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Power of 3

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David McCandlish, center, with postdoctoral researchers Anna Posfai and Juannan Zhou. Photo by Gina Motisi, 2020/ CSHL

By Daniel Dunaief

If cancer were simple, scientists would have solved the riddle and moved on to other challenges.

Often, each type of the disease involves a combination of changes that, taken together, not only lead to the progression of cancer, but also to the potential resistance to specific types of treatment.

Using math, David McCandlish, Assistant Professor at Cold Spring Harbor Laboratory, is studying how the combination of various disruptions to the genome contribute to the development of cancer.

McCandlish recently published a study with colleagues at Cold Spring Harbor Laboratory in the journal Proceedings of the National Academy of Sciences.

David McCandlish. Photo by Gina Motisi, 2020/CSHL

The research didn’t explore any single type of cancer, but, rather applied the method looking for patterns across a range of types of cancers. The notion of understanding the way these genetic alterations affect cancer is a “key motivating idea behind this work,” McCandlish said.

So far, the method has identified several candidates that need further work to confirm.

“Cancer would be a lot easier to treat if it was just one gene,” said Justin Kinney, Associate Professor at CSHL and a collaborator on the work. “It’s the combination that makes it so hard to understand.”

Ultimately, this kind of research could lead researchers and, eventually, health care professionals, to search for genetic biomarkers that indicate the likely effect of the cancer on the body. This disease playbook could help doctors anticipate and head off the next moves with various types of treatments.

“This could potentially lead to a more fundamental understanding of what makes cancer progress and that understanding would very likely open up new possibilities in cancer treatments,” Kinney said.

To be sure, at this point, the approach thus far informs basic research, which, in future years, could lead to clinical improvements.

“We are working on this method, which is very general and applicable to many different types of data,” McCandlish said. “Applications to making decisions about patients are really down the road.”

McCandlish described how he is trying to map out the space that cancer evolves in by understanding the shape of that space and integrating that with other information, such as drug susceptibility or survival time.

“We are trying to ask: how do these variables behave in different regions of this space of possibilities?” he said.

McCandlish is making this approach available to scientists in a range of fields, from those scientists interpreting and understanding the effects of mutations on the development of cancer to those researchers pursuing a more basic appreciation of how such changes affect the development and functioning of proteins.

“This is accessible to a wide array of biologists who are interested in genetics and, specifically in genetic interactions,” said McCandlish.

The main advance in this research is to take a framework called maximum entropy estimation  and improve its flexibility by using math to capture more of the underlying biological principals at work. Maximum entropy estimation is based on the idea of inferring the most uniform distribution of behaviors or outcomes with the least information that’s compatible with specific aspects of experimental observations.

Using this philosophy, scientists can derive familiar probability distributions like the bell curve and the exponential distribution. By relaxing these estimates, scientists can infer more complicated shapes.

This more subtle approach enhances the predictive value, which captures the distributions of data better, McCandlish explained. “We’re trying to capture and model cancer progression in a new and more expressive way that we hope will be able to tell us more about the underlying biology.”

The idea for this paper started when McCandlish, Kinney and  Jason Sheltzer, a former fellow at Cold Spring Harbor Laboratory and a current Assistant Professor of Surgery at Yale School of Medicine, discussed the possibilities after McCandlish attended a talk by Wei-Chia Chen, a post doctoral researcher in Kinney’s lab.

Chen will continue to pursue questions related to this effort when he starts a faculty position in the physics department at National Chung Cheng University in Taiwan this spring.

Chen will use artificial intelligence to handle higher dimensional data sets, which will allow him “to implement effective approximations” of the effect of specific combinations of genetic alterations, Kinney said.

Kinney believes teamwork made this new approach, which the high-impact, high-profile journal PNAS published, possible.

“This problem was an absolutely collaborative work that none of us individually could have done,” Kinney said. He described the work as having a “new exploratory impact” that provides a way of looking at the combination of genomic changes that “we haven’t had before.”

Working at Cold Spring Harbor Laboratory, which McCandlish has done since 2017, enables collaborations across different disciplines.

“We have this quantitative biology group, we also have people working on neuroscience, cancer, and plant biology,” McCandlish added.

McCandlish is also currently also working with Professor Zachary Lippman and his graduate student Lyndsey Aguirre to understand how multiple mutations interact to influence how the fruit on tomato plants develop.

“The idea is that there are these huge spaces of genetic possibilities where you can combine different mutations in different ways,” McCandlish explained. “We want to find those key places in that space where there’s a tipping point or a fork in the road. We want to be able to identify those places to follow up or to ask what’s special about this set of mutations that makes it such a critical decision point.”

A native of Highland Park, New Jersey, McCandlish was interested in math and science during his formative years. 

As for the work, McCandlish appreciates how it developed from the way these collative researchers interacted.

“This would never have happened if we weren’t going to each other’s talks,” he said.

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Qingyun Li. Photo by Xuecheng Chen

By Daniel Dunaief

Qingyun Li has a plan for carbon dioxide.

The newest hire in the Department of Geosciences at Stony Brook University, Li, who is an assistant professor, is a part of a team exploring carbon capture and storage.

“My work is expected to help reduce the amount of carbon dioxide released into the atmosphere,” Li said. It will “help people find ways to promote carbon dioxide mineralization for safer carbon dioxide storage” below the ground. While her work will help promote carbon storage, it doesn’t include capturing and transporting the gas.

By selecting sites carefully, researchers can store carbon dioxide for geologically long periods of time.

While carbon sequestration occurs on the scale of kilometers, Li often works on a minuscule level, at the nanometer to centimeter scale. Smaller scale alterations affect properties such as the permeability of the rock formation.

Li is trying to predict nucleation of a certain mineral in her computer models. She has done that for carbonate minerals, which could be what carbon dioxide becomes after it is stored in geologic formations.

A similar process of nucleation occurs in clouds, when fine particles form the nuclei around which gases condense to form water or ice.

Li used a small angle x-ray scattering synchrotron to explore important details about each particle. This technique, which doesn’t look directly at the particles, reveals through data analysis the particle’s shape, size and surface morphology and, eventually, the rate at which nucleation occurs.

For carbon dioxide sequestration, the minerals that provide nucleation start at the nanoscale, which give them a high specific surface area.

“That matters for later reactions to generate carbonate minerals,” Li said. “That’s one reason we care about the nanoscale phenomenon. The bulk minerals are generated starting from the nanoscale.” 

A larger surface area is necessary in the beginning to lead to the next steps.

Li’s work involves exploring how carbonate starts to form. Her earlier efforts looked at how calcium carbonate forms in the aqueous or water phase.

Carl Steefel, Head of the Geochemistry Department at the Lawrence Berkeley National Laboratory in California, worked with Li during her PhD research at Washington University in St. Louis. Steefel believes her research will prove productive.

