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Power of 3

Feinstein Institutes’ Drs. Kevin Tracey and Christina Brennan break down the current COVID-19 clinical trials and treatments. Photo courtesy of The Feinstein Institutes for Medical Research

By Daniel Dunaief

In a collaboration between Cold Spring Harbor Laboratory and Northwell Health’s Feinstein Institutes for Medical Research, doctors and researchers are seeking patients with mild to moderate symptoms of COVID-19 for an at-home, over-the-counter treatment.

The two-week trial, which will include 84 people who are 18 years old and older, will use a high, but safe dose of Famotidine, or PEPCID, in a double-blind study. That means that some of the participants will receive a placebo while others will get the Famotidine.

Volunteers will receive the dosage of the medicine or the placebo at home and will also get equipment such as pulse oximeters, which measure the oxygen in their blood, and spirometers, which measure the amount of air in their lungs. They will also receive a scale, a thermometer, a fitness tracker and an iPad.

Dr. Christina Brennan. Photo courtesy of The Feinstein Institutes for Medical Research

Northwell Health will send a certified phlebotomist — someone licensed to draw blood — to the participants’ homes to collect blood samples on the first, 7th, 14th, and 28th day of the study.

The study is the first time CSHL and Northwell Health have designed a virtual clinical trial that connects these two institutions.

“What is very powerful with our work with Cold Spring Harbor Laboratory is the ability to do a virtual trial and utilize patient-recorded outcome measures,” said Christina Brennan, a co-investigator on the study and Vice President for Clinical Research for Northwell Health. “I’m thrilled that we’re doing this type of virtual trial. It’s very patient-centric.”

While reports about the potential benefits of Famotidine have circulated around the country over the last year, this study will provide a data-driven analysis.

“If we study this in the outpatient population, then we might have an opportunity to see if [Famotidine] really does play a role in the reduction of the immune overreaction,” Brennan said.

At this point, researchers believe the drug may help reduce the so-called cytokine storm, in which the immune system becomes so active that it starts attacking healthy cells, potentially causing damage to organs and systems.

In an email, Principal Investigator Tobias Janowitz, Assistant Professor and Cancer Center Member at Cold Spring Harbor Laboratory, wrote that “there are some retrospective cohort studies” that suggest this treatment might work, although “not all studies agree on this point.”

In the event that a trial participant developed more severe symptoms, Janowitz said the collaborators would escalate the care plan appropriately, which could include interrupting the use of the medication.

In addition to Janowitz, the medical team includes Sandeep Nadella, gastroenterologist at Northwell, and Joseph Conigliaro, Professor of the Feinstein Institutes for Medical Research.

Janowitz said he does not know how any changes in the virus could affect the response to famotidine.

In the trial, volunteers will receive 80 milligrams of famotidine three times a day.

The dosage of famotidine that people typically take for gastric difficulties is about 20 milligrams. The larger amount per day meant that the researchers had to get Food and Drug Administration approval for an Investigational New Drug.

“This has gone through the eyes of the highest regulatory review,” Brennan said. “We were given the green light to begin recruitment, which we did on January 13th.”

Volunteers are eligible to join the study if they have symptoms for one to seven days prior to entering the trial and have tested positive for the virus within 72 hours.

Potential volunteers will not be allowed in the trial if they have had other medications targeting COVID-19, if they have already used Famotidine in the past 30 days for any reason, if they have severe COVID that requires hospitalization, have a history of Stage 3 severe chronic disease, or if they are immunocompromised by the treatment of other conditions.

Brennan said Northwell has been actively engaged in treatment trials since the surge of thousands of patients throughout 2020.

Northwell participated in trials for remdesivir and also provided the steroid dexamethasone to some of its patients. The hospital system transfused over 650 patients with convalescent plasma. Northwell is also infusing up to 80 patients a day with monoclonal antibodies. The hospital system has an outpatient remdesivir trial.

“Based on all our experience we’ve had for almost a year, we are continuously meeting and deciding what’s the best treatment we have available today for patients,” Brennan said.

Janowitz hopes this trial serves as a model for other virtual clinical trials and is already exploring several potential follow up studies.

Brennan said the best way to recruit patients is to have the support of local physicians and providers. 

People interested in participating in the trial can send an email to [email protected] or call 516-881-7067.

When the study concludes, the researchers will analyze the data and are “aware that information on potential treatments for COVID-19, no matter if the data show that a drug works or does not work, should be made available to the community swiftly,” Janowitz wrote in an email.

The decision to test this medicine as a potential treatment for COVID-19 arose out of a conversation between Director of the Cold Spring Harbor Laboratory Cancer Center Dave Tuveson and CEO of the Feinstein Institute Kevin Tracey.

“I got involved because I proposed and developed the quantitative symptom tracking,” Janowitz explained.

