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Power of 3

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Prateek Prasanna and Chao Chen at the NCI Informatics Technology for Cancer Research meeting in St. Louis in 2022.

By Daniel Dunaief

Cancer often involves numerous small changes before it become a full blown disease. Some of these alterations are structural, as otherwise healthy cells make subtle shifts that favor out of control growth that often defies the immune system and threatens the health of tissues, organs and the entire body.

Associate Professor Chao Chen and Assistant Professor Prateek Prasanna, both in the Department of Biomedical Informatics at Stony Brook University, recently received a four-year, $1.2 million grant from the National Cancer Institute to continue to develop an enhanced breast cancer imaging tool that could detect some of those changes.

Using advanced mathematical modeling and machine learning and working with clinical collaborators in radiology, radiation oncology, surgery and pathology, the researchers are developing a tool called TopoQuant. They hope they can provide a way to look at the changes in tissue architecture that occur during the growth and development of cancer and during radiation treatment.

Receiving the grant means “other researchers also think highly about the subject,” Chen explained. “This further boosts our confidence and is an approval for our effort so far.”

By combining two-dimensional and three-dimensional data, the Stony Brook researchers, including radiation oncologist Dr. Alexander Stessin, hope to provide an analytical tool that helps doctors and patients confronting cancer all the way from the early steps the disease takes to the ways it resists various treatments.

The researchers are using tomosynthesis and MRIs, both of which are three dimensional, and conventional mammographs, which are two dimensional.

Stessin will work closely to evaluate the efficacy of the TopoQuant framework to provide a predictive and useful interpretation of breast images.

The diagnostic and prognostic tool these scientists are developing has potential applications outside the world of breast cancer. The deep learning technique could help analyze images and information for other types of cancer as well as for various neurological challenges.

“In the tools we develop, a lot of the algorithms are domain agnostic,” said Prasanna.

The approach should work as long as the researchers can get structure-rich imaging data. To be sure, while this approach has had some promising early results, it has to proceed through numerous steps to help in the clinic.

In the meantime, the researchers plan to use the funds, which will support salaries and travel budgets for researchers, to continue to develop TopoQuant.

Chen and Prasanna envision providing physicians with an explanation of why artificial intelligence is guiding them towards a particular decision.

Doctors could “place more trust in a system like this,” Prasanna said. “It lends interpretability to an analysis that is typically more opaque.”

Healthy cells

When health care technicians gather information about breast cells, they often focus on developments in and around the cancer cells.

“The premise of the work” Chen and Prasanna are doing is to look at signals “even in the normal [healthy] areas of the breast, Prasanna said. “It’s important for physicians to look at these normal areas before they begin any treatment. What our tool lets them do is extract these signals.”

The process of developing this tool started about five years ago, as the scientists shared ideas and did preliminary studies. The work became more involved and detailed around 2020.

“The challenge is to have a harmonic combination between mathematical modeling and deep learning,” Chen explained. “Incorporating principled math modeling into deep learning is important yet not trivial.”

In their work, the researchers used phantom data called VICTRE from the Food and Drug Administration. They used simulated magnetic resonance images and validated that the method can extract the tissue structure faithfully across different breast density types. They are also using data from The Cancer Imaging Archive for initial model development.

At this point, the researchers have some evidence that the alpha version of the tool has been “promising” in the context of neoadjuvant chemotherapy, which they demonstrated in a paper they published in 2021.

The results from that study indicated different topological behavior of breast tissue characterized by patients who had different responses to therapy.

The researchers plan to continue to establish that the tools are properly characterizing what is happening. After that, they will validate the effort with a Stony Brook University Hospital cohort.

Clinicians from Rutgers are working with Chen and Prasanna and will do additional testing through external data sets.

Complementary skills

Chen and Prasanna, who have joint lab meetings and discuss their research every week, work in different parts of the campus. Chen’s lab is on the west campus, while Prasanna is in the east campus.

The researchers have combined their interests and skill sets to apply a computer science driven approach to medicine and the field of bioimaging analysis.

Chen does considerable work with topological information and machine learning. Prasanna, meanwhile, is also involved in the clinical world, combining his passions for engineering and medicine.

A native of Gansu Province in China, Chen lives near New York City and commutes to the university two or three times per week, working the other days from home and meeting with students and collaborators by Zoom.

When he first joined Stony Brook in 2018, Chen was concerned about jumping into a different department.

After visiting the department and speaking with Chair Joel Saltz and other faculty, he developed greater confidence when he learned of their passion for research, their research philosophy and the chemistry within the department.

Six years later, he thinks it was “the best career decision” he made.

A native of Cuttack, India, Prasanna and his wife Shubham Jain, who is in the faculty of Computer Science at Stony Brook, have worked together professionally.

The couple enjoys hiking and has been to 47 of the 63 national parks. One of their favorite parks is Katmai National Park and Preserve in Alaska.

Prasanna’s father’s family includes many physicians and his mother’s is involved in engineering. In his career, he has combined the professional focus from both sides of his family.

Early in his career, Prasanna worked on a project that used a smart phone to obtain fundus images of the eye to predict diabetic retinopathy.

At the time, he thought “this is where I want to be,” he recalled.

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Ellen Pikitch at the United Nations when she spoke at the 9th International Day of Women and Girls in Science back in February. Photo from E. Pikitch

By Daniel Dunaief

Even as Covid threatened the health of people around the world, a group of 30 leading researchers from a wide range of fields and countries were exchanging ideas and actions to ensure the sustainability of ocean fisheries.

Starting in 2020, the researchers, including Stony Brook University’s Endowed Professor of Ocean Conservation Science Ellen Pikitch, spent considerable time developing operating principles to protect the oceans and specific actions that could do more than ensure the survival of any one particular species.

Earlier this week, the researchers, who come from fields ranging from biology and oceanography to social sciences and economics, published a paper titled “Rethinking sustainability of marine fisheries for a fast-changing planet” in the Nature Journal npj Ocean Sustainability, as well as a companion 11 golden rules for social-ecological fisheries.

The researchers, who were led by first author Callum Roberts, Professor of Marine Conservation at the University of Exeter, plan to share their framework with policy makers and government officials at a range of gatherings, starting with Brussel’s Ocean Week and including the United Nations Ocean Conference in Nice.

“We felt something like this was needed in order to reach these audiences effectively,” said Pikitch.

The extensive work, which included two series of workshops, outlines ways to regenerate the ocean’s health and to put people before profits.

The authors suggest that fisheries need to address their contributions to the climate crisis through activities that are polluting, such as dumping fishing gear or plastics in the ocean, carbon intensive or destructive, through the disturbance of sediment carbon stores.

The paper suggests that lost or discarded fishing gear often make up the largest category of plastic waste in the open sea. This gear is not only polluting, but leads to ghost fishing, in which fish die in abandoned or discarded nets.