“She has an approach to science that combines that one-of-its-kind capabilities for studying nucleation with a deep understanding of modeling and how these open systems involving flow and transport work,” Steefel said. “The combination of these unique capabilities, in nucleating and in understanding reactive transport modeling, will put her a very good position.”

As of now, Li plans to study carbon sequestration in natural gas formations in shale, which has nanometer sized pores. The particles can change the permeability of the rock.

Some companies, like British Petroleum and ExxonMobil, have started to explore this method as a way to reduce their carbon footprint.

While geologic carbon sequestration has shown promising potential, Li believes the process, which she said is still feasible, could be decades away. She said it may need more policy support and economic stimuli to come to fruition.

Part of the challenge is to incorporate such carbon sequestration in the established market.

Scientists working in this field are eager to ensure that the stored carbon dioxide doesn’t somehow return or escape back into the atmosphere.

“People are actively investigating possible leakage possibilities,” Li wrote in an email. “We try to design new materials to build wells that resist” carbon dioxide deterioration.

Controlling pressure and injection rates could prevent various types of leaks.

In her earlier studies, Li explored how cement deteriorates when contacted with carbon dioxide-saturated brine. She hoped to find cracks that had self-healing properties. Other studies investigated this property of concrete.

It’s possible that a mineral could form in a fracture and heal it. In natural shale, scientists sometimes see a fracture filled with a vein of carbonate. Such self healing properties could provide greater reassurance that the carbon dioxide would remain stored in rocks below the surface. Li hopes to manage that to inhibit carbon dioxide leakage.

The assistant professor grew up in Beijing, China, studied chemistry and physics in college. She majored in environmental sciences and is eager to apply what she learned to the real world.

For her PhD, Li conducted research in an engineering department where her advisor Young-Shin Jun at Washington University in St. Louis was working on a project on geologic carbon dioxide sequestration. 

In her post doctoral research at SLAC National Accelerator Laboratory, which is operated by Stanford University, Li explored mineral reactions in shale, extending on the work she did on mineral reactions in concrete as a graduate student. She sought to understand what happens after hydraulic fracturing fluids are injected into shale. These reactions can potentially change how easily the mix of gas and oil flow through a formation.

With Stony Brook building a lab she hopes is finished by next spring, Li plans to hire one graduate student and one post doctoral researcher by next fall.

She is teaching a course related to carbon sequestration this semester and is looking for collaborators not only within geoscience but also within material science and environmental engineering.

Li is looking forward to working with other researchers at the National Synchrotron Lightsource 2 at Brookhaven National Laboratory, which provides beamlines that can allow her to build on her earlier research.

Li and her husband Xuecheng Chen, who are renting an apartment in South Setauket and are looking for a home close to campus, have a three-year old son and an 11-month old daughter.

Outside the lab, Li enjoys quality time with her family. A runner, Li also plays the guzheng, which she described as a wooden box with 21 strings.

Steefel, who wrote a letter to Stony Brook supporting Li’s candidacy to join the Geosciences Department, endorsed her approach to science.

“She’s very focused and directed,” Steefel said. “She’s not running the computer codes as black boxes. She’s trying to understand what’s going on and how that relates to her experiments and to reality.”

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Above, an AI-Grid prototype that is being built by the research team. Image courtesy of Stony Brook Power Lab

By Daniel Dunaief

The Department of Energy is energized by the possibility of developing and enhancing microgrids.

What are microgrids? They are autonomous local power systems that have small, independent and often decentralized energy sources. Often, they use renewable energy, like wind or solar power, although some use natural gas or diesel.

The DOE’s dedication to developing these microgrids may cut costs, create efficiencies and enhance energy reliability.

Peng Zhang. Photo from SBU

Peng Zhang, SUNY Empire Innovation Professor in the Department of Electrical and Computer Engineering at Stony Brook University, is leading a diverse team of researchers and industry experts who received $5 million of a $50 million investment the DOE recently made to developing, enhancing and improving microgrid technology.

Bringing together these energy experts, Zhang hopes to use artificial intelligence to create a usable, reliable and efficient source of energy, particularly during periods of power outages or disruption to the main source of energy.

“The traditional microgrid operation is based on models and human operators,” Zhang said. “We developed this data-driven or AI-based approach.”

Artificial intelligence can enhance the safety and reliability of microgrids that can receive and transmit power.

One of the objectives of the systems Zhang and his collaborators are developing will include protecting the power supplies against faults, accidents from natural disasters and cyberattacks.

“This project led by Professor Zhang is a great example demonstrating the impact of this novel research on essential infrastructure that we rely on daily,” Richard Reeder, Vice President for Research at Stony Brook University, said in a statement.

Zhang said he has verified the methods for this AI-driven approach in the lab and in a simulation environment.

“Now, it’s time to demonstrate that in more realistic, microgrid settings,” he said. He is working with microgrid representatives in Connecticut, Illinois and New York City. His team will soon work with a few representative microgrids to establish a more realistic testing environment.

The urgency to demonstrate the feasibility of this approach is high. “We need to kick the project off immediately,” said Zhang, whose team is recruiting students, postdocs, administrative staff and technicians to meet a two-year timeline.

The group hopes AI-grids can be used in different microgrids around the country. If the platform is generic enough, it can have wide applications without requiring significant modifications.

While operators of a microgrid might be able to know the ongoing status, they normally are not able to respond to contingencies manually. “It’s impossible for the operator to know the ongoing status” of power sources and power use that can change readily, Zhang explained. “That’s why we had to rely on a data driven approach.”

Additionally, end users of electricity don’t necessarily want their neighbors to know about their power needs. They may not want others who are using the same microgrid system to know what appliances or hardware are in their homes.

Instead, the system will rely on the data collected within each microgrid, which reflects the behavior at different intervals. Those energy needs can change, as people turn on a TV or unplug a wind turbine.

At the same time, the power system load and generation need to remain in balance. Microgrids that produce more energy than the system or end users need can send them to a utility grid or to neighboring microds or communities. If they don’t send that energy to others who might use it, they can lose some of that energy.

Power needs to be balanced between supply and demand. Storage systems can buffer an energy imbalance, although the cost of such storage is still high. Researchers in other departments at Stony Brook and Brookhaven National Laboratory are pursuing ways to improve efficiencies and reduce energy storage costs.

Balancing energy is challenging in most microgrids, which rely on intermittent and uncertain renewable energy sources such as sunlight. In this project, Zhang plans to connect several microgrids together into a “mega microgrid system,” that can allow any system with a surplus to push extra energy into one with a deficiency.

Microgrids aren’t currently designed to replace utilities. They may reduce electricity bills during normal operations and can become more useful during emergencies when supplies from utilities are lower.

While artificial intelligence actively runs the system, people are still involved in these programmable microgrids and can override any recommendations.