Weisen Shen. Photo by John Griffen/SBU

By Daniel Dunaief

Like so many others during the pandemic, Weisen Shen has had to pivot in his job.

An Assistant Professor in the Department of Geosciences at Stony Brook University, Shen has historically focused his efforts on understanding the geothermal heat flux, or the movement of heat from the core of the Earth, in Antarctica.

Constrained by travel restrictions created by the COVID-19 pandemic, Shen has decided to put his 180 seismometers to good use on Long Island.

“We have seismometers that stay in the basement of our building,” Shen said. “We can’t use them in Antarctica because of the travel ban and other complexities, and we want to make use of them in our community to understand the geology of Long Island.”

Shen is looking for students who might be interested in geology and who might like to plant a seismometer in their backyard, gathering information about how the flow of seismic waves deep beneath their homes and backyards reveals details about the structure, temperature and composition of the land miles below the surface.

Shen, who lives in Syosset, installed a seismometer in his own backyard, which has allowed him to see the signal from the local train station in Sayville. “We seek help from [the local community] to allow us to deploy a seismometer in their back or front yard for a month or so,” Shen said.

Planting a seismometer would involve digging a 15 centimeter by 15 centimeter hole that is 5 inches deep. Shen and his team would cover it. The seismometer wouldn’t need local electricity because it has a lithium battery. 

After about a month, the scientists would dig it out, put dirt back in, and return the backyard to the way it looked prior to taking these measurements.

The machine doesn’t make any noise and does not pick up any sounds from inside people’s homes.

The signal will contribute “to our understanding of the Earth,” Shen explained, including details about the crustal and mantle structure, seismic activities, and the Earth’s vibrations due to civil activities such as the rumbling of trains.

Shen is “more than happy to share data” with the people who host his seismometers. He also expects to produce a research paper based on his studies from Long Island.

He is charging the batteries and testing the instruments and plans to plant them in the field as early as the end of February.

People who would like to participate can reach out to Shen by sending him an email at [email protected] Please include “Volunteer Long Island Imager” in the subject line.

Recent Antarctica Studies

While Shen is focusing his geothermal expertise on Long Island, he hasn’t abandoned or ignored Antarctica, a region he has focused research efforts on because of the vulnerability of the ice sheet amid climate change. He is also interested in the geothermal structure in the area, which reveals information about its geology and tectonics, which remain mysteries residing below the ice. 

Grounded during the pandemic, Shen spent several months gathering and analyzing considerable available data, hoping to understand what happens deep below the frozen surface.

“We are trying to analyze so-called ‘legacy data’ that has been collected over the past two decades,” he said.

On a fundamental level, Shen is trying to quantify how much heat is coming out through the crust, which includes heat coming from the deeper earth in the mantle and the core as well as within the crust.

Traveling beneath the oceans towards the center of the Earth, which would be considerably hotter and more difficult than 19th century author Jules Verne’s fantastic fictional voyages, would expose people to temperatures that increase, on average, about 10 to 30 degrees celsius per kilometer.

Some of the heat comes from the way the planet formed. In addition, unstable isotopes of potassium, uranium and thorium release heat as they decay, which mostly happens within the Earth’s crust. 

In areas with large ice sheets sitting on top of the land, the geothermal heat can melt some of that ice, creating a layer of water that accelerates the ice sheet movement. Indeed, pulling an ice cube across dry ground takes more energy than dragging that same cube across a wet surface.

Moving ice more rapidly towards the periphery will increase melting which, coupled with climate change, could increase the amount of water in Antarctica, particularly in the western region.

Comparing the two ice melting effects, Shen believes global warming, which is more rapid and has shorter term outcomes, plays a more important role in changing the liquid characteristics of Antarctica than geothermal heating, which is longer term.

In collecting available legacy data, Shen analyzed information from the entire western part of Antarctica, as well as parts of the central and eastern regions.

Using a measure of the geothermal heat flux, Shen found some unexpected results, particularly on Thwaites Glacier, beneath which he found a large area with elevated geothermal heat flux. 

Studying geomagnetic data, he compared their results with the results from geomagnetically derived results. In the future, he will combine the two different methods to improve the assessment. 

In a publication last summer in Geophysical Research Letters, Shen presented a new map of the geothermal heat flux for Antarctica with a new resolution of 100 kilometers by 100 kilometers, which is a much higher resolution than earlier studies, which are typically done at 600 kilometer by 600 kilometer ranges.

In West Antarctica, he found a more modest heat flux, despite the area being more tectonically active.

Finally, a major take of the paper, Shen said, is that the Thwaites glacier has a high geothermal heat flux, which could explain why the ice moves more rapidly and readily.

As for his future work, in addition to exploring the seismology of Long Island, Shen said he would pursue his National Science Foundation grant to look for additional water in the boundary between the ice sheet and the mantle.

