tailor mental health and substance abuse questions that are relevant to the experience of the children she hopes to help.

“A lot of youth that needed these services, who had substance abuse and serious issues with mental health, weren’t going to school,” said Opara. “They weren’t in locations [where] a lot of researchers collect data.”

It didn’t make sense to collect the survey information from students in school when the people who need these services are not present in the system. “Meeting them where they are to figure out how to get them engaged” became a critical element to conceptualizing this study, said Opara. “There is no such thing as hard-to-reach populations.”

The NIH award Opara received encourages young researchers who recently completed their graduate work to engage in high-risk, high-return studies.

The risk in Opara’s work is that she won’t be able to recruit enough youth. She is, however, is convinced that her past experience in Paterson, a city filled with communities she’s grown to love, will enable her to find and reach out to targeted youth.

She’s currently in the first phase of her two-part effort; finding staff, figuring out ways to find people for her studies and designing questions relevant to them and their lives. In the second part of her research, she plans to provide mental health and substance abuse services.

Michelle Ballan, Associate Dean for Research in the School of Social Welfare, applauded Opara’s approach to her research.

“Venue-based sampling takes considerable work,” Ballan said. “It’s much easier to send a survey to schools.”

Indeed, this kind of effort “takes time, manpower and a tremendous understanding of how [Opara’s] inter-disciplinary focus is intertwined,” Ballan said. “She’s a family studies researcher, a social worker, and a public health researcher. Having those three areas of expertise, it’s not surprising that venue-based sampling was the one she chose.”

Opara is turning to some of the leaders in Paterson to advise her during this effort. She has created a community advisory board that represents youth and includes community leaders.

One of the challenges this year is that some of the sites where these youth might typically congregate may have fewer people during the pandemic. “It’s something we’re really focusing on in our first couple of meetings: where are the youth going?” Opara asked. She suggested sites could include basketball courts and parks. She is also exploring ways to recruit youth (between ages 13 and 21) online.

Opara is hoping to understand how the environment may impact people in the community as either a protective or a risk factor for substance abuse and mental health.

“What are some structures that could be serving as a protective buffer for kids who aren’t engaging in substance abuse and who don’t have negative mental health symptoms?” she asked.

On the other hand, she would like to identify those buildings or features that increase the trauma or risk and that might cause youth to mask their symptoms.

Once she finds these at-risk youths, Opara will ask about drug and alcohol use, lifetime drug use, their feelings about mental health and their levels of anxiety and depression. She also expects to ask about suicidal ideation.

When she understands the challenges and stressors, she hopes to create a culturally relevant, community based and neighborhood focused intervention. For this to work, she plans to recruit some of the people involved in the study to inform these solutions.

Opara is determined to make a difference for the city of Paterson.

“I don’t want to leave the community with nothing,” she said. “I don’t want to come in, collect data and leave. It’s important to create a sustainable change” that will “empower the community and empower youth.”

In Paterson, Opara recognizes the diversity of different neighborhoods, with people from different backgrounds, experiences and languages living in different blocks.

As a research assistant at Montclair, Opara said she encountered resistance at efforts to change neighborhoods, particularly when she was involved in programs to reduce the hours when liquor stores were open. She said youth mobilization, which included speaking about their experiences witnessing alcoholism in their neighborhoods, helped encourage the city council to pass the ordinance.

People came from other neighborhoods, bought alcohol, drank until they passed out and created a “really dangerous environment” as youth and teenagers were afraid to walk home past people who were drunk in the streets.

Opara appreciates the support of educators in the Paterson School District and the mayor, André Sayegh. She said her efforts may be particularly important in this environment, as New Jersey has cut funding from school-based youth services amid a declining budget caused by a slowing economy triggered by the pandemic.

If the program Opara creates works, she hopes other researchers can extend it to other communities.