In addition to having an alarm in the event that a system is unsafe or unstable, the systems have controllers in place who can restore the system to safer functioning. The programming is flexible enough to change to meet any utility needs that differ from the original code.

In terms of cybersecurity, the system will have three lines of defense to protect against hacking.

By scanning, the system can localize an attack and mitigate it. Even if a hacker disabled one controller, the control function would pop up in a different place to replace it, which would increase the cost for the attacker.

Stony Brook created a crypto control system. “If an attacker got into our system, all the information would be useless, because he would not understand what this signal is about,” Zhang said.

While he plans to publish research from his efforts, Zhang said he and others would be careful in what they released to avoid providing hackers with information they could use to corrupt the system.

For Zhang, one of the appeals of coming to Stony Brook, where he arrived two years ago and was promoted last month to Professor from Associate Professor, was that the university has one of the best and best-funded microgrid programs in the country.

Zhang feels like he’s settled into the Stony Brook community, benefiting from interacting with his neighbors at home and with a wide range of colleagues at work. He appreciates how top scholars at the Massachusetts Institute of Technology, Harvard and national labs have proactively approached Stony Brook to establish collaborations.

Zhang is currently discussing a Phase II collaboration on a microgrid project with the Navy, which has funded his research since his arrival. “Given the federal support [from the Navy], I was able to recruit top people in the lab,” he said, including students from Columbia and Tsinghua University.

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David Thanassi. Photo by Jeanne Neville
*Please note: This article was updated on Oct. 15 to include a reference to former President Bill Clinton (D) in the fifth paragraph.

By Daniel Dunaief

David Thanassi wants to give dangerous bacteria in the kidney a haircut.

No, not exactly, but Thanassi, Zhang Family Professor and Chair of the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University, has studied how hair-like structures called P pili in the bacteria Escherichia coli are assembled on the bacterial surface. 

These pili allow bacteria to hang on to the walls of the kidney, where urine would otherwise flush them out.

Learning about pili at different stages of development could provide a way to keep them from attaching themselves to the kidney and from entering the bloodstream, which could lead to the potentially lethal problem of bacterial sepsis. Indeed, this week, former President Bill Clinton (D) checked into the intensive care unit at the University of California Irvine Medical Center after a urinary tract infection spread to his bloodstream.

“We have been looking at this as a really important aspect of initiating infection from a bacteria’s point of view,” Thanassi said. “How do they build these structures” that lead to infection and illness?

Recently, Thanassi published the structure of these pili in the journal Nature Communication.

The current work builds on previous efforts from Thanassi to determine the structure of these pili in the bladder. He has been exploring how the thousands of proteins that make up the pili get transported and assembled in the correct order. “If we can understand that aspect, we can disrupt their assembly or function,” he said.

Urinary tract infections are a major infectious disease, particularly for women. Indeed, about half of all women will have at least one urinary tract infection, which can be uncomfortable and can require some form of medication. 

In some cases, the infections can be recurrent, leading to frequent infections and the repeated need for antibiotics.

The bacteria that cause these infections can become resistant to antibiotics, increasing the importance of finding alternative approaches to these infections, such as interfering with pili.

To be sure, the solution to reducing the bacteria’s ability to colonize the kidney or urinary tract would likely require other steps, as these invaders have additional ways beyond the pili to colonize these organs. Nonetheless, disrupting the way they adhere to the kidney could be a constructive advance that could lead to improved infection prevention and treatment.

One likely strategy could involve using an anti-pilus treatment in combination with other antibiotics, Thanassi explained.

For people who have recurrent infections, anti-pilus therapeutics could offer a solution without resorting to long-term antibiotics.

In his lab, Thanassi is interested in small molecules or chemicals that would disrupt the early stage in pili assembly. “We think of these as protein-protein interactions that are required to build these” pili, he said.

By using a fluorescence reporter, Thanassi and his colleagues can screen libraries of chemicals to determine what might inhibit the process.

As with many biological systems, numerous compounds may seem appropriate for the job, but might not work, as medicine often requires a specific molecule that functions within the context of the dynamic of a living system.

For the helpful bacteria in the gut, pili are not as important as they are for the harmful ones in the kidney, which could mean that an approach that blocked the formation of these structures may not have the same intestinal and stomach side effects as some antibiotics.

To determine the way these pili develop structurally, Thanassi and his lab used molecular and biochemical techniques to stop the assembly of pili at specific stages.

Bacteria assemble these pili during the course of about 30 minutes. An usher proteins serves as the pilus assembly site and pilus secretion channel in the bacterial outer membrane. The usher acts as a nanomachine, putting the pilus proteins into their proper order. A chaperone protein brings the pilus subunits to the usher protein.

In their development, the pili require a protein channel, which is an assembly site.

Thanassi started by working on the usher protein in isolation. The usher proteins function to assemble the thousands of pilus subunits that make up each pilus fiber. The process also involves chaperone proteins, which bind to nascent subunit proteins and help the subunits fold. The chaperone then delivers the subunit proteins to the usher for assembly into the pilus fiber. He used molecular and biochemical methods to express and purify the usher protein.

The assembly process involves interactions between chaperone-subunit complexes and the usher. Over the years, Thanassi has determined how the different proteins work together to build and secrete a pilus.

He was able to force the bacteria to express only one version of the assembly step and then isolate that developmental process.

The majority of the pilus is like a spring or a coil, which can stretch and become longer and straighter to act as a shock absorber, allowing the bacteria to grab on to the kidney cells rather than breaking.

Other researchers are studying how they might make the pili more brittle, preventing that spring-like action from working and compromising its ability to function.

“We’re trying to prevent the pili from assembling in the first place,” Thanassi explained. “Our approach is to try and get molecules that prevent the interaction from occurring.” He is looking at the specific function of one molecule that prevents the usher assembly platform from developing properly, which would wipe out the assembly site.

Thanassi credits former Stony Brook Professor Huilin Li, who is now Chair in the Department of Structural Biology at the Van Andel Institute in Grand Rapids, Michigan, with providing structural insights from his work with the cryo-electron microscoipe. The technology has “revolutionized the work we do,” said Thanassi.

Residents of Smithtown, Thanassi and his wife Kate Kaming, who is Senior Director of Cancer Development at Northwell Health Foundation, have two children. Joseph, 22, attends Northeastern University. Miles, 20, is studying at the Massachusetts Institute of Technology.

Thanassi grew up in South Burlington, Vermont and is an avid skier. He also enjoys mountain biking, walking and music.

Thanassi hopes this latest structural work may one day offer help either with the prevention of infections or with their treatment.

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A TRACER site similar to this one in Argentina is being constructed in Pearland, Texas. Photo courtesy of ARM

By Daniel Dunaief

Before they could look to the skies to figure out how aerosols affected rainclouds and storms around Houston, they had to be sure of the safety of the environment on the ground.