He is working on “using high frequency seismic records to look for data,” he said.

Valentina Bisogni. Photo from BNL

By Daniel Dunaief

Nature plays a wonderful game of hide-and-seek with its secrets.

One day, Joan might be searching for, say, an apple tree in the forest. Joan might consider all the elements that appeal to an apple tree. She might expect the journey to take two hours but, to her surprise, discovers a tree on the way.

That’s what happened to Valentina Bisogni, a physicist at Brookhaven National Laboratory. Bisogni, who works at the National Synchrotron Lightsource II, wanted to figure out how the thickness in a magnetic film affected traveling modes involving the spin property of electrons, known as spin waves. Specifically, she wanted to control the energy of the spin wave.

This might be important in future devices that involve passing along information through an electron’s spin rather than through charge, which is the current method. Controlling the spin wave could be another way to optimize the performance or improve the efficiency of future devices.

Transmitting charge creates unwanted heat, which can damage the components of an electronic device and limit its usefulness. Heat also creates energy inefficiencies.

Valentina Bisogni with a collection of tomatoes in a garden in Bellport Village. Photo by Claudio Mazoli.

Bisogni, who arrived at BNL in 2014, has been working on a beamline called Soft Inelastic X-ray Scattering, or SIX. Each of the new beamlines at the nearly billion-dollar facility has its own acronym and number that corresponds to their location in the accelerator ring.

Before she planned to apply an electric field that might control the spin wave, however, Bisogni figured she’d explore the way thinner iron materials affected the spin.

That’s when the metaphorical apple tree appeared, as the thickness of iron films, that were as thin as one to 10 nanometers, helped control the spin wave before applying any electric field.

“This result was not expected,” Bisogni said. This was preparatory work to a more detailed, dedicated study. 

“Not having had any benchmark of iron crystals in general with the technique I am using, it was logical to study this system from a bulk/ thin form to a very thin film,” she explained in an email.

Bisogni and a team from Yale University recently published the results of this work in the journal Nature Materials.

While this unexpected result is encouraging and could eventually contribute to the manufacture of electronic devices, Bisogni said this type of discovery helps build a fundamental understanding of the materials and their properties at this size.

“For people assembling or designing devices or wave guides, I think this is an ingredient that has to be considered in the future,” Bisogni said.

This kind of result could enable the optimization of device performance. When manufacturers propagate a signal based on spin dynamics, they would likely want to keep the same frequency, matching the signal along a medium from point A to point B.

The effect of the thickness on the spin was like a power log, which is not quite exponential as the experimenters tested thinner material, she said.

Bisogni plans to continue with this collaboration, as the group is “excellent in preparing and characterizing this kind of system.”

In the bigger picture, Bisogni is focused on quantum materials and altering their spin.

She is also overseeing the development of a system called Opera, which copies the working conditions of electronic devices. Opera is the new sample environment available at SIX and is developed within the research project to copy device-working conditions in the beamline’s measurement chamber.

Bisogni ultimately hopes her work may improve the energy efficiency of electronics.

A resident of Bellport Village, Bisogni lives with her partner Claudio Mazoli, who is the lead scientist for another beamline at the NSLS II, called the Coherent Soft X-ray Scattering, or CSX.

Bisogni said the couple frequently enjoy exchanging ideas and have an ongoing active collaboration, as they share several scientific passions.

The couple met at the European Synchrotron Radiation Facility in Grenoble, France when they were working in the same lab.

Bisogni was born and raised in Spoleto, which is in the province of Perugia in the center of Italy. Bisogni speaks Italian and English as well as French and German after her work experience in France, Germany and Switzerland.

Bisogni said she and Mazoli are “very food-centric” and can find numerous epicurean opportunities in the area of Long Island and New York City. The weather is also similar to home, although they miss their family and friends from Italy.

The couple purchased a house together during the pandemic and have been doing some work to shape the house to their needs. They remodeled the bathrooms in an Italian/ European style, purchased a German washing machine and dryer and painted some walls.

In the summer, Bisogni, who likes to eat, cook and grow vegetables, enjoys spinach, tomatoes and light-green zucchini.

As for her work, Bisogni is currently pleased with the state of her beamline, although she said its development took considerable team effort and time during the development, construction and commissioning.

At this point, her research team includes two and a half permanent scientists and two post-doctoral scientists. Within the team, they have two post-doc researcher positions looking to fill, one for her research project and another dedicated to her colleague’s research project.

Ultimately, Bisogni is excited with the opportunities to make fundamental discoveries at work.

“It is, in general, very exciting, as most likely you are doing something for the first time,” Bisogni explained in an email. “It is true that you may fail, since nobody is going to tell you if what you are doing is going to work or not, but if you get it right, then it is extremely rewarding.”

