Power of 3

From left, Research Assistant Onur Eskiocak, CSHL Fellow Semir Beyaz and graduate student Ilgin Ergin. Photo by Gina Motisi, 2019/CSHL.

By Daniel Dunaief

It’s a catch-22: some promising scientific projects can’t get national funding without enough data, but the projects can’t get data without funding.

That’s where private efforts like The Mark Foundation for Cancer Research come in, providing coveted funding for promising high-risk, high-reward ideas. Founded and funded by Pamplona Capital Management CEO Alex Knaster in 2017, the Foundation has provided over $117 million in grants for various cancer research efforts.

Tobias Janowitz

This year, The Mark Foundation, which was named after Knaster’s father Mark who died in 2014 after contracting kidney cancer, has provided inaugural multi-million dollar grants through the Endeavor Awards, which were granted to three institutions that bring scientists with different backgrounds together to address questions in cancer research. 

In addition to teams from the University of California at San Francisco and a multi-lab effort from Columbia University, Memorial Sloan Kettering Cancer Center and Johns Hopkins University School of Medicine, Cold Spring Harbor Laboratory scientists Tobias Janowitz and Semir Beyaz received this award.

“We are absolutely delighted,” Janowitz wrote in an email. “It is a great honor and we are excited about the work.” He also indicated that the tandem has started the first set of experiments, which have produced “interesting results.”

The award provides $2.5 million for three years and, according to Janowitz, the researchers would use the funds to hire staff and to pay for their experimental work.

Having earned an MD and a PhD, Janowitz takes a whole body approach to cancer. He would like to address how the body’s response to a tumor can be used to improve treatment for patients. He explores such issues as how tumors interact with the biology of the host.

Semir Beyaz

Semir Beyaz, who explores how environmental factors like nutrients affect gene expression, metabolic programs and immune responses to cancer, was grateful for the support of the Mark Foundation.

Beyaz initially spoke with the foundation about potential funding several months before Janowitz arrived at Cold Spring Harbor Laboratory. When the researchers, whose labs are next door to each other, teamed up, they put together a multi-disciplinary proposal.

“If the risks [of the proposals] can be mitigated by the innovation, it may yield important resources or new paradigms that can be incorporated into research proposals that can be funded by the [National Institutes of Health] and other government agencies,” Beyaz said.

Janowitz wrote that he had a lunch together in a small group with Knaster, who highlighted the importance of “high-quality data and high-quality data analysis to advance care for patients with cancer.”

Michele Cleary, the CEO of The Mark Foundation, explained that the first year of the Endeavor program didn’t involve the typical competitive process, but, rather came from the Foundation’s knowledge of the research efforts at the award-winning institutions.

“We wanted to fund this concept of not just studying cancer at the level of the tumor or tumor cells themselves, but also studying the interaction of the host or patient and their [interactions] with cancer,” Cleary said. “We thought this was a fantastic project.”

With five people on the Scientific Advisory Committee who have PhDs at the Foundation, the group felt confident in its ability to assess the value of each scientific plan.

Scientists around the world have taken an effective reductionistic approach to cancer, exploring metabolism, neuroendocrinology and the microbiome. The appeal of the CSHL effort came from its effort to explore how having cancer changes the status of bacteria in the gut, as well as the interplay between cancer and the host that affects the course of the disease.

From left, Becky Bish, Senior Scientific Director, Ryan Schoenfeld, Chief Scientific Officer and Michele Cleary, CEO of The Mark Foundation at a workshop held at the Banbury Center at Cold Spring Harbor Laboratory in September 2019. Photo by Constance Brukin.

These are “reasonable concepts to pursue, [but] someone has to start somewhere,” Cleary said. “Getting funding to dive in, and launch into it, is hard to do if you can’t tell a story that’s based on a mountain of preliminary data.”

Beyaz said pulling together all the information from different fields requires coordinating with computational scientists at CSHL and other institutions to develop the necessary analytical frameworks and models. This includes Cold Spring Harbor Laboratory Fellow Hannah Meyer and Associate Professor Jesse Gillis.

“This is not a simple task,” Beyaz said. The researchers will “collaborate with computational scientists to engage currently available state-of-the-art tools to perform data integration and analysis and develop models [and] come up with new ways of handling this multi-dimensional data.”