The authors suggest that labelling fishing gear could encourage better stewardship of the ocean. They also argued that fisheries management has historically focused on economic output, without considering social value and effects.

“We take the view that marine life is a public asset, and its exploitation and management should work for the benefit of local communities and the public,” the authors wrote in their paper.

Pikitch described the work as an “urgent” call to action and added that the researchers will be “meeting with policy makers, retailers, fishery managers and others to discuss these results and how they can be implemented.”

The researchers engaged in this effort to find a way to compile a collection of best practices that could replace a hodgepodge of approaches that overlook important elements of sustainability and that threaten fish species as well as ocean habitats.

“Fisheries are in bad shape worldwide and are degrading rapidly with overexploitation and climate change,” Philippe Cury, Senior Emeritus Researcher at the Institute of Research for Development in Marseille, France, said in a statement. “Efficient and renewed fisheries management can really help to restore marine ecosystems and to reconcile exploitation and biodiversity.”

Pikitch anticipated that some might offer pushback to the suggestions. “If you don’t get pushback, you’re probably not saying something that is important enough,’ she said.

Ecosystem focus

Using research Pikitch led in 2004 from a paper in Science, the group constructed one of the 11 actions around developing a holistic approach to the ocean habitat.

Pikitch’s expertise is in ecosystem based fishery management.

“Fish interact with one another, feed on one another, compete with one another and share the same habitats,” Pikitch said. “For those reasons alone and more, we need to stop managing species one at a time.”

Some policies currently protect ecosystems, including the spatial and temporal management of the Canadian lobster fishery to protect whales and the no-take marine reserves to protect artisanal reef fisheries in the Caribbean.

Still, these approaches need to be applied in other contexts as well.

While some people believed that researchers didn’t know enough to create and implement holistic guidelines, Pikitch and her colleagues suggested that it’s not “necessary to know everything if we use the precautionary principle.”

Pikitch suggested that the Food and Drug Administration takes a similar approach to approving new medicines.

The FDA requires that researchers and pharmaceutical companies demonstrate that a drug is safe and effective before putting it on the market.

Fisheries are making some headway in this regard, but “much more is needed,” she said.

Subsidy problem

The authors highlighted how government subsidies are problematic.

“Many fisheries are highly carbon intensive, burning large quantities of fossil fuels often made cheaper by capacity-enhancing government subsidies,” the authors noted in the paper. “Among the worst performers in terms of fuel burned per tonne of landing gears are crustacean fisheries, fisheries that operate in distant waters, deploy heavy mobile gears like trawls, or target high value, low yield species like swordfish; most of them propped up by subsidies.”

When overfishing occurs, companies switch to catching less exploited species, even when they don’t have any data about new catches. The new species, however, soon become overfished, the authors argued.

In urging fisheries management to support and enhance the health, well-being and resilience of people and communities, the scientists add that abundant evidence of widespread human rights abuses occurs in fishing, including coercive practice, bonded, slave and child labor and unsafe, indecent and unsanitary living and working conditions.

“Abuses at sea continue and more needs to be done to stop this,” Pikitch explained.

Additionally, the authors hope to give a voice to the global south, which is “often ignored in many of these discussions about how to appropriately manage these fisheries,” she suggested.

A beginning

While the paper was published, Pikitch explained that she sees this as the beginning of change and improvement in creating sustainable fisheries policies. She anticipates that the collection of talented scientists will continue the work of protecting a critical resource for human and planetary survival.

“This group will continue to work together to try get this work implemented,” she said. “I’m enormously proud of the result.”

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From left, Oscar Rivera-Cruz from the University of Puerto Rico, BNL materials scientist Anibal Boscoboinik, Alexander Bailey from West Virginia State University, and Jeremy Lopez from the University of Puerto Rico. Photo courtesy of BNL

By Daniel Dunaief

It’s been a banner year for ideas and potential products that trap noble gases at Brookhaven National Laboratory. So-named for their full complement of electrons, noble gases tend to be less reactive than other atoms that can add electrons to their outer shells.

While their name sounds grandiose, these gases are anything but, particularly when people inhale the radioactive and prevalent gas radon, which can cause lung cancer or when the decay of uranium into xenon makes a nuclear reactor less efficient.

When he was studying how hydrocarbons react at the active site of zeolite models, Brookhaven National Laboratory’s material scientist Anibal Boscoboinik made an accidental discovery about a decade ago that some nanomaterials, which are incredibly small, trap these gases.

Among several other projects he’s working on, Boscoboinik has since studied these nanocages, learning about the trapping mechanism and making variations of these materials and trapping methods that can be useful for a wide range of applications. 

The Battelle Memorial Institute, which partners with Stony Brook University to form Brookhaven Science Associates and manages nine national labs across the country, named Boscoboinik an “inventor of the year” for his work developing these materials.

Battelle awards an inventor of the year to a researcher from each institution under its management, recognizing efforts that contribute to science or engineering and that can have a positive impact on society.

“It feels really good to be recognized for the work,” said Boscoboinik, who is proud of the many people who made this progress possible directly and indirectly. “It would be amazing if we get to see something that stemmed from an accidental discovery doing very basic fundamental research becoming a real-life application that can benefit society.”

At the same time, three students from minority serving institutions were selected to receive seed grants as a part of MSI (for Minority Serving Institutions) Connect at BNL, in which they seek to commercialize a way to remove radon from the air.

They may work in a business to business model to supply other companies that can incorporate their materials into products.

The students, Jeremy Lopez Flores and Oscar Rivera-Cruz from the University of Puerto Rico and Alexander Bailey from West Virginia State University, will enter phase 2 in the process. The next phase of funding comes from other sources, such as FedTech. Boscoboinik will advise the students as they develop the company and any potential products.

These undergraduate students are looking to remove radon from the air at a concentration of four picocuries per liter, which is equivalent to smoking eight cigarettes a day.

“I am certainly pleased that the value of our collective output was recognized,” said Bailey, who is from St. Albans, West Virginia, in an email. Bailey, a sophomore double majoring in chemistry and math, plans to attend graduate school after completing his undergraduate studies.

Rivera-Cruz, who is a senior majoring in Cellular and Molecular Biology, appreciated the guidance from Boscoboinik, whom he described in an email as an “incredible resource for the team” and suggested that the team was “extremely grateful and lucky” to have Boscoboinik’s support.

In other research

As a staff member at the Center for Functional Nanomaterials, Boscoboinik spends half his time working with scientists from around the world who come to the CFN to conduct experiments and half his time working on his own research.

The process of granting time to use the facilities at BNL is extremely competitive, which means the projects he works on with other scientists are compelling. “While I help them with their research, I get to learn from them,” he said.

Boscoboinik regularly works with the group of Professor Guangwen Zhou from Binghamton University. In recent work, they explored the dynamics of peroxide formation on a copper surface in different environments.