Researchers from several institutions, including Brookhaven National Laboratory, originally planned to begin collecting data that could one day improve weather and even climate models on April 15th of this year.

The pandemic, however, altered that plan twice, with the new start date for the one-year, intensive cloud, study called TRACER, for Tracking Aerosol Convection Interactions, beginning on Oct. 1st.

The delay meant that the “intensive observational period was moved from summer 2021 to summer 2022,” Michael Jensen, the Principal Investigator on Tracer and a meteorologist at Brookhaven National Laboratory, explained in an email.

Scientists and ARM staff pose during planning for TRACER (left to right): Iosif “Andrei” Lindenmaier, ARM’s radar systems engineering lead; James Flynn, University of Houston; Michael Jensen, TRACER’s principal investigator from Brookhaven National Laboratory; Stephen Springston, ARM’s Aerosol Observing System lead mentor (formerly Brookhaven Lab, now retired); Chongai Kuang, Brookhaven Lab; and Heath Powers, site manager for the ARM Mobile Facility that will collect measurements during TRACER. (Courtesy of ARM)

At the same time, the extension enabled a broader scientific scope, adding more measurements for the description of aerosol lifecycle and aerosol regional variability. It also allowed the researchers to include air quality data, funded by the National Aeronautics and Space Administration and urban meteorology, funded by the National Science Foundation.

The primary motivation for the project is to “understand how aerosols impact storms,” Jensen explained in a presentation designed to introduce the TRACER project to the public.

Some scientists believe aerosols, which are tiny particles that can occur naturally from trees, dust and other sources or from man-made activities like the burning of fossil fuels, can make storms stronger and larger, causing more rain.

“There’s a lot of debate in the literature” about the link between aerosols and storms, Jensen said.

Indeed, there may be a “sweet spot” in which a certain number or concentration of aerosols causes an invigoration of rainstorms, while a super abundance beyond that number reverses the trend, Jensen added.

“We don’t know the answers to those questions,” the BNL scientist said. “That’s why we need to go out there and take detailed measurements of what’s going on inside clouds, how precipitation particles are freezing or melting.”

Even though aerosols are invisible to the naked eye, they could have significant impacts on how mass and energy are distributed in clouds, as well as on broader atmospheric processes that affect weather patterns.

The TRACER study, which is a part of the Department of Energy’s Atmospheric Radiation Measurement, or ARM, user facility, could “help forecast heavy rains that can cause flash flooding,’ said Chongai Kuang, atmospheric scientist and TRACER co-investigator at BNL.

The TRACER study will explore the way sea and bay breeze circulations affect the evolution of deep convective storms as well as examining the influence of urban environments on clouds and precipitation.

Several additional funding agencies have stepped in to address basic scientific questions, including the National Aeronautics and Space Administration’s efforts to address air quality issues in Houston and the Texas Commission on Environmental Quality, which funded a study on ozone and low-level atmospheric mixing.

“Our original TRACER field campaign provided a seed for what is now a major, multi-agency field campaign with a significantly expanded scientific scope,” Jensen explained in an email.

A joint team from BNL and Stony Brook University is developing new software to scan the precipitation radar system to select and track storm clouds to observe the rapid development of these storms. Additionally, aerosol instrumentation will help provide updated information on the precursor gases and the smallest aerosol particles at the earliest stages of the aerosol cycle, Jensen explained.

Ultimately, the data that these scientists gather could improve the ability to forecast storms in a range of areas, including on Long Island.

“Understanding sea breezes and the coastal environment is a very important aspect of TRACER,” Jensen said. “Even though it’s not the preliminary focus, there’s an opportunity to learn new science, to improve weather forecasting and storm forecasting for those coastal environments.”

Researchers chose Houston because of their desire to study a more densely populated urban area and to understand the way numerous factors influence developing clouds, weather patterns and, ultimately, the climate.

“We know the urban environment is where most people live,” Jensen said. “This is taking us in new directions, with new opportunities to influence the science” in these cities.

Researchers plan to collect information about clouds, aerosols and storms everywhere from ground-based instruments stationed at four fixed sites, as well as through mobile facilities, to satellite images.

The program operates a tethered balloon which is “like a big blimp that goes up half a mile into the atmosphere,” said Heath Powers, the Atmospheric Radiation Measurement facility site manager for Tracer from Los Alamos National Laboratory.

The tethered balloon is located at Smith Point, Texas, on the eastern shore of Galveston Bay and will do low-level profiling of aerosols, winds, thermodynamics and ozone as it is influenced by bay breeze circulation, Jensen explained.

The National Science Foundation is planning to bring a C-130 plane to conduct overflights, while the group will also likely use drones, Powers added.

The TRACER study will launch around 1,500 weather balloons to gather information at different altitudes. The research will use over four dozen instruments to analyze meteorology, the amount of energy in the atmosphere and the air chemistry.

“Clouds are the big question,” Powers said. “Where they form, why they form … do they rain or not rain. We are well-positioned to get at the core of a lot of this” through the information these scientists gather.

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Dave Tuveson. Photo by Gina Motisi/CSHL

By Daniel Dunaief

While one bad apple might spoil the bunch, the same might be true of one bad cancer gene.

Cold Spring Harbor Laboratory’s Cancer Director Dave Tuveson and Derek Cheng, who earned his PhD from Stony Brook University while conducting research in Tuveson’s lab, recently explored how some mutant forms of genes in pancreatic cancer can involve other proteins that also promote cancer.

A gene well-researched in Tuveson’s lab, mutated KRAS promotes cell division. Mutant versions of this gene continue to produce copies of themselves, contributing to cancer.

Derek Cheng

Turning off or blocking this gene, however, doesn’t solve the problem, at least not in the laboratory models that track a cancer cell’s response.

In laboratory models of pancreatic cancer, a disease for which the prognosis is often challenging, other proteins play a role, creating what researchers call an “adaptive resistance” to chemotherapy.

In a paper published in the journal Proceedings of the National Academy of Sciences, Cheng, who is the first author and is currently in his final year of medical school at the Stony Brook Renaissance School of Medicine, and Tuveson showed that a protein called RSK1 interacts at the membrane with mutated KRAS. When KRAS is inhibited, the RSK1 protein, which normally keeps RAS proteins dormant, becomes more active.

“If you antagonize KRAS, you would get a rebound” as the cancer cells develop a resistance to the original drug, Tuveson said. “We found a feedback loop.”

The research “focused on identifying protein complexes with oncogenic KRAS that would potentially be relevant in pancreatic cancer,” Cheng explained in an email. “My work suggests that an RSK1/NF1 complex exists in the vicinity of oncogenic KRAS.”

While Cheng was able to show that the role of membrane-localized RSK1 provided negative regulation of wild-type RAS, it “remains to be studied what the role of the RSK1 at the membrane [is] in the context of oncogenic KRAS.”

