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Power of 3

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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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Mario Shields Photo by David Cardona-Jimenez

By Daniel Dunaief

Friend or foe? The question isn’t as easy in the world of molecular biology as it might be after captains pick players for a team.

An important biomolecule in one context could trigger the growth or spread of cancer, while in another system or organ, that same signal might suppress or stop the development or growth of a disease that can threaten people’s health.

So it is for G-proteins, which, in some tumors, serve as tumorigenic signaling hubs that participate in invasion and metastasis and promote inflammation and immune evasion.

In tumors “there was this notion that it works in a certain way, driving tumor development and progression,” said Mario Shields, Associate Professor of Research Pathology at Stony Brook University. “We had that original hypothesis when we investigated it in pancreatic cancer. We found that it’s the opposite.”

Indeed, when the specific proteins he studies, called G alpha 13, are absent, mouse models develop well-differentiated tumors that reduce their survival.

“My research now is to understand why it’s playing the opposite role that we initially expected,” Shields, who joined Stony Brook in July after six years at Northwestern University.

Having worked at Cold Spring Harbor Laboratory in the lab of Mikala Egeblad from 2012 to 2018, Shields is returning to the Long Island area with a focus on defeating a problematic type of cancer that steals precious time from people and robs families of important members.

“I have come to appreciate the dire situation of people who are diagnosed with pancreatic cancer,” Shields said. “We need to figure out how to lower the curve.”

A recipient of the National Cancer Institute’s Moonshot Award, Shields is one of the first 11 Cancer Moonshot Scholars who received a total of $5.4 million.

The program, which was launched by the Biden administration in the summer of 2023, seeks to advance cancer science while diversifying the pool of early-stage researchers and approaches to research that NCI funds.

The goal of the program is to inspire and support scientists from diverse backgrounds, including those from underrepresented groups in the biomedical sciences.

The NCI award, which Shields brings with him to Stony Brook, will support his efforts.

Egeblad, who is now Bloomberg Distinguished Professor of Tumor Microenvironment, has stayed in contact with Shields since he left her group. The work he’s doing is “very important” in understanding the “basic mechanism of pancreatic cancer progression” as he has been “very successful in making discoveries and raising funds for his research.”

Egeblad appreciates his contribution to her lab. Shields “was responsible for establishing our research program in pancreatic cancer,” she explained. “Before he joined my lab, I had only worked on breast cancer and [Shields] established the various models to also study pancreatic cancer — models that we are still using.”

Building on CSHL work

At CSHL, Shields worked in Egeblad’s lab and received advice and oversight from David Tuveson, Cancer Center Director at CSHL, who developed the mouse model Shields uses.

Shields has been using human and mouse cell lines to interrogate the mechanism of action of these G proteins in suppressing cancer. 

At Stony Brook, he plans to use patient samples to develop patient-derived tumor specimens.

The major hub of what Shields is studying is the mTOR pathway, which stands for mammalian/ mechanistic target of rapamycin. First isolated in a bacteria on Easter Island in the middle of the 20th century, rapamycin is an immunosuppressant drug.

Any defects that activate the mTOR pathway can lead to the growth and development of cancer.

A developing field

Shields explained that the G protein he is studying, G alpha 13, is a “niche” area right now, with few other labs pursuing the same mechanistic pathway. The G proteins are of more interest to molecular pharmacology and drug design.

In his studies, Shields hopes to use the information on the response to changes in the protein to predict how patients respond to therapy that inhibits the mTOR pathway.

Specifically, he is exploring how alterations in the microenvironment can cause the tumor to progress in pancreatic cancer.

Shields has found some “interesting dependencies” in the mechanism he’s studying. In the first year of work at Stony Brook, he would like to figure out how Ga13 regulates mTOR signaling, as the current context dependency is vague.

The gene that codes for this protein is not heavily mutated. Shields anticipates that a threshold level of the protein may be responsible for conveying its benefit in suppressing cancer, rather than a specific mutational change.

He is eager to explore whether nutrient availability plays a role in cancer progression through the reduction in this G protein. He has exploring that in vitro and is curious how that will translate at the organismal level.

Returning to Long Island

Shields had recently been Research Associate Professor in the Department of Medicine at the Feinberg School of Medicine at Northwestern University.

Having worked at Cold Spring Harbor Laboratory, Shields felt comfortable moving back to the Long Island area.

“Stony Brook is a good place to do research,” said Shields.

Additionally, Shields was impressed with the number of people who had presented their research from Pathology Chair Kenneth Shroyer’s lab at a conference.