In his own work, Boscoboinik is also interested in trying to help the nuclear energy community.

During the breakdown of radioactive uranium, the process heats up water in a tank, moving a turbine that produces energy.

The breakdown of uranium, however, produces the noble gas xenon, which is a neutron absorber, making reactors less efficient.

Boscoboinik anticipates that any new product that could help the field of nuclear energy by removing xenon could be a decade or more away. “This is a highly regulated industry and changes in design take a very long time,” he explained.

Boscoboinik is also collaborating with researchers from Johns Hopkins University on metal organic frameworks. Some molecules pass through these frameworks more rapidly than others, which could enable researchers to use these frameworks to separate out a heterogeneous collection of molecules.

Additionally, he is developing processes to understand dynamic conditions that affect different types of reactions. At this point, he has been looking at the oxidation of carbon monoxide, which he called the “drosophila” of surface science for its widespread use and versatility, to develop the methodology. In oxidation, carbon monoxide mixes with oxygen to make carbon dioxide.

In his work, Boscoboinik has collaborated with Qin Wu, who deploys artificial intelligence to interpret the data he generates in his experiments.

The long-term plan is to develop complex-enough algorithms that suggest experiments based on the analysis and interpretation of data.

Outside the lab

Boscoboinik is a part of a collaborative effort to combine science and music. “We use music as a way to enable conversations between scientists and the general public” to help make the sometimes complex and jargon-laden world of science more accessible, he said.

In Argentina, research groups have taken famous musicians to the lab to perform concerts while encouraging conversations about science. During the course of their visits, the musicians speak with scientists for the benefit of the public. In prior seasons, the musicians used popular songs to relate to the research the scientists they interview do. Part of the plan is to make new songs related to the research.

Boscoboinik is part of a collaboration between Music for Science, the network of Argentinian scientists abroad, and the Argentinian diplomatic missions, including the embassies and the consulates. At some point in the future he may create a show that relates noble gases and music.

As with his some of his scientific work, the connection between music and research is a developing proof of concept that he hopes has broader appeal over time.

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Minghao Qiu presenting at the American Geophysical Union Conference in San Francisco last year. Photo courtesy of M. Qiu

By Daniel Dunaief

When Minghao Qiu woke up in Beijing on Jan. 12, 2013  during his freshman year in college, he couldn’t believe what he was seeing or, more appropriately, not seeing. The worst air pollution day in the history of the city mostly blocked out the sun, making it appear to be closer to 8 p.m. than a typical morning.

Minghao Qiu

While Qiu’s life path includes numerous contributing factors, that unusual day altered by air pollution had a significant influence on his career.

An Assistant Professor at Stony Brook University, Qiu straddles two departments that encapsulate his scientific and public policy interests. A recent hire who started this fall, Qiu will divide his time equally between the School of Marine and Atmospheric Sciences and the Renaissance School of Medicine’s Program in Public Health.

Qiu studies fundamental questions in atmospheric sciences as they influence human health.

He is part of several new hires who could contribute to the climate solutions center that Stony Brook is building on Governors Island and who could provide research that informs future policy decisions.

Noelle Eckley Selin, who was Qiu’s PhD advisor at the Massachusetts Institute of Technology and is Professor in the Institute for Data, Systems and Society and the Department of Earth, Atmospheric and Planetary Sciences, suggested Qiu is a valuable scientific, policy and educational asset.

“Stony Brook is doing a lot to address climate in a serious way with great research,” Selin said. Qiu joining the institution “could really help out the university’s broader climate efforts and make them more impactful.”

Selin appreciated how Qiu was eager to dive deeper into questions, wanting to ensure that conclusions were valid and asking how to use data to test various ideas.

As a mentor, Qiu has proven inspirational.

“A lot of my current students will go and talk to him and come back to me and say, ‘[Qiu] had five excellent ideas on my project,’” Selin said. “That’s characteristic of how he works. He’s really generous with his time and is always thinking about how to look at problems.”

Policy focus

Using causal inference, machine learning, atmospheric chemistry modeling, and remote sensing, Qiu focuses on environmental and energy policies with a global focus on issues involving air pollution, climate change and energy transitions.

Qiu would like to address how climate change is influencing the air people breathe. Increasing heat waves and droughts cause people to use more energy, often through air conditioning. The energy for the electricity to power temperature controls comes from natural gas, coal, or fossil fuels, which creates a feedback loop that further increases pollution and greenhouse gases.

“Our work tries to quantify this,” Qiu said.

He also analyzes the impact of climate change on wildfires, which affects air quality.

In a research paper published last year, Qiu joined several other scientists to analyze the impact of wildfires on air quality.

The study, published in the journal Nature, found that since at least 2016, wildfire smoke eroded about a quarter of previous decades-long efforts to reduce the concentration of particulates above 2.5 microgram in several states.

Wildfire-driven increases in ambient particulates are unregulated under air pollution laws.

The authors showed that the contribution of wildfires to regional and national air quality trends is likely to grow amid a warming climate.

In his research, Qiu seeks to understand how to use energy and climate policy to address air pollution and greenhouse gases.

“Renewable energy and climate policy in general provides potential benefits,” Qiu said.

He uses publicly available data in his models.

New York pivot

While wildfires have been, and likely will continue to be, an area of focus for his work, Qiu plans to shift his focus to the kind of pollution that is typically more prevalent in New York.

In large urban cities, pollution often comes from a concentration of traffic, as people commute to and from work and drive to the city for entertainment and cultural events.

“We are going to pivot a little bit, especially to factors that are more relevant” to the Empire State, he said.

While climate change is a broad category that affects patterns across the world, air pollution and its impacts are more regional.

“The biggest impact of air pollution happens locally” particularly in terms of health effects, Qiu said.

From Beijing to MIT

Born and raised in Beijing, Qiu began connecting how climate or energy policy influences air pollution at MIT.

“When I started my PhD, there was not much real world data analysis” that linked how much renewable energy helps air quality, Qiu said. “We have historical data to do that, but it’s a lot more complex.”

After he graduated from MIT, Qiu moved to Stanford, where he shifted his focus to climate change.

“There, I got to collaborate more directly with people in the public health domain,” he said, as he focused on wildfires.

Personal choices

Despite studying air pollution and climate change, Qiu does not have HEPA filters in every room and, by his own admission, does not live a particularly green life. He does not have an electric car, although he plans to get one when he needs a new vehicle. He urges people not to sacrifice the living standards to which they are accustomed, which can include eating their preferred foods and traveling to distant points in the world.

Qiu believes there are choices individuals can make to help, but that the kind of decisions necessary to improve the outlook for climate change come from centralized government policy or large enterprises.

“I have great respect for people who change their personal behavior” but he recognizes that “this is not for everyone.”

A resident of Hicksville, Qiu lives with his wife Mingyu Song, who is a software engineer. The couple met when they were in high school.