Cleary is confident Janowitz and Beyaz will develop novel and unexpected insights about the science. “We’ll allow these researchers to take what they learn in the lab and go into the human system and explore it,” she said.

The researchers will start with animal models of the disease and will progress into studies of patients with cancer. The ongoing collaboration between CSHL and Northwell Health gives the scientists access to samples from patients.

With the Endeavor award, smaller teams of scientists can graduate to become Mark Foundation Centers in the future. The goal for the research the Foundation funds is to move towards the clinic. “We are trying to join some dots between seemingly distinct, but heavily interconnected, fields,” Beyaz said.

Beyaz has research experience with several cancers, including colorectal cancer, while Janowitz has studied colorectal and pancreatic cancer. The tandem will start with those cancers, but they anticipate that they will “apply similar kinds of experimental pipelines” to other cancer types, such as renal, liver and endometrial, to define the shared mechanisms of cancer and how it reprograms and takes hostage the whole body, Beyaz said. 

“It’s important to understand what are the common denominators of cancer, so you might hopefully find the Achilles Heel of that process.”

While Cleary takes personal satisfaction at seeing some of the funding go to CSHL, where she and Mark Foundation Senior Scientific Director Becky Bish conducted their graduate research, she said she and the scientific team at the foundation were passionate to support projects that investigated the science of the patient.

“No one has tried to see what is the cross-talk between the disease and the host and how does that actually play out in looking at cancer,” said Cleary, who earned her PhD from Stony Brook University. “It’s a bonus that an institution that [she has] the utmost respect for was doing something in the same space we cared” to support.

The CSHL research will contribute to an understanding of cachexia, when people with cancer lose muscle mass, weight, and their appetite. Introducing additional nutrition to people with this condition doesn’t help them gain weight or restore their appetite.

Janowitz and Beyaz will explore what happens to the body physiologically when the patient has cachexia, which can “help us understand where we can intervene before it’s too late,” Cleary said.

The CSHL scientists will also study the interaction between the tumor and the immune system. Initially, the immune system recognizes the tumor as foreign. Over time, however, the immune system becomes exhausted.

Researchers believe there might be a “tipping point” in which the immune system transitions from being active to becoming overwhelmed, Cleary said. People “don’t understand where [the tipping point] occurs, but if we can figure it out, we can figure out where to intervene.”

Scientists interested in applying for the award for next year can find information at the web site: https://themarkfoundation.org/endeavor/. Researchers can receive up to $1 million per year for three years. The Mark Foundation is currently considering launching an Endeavor call for proposals every other year.

 

Illustration depicting Falcatakely amid nonavian dinosaurs and other creatures during the Late Cretaceous in Madagascar. (Credit: Mark Witton)

By Daniel Dunaief

Dromomeron and Falcatakely lived nowhere near each other. They also lived millions of years apart, offering the kind of evolutionary pieces to different puzzles that thrill paleontologists.

Left, Alan Turner holds a model of the maxilla of Falcatakely, with a CT reconstruction on his computer screen.

These two creatures, the first a three-foot long dinosaur precursor discovered in Ghost Ranch, New Mexico, and the second a crow-sized bird fossil discovered in Madagascar, have taken center stage in recent scientific circles.

What they have in common is Alan Turner, Associate Professor in the Department of Anatomical Sciences at the Renaissance School of Medicine at Stony Brook University.

The discoveries, which were made over a decade ago, were recently parts of publications in consecutive issues of the prestigious journal Nature. “It’s really exciting,” Turner said. “I definitely feel fortunate” to contribute to these two publications.

Turner, who is not the lead author in either study, emphasized that these papers were only possible through teamwork. “These large, collaborative efforts are one of the ways these really significant discoveries can happen,” he said.

The work that includes Dromomeron, in particular, is one that “any one of our groups couldn’t have done [alone]. It hinged on a series of discoveries across multiple continents.”

Each paper helps fill out different parts of the evolutionary story. The Dromomeron discovery helps offer an understanding of a major evolutionary transition from the Triassic Period, while the Falcatakely find offers a look at the diversification of birds during the Cretaceous Period.

Dromomeron

Starting with the paper in which Dromomeron appears, researchers used a collection of dinosaur precursor fossils to study a smaller group of animals called lagerpetids, whose name means “rabbit lizard” or “rabbit reptile.”