“Further discussions [with Shroyer] indicated we have areas of common interest in terms of pancreatic cancer,” Shields added.

Shields appreciates the greenness of Long Island. When he worked at CSHL, he enjoyed walking on trails and enjoyed the variety of fall colors.

Shields brought one person with him from Northwestern and plans to have a lab of about six people.

As for running his lab, Shields plans to “be patient” and to “see where people are coming from and what they are capable of” as he takes on the role of mentor for members of his lab at Stony Brook.

Shields hopes to inspire and encourage under represented groups to pursue careers in science, technology, engineering and math.

Egeblad suggested that Shields is warm and calm, which “helps those entering the field really take to his instruction.” She added she believes he is an inspiration to many young scientists.

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Simon Birrer Photo by Andrea Hoffmann

By Daniel Dunaief

When he was young, Simon Birrer asked his parents for a telescope because he wanted to look at objects on mountains and hills.

Simon Birrer.  Photo Studio, Mall of Switzerland

While he was passionate about science and good at math, Birrer didn’t know at the time he’d set his sights much further away than nearby hills or mountains in his professional career.

An Assistant Professor in the department of Astronomy and Physics at Stony Brook University, Birrer uses telescopes that generate data from much further away than nearby hills as he studies the way light from distant galaxies bends through a process called gravitational lensing. He also works to refine a measure of the expansion of the universe.

“All matter (including stars in galaxies) are causing the bending of light,” Birrer explained in an email. “From our images, we can infer that a significant fraction of the lensing has to come from dark (or more accurately: transparent) matter.”

Dark matter describes how a substance of matter that does not interact with any known matter component through a collision or pressure or absorption of light is transparent.

While they can’t see this matter through various types of telescopes, cosmologists like Birrer know it’s there because when it gets massive enough, it creates what Albert Einstein predicted in his theory of relativity, altering spacetime. Dark matter is effectively interacting with visible matter only gravitationally.

Every massive object causes a gravitational effect, Birrer suggested.

When a single concentration of matter occurs, the light of a distant galaxy can produce numerous images of the same object.

Scientists take several approaches to delens the data. They rely on computers to perform ray-tracing simulations to compare predictions with the astronomical images.

The degree of lensing is proportional to the mass of total matter.

Birrer uses statistics and helps draw conclusions about the fundamental nature of the dark matter that alters the trajectory of light as it travels towards Earth.

He conducts simulations and compares a range of data collected from NASA Hubble and the James Webb Space Telescope.

Hubble constant

Beyond gravitational lensing, Birrer also studies and refines the Hubble constant, which describes the expansion rate of the universe. This constant that was first measured by Edwin Hubble in 1929.

“An accurate and precise measurement of the Hubble constant will provide us empirical guidance to questions and answers about the fundamental composition and nature of the universe,” Birrer explained.

During his postdoctoral research at UCLA, Birrer helped develop a new “formalism to measure the expansion history of the universe accounting for all the uncertainty,” Tomasso Treu, a Vice Chair for Astronomy at UCLA and Birrer’s postdoctoral advisor. “These methodological breakthroughs lay the foundation for the work that is being done today to find out what is dark matter and what is dark energy,” which is a force that causes the universe to expand at an accelerating rate.

Treu, who described Birrer as “truly outstanding” and one of the ‘best postdocs I have ever interacted with” in his 25-year career, suggested that his former student was relentless even after impressive work.

Soon after completing a measurement of the constant to two percent precision, Birrer started thinking of a “way to redo the experiment using much weaker theoretical assumptions,” Treu wrote in an email. “This was a very brave thing to do, as the dust had not settled yet on the first measurement and he questioned everything.”

The new approach required considerable effort, patience and dedication.

Birrer was “motivated uniquely by his intellectual honesty and rigor,” Treu added. “He wanted to know the answer and he wanted to know if it was robust to this new approach.”

Indeed, researchers are still executing this new measurement, which means that Treu and others don’t know how the next chapter in this search. This approach will, however, lead to greater confidence in whatever figure they find.

Larger collaborations

Simon Birrer. Photo by Rebecca Ross

Birrer is a part of numerous collaborations that involve scientists from Europe, Asia, and Middle and South America.

He contributes to the Legacy Survey of Space and Time (LSST). A planned 10-year survey of the southern sky, the Vera C. Rubin Observatory is under construction in northern Chile.

The Simonyi Survey Telescope (SST) at the observatory will survey half the sky every three nights. It will provide a movie of that part of the sky for a decade.