KRAS is a molecular switch that turns on and off with the help of other proteins. With certain mutations, the switch doesn’t turn off, continuing to signal for copying and dividing, which are hallmarks of cancer cells. With specific activating mutations, the switch can lose its ability to turn off and constitutively signal for proliferation, metabolic reprogramming, and other behaviors characteristic of cancer cells, Cheng explained.

A cell with an oncogenic KRAS has the tendency to be more fit than a normal cell without one. Such cells will likely grow at a faster rate under stressful conditions, which, over time, can enable them to outcompete normal cells, Cheng continued.

When KRAS is in an oncogenic state, another protein, called RSK1 is hanging around the membrane. RSK1 has several functions and can participate in numerous cellular signaling pathways.

KRAS cytoplasm

While RSK1 is involved in protein translation by phosphorylating S6 kinase, it also has other functions at the plasma membrane, where it shuts down wild type RAS proteins.

Other researchers have suggested a negative feedback for RSK1 and NF1.

“Our contribution demonstrated some relevance of this interaction in pancreatic cancer cells,” Cheng explained in an email.

Cheng said RSK is known to have various effects, depending on the context. In the paper, the scientists showed that RSK has a “negative feedback properties, such as that, upon the removal of mutant KRAS, it has this negative regulatory role.”

Graduate student Sun Kim and post doctoral researchers Hsiu-Chi Ting and Jonathan Kastan are currently exploring whether RSK has a pro-oncogenic function on the membrane in the tumor cell.

So far, these studies suggest that while a direct inhibitor against oncogenic KRAS would likely be the greatest target for an effective therapy, cancer cells may still be able to use signals from other RAS isoforms.

“A combination of targeting KRAS and modulating regulators of RAS such as RSK1/NF1 and SOS1 may enhance therapeutic efficacy,” Cheng suggested.

Cheng is grateful for the opportunity to learn from numerous Tuveson lab members on ways cancer cells differ from healthy cells.

The discovery of the potential roles of RSK1 in cancer provides some possible explanation for the potential resistance mechanisms of mutant KRAS inhibitors.

While he was encouraged that a prestigious journal published the research, Tuveson said he hopes this type of observation “will lead to something that will be useful for a pancreatic cancer patient and not just” provide compelling ideas.

Cheng attended medical school for two years before joining Tuveon’s lab for the next six years.

Cheng defended his thesis in 2020 during the pandemic on a zoom call.

“I was one of the first people to defend with this format for both CSHL and SBU,” Cheng explained. “I was able to invite many friends and family that probably would not have been able to make the trip.”

Cheng’s family has battled cancer, which contributed to his research interests.

When he was an undergraduate, he had an uncle develop glioblastoma, while another uncle and his grandfather developed colon cancer.

“I knew I wasn’t going to be able to do much about their medical condition, but I wanted to work on something that people cared about,” Cheng explained.

Outside of the lab, Cheng enjoys working on his car and his motorcycles. He feels a sense of autonomy working on his own projects.

He’s most proud of a motorcycle for which he rebuilt the front end with parts from another model to outfit a larger brake system.

A native of St. Louis, Cheng is a fan of the hockey team, the Blues. He owns a game-worn jersey from almost every member of the 2019 cinderella team that won the Stanley cup, with some of those jerseys coming from Stanley Cup final games.

Cheng plans to apply to residency in internal medicine this year because he wants to continue applying what he learned in his scientific and medical training.

The clinical work reminds him to treat patients and not just the tumors, while scientific research trained him to loo at evidence and literature carefully to find clinical gaps, he explained.

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Semir Beyaz (center) with research assistant Onur Eskiocak, left, and graduate student Ilgin Ergin. Photo by Gina Motisi/CSHL

By Daniel Dunaief

High fat diets present numerous health problems for humans and mice, which are often used as a model organism to understand disease.

In a recent multi-disciplinary study with mice, Cold Spring Harbor Laboratory Fellow Semir Beyaz and 32 colleagues from 15 other institutions explored how a high fat diet affects the development of intestinal tumors.

Semir Beyaz. Photo by Gina Motisi/CSHL

The diverse team of scientists brought together a range of expertise to discover the way a high fat diet disrupts the cross talk among the microbiome, stem cells and immune cells, triggering tumors through the reduction in the expression of an important gene, called major histocompatibility complex II, or MSC-II.

“This work nicely integrates efforts in stem cell biology, immunology, microbiology and metabolism in the context of understanding how diet is linked to cancer,” Beyaz explained in an email. With such interdisciplinary studies, “we hope to improve our understanding” of the mechanisms that link nutrition to diseases.

The paper, published in Cell Stem Cell, for which Beyaz is the first and corresponding author, shows how a high fat diet leads to immune evasion of tumor initiation stem cells due to the suppression of the immune recognition molecule MHC-II.

At the center of this study, the MHC-II gene encodes a protein that presents antigens, or foreign substances, to the immune system. When a cell is infected or cancerous, immune cells detect the unwelcome agents through their surveillance of MHC molecules, Beyaz said.

A high fat diet also results in the alteration of immune cells in the micro environment and the signals that they produce, called cytokines.

“The novel finding of our study is that the crosstalk between stem cells, microbes and immune cells is critical for eliminating tumor initiating cells and this cross talk is dampened in response to a high fat diet, demonstrating a mechanistic basis for how high fat diets may promote cancer,” said Beyaz.

A current hypothesis, which has some supporting evidence in Beyaz’s study, suggests that diet-related factors might facilitate early onset colorectal cancer.

To be sure, researchers need to conduct more work to understand the environmental factors that facilitate early onset colorectal cancer, Beyaz explained. “The knowledge of what causes early onset colorectal cancer in young adults is very limited,” he added.

Semir Beyaz with visiting clinical researcher Aaron Nizam (left) and research tech Katherine Papciak. Photo by Gina Motisi/CSHL

Beyaz believes diet is one of the most important environmental factors that contribute to cancer risk. Diet could affect sleep, stress and other factors.

“There are so many things we don’t know about how diet affects our body,” he said. “That’s why I’m very excited to work on understanding these mechanisms.”

Beyaz said the mice in his study consumed a lard-based pro-obesity diet that was high in carbohydrates.

A diet that is lower in carbohydrates and higher in fat is more similar to a ketogenic diet, which could have other outcomes. His ongoing studies are trying to tease apart some of these differences.

To counteract the effect of diet on the development of cancer, Beyaz plans to activate the altered pathways by using either microbes or small molecule drugs.

“We believe if we promote immune surveillance by activating these pathways, we can elicit preventative and therapeutic strategies against cancer,” he explained.

Additionally, in his ongoing research, Beyaz plans to address numerous other questions that link diet to disease.