These creatures lived during the age of the earliest relatives of lizards, turtles and crocodylians.

Above, a reconstruction of a pterosaur, a lagerpetid from the Triassic Period/Rodolfo Nogueria

Pterosaurs, which have a characteristic elongated fourth finger that forms a large portion of their wing, lived 160 million years ago, which means that the earlier, flightless lagerpetids roamed the Earth about 50 million years before pterosaurs.

Turner discovered Dromomeron in Ghost Ranch, New Mexico 14 years ago. Since then, other scientists have unearthed new bones from this prehistoric rabbit lizard group in North America, Brazil, Argentina and Madagascar.

Scientists involved in this paper used micro-CT scans and 3D scanning to compare lagerpetid and pterosaur skeletal fossils to demonstrate overlaps in their anatomy. The shape and size of the brain and inner ear of these lagerpetid fossils share similarities with pterosaurs.

The inner ear, Turner explained, is particularly important for animals like the pterosaur, which likely used it the way modern birds do when they are in flight to help determine their location in space and to keep their balance.

Lagerpetids, however, didn’t fly, so paleontologists aren’t sure how these ancient rabbit lizards used their inner ear.

Turner said the Dromomeron discovery was initially more of a curiosity. In fact, when researchers found it, “we had a blackboard in this collection space where we were working,” Turner recalled. “It was unceremoniously referred to as ‘Reptile A.’ There weren’t a lot of things to compare it to. At that point we knew we had a thing but we didn’t know what it was.”

A colleague of Turners, Randall Irmis, Chief Curator and Curator of Paleontology, Associate Professor of Geology and Geophysics at the University of Utah, traveled to Argentina, where he noticed a creature that was similar to the find in New Mexico.

Irmis’s trip “allowed our team to confirm our comparison [between Dromomeron and Lagerpeton] first-hand. From there, we were able to build out the larger evolutionary context,” Turner explained in an email.

Falcatakely

Meanwhile, Turner and Patrick O’Connor, Professor of Anatomy and Neuroscience at Ohio University and lead author on the study, shared their discovery of a bird they located in Madagascar that they called Falcatakely.

The bird’s name is a combination of Latin and Malagasy, the language of the island nation of Madagascar, which means “small scythe” and describes the beak shape.

Right, an artist reconstruction of the Late Cretaceous enantiornithine bird Falcatakely forsterae with its unique beak/Sketch by Mark Witton

The scientists found a partial skull in a quarry in Madagascar. The fossil was embedded in rocks. Turner and O’Connor analyzed it through CT scanning and through careful physical and digital preparation by their colleague Joe Groenke, laboratory coordinator for the O’Connor lab.

The discovery of grooves on the side of the face for a beak took the researchers by surprise.

“As the face began to emerge from the rock, we immediately knew that it was something very special, if not entirely unique,” O’Connor said in a press release. 

“Mesozoic birds with such high, long faces are completely unknown, with Falcatakely providing a great opportunity to reconsider ideas around head and beak evolution in the lineage leading to modern birds.”

As with the Dromomeron find, the discovery of Falcatakely didn’t provide a eureka moment when the scientists found it 10 years ago.

“We didn’t know [what we had] when we collected this material,” Turner said. “It wasn’t until we CT scanned the block in an effort to begin the preparation that we said, ‘Wait a second. There’s something really weird in this block. The flat part turned out to be the side of the face.”

Turner originally thought it could have been the breast bone of a larger dinosaur. During the pandemic, he has come back to projects that have been sitting around for several years. Some have “probably danced on the periphery that have now come to the dance,” in terms of his focus.

In looking back on the ingredients that made these two Nature papers possible, Turner added another element. These publications underline “the importance of investing in long term field work expeditions,” he said.

Michael Schatz and Aspyn Palatnick. Photo by Lauryl Palatnick

By Daniel Dunaief

Michael Schatz, Adjunct Associate Professor at Cold Spring Harbor Laboratory, saw some similarities to his own life when he met the then 14-year old Aspyn Palatnick.