When he’s not working on climate models, he enjoys playing basketball and, at just under six feet tall, typically plays shooting guard.

As for his research, Qiu does “rigorous scientific research” that draws from historical data.

“I feel a sense of urgency that we would like to get the answers to many of the scientific evidence as quickly as possible to communicate to policy makers,” he said.

He wants his research to be impactful and to help policy makers take “appropriate measures.”

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Assistant Professor Michael Lukey and postdoctoral researcher Yijian 'Evan' Qiu. Photo courtesy of Michael Lukey lab

By Daniel Dunaief

Cancer is a dangerous and wily adversary. Just when researchers think they have come up with a plan to defeat a deadly disease that takes many forms and that attacks different organs, cancer can figure out a way to persist.

Researchers have known that breast cancer uses the amino acid glutamine to power its high energy needs. To their disappointment, when they’ve blocked glutamine or reduced its availability, cancer somehow carries on.

An adaptable foe, cancer has figured out how to find an alternative metabolic pathway that can use the same energy or carbon source when its level gets low.

Cold Spring Harbor Laboratory Assistant Professor Michael Lukey and postdoctoral researcher Yijian “Evan” Qiu have discovered how a form of breast cancer has a back up plan, enabling it to survive despite glutamine deprivation.

“Analysis of tumor samples has revealed that glutamine is often depleted within the tumor microenvironment, so we were interested in understanding how seemingly ‘glutamine addicted’ cancer cells adapt to this challenge,” Lukey explained..

In research published last week in the journal Nature Metabolism, the Cold Spring Harbor Laboratory researchers discovered and quieted a type of breast cancer’s alternate energy source.

This form of breast cancer typically uses glutamine, which is one of the most common amino acids, to power its disease-driven machinery. When Qiu and Lukey blocked the formation of alpha-ketoglutarate, which is a metabolite normally derived from glutamine and then glutamate, they significantly repressed the growth of tumors in animal models of the disease.

Cancer cells turn on this alternative pathway that can catalyze glutamate into alpha-ketoglutarate.

“Cancer is always evolving and adapting,” said Qiu. “We need to stay ahead as scientists.”

The results of this research suggest a possible approach to treating cancer, depriving the disease of ingredients it needs to feed the kind of runaway growth that threatens human health. Limiting key ingredients could come from applying specific inhibitors, extracellular enzymes or antimetabolites.

Their work could have implications and applications in other forms of cancer.

The time between observing a promising result in the lab and a new therapy typically takes years. In this case, however, treatments that use inhibitors of glutamine have been well-tolerated in animals and humans. Qiu also did not observe any side effects in animal models in his study, which could potentially accelerate the process of creating a new therapy.

To be sure, developing treatments that cut off cancer’s primary and back up energy supply may not be sufficient, as cancer may have other metabolic moves up its figurative sleeves.

“Cancer cells typically exhibit metabolic flexibility, such that they can adapt to a variety of metabolic stresses,” said Lukey. “It remains to be seen if they can ultimately adapt to long-term blockade of the axis that we identified, but so far we have not seen this happen.”

A search for the back up plan

Qiu and Lukey speculated at the beginning of Qiu’s Cold Spring Harbor Laboratory experience in August of 2020 that cancer cells likely had another energy option.

“The fact that cancer cells that should be dependent on glutamine adapted in glutamine-free media in weeks made me believe that the cancer cells must have such a plan B,” Qiu explained.

To figure out why glutamine inhibitors weren’t shrinking tumors in animal models or humans, Qiu removed glutamine from cancer cells, causing over 99.9 percent of the cells to die. A few, however, survived and started proliferating in weeks.

Qiu used RNA-seq analysis to compare the parental and adaptive cells and found that the cells that are glutamine independent upregulated a serine synthesis pathway. These adaptive cells used PSAT1, or phosphoserine aminotransferase 1, to produce alpha-ketoglutarate.

As for human patients, the scientists don’t know what kind of stress is activating a Plan B for metabolism, which they are currently exploring.

A ‘passion’ for the field

Lukey and Qiu submitted the paper for publication about a year ago. After conducting additional experiments to verify their findings, including confirming that some of the metabolite entered the cell, these researchers received word that Nature Metabolism would publish the research.

Lukey appreciated Qiu’s passion for science and suggested his postdoctoral researcher combines his technical proficiency with good ideas to generate promising results.

Lukey suggested that researchers in the field have developed a growing consensus that effective strategies to target tumor metabolism will likely involve combination therapies that disrupt a critical metabolic pathway in cancer cells and simultaneously block the adaptive response to that intervention.

From China to Buffalo to LI

Born in Yiyang, Hunan province in China, Qiu moved several times during his childhood, to Sanya, Hainan and Changsha, Hunan.

Qiu knew he wanted to be a scientist when he was young. He enjoyed watching ants, observing the types of food they carried with them. He earned his PhD from Clemson University in South Carolina, where he built his knowledge about metabolism-related research and benefited from the guidance of his mentor James Morris.

Qiu and his wife Peipei Wu, who is a postdoctoral researcher in Chris Hammell’s lab and focuses on epigenetic gene regulation in skin stem cell development, live in Oyster Bay.

The scientific couple don’t have much overlap in their work, but they do get “lots of inspiration from each other, during our discussion outside of work,” said Qiu.

Qiu enjoys fishing and caught and ate a catfish from the Hudson River. He appreciates drawing scenery, animals and a range of other visuals, including cartoon characters. He designed T-shirts for his department during his PhD.

As for his research, Qiu hopes the metabolism finding may lead to new treatments for cancer. He also suggested that this approach may help with other cancers.

“What I have found in my study can be applied for many other cancer types that are also dependent on glutamine, such as lung and kidney cancer,” he said. He also can not rule out “the possibility that the treatment may help reduce metastasis.”

An important topic for follow up studies, Lukey suggested, is to address how the metabolic interventions Qiu used might affect immune cells and the anticancer immune response.

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Pixabay photo

By Daniel Dunaief

Benjamin Luft. Photo courtesy of SBU

They bother us, particularly in the summer, but they don’t need us.

The 23 species of Borrelia bacteria, which cause Lyme disease, have been around for millions of years, dating back to when the continents were all linked together like pieces of a puzzle in Pangea. The bacteria likely infected early mammals in those days.

In a recent paper in the journal mBIO, researchers from over 12 institutions put together the genetic sequence of these bacteria, which include 47 strains.

The scope of the work “was enormous and we were lucky” to have so many dedicated investigators, said Ben Luft, Edmund D. Pellegrino Professor of Medicine at the Renaissance School of Medicine at Stony Brook University, including lead senior author Weigang Qiu, Professor of Biology at Hunter College of the City University of New York.