 

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Strycker in the Antarctic with chinstrap penguins
Noah Strycker photographing birds in Bali
Noah Strycker with a northern saw-whet owl
A turkey vulture

By Daniel Dunaief

Noah Strycker once made a bet with a cruise ship full of passengers: if any of them spotted him without binoculars at any point during a 14-day trip, he would buy them all drinks. Even with that incentive, no one won a free drink, in large part because Strycker’s passion for birds means his binoculars are never out of arm’s reach.

A master’s candidate in Heather Lynch’s lab at Stony Brook University, Strycker, who has turned his world travels in search of his feathered friends into books, is working through the second year on Lynch’s specialty: penguins.

As a part of the team, Strycker is contributing to a population analysis of chinstrap penguins. Last year, he ventured to Antarctica with a field team for several months to count colonies of these six-to-ten pound birds.

The “piece de resistance” of that journey was a trip to Elephant Island, which is where, over 100 years earlier, Ernest Shackleton and his crew were marooned for several months before their rescue.

During Strycker’s journey to the famous but uninhabited island, the team counted the number of chinstrap and compared the population to the last known count, which occurred 50 years ago.

They determined that the chinstrap has had a significant decline, in some cases losing more than half its population in some areas. After a survey of Elephant Island and Low Island, the research team suggested that the decline in the chinstrap’s main source of food, krill, likely caused this reduction.

As for this year, Strycker had planned to travel back to Antarctica until the pandemic caused the cancellation of the trip. He is conducting a literature search to find previous chinstrap penguin counts. In the final part of his master’s program, he will help provide an updated assessment for the International Union for the Conservation of Nature.

While the IUCN provides information on threatened or endangered species, Strycker recognizes that the chinstrap won’t likely be on that list. “There are many millions of them,” he explained in a recent interview. “[But] they are declining. We are trying to give the IUCN updated information.”

Lynch’s lab will provide information for IUCN’s green list, which is for species that aren’t endangered. Species on this list might benefit from additional information that could help shape a future conservation strategy.

Strycker, who traveled to 41 countries in 2015 to count as many birds as possible in a year, appreciated and enjoyed his interaction with penguins. These flightless birds have no fear of humans so they waddled up to him and untied his shoelaces. They also fell asleep next to his boot and preened the side of his black wind pants.

Strycker landed in the world of penguins when he was working as a naturalist guide on a cruise ship and met Lynch, whose team was on the same boat.

Lynch was delighted with the chance to add Strycker to her team. “One of the most difficult things about our work is that there is such a steep learning curve for doing Antarctic field research,” Lynch explained in an email. “To grab someone like [Strycker] with so much Antarctic experience under his belt was just fantastic.”

Lynch appreciates how Strycker led the chinstrap survey work, not just in collecting the data but also in analyzing and writing it up. Strycker is “a terrific writer (and very fast, too) and his finesse with writing helped us get our research out for review faster than would normally be possible,” she said.

After seeing and hearing birds around the world, Strycker has an unusual favorite — the turkey vulture. When he was in high school in Eugene, Oregon, Strycker watched a nature documentary with David Attenborough in which the host put rotting meat out in a forest. In no time at all, turkey vultures discovered the feast. “That is the coolest thing I’ve seen,” Strycker recalls thinking.

Months later, he discovered a road kill deer while he was driving. He put the dead animal in the trunk of his ’88 Volvo Sedan and dumped it in his front yard, waiting to see if he could duplicate Attenborough’s feast. Fairly soon, 25 turkey vultures arrived and were sitting on the roof of his house. The neighbors didn’t complain because Strycker grew up on a dead end, 20 acres from the nearest house.

Fortunately for him, his parents didn’t seem too upset, either. “When they realized that their only child had become addicted to birds at a young age, they rolled their eyes and said that there’s much worse things that he could become addicted to,” Strycker recalled.

As for Long Island, Strycker said the area is currently in fall migration season. All the birds that nested in Canada are passing through New York on their way to spend the winter in warmer climates.