Palatnick, who was a student at Cold Spring Harbor High School, had been developing games for the iPhone. When he was that age, Schatz, who is also a Bloomberg Distinguished Associate Professor of Computer Science and Biology at Johns Hopkins University, stayed up late into the evening programming his home computer and building new software systems.

Meeting Palatnick eight years ago was a “really special happenstance,” Schatz said. He was “super impressed” with his would-be young apprentice.

When he first met Schatz, Palatnick explained in an email that he “realized early on that he would be an invaluable mentor across research, computer science, and innovation.”

Palatnick was looking for the opportunity to apply some of the skills he had developed in making about 10 iPhone games, including a turtle racing game, to real-world problems.

Knowing that Palatnick had no formal training in computer science or genetics, Schatz spent the first several years at the white board, teaching him core ideas and algorithms.

“I was teaching him out of graduate student lecture notes,” Schatz said.

Schatz and Palatnick, who graduated with a bachelors and master’s from the University of Pennsylvania and works at Facebook, have produced a device which they liken to a “tricorder” from Star Trek. Using a smart phone or other portable technology, the free app they created called iGenomics is a mobile genome sequence analyzer.

The iPhone app complements sequencing devices Oxford Nanopore manufactures. A mobile genetic sequencer not only could help ecologists in the field who are studying the genetic codes for a wide range of organisms, but it could also be used in areas like public health to study the specific gene sequences of viruses like SARS-CoV-2, which causes COVID-19.

In a paper published in GigaScience, Schatz and Palatnick describe how to use iGenomics to study flu genomes extracted from patients. They also have a tutorial on how to use iGenomics for COVID-19 research.

While developing the mobile sequencing device wasn’t the primary focus of Schatz’s work, he said he and others across numerous departments at Johns Hopkins University spent considerable time on it this summer, as an increasing number of people around the world contracted the virus.

“It very rapidly became how I was spending the majority of my time,” said Schatz.

Palatnick is pleased with the finished product.

“We’ve made DNA sequence analysis portable for the first time,” he explained in an email.

Palatnick said the app had to use the same algorithms as traditional genomics software running on supercomputers to ensure that iGenomics was accurate and practical. Building algorithms capable of rendering DNA alignments and mutations as users tapped, scrolled and pinched the views presented a technical hurdle, Palatnick wrote.

While Schatz is optimistic about the vaccinations that health care workers are now receiving, he said a mass vaccination program introduces new pressure on the virus.

“We and everyone else are watching with great interest to see if [the vaccinations] cause the virus to mutate,” Schatz said. “That’s the big fear.”

Working with the sequences from Nanopore technology, iGenomics can compare the entire genome to known problematic sequences quickly. Users need to get the data off the Oxford Nanopore device and onto the app. They can do that using email, from Dropbox or the web. 

In prior viral outbreaks, epidemiologists traveled with heavier equipment to places like West Africa to monitor the genome of Ebola or to South and Central America to study the Zika virus genome.

“There’s clearly a strong need to have this capability,” Schatz said.

Another iGenomics feature is that it allows users to airdrop any information to people, even when they don’t have internet access.

Schatz urged users to ensure that they use a cloud-based system with strong privacy policies before considering such approaches, particularly with proprietary data or information for which privacy is critical.

As for COVID-19, people with the disease have shown enough viral mutations that researchers can say whether the strain originated in Europe or China.

“It’s kind of like spelling mistakes,” Schatz said. “There are enough spelling mistakes where [researchers] could know where it came from.”

Palatnick described iGenomics as an “impactful” tool because the app has increased the population of people who can explore the genome from institutional researchers to anyone with an iPhone or iPad.

In the bigger picture, Schatz is broadly interested in learning how the genome creates differences.

“It’s important to understand these messages for the foods we eat, the fuels we use, the medicines we take,” Schatz said. “The next frontier is all about interpretation. One of the most powerful techniques is comparing one genome to another.”

Schatz seeks out collaborators in a range of fields and at numerous institutions, including Cold Spring Harbor Laboratory.

Schatz and W. Richard McCombie, Professor at CSHL, are studying the genomes of living fossils. These are species that haven’t evolved much over millions of years. They are focusing on ancient trees in Australia that have, more or less, the same genetic make up they did 100 million years ago.

As for Palatnick, Schatz described his former intern and tricorder creating partner as a “superstar in every way.” Schatz said it takes considerable fortitude in science, in part because it takes years to go from an initial idea on a napkin to something real.