The work, which took about a decade to complete, could provide a valuable resource to researchers and doctors today and in the future. The genetic information could lead to advances in diagnostics, treatment and prevention of Lyme disease.

Scientist could use the database to compare the genomes of different species and variations that cause different symptoms to help diagnose the likely severity of an infection as well as to search for specific pathways that lead to the virulence of an infection.

Some infections can lead to fever, headaches, fatigue and a skin rash. Starting with the bite of an intermediate host such as a tick, these infections, when left untreated, can lead to problems in the joints, heart, and nervous system.

The number of new cases of Lyme disease each year has been climbing, reaching close to 500,000 per year in the United States.

Researchers added that creating a genetic catalog of the different bacterial species can also help current and future scientists and doctors manage new threats from strains of bacteria that move into new areas amid climate change.

These species haven’t interacted with each other in the past, but climate change may create opportunities for bacteria to create recombinant genes, presenting new threats to human health.

“You may start seeing things that you didn’t see before,” said Luft. “We don’t know what’s going to happen” amid climate change. “There might be new forms” of Lyme disease.

The challenge with Lyme is not necessarily what happens in 2024, but how it might change in 20 years, when organisms develop a new pathogenicity.

Lyme on four continents

An international team of researchers sequenced the genomes of many species of Borrelia, the cause of Lyme disease. By comparing these genomes, the researchers reconstructed the evolutionary history of Lyme disease bacteria. The map shows many of the global regions where the team sequenced a species. Borrelia burgdorferi, the most common cause of disease, is indicated in red. Other species are indicated by different colors. Image created by Saymon Akther

In addition to generating a database of the Lyme disease bacterial genome, the researchers wanted to develop an understanding of its phylogenetic history.

“The goal really was to show how genetically diverse Borelia is throughout the world,” said Luft.

The researchers gathered genetic data from this bacteria, which was sampled in Europe, Asia, and North and South America.

By collecting the genetic information in each of these locations, the scientists were able to recreate the history of a bacteria that’s lasted considerably longer than many other organisms that have since become extinct.

“The genetic make up (genes and plasmids) hasn’t changed very much since the last common ancestor on Pangea (otherwise we would see different sets of genes and plasmids from different continents),” explained Qiu.

An extensive collaboration

Qiu and Luft were grateful for all the work scientists around the world did to contribute to this study.

On Long Island, Lyme disease is transmitted mainly by the bite of an infected deer tick, also is known as the black-legged tick.

The team of Claire Fraser and Emmanuel Mongodin at the University of Maryland School of Medicine and Richard G. Morgan of New England Biolabs helped use next generation sequencing to determine the bacterial genome.

Indeed, Fraser was the first to map the complete genetic code of a free-living organisms. She worked with the Haemophilus influenza, which causes respiratory infections and meningitis in infants and young children, according to the University of Maryland School of Medicine.

Qiu, who earned his Phd from Stony Brook in 1999, suggested that the effort required regular, ongoing work. He supervised Dr. Saymon Akther for her thesis work, which was the basis of the paper. He also performed additional evolutionary analysis.

“For the past two years, we have been having weekly meetings on zoom,” said Qiu. “It’s a big relief” that the researchers published the study and shared the information with the scientific community.

Qiu credited Luft with being a consistent coordinator of the sequencing effort and diversity study for over 20 years.

The next steps

At this point, Luft and his colleagues are eager to share the information with the broader scientific community.

The researchers hope experts in artificial intelligence, bioinformatics and computer programming can use the data to understand more about the genome and develop potential therapeutic targets.

Luft is eager to see “how smart people take advantage of a decade’s worth of work that has been very carefully done, to move it all forward,” he said. “We have certain ideas that we are doing” to fill in the gaps.

Qiu has some existing grants he’s using to work on diagnostics and vaccine development.

Qiu, along with chemistry-department colleague Brian Zeglis, and Lyme diagnostic/ vaccine researcher Maria Gomes-Solecki, has a joint NIH/ NIAID grant to develop a novel PET-based technology to detect Lyme pathogens in vivo. They have also proposed a new Lyme vaccine design strategy.

Additional sequencing of the variable plasmid, which is not a part of the chromosomal DNA but can replicate independently, would continue to help determine what genetic codes contribute to the level of virulence for each strain or species.

“That’s like the last mile for the communication network,” said Qiu. The challenges include annotating the genomes, providing comparative analysis and using informatics development to share the genome variability with the research community.

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From left, Xianghui Xiao, Yang Yang, and Qun Liu Photo by David Rahner/BNL
From left, Yang Yang, Qun Liu and Xianghui Xiao. Photo by David Rahner/BNL
From left, Qun Liu, Yang Yang, and Xianghui Xiao. Photo by David Rahner/BNL
From left, Xianghui Xiao, Qun Liu and Yang Yang. Photo by David Rahner/BNL

By Daniel Dunaief

Superman’s x-ray and heat vision illustrate an important problem.  On the one hand, the x-ray vision comes in handy if Superman is looking outside, say, at a bank and can see thieves dressed like the Hamburgler as they try to steal from a vault. On the other hand, Superman has heat vision, which he uses in battles to blow up concrete blocks or tear open a hole in a wall.

But, aside from a few realities getting in the way, the struggle scientists using x-rays to see inside cells contend with tracks with these two abilities.

Researchers would ideally like to use x-rays to see the inner workings of a cell. X-rays can and do act like Superman’s heat vision, causing damage or destroying the cells they are trying to study.

Recently, scientists at Brookhaven National Laboratory, however, figured out how to protect and preserve cells, providing an opportunity to study them without causing damage.

Not only that, but, to extend the fictional metaphor, they used the equivalent of Wonder Twin Powers, combining the structural three-dimensional picture one beamline at the National Synchrotron Lightsource II can produce with the two-dimensional chemical image from another.

After three years of hard work, researchers including Qun Liu, structural biologist; Yang Yang, associate physicist; and Xianghui Xiao, FXI lead beamline scientist, were able to use both beamlines to create a multimodal picture of a cell on different scales and with different information.

“Each beamline can create a full picture, but providing only partial information (structure or chemicals),” Liu said. “The correlative imaging for the same cell using two different beamlines provides a more comprehensive” image.

The key to this proof of concept, Liu explained, was in developing a multi-step process to study the cells.

“The novelty is how we prepared the samples,” said Liu. “We can take the sample from one beamline, move it to a second one, and can collect data from the same orientation. Before this, it was not easy” to put together that kind of information.

In a paper published in the journal Nature Communications Biology, the scientists detailed the cell preparation technique and showcased the results.

The potential application of this technique extends in numerous directions, from finding the way new pathogens attack cells, to understanding the location and site of action of pharmacological agents, to understanding the progression of disease, among other applications.

“Our technique combines both X-ray fluorescence and X-ray nano-tomography so we can study the entire cell for both the elements and the structure correlatively,” Yang explained.