The migration patterns typically start with shorebirds in August, transition to warblers in September and to waterfowl, such as ducks and geese, which appear in October and November.

“This fall has also been exciting because several species of northern songbirds have ‘irrupted’ south, so we’re seeing unusually high numbers of them on Long Island,” said Strycker. This month, red-breasted nuthatches, purple finches, and pine siskins have appeared in large numbers, which doesn’t happen every year.

At this time of year, birds sometimes get lost outside their usual range. Last week, a painted redstart, which should be in Arizona, arrived in Floyd Bennett Field in Brooklyn.

“I was out there at dawn the next morning, along with half the birder population of New York, but unfortunately it had already moved on,” said Strycker.

People interested in tracking bird migration by radar can use the website birdcast.info, which can predict bird migration like the weather using radar data. Strycker advises interested birders to type “Stony Brook” into their local Bird Migration Alert tool.

Once he earns his degree, Strycker plans to build on and share his experiences.

He would like to write books, give presentations and “generally inspire the world about birds.”

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Partha Mitra at the Shanghai Natural History Museum in China where he was giving a talk to children on how birds learn to sing.

By Daniel Dunaief

Throw a giant, twisted multi-colored ball of yarn on the floor, each strand of which contains several different colored parts. Now, imagine that the yarn, instead of being easy to grasp, has small, thin, short intertwined strings. It would be somewhere between difficult and impossible to tease apart each string.

Instead of holding the strings and looking at each one, you might want to construct a computer program that sorted through the pile.

That’s what Partha Mitra, a professor at Cold Spring Harbor Laboratory, is doing, although he has constructed an artificial intelligence program to look for different parts of neurons, such as axons, dendrites and soma, in high resolution images.

Partha Mitra at the Owl Cafe in Tokyo

Working with two dimensional images which form a three dimensional stock, he and a team of scientists have performed a process called semantic segmentation, in which they delineated all the different neuronal compartments in an image.

Scientists who design machine learning programs generally take two approaches: they either train the machine to learn from data or they tailor them based on prior knowledge. “There is a larger debate going on in the machine learning community,” Mitra said.

His effort attempts to take this puzzle to the next step, which hybridizes the earlier efforts, attempting to learn from the data with some prior knowledge structure built in. “We are moving away from the purely data driven” approach, he explained.

Mitra and his colleagues recently published a paper about their artificial intelligence-driven neuroanatomy work in the journal Nature Machine Intelligence.

For postmortem human brains, one challenge is that few whole-brain light microscopic data sets exist. For those that do exist, the amount of data is large enough to tax available resources.

Indeed, the total amount of storage to study one brain at light microscope resolution is one petabyte of data, which amounts to a million megapixel images.

“We need an automated method,” Mitra said. “We are on the threshold of where we are getting data a cellular resolution of the human brain. You need these techniques” for that discovery. Researchers are on the verge of getting more whole-brain data sets more routinely.

Mitra is interested in the meso-scale architecture, or the way groups of neurons are laid out in the brain. This is the scale at which species-typical structures are visible. Individual cells would show strong variation from one individual to another. At the mesoscale, however, researchers expect the same architecture in brains of different neurotypical individuals of the same species.

Trained as a physicist, Mitra likes the concreteness of the data and the fact that neuroanatomical structure is not as contingent on subtle experimental protocol differences.

He said behavioral and neural activity measurements can depend on how researchers set up their study and appreciates the way anatomy provides physical and architectural maps of brain cells.

The amount of data neuroanatomists have collected exceeds the ability of these specialists to interpret it, in part because of the reduction in cost of storing the information. In 1989, a human brain worth of light microscope data would have cost approximately the entire budget for the National Institutes of Health based on the expense of hard disk storage at the time. Today, Mitra can buy that much data storage every year with a small fraction of his NIH grant.

“There has been a very big change in our ability to store and digitize data,” he said. “What we don’t have is a million neuroanatomists looking at this. The data has exploded in a systematic way. We can’t [interpret and understand] it unaided by the computer.”