Down the road, Schatz wouldn’t be surprised if Palatnick took what he learned and developed and contributed to the founding of the next Twitter or Facebook.

“He has that kind of personality,” Schatz said.

Carlos Simmerling

By Daniel Dunaief

They know what happens. They’re just not sure how it happens.

Carlos Simmerling, Marsha Laufer Endowed Professor of Physical and Quantitative Biology and Professor of Chemistry at Stony Brook University, has spent over 22 years trying to answer the question of how processes at a molecular level occur.

Using chemistry, physics and computer programs he helped create, Simmerling determines the intermediate structural changes that occur with biomolecules such as nucleic acids and proteins, which would be extremely difficult to impossible to do at a bench or in a laboratory.

In March, as the United States was in the beginning of various school and office lockdowns in response to the spread of the pandemic, Simmerling endured the same discomfort and loss of control.

Researchers at Brookhaven National Laboratory, including Kerstin Kleese van Dam, Director of the Computational Science Initiative, reached out to Simmerling to see if his lab might use their experience and tools to understand the spike protein on the coronavirus that causes COVID-19.

Except for two people who were on the cusp of finishing their PhD’s, everyone else in the lab “shifted to work on this instead. We put everything else on hold and it’s been nonstop since March.”

Simmerling said he and his lab group decided at a special lab meeting on March 13th that it was important to contribute whatever they could to this unprecedented crisis.

Without the same kind of restrictions or limitations that lab groups that depend on working at a bench or conducting in-person experiments might have, the Simmerling group could work every day, forging ahead to understand the way the protein operates and to look for critical steps or weaknesses that might assist doctors down the road.

Recently, Simmerling and his lab group exchanged emails over Thanksgiving, during which the group felt this commitment to COVID research gave them a “shared purpose” and helped them feel as if they were “doing something.”

While the Simmerling lab appreciated the opportunity to contribute to efforts to combat COVID-19, they also recently received a national award in high-performance computing. Called the Gordon Bell Special Prize, the award recognizes “outstanding research achievement towards the understanding of the COVID-19 pandemic through the use of high-performance computing.”

The award, which was announced at the virtual SuperComputing 2020 Conference and recognizes the work of the Simmerling lab and some collaborators they worked with since early in the pandemic, includes a $10,000 prize.

The kind of research Simmerling and his team conducted may help either with this specific virus or with any others that might threaten human health again.

“We were not well prepared in science and humanity in general,” Simmerling said. “We have to come up with better tools.”

While he is pleased that pharmaceutical companies are getting closer to introducing vaccines for COVID-19, Simmerling said any such solutions would apply to this specific virus and not to any subsequent forms of coronavirus or other potential threats to human health.

People who contracted SARS or MERS, which are coronavirus cousins, didn’t develop an immunity to COVID-19.

“Even if we all get vaccinated, that won’t help us for the next one, and we’ll likely have other ones,” Simmerling explained. “Science needs to do a better job getting deeper into how these work.”

At this point, the models Simmerling and his staff have created are working and are providing the kind of clues that could contribute to providing suggestions for future experiments. The lab is “now at the stage where we are seeing new things not seen in the experiments and suggesting new experiments to test our hypotheses,” said Simmerling.

His lab has focused on the dynamics of proteins and other biomolecules to see how they move around in time. He simulates the shape changes when molecules interact, including in the 2000s when he worked on proteins in the human immunodeficiency virus.

Simmerling likens the study to the process of shaking other people’s hands. When two people come together, their hands adapt to each other when they interact, changing shape as they move up and down.

With the spike protein in COVID-19, scientists have seen what it looks like before it interacts. The structure after it unlocks the cell is fuzzier and scientists aren’t sure if they are relevant to the actual virus or something vaguely similar to it.

“We only get snapshots at the beginning and the end,” he said. “What we need to do is figure out how it works.”

He uses software his lab has developed with a few other labs in the country. Scientists around the world use this Amber system. They take steps in time and calculate the forces on the atom, which requires millions of iterations.

Simmerling said other people sometimes think he and his team download the structure, plug it into a computer, run it and then publish a paper. That’s far from the case, as the computer does the number crunching, but people like Simmerling spend considerable time trying to understand a molecule like the spike protein well enough to develop ideas about how it might move and change.