Supported by the Department of Energy Biopreparedness Initiative, the scientists are doing basic research and developing techniques and protocols and procedures in preparation for the next pandemic. They have 10 projects covering different pathogens and aspects. Liu is the principal investigator leading one of them. 

To be sure, at this point, the technique for preserving and studying cells with these beamlines is in an early stage and is not available to labs, doctors, or hospitals on a routine basis to test biological samples.

Nonetheless, the approach at BNL offers an important potential direction for clinical and fundamental benefits. Clinically, it can help with disease diagnosis, while it can also be used to study stresses of cells and tissues under metal deficiency or toxicity. Many cancers include a malfunction in the homeostasis, including zinc, copper and iron.

Fixing and re-fixing

The process of preparing the samples required three steps.

The researchers started with a chemical fixation with paraformaldehyde to preserve the structure of the cell. They then used a robot that rapidly froze the sample by plunging it into liquid ethane and then transferring it to liquid nitrogen.

They freeze-dried the cells to turn the water into ice that is not crystallized. As a part of that process, they left the cells in a controlled vacuum to turn the ice slowly into gas. Removing water is key because the liquid would otherwise be too mobile for x-rays to measure anything reliably. After absorbing the x-rays, the liquid would heat up and further deform the cells.

The preparation work takes one to two days.

“If you fail in any of the steps, you have to start all over again,” said Yang.

Zihan Lin, who is a postdoctoral researcher in Liu’s lab and the first author on the paper, spent more than a year polishing and preparing the technique.

“We believe the cells were preserved [near] their close-to-native status,” said Yang.

They used an X-ray computed tomography (XCT) beamline, which provides a three-dimensional view of the structure of the cell. They also placed the samples in an X-ray fluorescence beamline (XRF), which provided a two-dimensional view of the same cells.

In the XRF beamline, scientists can find where trace elements are located inside a cell.

Liu is collaborating with researchers at other labs to understand the molecular interactions between sorghum, an important grain crop, and the fungus Colletotrichum sublineola, which can damage the leaves of the plant.

The DOE funded project is a collaboration between BNL and three other national laboratories.

Liu is grateful for the help and support he and the team received from the staff working at both beamlines, as well as from the biology department, NSLS-II, BNL, and DOE. The imaging may help create bioenergy crops with more biomass and less disease-caused yield loss, he suggested.

Future work

Current and ongoing work is focused on the potential physiological states of the cell, addressing questions such as why metals are going to specific areas.

Yang is the science lead for a team developing the Quantitative Cellular Tomography beamline at the NSLS-II. Within five years, this beamline will provide nanoscale resolution of frozen cells without requiring chemical fixation.

This beamline, which will have a light epi-fluorescence microscope, will add more detail about sub-cellular structure and will not require frozen cells to have chemical fixation.

While the proof of concept approach with these beamlines is still relatively new, Yang said she has received feedback from scientists interested in its potential.

“We have quite a few people from biology departments that are interested in this technique” to study biomass related structures, she said.

A future research direction could also involve seeing living cells. The resolution would be compromised, as the X-rays would induce changes that make it hard to separate biological processes from artifacts.

“This could be a very good research direction,” Liu added.

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Hiro Furukawa Photo courtesy of CSHL

By Daniel Dunaief

Following a relentless drive to succeed, scientists have a great deal in common with athletes.

In addition to putting in long hours and dedicating considerable energy to improving their results, these talented professionals also enjoy moments of success — large and small — as opportunities to appreciate the victories and then build to greater challenges.

And so it is for Hiro Furukawa, a Professor at Cold Spring Harbor Laboratory.

Hiro Furukawa. Photo courtesy of JMSA

Working with a team of scientists including at Emory University, Furukawa recently published a paper in the prestigious journal Nature in which he demonstrated the long-sought structural process that leads to the opening of an important channel in the brain, called the NMDAR receptor.

When this cellular channel doesn’t function correctly, it can lead to numerous diseases, including Alzheimer’s and depression. Understanding the structural details of this channel could, at some point in future research, lead to breakthrough treatments.

“Each moment of discovery is exciting and priceless,” Furukawa explained. “When I finally see what I have sought for many years — in this case, the mechanism of NMDAR channel opening — it fills me with immense euphoria, followed by a sense of satisfaction.”

That sounds like the kind of mountaintop moment that star athletes whose achievements people applaud share once they’ve reached a long-desire milestone, like, perhaps, winning a gold medal in the Olympics.

The thirst for more for Furukawa, as it is for those with a passion for success in other fields beyond science and athletics, is unquenchable and unrelenting.

“This feeling is fleeting,” he added. “Within a few hours, a flurry of new questions arising from the discovery begins to occupy my mind.”

Indeed, Furukawa suggested that he expects that many other scientists share this experience.

Forming a winning team

Furukawa and Stephen Traynelis, Professor and Director in the Department of Pharmacology and Chemical Biology at Emory University School of Medicine in Atlanta, started to work together on a series of modulators for the NMDAR protein about eight years ago.

Hiro Furukawa. Photo courtesy of JMSA

This particular protein binds to the neurotransmitter glutamate and to glycine, which is another compound. Once bound to both, the channel, as if responding to the correct combination in a garage door, opens, creating electrical signals that contribute to brain functions.

To study the way the binding of these molecules opened the channel, the researchers needed to figure out how to keep the receptor in the open position.

That’s where a combination of work in the labs of Traynelis and Dennis Liotta, also a Professor at Emory, came in. Liotta’s lab made over 400 analogs that Traynelis ran in his lab.

Liotta created a compound called EU-1622-A, which is now known as EU-1622-240, that upregulates NMDAR activity, Furukawa explained.

“We used cryo-EM [electron microscopy] to capture the NMDAR structure with the compound, validated its conformation through electrophysiology and elucidated the activation mechanism,” he said.

Incorporating EU-1622-240 along with glycine and glutamate into the GluN1-2B NMDAR sample, which is a specific subtype and is the easiest to work with, enabled a visualization of the open channel.

Furukawa described the compound Traynelis created at Emory as the “key factor in capturing the open channel conformation.”

Determining the structure of a functioning protein can provide clues about how to alter those that may be contributing to the onset or progression of a disease.

To be sure, Furukawa recognizes the work as one step in what’s likely to involve an extensive research journey.

“We still have a long way to go, but we’ve made progress,” Furukawa said. “In this study, a compound bound to NMDAR gave us a clue on how to control the frequency of ion channel openings. Both hyperactive and hypoactive functions of NMDAR ion channels have been implicated in Alzheimer’s disease, so being able to regulate NMDAR activity would be significant.”

Furukawa can’t say for sure if this compound could alleviate the symptoms of certain diseases, but it serves as a new series of potentially clinically relevant options to test.

The researchers are developing a method to purify NMDAR proteins from animal tissues. Once they accomplish that task, they should be able to isolate NMDAR from Alzheimer’s brains to compare them to a normally functioning protein.