An increasing number of studies are exploring how diet and microbes affect cancer, which he described as a “hot topic.”

Beyaz believes a high fat diet might turn on or off some genetic sequences, enabling the latent development of cancer.

His unique niche involves searching for a connection between diet and perturbations that affect cross talk among cells. While this field has numerous challenges, Beyaz suggested he was “drawn” to that difficulty.

Beyaz’s expertise is in stem cell biology and immunology. He appreciates and enjoys the opportunity to interact with researchers from other disciplines that could lead to actionable progress.

Hannah Meyer. Photo from CSHL

While science has to be reductionistic and focused on one molecule or cells at times, new conceptual and technical advances have made it possible for the lines between disciplines in biology to disappear slowly, he explained.

Beyaz and his colleagues are looking forward to taking some of the next steps in this effort.

For starters, he is excited to expand this study, to understand whether there is a threshold for a high fat diet that favors the growth of tumors. Diets that fall below a potential threshold might not promote the growth or development of tumors.

Such a threshold could become clinically relevant, providing health care workers with a pre-cancerous marker that could signal the need for lifestyle changes and medical vigilance that could stave off or avoid the formation of disease-bearing and life-threatening tumors.

“We have some ongoing work to delineate such thresholds and proxies,” Beyaz said. Additionally, they would like to see whether this effect is reversible, to determine whether an altered microbiome might promote the expression of MHC-II, which could derail the tumor forming process.

Pawan Kumar. Photo from SBU

Beyaz’s collaborators on this work include Hannah Meyer, who is a fellow at Cold Spring Harbor Laboratory Fellow, and Pawan Kumar, who is an Assistant Professor in the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University.

In his life outside the lab, Beyaz, who enjoys fishing, gardening, and hiking, avoids excessive sugar and fat consumption. He doesn’t eat fast food or consume sugary drinks.

Originally from the town of Samandag which is near the Mediterranean Sea in the southeastern part of Turkey, Beyaz enjoys cooking and is fond of making lamb, beef, chicken and eggplant kebabs.

When he was growing up, Beyaz said science was a passion for him.

“It is not a job or a career,” he explained. “It is the way I find meaning in life, by learning how to ask and (sometimes) answer questions at the edge of cumulative human knowledge.”

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Ellen Pikitch. Photo from Stony Brook University

By Daniel Dunaief

Preserving the oceans of the world will take more than putting labels on sensitive areas or agreeing on an overall figure for how much area needs protection.

It will require consistent definitions, guidelines and enforcement across regions and a willingness to commit to common goals.

A group of 42 scientists including Ellen Pikitch, Endowed Professor of Ocean Conservation Sciences at the School of Marine and Atmospheric Sciences at Stony Brook University, recently published a new framework developed over more than 10 years in the journal Science to understand, plan, establish, evaluate and monitor ocean protection in Marine Protected Areas (MPAs).

“We’ve had MPAs for a long time,” said Pikitch. Some of them are not actively managed, with activities that aren’t allowed, such as fishing or mining, going on in them. “They may not be strongly set up in the first place to protect biodiversity. What this paper does is that it introduces a terminology with a lot of detail on when an MPA qualifies to be at a certain level of establishment and protection.”

These scientists, who work at 38 institutions around the world, created an approach that uses seven factors to derive four designations: fully protected, highly protected, lightly protected, and minimally protected.

If a site includes any mining at all, it is no longer considered a marine protected area.

Fully protected regions have minimal levels of anchoring, infrastructure, aquaculture and non-extractive activities. A minimally protected area, on the other hand, has high levels of anchoring, infrastructure, aquaculture and fishing, with moderate levels of non-extractive activities and dredging and dumping.

Using their own research and evidence from scientific literature, the researchers involved in this broad-based analysis wanted to ensure that MPAs “have quality protection,” Pikitch explained. “The quality is as important, if not moreso, than the quantity.”

The researchers are pleased with the timing of the release of this paper, which comes out just over a month before the United Nations’ Convention on Biological Diversity, which will meet virtually in October. Over 50 countries, including the United States, have already agreed to protect 30 percent of the ocean by 2030.

Pikitch called this a “critical time to get this information in front of decision makers.” The meeting will occur in two parts, with the second one set for an in-person gathering in China in April.

The point of the paper is to “help clarify what is an MPA, how do we distinguish different types and their outcomes,” Pikitch added.

The people who attend the CBD meeting range from high level government officials all the way up to the president of small countries.

About a decade ago, an earlier convention targeted protecting 10 percent of the oceans by 2020. The world fell short of that goal, with the current protection reaching about 7.7 percent, according to Pikitch.

Indeed, amid discussions during the development of this new outcome-based approach to MPAs, some researchers wondered about the logic of creating a target of 30 percent within the next nine years even as the world fell short of the earlier goal.

Some people at the meetings wondered “should we be pushing these things when a lot of them are failing?” Pikitch recalled of a lively debate during a meeting in Borneo. “Part of the answer is in this paper. These [earlier efforts] are failing because they are not doing the things that need to be done to be effective. It definitely helped us inform what we should be thinking about.”

Enabling conditions for marine protected areas go well beyond setting up an area that prevents fishing. The MPA guidelines in the paper have four components, including stages of establishment, levels of protection, enabling conditions and outcomes.

The benefits of ensuring the quality of protecting marine life extends beyond sustaining biodiversity or making sure an area has larger or more plentiful marine life.

“More often than not, it’s the case that MPAs do double duty” by protecting an environment and providing a sustainable resource for people around the area, Pikitch said. Locally, she points to an effort in Shinnecock Bay that provided the same benefits of these ocean protection regions. 

In the western part of the bay, Pikitch said the program planted over 3.5 million hard clams into two areas. In the last decade, those regions have had an increase in the hard clam population of over 1,000 percent, which has provided numerous other benefits.

“It demonstrates the positive impact of having a no-take area,” Pikitch said.

At the same time, the bay hasn’t had any brown tides for four straight years. These brown tides and algal blooms can otherwise pose a danger to human health.

By filtering the water, the clams also make it easier for eel grass to grow, which was struggling to survive in cloudier waters that reduce their access to light. With four times as much eel grass as a decade ago, younger fish have a place to hide, grow and eat, increasing their abundance.

Being aware of the imperiled oceans and the threats humans and others face from a changing planet has sometimes been a struggle for Pikitch.

The marine researcher recalled a time when four hurricanes were churning at the same time in the Atlantic.

“I went to bed and I have to admit, I was really depressed,” Pikitch said.

When she woke up the next morning, she had to teach a class. She regrouped and decided on a strategic message.

“This is reality,” she told her class. “We have to accept this is the world we made. Everything we do that can make a positive difference, we do.”

Pikitch is encouraged by the work done to develop a new MPA framework.

These protected areas “provide a sustainable pathway to ensure a healthy ocean and to provide a home for future biodiversity,” she said.