Simmerling took a circuitous route to the world of using chemistry and physics on a computer. When he entered college at the University of Illinois at Chicago, he wanted to be a chemist. The only problem was that he didn’t enjoy working in the lab with all the chemicals.

Half way through his college education, he left school and started working at a computer company. Eight years later, he decided to return to college, where he planned to earn his chemistry degree.

“When I went back to school, I told my [teaching assistant] that I wish I could do [chemistry] on computers rather than experiments,” Simmerling said. “He introduced me to the professor [Ron Elber] who became my PhD advisor. That brought together things I was interested in.”

He knew programming and how to use computers.

“Sometimes, you’re the sum of your choices,” Simmerling said.

He and his wife Maria Nagan, who also does computer modeling at Stony Brook University, live in Port Jefferson. In non-pandemic times, Simmerling enjoys sailing throughout the year.

As for the prize, Simmerling said the “recognition is nice” and he would like his lab to contribute to “models to change how we combat infectious disease.”

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.

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.”

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.

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.”

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.

Ijeoma Opara. Photo by Emmanuel Igbokwe of Emman Photography

By Daniel Dunaief

The daughter of Nigerian immigrants, Ijeoma Opara was born in Jersey City, New Jersey. Her first name means “safe journey” in Igbo, the language of Nigeria, and is something people say when they wish each other a good trip.

For Opara, her first name has proven prophetic, as this social worker is determined to help youth in Paterson make a safe journey through the challenges of substance abuse and mental health issues.

Recently, Opara became the first social worker to receive a $1.84 million Early Independence Award from the National Institutes of Health.

Apart from her unusual scientific background in a field dominated by award recipients who work in the natural sciences, like biochemistry and physics, Opara also stands out for her background.

Ijeoma Opara. Photo by Emmanuel Igbokwe of Emman Photography

“At the National Institutes of Health, there’s been a lot of discussion about how black scientists don’t get as much funding as [their] white counterparts,” Opara said. Black scientists don’t often receive early competitive grants.

Michelle Ballan, Associate Dean for Research in the School of Social Welfare at Stony Brook University, recruited Opara. She appreciated Opara’s “grit and tenacity.”

Ballan encouraged Opara to apply for the Early Intervention Award. With Ballan in her corner, Opara put that determination to work.

Ballan described how readily Opara responded to guidance.

“She not only accepted constructive feedback, she built upon it,” Ballan said.

When Opara applied for the award, she suspected she had little chance of receiving it. “Someone like me, who went to a state school in Montclair, New Jersey” writing about urban, black and hispanic youth has never receiving this kind of funding support, she said.

Opara received a score in March that she didn’t understand. She sent her score to her two mentors, Ballan and director of the REIDS program at Yale Dr. Trace Kershaw, and asked what it meant. Dr. Kershaw said it was almost a perfect score and told her she would likely receive the grant.

In July, she received an email congratulating her on her selection.

“I started screaming,” Opara said. She told her close friends and colleagues, but she couldn’t share the news on social media until the NIH press release came out in October.

She was so excited about the opportunity that she celebrated with a large order of food and ate herself into oblivion that first weekend. Her indulgent feast included Oreo cheesecake from The Cheesecake Factory and chicken and waffles from her favorite brunch place.

“I got so sick,” Opara laughed.

While Opara was thrilled that the award came, she felt another emotion mixed in with her elation. She said part of her felt guilty because she and other black researchers would like to see more representation in these awards and grant mechanisms.

Opara has appreciated the support she has received from other scientists.

“So many black colleagues, even people I didn’t know, saw this as a win not just for me but for all of us,” Opara said. Other graduate students and postdocs have reached out to her since the press release came out, asking for advice on applying for high reward and high risk awards and other NIH grants.

Opara is grateful for the confidence and support from Ballan.

Indeed, Ballan believes Opara is a “role model for all women, especially women of color in research intensive fields.”

When Opara interviewed at Stony Brook, Ballan told her that she “wanted to make sure you are very successful.”

Even early in her tenure at Stony Brook, which will start with extensive work in Paterson, New Jersey, Opara feels Ballan has “lived up to that promise.”