Furukawa suggested that it’s probable that specific NMDAR conformations are stabilized to different extents in various diseases compared to normal brains.

The researchers have not yet presented this work at meetings. First author Tsung-Han Chou, who is a postdoctoral fellow in Furukawa’s lab, plans to present the work at upcoming conferences, such as the Biophysical Society Meeting.

The review process for the research proceeded quickly, as the team submitted the paper in February of this year. 

Next steps

As for what’s next, Furukawa suggested that the team planned to solidify their findings.

“We must determine if the channel opening mechanism applies to other types of NMDARs,” he said. “Although we observed that EU1622-A compound binds to NMDAR, its structure was not sufficient resolved.”

To facilitate the re-design of EU1622-240, the scientists will need to improve the cryo-EM map resolution.

Traynelis, meanwhile, said that he and Liotta are synthesizing new modulators in this class and related classes and are working on mechanisms of action for this series at all NMDA receptors as well as actions in neuronal systems.

“We have a robust synthetic program with our collaborator [Liotta], whose laboratory is synthesizing many new modulators in this class and related classes,” Traynelis explained.

Traynelis added that his goal is to “develop new medicines to address unmet clinical needs. We want to find new and effective therapeutic treatments that help patients.”

The Emory professor is excited about the “potential development of positive NMDA receptor allosteric modulators that could enhance NMDA receptor function.”

Broader perspective

Furukawa, who lives in Cold Spring Harbor and whose sons Ryoma, 16 and Rin, 13, attend senior and junior high school, respectively, was interested in international politics and economics when he attended Tufts University as an undergraduate.

These non-science topics provide additional perspective that enrich his life.

“I remain very interested in understanding history and the reasons behind current events in Europe, the Middle East, and the U.S.,” he said. “This endeavor is far more challenging than decoding NMDAR structures and functions.”

As for his collaborations, Furukawa suggested that the findings from this research inspire him to continue to search for more answers and greater scientific achievements.

“We will continue to unravel these mysteries in future studies,” Furukawa said. “The best is yet to come.”

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Jesús Pérez Ríos at the New York Public Library in 2023. Photo by Anne Martinez Hoth

By Daniel Dunaief

When he’s looking to relax, he builds and rebuilds some of the LEGO sets in his house in East Setauket. One of the things he likes best about being on Long Island, where he’s lived for the last two years, is that he can be alone to think and develop new ideas.

To hear Jesús Pérez Ríos describe himself, he is “just a kid having fun.” An Assistant Professor in the Department of Physics and Astronomy at Stony Brook University, Pérez Ríos enjoys bridging scientific knowledge, applying his physics background to questions, problems and puzzles in other fields.

Recently, the Stony Brook physicist, who is also an affiliated faculty member at the Institute for Advanced Computational Sciences, collaborated with Stefan Willitsch, Professor in the Department of Chemistry at the University of Basel in Switzerland, to explore the forces that might be inhibiting the reaction between hydroquinone and neon.

In a paper published in the journal Nature Chemistry, Pérez Ríos, Willitsch and members of their teams described in detail several potentially opposing forces that affect the reactivity in the experiment.

Jesús Pérez Ríos at the Barnes and Noble in New York City in 2022 with Lego batman. Photo by Anne Martinez Hoth

“I started collaborating with [Willitsch] because he had accurate results, and it was hard to explain the observations,” said Pérez Ríos. “We had a hypothesis but needed to develop models to test it.”

Pérez Ríos described two interactions in detail. One is due to the long range atom-molecule interactions and the other comes from internal rotational dynamics.

With the experiments in Willitsch’s lab and the theory developed by Pérez Ríos and his colleagues, they highlighted the role of rotational quantum states in a hydroquinone-neon chemi-ionization reaction. A similar mechanism and approach may be suitable for other reactions as well, such as molecular ion-atom reactions.

These molecules are akin to puzzle pieces coming together. Instead of a two-dimensional alignment where pieces find each other and lock together in their complementary parts, these pieces also have rotational effects that can cause a misalignment.

“That is one of our key findings,” Pérez Ríos explained. “It is like the shape of the puzzle piece evolves depending on the molecule’s collision energy and internal state.”

The results presented in the scientific paper are in the realm of fundamental research, with no “immediate practical application in synthesis or catalysis,” explained Willitsch.

Nonetheless, the insights gained through this collaboration “leads to a better understanding of the relevant reaction mechanisms and thus enables a more efficient design of future chemical reactions.”

At this point, Willitsch has presented the work at several conferences, where he has found a receptive audience and expects it will “foreseeably stimulate further work in the field.”

A search for answers

Pérez Ríos explained that Willitsch had some possible explanations for his data, but he did not have a mathematical model to test his hypothesis.

Jesus Pérez Ríos in Port Jefferson in 2022. Photo by Anne Martinez Hoth

“He mentioned the experimental details to me and we discussed the data,” said Pérez Ríos, who has known Willitsch for about 12 years. “Then, we started to do calculations from our side.”

Pérez Ríos has a team of 7 PhD students, one postdoctoral researcher, one Master’s candidate and three undergraduates.

Members of his lab work on simulations of physical phenomena regarding atomic and molecular processes. Additionally, they work on machine learning applications to atomic and molecular physics, exploring ways to teach a machine classical mechanics or quantum mechanics through chemical reactions.

In the reaction he was studying, Willitsch was working with hydroquinone, which has two conformers. These are two molecules with the same chemical formula that have two different structures.

Willitsch was able to select for a particular type of conformer in its reaction with neon.

Pérez Ríos considered many possibilities and models, none of which was fully satisfactory. 

An insight at a conference

When he was at an Air Force Office of Scientific Research review program in Washington DC, Pérez Ríos was considering the problem from numerous perspectives.

He had tried many possibilities, but none were convincing. He needed something new.

“I had the physical picture of the model during a conference: in a break, I started to work on the code, and, in a few hours, I had something ready to get some very preliminary results,” Pérez Ríos recalled.

Willitsch enthusiastically embraced the preliminary results and the group decided to make it more realistic, developing the version of the code to explain Willitsch’s data.

The dynamics simulations were ready in a month, with extra checks conducted for another month to ensure everything was correct. The joint effort took over a year and a half to produce a fulfilling explanation.

Many of Pérez Ríos’s collaborators come from different disciplines, which gives the Stony Brook Assistant Professor an opportunity to learn about a variety of topics. He has worked with particle, atmospheric, atomic and plasma physicists and spectroscopists and chemists.

Pérez Ríos suggested that a physics perspective can help in a variety of settings, even including household problems and daily challenges.

Echoing a theme from the main character Jason Nesmith (played by Tim Allen) in the movie Galaxy Quest, Pérez Ríos said, “you can never surrender.”