The telescope and camera are expected to produce over 5.2 million exposures in a decade. In fewer than two months, a smaller commissioning camera will start collecting the first light. The main camera will start collecting images within a year, while researchers anticipate gathering scientific data in late next year or early in 2026.

The LSST is expected to find more strong gravitational lensing events, and in particular strongly lensed supernovae, than any prior survey.

Birrer is the co-chair of the LSST Strong Lensing Science Collaboration and serves on the Collaboration Council of the LSST Dark Energy Science Collaboration.

Birrer is also a part of the Dark Energy Survey, which was a predecessor to LSST. Researchers completed data taking a few years ago and are analyzing that information.

From mountains to the island

Born and raised in Lucerne, Switzerland, Birrer, who speaks German and the Swiss dialect, French and English, found physics and sociology appealing when he was younger.

“I was interested in how the world works,” he said.

While attending college at ETH Zurich in Switzerland, he became eager to address the numerous unknown questions in cosmology and astrology.

“How little we know about” these fields “dragged me in that direction,” said Birrer.

An avid skier, mountaineer and soccer player, Birrer bikes the five miles back and forth to work from Port Jefferson.

In addition to adding a talented scientist, Stony Brook also brought on board an effective educator.

Birrer is “knowledgeable and caring, patient and at the same time, he knows how to challenge people to achieve their best,” Treu explained. “I am sure he will be a wonderful addition to the faculty and he will play a leading role in training the next generation of scientists.”

In terms of the advice he found particularly helpful in his career, Birrer suggested he needed a nudge to combine his passion for theory with the growing trove of available data. His PhD advisor told him to “touch the data,” he said. The data keeps him humble and provides a reality check.

The friction between thought and data “leads to progress,” Birrer added. “You never know whether the thoughts are ahead of the experiments (data) or whether the experiments are ahead of the thoughts.”

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From left, Adrian Krainer and Danilo Segovia with the Breakthrough Prize, which Krainer won in 2018. Photo from Danilo Segovia

By Daniel Dunaief

For many young children, the ideal peanut butter and jelly sandwich doesn’t include any crust, as an accommodating parent will trim off the unwanted parts before packing a lunch for that day.

Similarly, the genetic machinery that takes an RNA blueprint and turns it into proteins includes a so-called “spliceosome,” which cuts out the unwanted bits of genetic material, called introns, and pulls together exons.

Adrian Krainer. Photo from CSHL

When the machinery works correctly, cells produce proteins important in routine metabolism and everyday function. When it doesn’t function correctly, people can contract diseases.

Danilo Segovia, a PhD student at Stony Brook University who has been working in the laboratory of Cold Spring Harbor Laboratory Professor Adrian Krainer for seven years, recently published a study in the Proceedings of the National Academy of Sciences about an important partner, called DDX23, that works with the key protein SRSF1 in the spliceosome.

“We obtained new insights into the splicing process,” said Krainer, who is the co-leader of the Gene Regulation & Inheritance program in the Cancer Center at CSHL. “The spliceosome is clearly important for every gene that has introns and every cell type that can have mutations.”

Krainer’s lab has worked with the regulator protein SRSF1 since 1990. Building on the extensive work he and members of his lab performed, Krainer was able to develop an effective treatment for Spinal Muscular Atrophy, which is a progressive disease that impacts the muscles used for breathing, eating, crawling and walking.

In children with SMA, Krainer created an antisense oligonucleotide, which enables the production of a key protein at a back up gene through more efficient splicing. The treatment, which is one of three on the market, has changed the prognosis for people with SMA.

At this point, the way DDX23 and SRSF1 work together is unclear, but the connection is likely important to prepare the spliceosome to do the important work of reading RNA sequences and assembling proteins.

Needle in a protein haystack

Thanks to the work of Krainer and others, scientists knew that SRSF1 performed an important regulatory role in the spliceosome.

What they didn’t know, however, was how other protein worked together with this regulator to keep the machinery on track.

Danilo Segovia in the lab at Cold Spring Harbor Laboratory. Photo by Constance Burkin/CSHL

Using a new screening technology developed in other labs that enabled Segovia to see proteins that come in proximity with or interact with SRSF1, he came up with a list of 190 potential candidates.

Through a lengthy and detailed set of experiments, Segovia screened around 30 potential proteins that might play a role in the spliceosome.

One experiment after another enabled him to check proteins off the list, the way prospective college students who visit a school that is too hilly, too close to a city, too far from a city, or too cold in the winter do amid an intense selection process.