Qiang Li. Photo courtesy of BNL

By Daniel Dunaief

Decades ago, most people could only tune to shows like The Jetsons to imagine interactive televisions in which people could see each other during conversations.

Qiang Li. Photo courtesy of BNL

In modern times, hand held devices and laptop computers have turned those science fiction ideas into everyday realities, as people can tell their phones to call their mom, to provide the outdoor temperature or to help them recall the name of a movie they saw decades ago.

These helpful technological devices, however, may some day go the way of the clunky desktop computers of yesteryear, as scientists around the world work to turn the vision of a quantum computer into a reality.

Scientists hope to develop a next generation of quantum computer that is faster, smarter, more flexible and more energy-efficient than current technological devices. They hope these devices could be the key to future technological breakthroughs, inspiring them to figure out how to bring the theory to life.

Collaborating with scientists at Ames Laboratory in Iowa, Qiang Li, SUNY Empire Innovation Professor in the Department of Physics and Astronomy at Stony Brook University and Leader of the Advanced Energy Materials Group at Brookhaven National Laboratory, recently published a study in the journal Nature Materials that provided fundamental information that might contribute to the field of quantum computers.

The group of scientists, which included Li’s PhD student Pedro Lozano, discovered a light-induced switch that twists the crystal lattice of a semimetal, turning on an electron current that the team believes is nearly dissipationless.

When currents move through wires between utilities and people’s homes and offices, that current encounters resistance, losing energy along the way, as if the movement towards the home created a tax on the journey. Similarly, dissipation inside an electronic device can sap some of the energy needed to transmit information or a signal, reducing the effectiveness of the process.

Li and BNL physicist Genda Gu synthesized, patterned and characterized the material at BNL, while Jigang Wang, a senior scientist at Ames Laboratory, performed the light-induced lattice twisting. The team helped create the light-induced switch.

Li described the effort as “fundamental research” and cautioned that any such advancement is more of a principal study, rather than a step closer to making any new qubit (the basic unit of quantum information) device.

“This is an experimental study to show that this is possible,” Li said. “It’s a demonstration of feasibility that you can harness chirality for building quantum information systems.”

With chirality, electrons have a handedness based on whether their spin and momentum are aligning in the same or opposite direction.

Once electrons have chirality, they can travel much easier, enabling a more direct and predictable route from one place to another.

Scientists like Li would like to create physical systems that enable them to control the chirality, preventing the spin from switching from one direction to the other.

Numerous factors can disrupt the chirality of an electron, including imperfections in the material.

A pulse-triggered light-induced switch can change the topology of a Weyl semimetal, making it possible to enable the movement of electrons that are nearly dissipationless. “For pure electronics, even computer chips, electrons consume a lot of energy because of electrical resistance,” Li said. “A chiral current [however] will travel without resistance, in ideal cases without chirality flipping.”

Chiral electrons travel through the semimetal at a speed as high as 1/300th of the speed of light and can travel considerably further before a collision that alters its direction, speed, or other particle properties. The mean free path, which is the average distance a particle will travel between such disruptive events, for a typical metal is nanometers. By contrast the chiral electrons can move micrometers, which is thousands of times longer.

An unperturbed chiral electron could travel further distances over shorter intervals, carrying preserved coded information without losing much energy during movement. 

Scientists have sought ways to create a path through which electrons travel with this predictable spin. They can break chiral symmetry by applying a magnetic field, which led to the discovery of the chiral magnetic effect by a team of scientists from BNL and Stony Brook University, including Dmitri Kharzeev, in 2014.  

For this work, Li received the Brookhaven Science and Technology Award in 2019.

“Using a magnetic field is problematic for some computations,” he said. Besides, people don’t want a “big magnet around your computers.”

Another way is to send in the laser pulse, creating left-handed or right-handed polarization.

To determine the ideal pulse to change the material, Li and Wang partnered with several theorists from Ames Lab and Ilias Perakis, Professor and Chair of Physics at the University of Alabama — Birmingham.

The theorists conducted detailed analysis of the lattice vibrations and the ideal pulse energy needed to break symmetry in the Weyl semimetal. “There is a very strong collaboration between the theorists and the experimentalists,” Li said.

While the research remains fundamental and is unlikely to generate a specific product any time soon, Li said it has “attracted a lot of attention” from other scientists and is a significant step forward in establishing the basic principles for topology-enabled quantum logic and information systems.

Li and Wang have been collaborating on this project for about two years as scientists around the world are in a “horse race” to produce results in the arena of quantum computing.

A resident of Setauket, Li and his wife Meiling Shih, have two children. Shih, who worked in the Stony Brook Pharmacological Science Department and later at Morgan Stanley, is retired and is now a volunteer instructor of a Tai Chi class for local seniors, 

Li enjoys jogging and runs a few miles every other day.

Down the road, Li hopes to address how to make the two quantum bits talk to each other.

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.”