 Pérez Ríos added that you “are the only one putting limits on yourself. However, you need to pick the battles worth fighting, which is a very difficult matter.”

More American than Americans

A resident of East Setauket where he lives with his wife Anne Martinez Hoth, Pérez Ríos grew up in Guardamar del Segura, a small town in Alicante, Spain.

The son of restaurant owners,  Pérez Ríos said he didn’t travel during summers to the beach, the way many of his friends did.

When he wasn’t helping in the restaurant, he used his free time to learn about math, zoology, genetics, chemistry and physics.

He enjoys living on Long Island and in the United States. His wife suggests he is “more American than the Americans” because he likes the American job philosophy and the freedom.

At Stony Brook, Pérez Ríos teaches quantum mechanics to undergrads, some of whom say he is strict.

“I have a very particular approach focusing on learning to think rather than knowing how to solve a problem,” he said.

As a research partner, Pérez Ríos is an unusual find, bringing constructive and valuable insights to discussions.

“I have rarely collaborated with someone so energetic and broadly interested” as Pérez Ríos, Willitsch said. “I particularly value his pragmatic approach and that he is not afraid to leave his comfort zone to delve into totally new classes of problems, which have not been tackled before either by himself or others.”

Willitsch added that few scientists have the same broad knowledge of physics and chemistry, which is “vital to push this interdisciplinary frontier.”

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Qingtao Sun, postdoctoral researcher at CSHL, presents a poster of the cachexia research taken at a Society for Neuroscience meeting in 2023 in Washington, DC. Photo by Dr. Wenqiang Zheng

By Daniel Dunaief

Cancer acts as a thief, robbing people of time, energy, and quality of life. In the end, cancer can trigger the painful wasting condition known as cachexia, in which a beloved relative, friend or neighbor loses far too much weight, leaving them in an emaciated, weakened condition.

A team of researchers at Cold Spring Harbor Laboratory has been studying various triggers and mechanisms involved in cachexia, hoping to find the signals that enable this process.

Recently, CSHL scientists collaborated on a discovery published in the journal Nature Communications that connected a molecule called interleukin-6, or IL-6, to the area postrema in the brain, triggering cachexia.

By deleting the receptors in this part of the brain for IL-6, “we can prevent animals from developing cachexia,” said Qingtao Sun, a postdoctoral researcher in the laboratory of Professor Bo Li.

Through additional experiments, scientists hope to build on this discovery to develop new therapeutic treatments when doctors have no current remedy for a condition that is often the cause of death for people who develop cancer.

To be sure, the promising research results at this point have been in an animal model. Any new treatment for people would not only require additional research, but would also need to minimize the potential side effects of reducing IL-6.

Like so many other molecules in the body, IL-6 plays an important role in a healthy system, promoting anti- and pro-inflammatory responses among immune cells, which can help fight off infections and even prevent cancer.

“Our study suggests we need to specifically target IL-6 or its receptors only in the area prostrema,” explained Li in an email.

Tobias Janowitz, Associate Professor at CSHL and a collaborator on this project, recognized that balancing therapeutic effects with potential side effects is a “big challenge in general and also is here.”

Additionally, Li added that it is possible that the progression of cachexia could involve other mechanistic steps in humans, which could mean reducing IL-6 alone might not be sufficient to slow or stop this process.

“Cachexia is the consequence of multi-organ interactions and progressive changes, so the underlying mechanisms have to be multifactorial, too,” Miriam Ferrer Gonzalez, a co-first author and former PhD student in Janowitz’s lab, explained in an email.

Nonetheless, this research result offers a promising potential target to develop future stand alone or cocktail treatments.

The power of collaborations

Working in a neuroscience lab, Sun explained that this discovery depended on several collaborations throughout Cold Spring Harbor Laboratory. 

“This progress wouldn’t be possible if it’s only done in our own lab,” said Sun. “We are a neuroscience lab. Before this study, we mainly focused on how the brain works. We have no experience in studying cachexia.”

This paper is the first in Li’s lab that studied cachexia. Before Li’s postdoc started this project, Sun had focused on how the brain works and had no experience with cachexia.

When Sun first joined Li’s lab three years ago, Li asked his postdoctoral researcher to conduct an experiment to see whether circulating IL-6 could enter the brain and, if so where.

Sun discovered that it could only enter one area, which took Li’s research “in an exciting direction,” Li said.

CSHL Collaborators included Janowitz, Ferrer Gonzalez, Associate Professor Jessica Tolkhun, and Cancer Center Director David Tuveson and former CSHL Professor and current Principal Investigator in Neurobiology at Duke University School of Medicine Z. Josh Huang.

Tollkuhn’s lab provided the genetic tool to help delete the IL-6 receptor.

The combination of expertise is “what made this collaboration a success,” Ferrer Gonzalez, who is now Program Manager for the Weill Cornell Medicine partnership with the Parker Institute for Cancer Immunotherapy, explained in an email.

Tuveson added that pancreatic cancer is often accompanied by severe cachexia.

“Identifying a specific area in the brain that participates in sensing IL-6 levels is fascinating as it suggests new ways to understand physiological responses to elevated inflammation and to intervene to blunt this response,” Tuveson explained. “Work in the field supports the concept that slowing or reversing cachexia would improve the fitness of cancer patients to thereby improve the quality and quantity of life and enable therapeutic interventions to proceed.”

Tuveson described his lab’s role as “modest” in promoting this research program by providing cancer model systems and advising senior authors Li and Janowitz.

Co-leading an effort to develop new treatments for cachexia that received a $25 million grant from the Cancer Grand Challenge, Janowitz helped Sun understand the processes involved in the wasting disease. 

Connecting the tumor biology to the brain is an “important step” for cachexia research, Janowitz added. He believes this step is likely not the only causative process for cachexia.

Cutting the signal

After discovering that IL-6 affected the brain in the area postrema, Sun sought to determine its relevance in the context of cachexia.

After he deleted receptors for this molecule, the survival period for the test animals was double that for those who had interleukin 6 receptors in this part of the brain. Some of the test animals still died of cachexia, which Sun suggested may be due to technical issues. The virus they used may not have affected enough neurons in the area postrema.

In the Nature Communications research, Sun studied cachexia for colon cancer, lung cancer and pancreatic cancer.

Sun expects that he will look at cancer models for other types of the disease as well.

“In the future, we will probably focus on different types” of cancer, he added.

Long journey

Born and raised in Henan province in the town of Weihui, China, Sun currently lives in Syosset. When he’s not in the lab, he enjoyed playing basketball and fishing for flounder.

When he was growing up, he showed a particular interest in science.

As for the next steps in the research, Sun is collaborating with other labs to develop new strategies to treat cancer cachexia.

He is eager to contribute to efforts that will lead to future remedies for cachexia.

“We are trying to develop some therapeutic treatment,” Sun said.

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