Then, on Feb. 15 of last year, about six years after he started his work in Krainer’s lab, Segovia had a eureka moment.

“After doing the PhD for so long, you get that result you were waiting for,” Segovia recalled.

The PhD candidate didn’t tell anyone at first because he wanted to be sure the interaction between the proteins was relevant and real.

“Lucky for us, the story makes sense,” Segovia said.

Krainer appreciated Segovia’s perseverance and patience as well as his willingness to help other members of his lab with structural work.

Krainer described Segovia as the “resident structural expert who would help everybody else who needed to get that insight.”

Krainer suggested that each of these factors had been studied separately in the process, without the realization that they work together.

This is the beginning of the story, as numerous questions remain.

“We reported this interaction and now we have to try to understand its implications,” said Krainer. “How is it driving or contributing to splice assembly.”

Other factors also likely play an important role in this process as well.

Krainer explained that Segovia’s workflow allowed him to prioritize interacting proteins for further study. Krainer expects that many of the others on the list are worth further analysis.

At some point, Krainer’s lab or others will also work to crystallize the combination of these proteins as the structure of such units often reveals details about how these pieces function.

Segovia and Krainer worked together with Cold Spring Harbor Laboratory Professor Leemor Joshua-Tor, who does considerably more biochemistry work in her research than the members of Krainer’s lab.

When a cowboy met a witch

A native of Montevideo, Uruguay, Segovia came to Stony Brook in part because he was conducting research on the gene P53, which is often mutated in forms of human cancer.

Segovia had read the research of Ute Moll, Endowed Renaissance Professor of Cancer Biology at Stony Brook University, who had conducted important P53 research.

“I really liked the paper she did,” said Segovia. “When I was applying for college in the United States for my PhD, I decided I’m for sure going to apply to Stony Brook.”

Even though Segovia hasn’t met Moll, he has benefited from his journey to Long Island.

During rotations at CSHL, Segovia realized he wanted to work with RNA. He found a scientific connection as well as a cultural one when he discovered that Krainer is from the same city in Uruguay.

Krainer said his lab has had a wide range of international researchers, with as many as 25 countries represented. “The whole institution is like that. People who go into science are naturally curious about a lot of things, including cultures.”

Segovia not only found a productive setting in which to conduct his PhD research, but also met his wife Polona Šafarič Tepeš, a former researcher at Cold Spring Harbor Laboratory who currently works at the Feinstein Institute for Medical Research. Tepeš is originally from Slovenia.

The couple met at a Halloween party, where Segovia came as a cowboy and Tepeš dressed as a witch. They eloped on November 6, 2020 and were the first couple married after the Covid lockdown at the town hall in Portland, Maine.

Outside of the lab, Segovia enjoys playing the clarinet, which he has been doing since he was 11.

As for science, Segovia grew up enjoying superhero movies that involve mutations and had considered careers as a musician, scientist or detective.

“Science is universal,” he said. “You can work wherever you want in the world. I knew I wanted to travel, so it all worked out.”

As for the next steps, after Segovia defends his thesis in July, he is considering doing post doctoral research or joining a biotechnology company.

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Clockwise from top left, Musankwa sanyatiensis leg bones as they were discovered in the ground on Spurwing Island, Lake Kariba, Zimbabwe. Image courtesy of Paul Barrett; Musankwa sanyatiensis fossil bones in situ, after mechanical preparation, and after CT scanning. Image courtesy of Paul Barrett; and an artist reconstruction of Musankwa sanyatiensis showing position of fossil bones (in blue). Rendering by Atashni Moopen

By Daniel Dunaief

The dinosaur family tree has few members in Zimbabwe, as only four fossils have been found in the region.

Kimberley Chapelle

Recently, researchers from several universities, including Kimberley “Kimi” Chapelle, Assistant Professor in the Department of Anatomical Sciences in the Renaissance School of Medicine at Stony Brook University, described a new species of dinosaur from a 210 million year-old fossilized hind leg in the journal Acta Palaeontologica Polonica.

Reconstructing the entire dinosaur from the bones they discovered in Lake Kariba, the scientists, led by Paul Barrett from the Natural History Museum of London, estimated that this plant-eating sauropodomorph weighed about 850 pounds and was among the larger dinosaurs in the late Triassic period.

The first new dinosaur species described in the Mid-Zambezi Basin of Northern Zimbabwe in more than 50 years, the sauropodomorph survived a mass extinction event that wiped out about 76 percent of all terrestrial and marine creatures. The sauropodomoprh group includes animals like the enormous Brontosaurus, which came later in the evolution of the lineage. Chapelle was on the field expedition in 2017 when Barrett noticed the fossil sticking out of the ground.