Mitra described the work as a “small technical piece of a larger enterprise,” as the group tries to address whether it’s possible to automate what a neuroanatomist does. Through this work, he hopes computers might discover common principals of the anatomy and construction of neurons in the brain.

While the algorithms and artificial intelligence will aid in the process, Mitra doesn’t expect the research to lead to a fully automated process. Rather, this work has the potential to accelerate the process of studying neuroanatomy.

Down the road, this kind of understanding could enable researchers and ultimately health care professionals to compare the architecture and circuitry of brains from people with various diseases or conditions with those of people who aren’t battling any neurological or cognitive issues.

“There’s real potential to looking at” the brains of people who have various challenges, Mitra said.

The paper in Nature Machine Intelligence reflected a couple of years of work that Mitra and others did in parallel with other research pursuits.

A resident of Midtown, Mitra, his wife Tatiana and their seven-year-old daughter have done considerable walking around the city during the pandemic.

The couple created a virtual exhibit for the New York Hall of Science in the Children’s Science Museum in which they described amazing brains. A figurative sculptor, Tatiana provided the artwork for the exhibition.

Mitra, who has been at Cold Spring Harbor Laboratory since 2003, said neuroanatomy has become increasingly popular over the last several years. He would like to enhance the ability of the artificial intelligence program in this field.

“I would like to eliminate the human proofreading,” he said. “We are still actively working on the methodology.”

Using topological methods, Mitra has also traced single neurons. He has published that work through a preprint in bioRxiv.

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Above, a Vanderbilt educator conducts science demonstrations for children.

Did you know? The Suffolk County Vanderbilt Museum’s Reichert Planetarium, 180 Little Neck Road, Centerport offers free earth science and astronomy demonstrations all day for young children each Saturday and Sunday from noon to 5 p.m.

Dave Bush, director of the Planetarium, said the demonstrations, which are included in the price of admission, are performed by Vanderbilt educators using science kits.

One demonstration (see photo on right) shows how clouds are created in the atmosphere. A few drops of isopropyl alcohol are placed in a clear soda bottle, and the bottle is pressurized. When the pressure is released, a cloud is formed by condensation.  This shows that clouds can form when the atmospheric pressure is low.

“Although the planetarium theater remains closed, we are happy to be able to share these Earth and space science toolkits with families,” he said. “This is yet another opportunity to explore, learn and have fun while visiting the museum.”

For more information, visit www.vanderbiltmuseum.org.

Photos courtesy of Suffolk County Vanderbilt Museum

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Christina Joselevitch

By Daniel Dunaief

Children knock on the door of 1313 Gluto Lane, a favorite house for Halloween. The resident, known for providing coveted confections at a rapid rate, immediately comes to the door, asks no questions about the Halloween costumes that might slow the process down and, with almost super-human speed, dumps candy into open bags and closes the door.

Word spreads about the house on Gluto Lane. Soon, the doorbell rings at a furious pace, with children eager to get the best candy of this difficult year and move on to the next house.

At first, with Trick or Treaters coming at a regular pace, the process works, but then, something goes awry, creepy music begins and the door doesn’t open.

That’s what’s happening in bipolar retinal cells in the goldfish Christina Joselevitch, a Postdoctoral Associate in the Neurobiology and Behavior Department at Stony Brook University’s Renaissance School of Medicine, is studying.

Known for their incredible speed at releasing neurotransmitters stored in circular vesicles, these bipolar retinal cells go through a depression in which they can’t release the neurotransmitter glutamate despite repeated signals for the release of the neurotransmitter.

“When you stimulate those cells very strongly, with two stimuli close apart, they suffer depression,” Joselevitch said. “Nobody knew why, if they’re able to signal constantly, they should suffer from depression.