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Chemist John Moses on the campus of Cold Spring Harbor Laboratory. Photo from CSHL

By Daniel Dunaief

If you build it, he will come.

That’s an iconic line from the movie “Field of Dreams,” starring Kevin Costner, in which a mythical voice calls to the Iowa farmer, encouraging him to plow through his corn to build a baseball field so the ghosts of past baseball players can entertain a modern audience.

It seems only fitting that this year, in which Major League Baseball hosted its first professional game in Iowa near the set of the popular movie, chemists have built something they hope brings together numerous other chemicals to produce products with various applications, from drug discovery to materials science.

About 120 years ago, researchers in France discovered a highly reactive gas called thionyl tetrafluoride, whose chemical symbol is SOF4.

The gas has numerous potential applications because researchers can control its reactions and derivatives. Scientists can swap each sulfur-fluorine bond with a bond between sulfur and something with desirable properties or applications.

While the gas serves as a potential building block, it is scarce and is not commercially available.

Thionyl tetrafluoride is “very reactive,” said chemist and Cold Spring Harbor Laboratory Professor John Moses. “It’s not something the Average Joe wants. It’s dangerous chemistry.” It was largely overlooked until the 1960’s, when chemists at DuPont reinvestigated it.

Once Suhua Li, the lead author of a recent paper in Nature Chemistry and a former post doctoral researcher in Nobel-prize winner K. Barry Sharpless’s lab at Scripps Research Institute in La Jolla, California, generated more of this gas, the team could work together to determine the types of connections that might be possible. 

While the research was a group effort in terms of planning and ideas, Li, who did the vast majority of the synthesis of the gas, is “the hero,” Moses said. “The gas itself, and reagents used to make the gas, are potentially very dangerous, and it takes courage and confidence to attempt such chemistry. ([Li] even had a bit of a mishap, to say the least, but still went ahead and tried again.”

Moses also appreciates how “ideas are just ideas until somebody takes the initiative to put them into practice.”

Moses, Sharpless, and Scripps Research Institute Associate Professor Peng Wu developed the polymer chemistry, while Hans Zuilhof of Wageningen University in the Netherlands helped elucidate the helical structure of the polymers.

The team used a technique Sharpless calls “click chemistry” to explore the substances they could create with this gas.

Thionyl tetrafluoride acts like a lego building block that can be connected with other building blocks in several dimensions.

Click reactions create defined products with absolute reliability, Moses explained. Scientists get what they expect, which is not always true in chemistry.

“In some reactions, you take A and B and you don’t always get C,” Moses said. “You get C as a major product, but you also get D, E and F.”

In click chemistry, however, the combination of A and B is guaranteed to produce C.

Some click reactions run better in water, or at least when water is present. Water is non-toxic, inflammable, inexpensive and a good heat sink.

Click philosophy is about using reliable reactions for the purpose of function discovery.

With thionyl tetrafluoride, Li and the other researchers made about 30 polymers, each of which had original structures using different fragments.

The group managed to attach antibiotics to a thionyl tetrafluoride-derived polymer and demonstrated that it retains antibacterial function.

As long as the module has a handle to exchange with the sulfur-fluorine bond, the gas has a broad range of potential applications.

With thionyl tetrafluoride as his inspiration, Moses coined the term multidimensional click chemistry, which identifies the gas a multi dimensional hub.

The chemists used a regular party balloon to transfer the gas, which is connected to a syringe and a needle. They inserted the needle through a rubber septum into a sealed flask. The reaction with reagents in the flask is straightforward to perform once the gas is available, Moses said.

Born and raised in Wrexham, North Wales, a town aglow after actors Ryan Reynolds and Rob McElhenney last year bought a 156-year-old local soccer team, Moses had no interest in science when he was young, although he was curious about life in general.

He left school to work in a factory that made life rafts and buoyancy jackets when he was 16.

The factory had a distinct odor of toluene and glue.

“It was dreadful,” he recalls. “I was lucky to escape that life.”

He eventually landed an apprenticeship at a company called App-Chem, that allowed him to study physics and chemistry in college one day per week. 

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Michelle and Paul Paternoster

By Daniel Dunaief

Part 2

Three families and their foundations jump-started a research mission on Long Island that offers a chance for change. Their stories reflect a desire to remember their family members and a need to offer hope and help to others.

Christina Renna

Christina Renna with sister Rae Marie Renna

Phil Renna waited while his 16-year old daughter Christina spoke with her doctor. He and his wife Rene had decided to allow their daughter, who was battling a form of connective tissue cancer called rhabdomyosarcoma (RMS), to be involved in decisions about her treatment.

When Christina came out of the room, Phil, director of operations in the communications department at Cold Spring Harbor Laboratory, asked if he should also speak with the doctor. Christina said it wasn’t necessary. On the way home, she told him it had to be a “really good Christmas.”

He knew what that meant, although she also asked him not to tell anyone how close she was to the end of her life.

Renna and parents throughout the country have had to cope with the agony of rhabdomyosarcoma, which mostly affects children. People battling this cancer have turned to medicine for help, only to find that the treatment options are limited.

That, Renna and others say, was as unacceptable to them when their children were battling cancer as it is now, when the next generation is struggling with this illness.

RMS doesn’t receive the same level of funding nationally as cancers that affect more people, such as breast, lung and prostate cancer, but the agony and suffering are just as significant.

Amid their battles with the disease, families have turned to their support groups, including friends, extended family, and community members to raise funds for basic research, hoping grass roots efforts allow future generations to have longer, healthier lives.

Supported by these funds and a willingness to fill a research gap, Cold Spring Harbor Laboratory CEO Bruce Stillman has backed efforts to gather information and to support research that may also help people with other forms of cancer.

Renna, who lives in Lindenhurst, struggled with his role as father and protector when Christina developed rhabdomyosarcoma.

“I’m supposed to protect my kids,” Renna said. “I should be able to tell them, ‘It’s going to be okay.’”

Renna went to Stillman to ask whether Christina, who was a patient at Memorial Sloan Kettering, might get better care somewhere else.

After conducting some research, Stillman told his colleague about the lack of basic research and other treatment options.

“That was a crushing moment for me,” Renna said.

During treatment, Christina had to be at Memorial Sloan Kettering at 7 a.m., which meant he and Christina’s mother Rene got in the car at 5 a.m. with their daughter.

Renna dropped them off, drove back to work, where he’d put in a full day, drive back to the hospital and return home at 10:30 p.m.

“That was every night, five days a week,” Renna recalled. While those were tough days, Renna said he and his wife did what they needed to do for their daughter.

Five years after his daughter died at the age of 16, Renna drove home from work one day to find his shirt was wet. It took him a while to realize the moisture came from the tears, as he cried his way back to his house. At one point, he thought he had post-traumatic stress disorder.