The discovery was “extremely exciting, as there was a high chance it was going to be something new,” said Chapelle. “It was well-preserved in articulation and we knew the bones came from the same individual.” She participated in the lengthy process that involved excavating the rare find, creating a reconstruction, isolating the bones to look at the structure, describing the fossil and comparing it to other, closely-related dinosaurs to determine where it sits on the family tree.

The researchers named this species Musankwa sanyatiensis, using the name of the houseboat Musankwa on which they lived and worked as they searched for fossils during the dry seasons around the man-made Lake Kariba.

“Musankwa is cool because it’s one of only a handful of dinosaurs from Zimbabwe, a country with amazing fossil resources that have yet to be fully discovered,” explained Jonah Choiniere, a Professor in the Evolutionary Studies Institute at the University of Witwatersrand in Johannesburg South Africa, who served as Chapelle’s PhD advisor. “Because we don’t have any specimens of Musankwa in similar-age rocks in South Africa, it tells us that during the Triassic period there might have been slightly different species groups of dinosaurs in the two countries.”

The Earth looked considerably different when this long-necked dinosaur was searching for its plant meal, as the land masses of the planet were combined in one supercontinent called Pangaea. In that time, Musankwa’s predators likely included meat-eating therapods and crocodile-like reptiles, which are ancestors of modern crocodiles.

Keep your head up

Hunting for fossils in Zimbabwe, which presented an opportunity for this kind of discovery, came with some challenges.

Kimberley Chapelle with Jonah Choiniere at Lake Kariba. Photo from Jonah Choiniere.

For starters, researchers lived aboard the houseboat Munsankwa, whose name in the Tongan dialect means “boy close to marriage.” Lake Kariba, which was created between 1958 and 1963 and is the largest artificial lake and reservoir by volume, gets “really hot in the summer and all you want to do is swim,” said Chapelle.

That, however, is ill-advised, as modern crocodiles roam the waters of the lake so regularly that people stay far from the shoreline.

To combat the heat, Chapelle drank plenty of water, applied regular sunscreen and wore large hats and long sleeves to keep the strong rays of the sun off her skin. Additionally, the researchers worked between morning and afternoon. The scientific expedition had an armed game ranger with them, to keep scientists safe.

“When you’re looking at fossils, you are always looking at the ground,” Chapelle said. At one point, she looked up and saw a hippo about 50 feet from her. “You have to remember to be aware of your surroundings,” she  said.

Field experience

Choiniere, who inspired his former student to consider entering the field when he first arrived at the University of Witwatersrand, saw Chapelle in action when she first did some field work.

Chapelle’s scientific curiosity never faltered, despite some significant field misadventures that included staying in a rotten old farmhouse without plumbing, sleeping in tents in the freezing cold in the backyard of a rural pub, hiking through brambles over the side of a mountain, and touring around Germany eating nothing but stewed cabbage and pork in brown sauce, and staying three to a hostel room to save money.

“In [Chapelle’s] case, there was never any doubt — she loved the field from day one and has never looked back,” Choiniere explained.

Choiniere believes Chapelle has a “unique skillset among paleontologists,” as her talents include math, observations of shape and structure, histology, three-dimensional data processing and field work. Beyond her diverse skills, Choiniere appreciated Chapelle’s time management skills and her pleasant demeanor, which enabled her to greet him with a smile even when he delivered his part later than she anticipated.

A promising LI start

Chapelle, who started working at Stony Brook at the end of January, is enjoying a return to New York. A native of Johannesburg, South Africa, she  had done a postdoctoral fellowship at the American Museum of Natural History in 2021.

A current resident of Rocky Point, Chapelle lives close to the beach. She and her husband Dominic Stratford, an Adjunct Professor at Stony Brook and Archaeologist and Associate Professor at the University of the Witwatersrand in Johannesburg, brought their Australian Shepherd named Shango with them.

A runner who recently completed the Shelter Island 10K and who loves taking pictures, Chapelle, who is the daughter of a doctor, originally thought she’d want to become a veterinarian. When she took a course in her third year of college with Choiniere, she was hooked by the link between evolution and anatomy.

As for the recent paper, Chapelle is pleased that people can read about this newly discovered dinosaur.

“This is years and years of work that gets put into this,” she said. “It also gives us a push to keep finding new things and publishing.”

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