To be sure, Joselevitch was working with extreme stimulation to probe the limits of the system and understand its underpinnings. This is not necessarily how these cells work. She said the researchers don’t know if retinal neurons experience synaptic depression under normal conditions and what function depression would have in bipolar cell physiology, in vision or in signaling processing in general.

In a recent publication in the Journal of Neuroscience, Joselevitch described at least two processes that contribute to this slowdown, which she describes as the rate limiting steps. The vesicles need to get to the membrane and they need to get ready to mature before they are release. Once vesicles move towards the cell membrane, they don’t immediately fuse and send their neurotransmitter into the synapse between cells. In some cells, such as the retinal photoreceptors and bipolar cells and in hair cells of the ear and lateral line in fish and in cells of the pineal gland, they gather in a ribbon close to calcium entry points.

Scientists have two theories of the ribbon function. The first is that it could act as a conveyor belt and speed up vesicle priming and delivery to the membrane and the second is that it could set a constant pace for vesicle delivery.

Joselevitch’s results suggest that the vesicles attach to the ribbon, where they go through a maturation process. These paired-pulse depressions don’t just occur in fish: they also affect the ability of mammalian cells to respond to a second stimulus.

These cellular phenomena show the limits of the system. Indeed, Joselevitch likened the process to a car that has reached its maximum speed. Pushing down harder or more on the accelerator won’t enable further acceleration.

The impact of this work is “broad,” she said. Studying this process could enable a stronger awareness of the steps in fast-acting processes in the nervous system. Such research could also provide an understanding about processes that go awry in various neurological diseases.

In an email, Professor Lonnie Wollmuth, who is the principal investigator for the Stony Brook lab in which Joselevitch works, described Joselevitch as “invaluable to our on-going efforts to study presynaptic mechanisms in the retina.” He wrote that she was an “outstanding and very careful scientist” who is “passionate” about her research and has served as a mentor for others in the lab.  Joselevitch has been working in Wollmuth’s lab for about 16 months.

Synaptic transmission is fundamental to all brain function, Wollmuth explained. “Changes in the strength of synaptic transmission underlie basic higher order brain functions like learning and memory,” the Stony Brook Professor wrote. Joselevitch’s experiments “reveal mechanisms of presynaptic vesicle release at all synapses and provide novel insights into the processing of vesicles at ribbon synapses.”

Based on Joselevitch’s work, Wollmuth’s lab has submitted a large National Institutes of Health grant to the National Eye Institute to study the molecular components of presynaptic release in the retina. She has also started to integrate her work with Alzheimer’s Disease, as proteins found in that disease disrupt the molecular machinery involved in presynaptic release.

A native of Brazil, Joselevitch has been at Stony Brook University since last July. She is on sabbatical with the University of São Paulo. She is hoping to participate in these studies in New York for a few more years.

She said she was “always a nerd,” and liked to study languages. With varying levels of proficiency, she speaks five languages: Portuguese, English, German, Dutch, and Spanish. At one point, she wanted to be an astronaut, but her mother Carmen dissuaded her from pursuing that interest.

Joselevitch had planned to return to Brazil to see her family in April, but had to cancel that plan because of a travel ban from the COVID-19 pandemic. She said her parents have been “good sports” and her father has bought a smartphone so he can talk through Skype or WhatsApp with his scientist daughter.

Joselevitch enjoys biking, hiking, singing and playing guitar and has been productive during the pandemic, writing papers and proposals. Stony Brook is nominating her work for consideration for the Warren Alpert Distinguished Scholar Award.

Wollmuth wrote that Joselevitch’s research forms “the foundation for future experiments to address the molecular components of vesicle dynamics.” Once they are identified, researchers can modulate and protect them in brain diseases.

Citing author James Joyce, Joselevitch explained her focus on neurons in the fish eye, which, she hopes, may lead to a broader understanding of neurology and disease. When asked why he wrote about Dublin when he could describe other places he’s visited, Joyce responded, “In the particular is contained the universal.”

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