Renna continues to raise money to support research into this disease, while also helping people create and develop their own foundations, often after enduring similar pain.

“Every single foundation that has come and given money to the lab, I have personally met with,” he said. “I helped our advancement team onboard them.”

As someone who has lost a child and understands what a parent can be feeling, Renna is committed to helping others cope with their grief. 

“For me, it is about helping the lab, but also about helping families honor the memory of their child in a meaningful way and what better way than to help another family and perhaps find a cure,” he wrote in an email.

Renna believes investments in research will pay off, helping to answer basic questions that will lead to better treatments down the road.

So far, the foundation has given $387,300 to Cold Spring Harbor Laboratory for research. They also gave $50,000 to Make-a-Wish in Suffolk, and $25,000 to local scholarships. The foundation supported Memorial Sloan Kettering with an iPad program. Ultimately, Renna believes in the ongoing return from research investments.

“Everybody wants to find and fund the silver bullet,” he said. “Everybody wants to give money to fund a clinical trial. Basic research is where the discoveries are made.”

Renna urged people creating foundations to have a strong board that included business people and that might also have a scientific or medical advisory element. He also suggested funding foundations a year ahead of time. That helped his foundation in 2020, when finding donors became more challenging during the pandemic.

Being at Cold Spring Harbor Laboratory and helping others get through darker days that are all too familiar to him gives Renna comfort. “I know, in some way, every single day, I’m making an impact,” he said. “How measurable it is, I don’t know. There are days when I’m pretty proud.”

As far as he feels they have come, Renna said it’s not the time to look back, but to press ahead.

T.J. Arcati

A former summer intern in Bruce Stillman’s lab when he attended Notre Dame, T.J. Arcati was married and had two children when he succumbed to sarcoma.

“We know what we went through,” said his father, Tom Arcati, an oral and maxillofacial surgeon in Huntington. “He left a son and a daughter without a dad.”

Tom and his wife Nancy, who raised T.J. in Lloyd Harbor and live in Huntington, were with their son for his treatments and therapies.

Tom and Nancy Arcati are determined to extend people’s lives by more than a year or two and are actively engaged with other families who are coping in the midst of the cancer storm. “I’m talking to people now that unfortunately are going through what we did seven years ago,” Tom Arcati said.

While the Arcatis support other families, their empathy “brings you back to a place you never really leave,” Nancy Arcati said. These interactions “keeps T.J.’s life on people’s minds and in their hearts.”

Tom Arcati tries to be a source of solace to people who are trying to gather information.

In the aftermath of TJ’s death at the age of 34, Arcati reached out to Stillman to see if the lab could work towards better treatments.

One Saturday, Arcati and his son Matthew went to Stillman’s house, where they sat in his living room, with Stillman drinking tea and Arcati having coffee.“What do you think?” Arcati recalled asking. “Are you going to do sarcoma research?” Stillman looked back at his guest and mentioned that he was thinking about it. Stillman called Arcati a few days later.

“When he called me, he said, ‘We’re a cancer institute. We should be doing sarcomas.’ That’s how I remember this whole thing going down. It was pretty heart warming.”

The first step for CSHL was to host a Banbury conference. The site of international meetings on a range of scientific topics since 1978, the Banbury center brings together experts in various fields. The meetings provide a forum for scientific advances and result in various publications. By holding a Banbury Center meeting, CSHL helped advance research into sarcomas.

The Arcatis have remained active in the Friends of T.J. Foundation, which TJ and several college friends founded in 2009 after T.J. was diagnosed with sarcoma. They have stayed in close contact with CSHL Professor Chris Vakoc and his PhD student Martyna Sroka, who regularly keeps him informed of her progress. Sroka has spoken at some of the outings for the Friends of TJ Foundation. This year, Stillman will speak at the September 13th fundraiser at the Huntington Country Club.

“It’s really imperative that people who are supporting us know what their dollars are being spent on,” Arcati said.

The Friends of TJ Foundation has raised about $50,000 each year, bringing their total fundraising to about $400,000.

Arcati hopes something positive can come out of the losses the families who are funding Vakoc’s research suffered.

“If we can save one kid’s life somewhere by doing what we’re doing, then this whole process is worth it,” Arcati said.

Michelle Paternoster

Michelle Paternoster of Lindenhurst developed sarcoma in her sinuses. Her husband Paul Paternoster helped her through 38 surgeries, over 90 radiation treatments and several rounds of chemotherapy.

Michelle and Paul Paternoster

The couple tried immune therapy in the Bahamas in the fall of 2008 and went to New York in 2011 for treatment.

“We drove [to the city] for 90 days” excluding weekends, Paternoster recalled. The treatments seemed to have a positive effect during the trial, but shortly afterward, the cancer continued growing.

After Michelle died in 2013 at the age of 34, Paternoster was determined to help others, initially asking supporters to contribute to the fundraising effort from the Arcatis.

Donations to the Friends of T.J. Foundation reached $30,000, which helped underwrite the Banbury conference at Cold Spring Harbor Laboratory. Michelle and T.J. had seen each other in the radiation suite in the halls of Memorial Sloan Kettering.

Paternoster then started the Michelle Paternoster Foundation for Sarcoma Research. The President of Selectrode Industries Inc., which manufactures welding products and has two factories in Pittsburgh, Paternoster wanted to help people at a clinical level.

Through Michelle’s Clubhouse, he partnered with the Children’s Hospital of Pittsburgh, paying for hotels of pediatric cancer patients when the Ronald McDonald house is full. The clubhouse also provides gift cards to help pay for gas, tolls and copays on prescriptions.

“Knowing how difficult it is to go through this, I can’t imagine what it’s like to not have that capability” to pay for basic needs during treatment, Paternoster said. “That is why it is so important for our board to do something at the clinical level to support families in this battle.”

Paternoster said the relatively small but growing size of the group dedicated to helping each other makes each person’s contribution that much more important.

“Normally, when you’re doing any kind of charity work, you feel like you’re a tiny part of this project, especially when it comes to [diseases like] breast cancer and things that impact millions of people,” Paternoster said. When he attended the Banbury conference that launched the research effort at Cold Spring Harbor Laboratory, he said “you felt you could make a difference. You’re sitting in a room with 25, 30 people max. That was the entire effort to eradicate this disease.”

Paternoster, who lives in Cold Spring Harbor, called the collaboration that came out of the meeting “astounding.”

The Michelle Paternoster Foundation has raised $500,000, with about $350,000 of that supporting the work at Cold Spring Harbor Laboratory.

Ultimately, like the other families who raise funds, stay informed and offer help to strangers battling an all-too-familiar disease, Paternoster feels that the opportunity to make a meaningful contribution inspires him.

“That’s our dream,” he said, “to find a cure, so other people don’t have to feel what we felt.”

To read Part 1 of the article click here.

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