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Above, the Condor telescope in New Mexico which is a model for a similar telescope Lanzetta will be building this year in Chile as a Fulbright Scholar. Photo courtesy of Condor Team

By Daniel Dunaief

Five years later, Kenneth Lanzetta is bringing a telescope to Chile.

Professor Kenneth Lanzetta, PhD
Photo courtesy SBU

In 2019, Lanzetta, who is a Professor in the Department of Physics and Astronomy at Stony Brook University, was planning to install a sophisticated state-of-the-art telescope in Chile that could look deep into the dark night sky for low-surface brightness and point sources. The onset of Covid in early 2020, however, disrupted that plan, as Chile closed its borders, leaving him scrambling to find a new site.

“I looked for an alternative I could drive to,” said Lanzetta, as flying was strongly discouraged.

He settled on the Dark Sky New Mexico observatory near Animas to set up a Condor Array Telescope.

Lanzetta had various manufacturers ship components to the site. At the end of 2020, he, his wife Robin Root, and his daughter Ciara drove across the country.

He had originally intended to spend about two weeks in the state. After many problems and delays, he and his wife stayed for more than four months, until early 2021. Ciara returned to college in London in the middle of January.

Lanzetta and Root moved every two weeks, expecting that they would be able to return to Long Island. Each time, delays in the project extended their stay. They figured they visited almost every airbnb in the area.

“I spent Covid in a very isolated part of New Mexico and I didn’t have to be back in Stony Brook,” Lanzetta said. “I had the ability to teach online.”

A view created by Condor and computer technologies of extremely faint shells of ionized gas surrounding the dwarf nova Z Camelopardalis.
Photo from Kenneth M. Lanzetta

While the New Mexico site worked out better than he could have imagined, producing enough information to leave him “awash in data” as he works to publish his findings, Lanzetta is planning to spend the next academic year in Chile. He will split his time between Concepción, Santiago, San Pedro and Cerro Taco, which is where he will install the new Condor telescope at an altitude of 5,200 meters, or 17,060 feet at Atacama National Park.

Lanzetta will serve as a Fulbright Scholar for the 2024-2025 academic year.

The Fulbright scholarship “recognizes the potential of the ‘Condor Array Telescope’ that is based on a possibly paradigm shifting astronomical telescope technology,” Chang Kee Jung, Distinguished Professor and Chair of the Department of Physics and Astronomy, said in a statement. “Deploying Condor in Atacama, a premier site for telescopes, opens up a greater opportunity for discoveries.”

That altitude and the expected clear skies in the South American nation will give Lanzetta and his colleagues an opportunity to study extremely faint images that would otherwise be more challenging or even impossible to see from other locations. The good weather and dark conditions also help.

Kenneth Lanzetta in the Atacama Desert. Photo by Robin Root.

The park has a road for access and an optical fiber connection, which makes it possible for him to do what they want to do at the site.

The site is at a high enough altitude that Lanzetta will need to breathe bottled oxygen.

The Stony Brook scientist will build as much of the telescope as he can at a lower elevation, ship it to the site and bolt it in place.

The Condor telescope will use refracting optics from several smaller telescopes into the equivalent of one larger telescope that uses newer and faster complementary metal oxide semiconductor sensors.

Most, but not all, of the components of the telescope are off the shelf. The recent development of extremely capable CMOS sensors, which are used in cell phones, back up cameras for cars and in industry, were not available in an inexpensive commercial format as recently as five years ago.

What Lanzetta plans to do in Chile is replicate the successful effort in New Mexico to capture more light signals in space that are beyond the limits of what conventional telescopes can distinguish.

He plans to create a telescope that, when it functions as it should, can operate autonomously, allowing him to control it from anywhere in the world as it transmits data back to his computers at Stony Brook.

New Mexico results

Lanzetta recently returned from an international conference in Aspen, Colorado, where he presented several results.

Condor revealed intergalactic filaments, which might provide glimpses of the cosmic web. He is actively working on this.

Computer simulations of structure formation in the universe has shown how structure came to be from a universe that was initially smooth.

The simulations suggest dark matter is distributed in a hierarchical fashion, with superclusters, clusters and groups of galaxies connected by filamentary structures that resemble a cosmic web.

Lanzetta has been working to see glowing gas of the cosmic web and he and his colleagues believe it is within reach of the current and the new Condor Atacama.

Higher than Chile?

With the increased visibility at the higher altitude site in Chile, researchers recognize that gathering information even further up in the atmosphere increases the likelihood of finding images from faint objects.

At the Aspen conference, scientists discussed the possibility of launching telescopes designed to study the extremely faint universe on balloons, which might be faster and cheaper than attempting to do this from space.

A resident of Smithtown, Lanzetta lives with his wife Root, who is planning to spend the year in Chile with him. Lanzetta’s son Ryan is finishing his PhD in theoretical condensed matter physics at the University of Washington, while his daughter Ciara is finishing her master’s degree in costume design at the University of Glasgow in Scotland.

Growing up in Warminster, Pennsylvania, Lanzetta and his father Anthony used to build things together. When he was 13, Lanzetta had an advanced class radio license. His father helped put together a radio transmitter and receiver and they installed various antennas on the roof.

His father had an undergraduate degree in physics and worked as an engineer. With Ryan’s educational experience, the family has three generations of Lanzettas with degrees in physics.

Lanzetta’s father had a telescope that they used to look at the moon and Saturn. In 1969, when astronauts Neil Armstrong and Buzz Aldrin were walking on the moon, he recalls his father telling him the astronauts were too small to see.

“This is what I was going to do from the time I was conscious,” he said. “It was always the way it was going to be.” 

Indeed, Lanzetta realizes how “lucky I’ve been to be able to spend my entire life” doing this work.

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Joshua Homer. Photo by Constance Burkin

By Daniel Dunaief

Even as some antibiotics and anti cancer treatments help beat back infections and diseases such as cancer, pathogens and diseases can develop resistance that render these treatments less effective.

Researchers at pharmaceutical companies and universities spend considerable time trying to ensure therapies continue to work. Companies make derivatives of existing drugs or they combine drugs to reduce resistance. They also develop new agents to combat drug-resistant tumors.

Using a chemical process that won his mentor K. Barry Sharpless a Nobel Prize, John Moses, a Professor at Cold Spring Harbor Laboratory, has deployed a new version of click chemistry to assemble biologically active compounds quickly and effectively, which could be used for further development into potential therapies.

Akin to fastening a seatbelt or assembling LEGO blocks, click chemistry benefits from an efficient system to create reliable end products, with the additional advantage of minimizing waste products or impurities.

Recently, Research Investigator Joshua Homer, who has been in Moses’s lab for over three years, published a paper in Chemical Science in which he created several libraries of over 150 compounds. He screened these for activity in anticancer or antibiotic assays.

The newer click process, called Accelerated SuFEx Click Chemistry, or ASCC, involves “less synthetic steps,” said Homer. ASCC can use functional groups like alcohols, that are naturally found in numerous commercially available compounds, directly. Homer can and has used commercially available alkyl and aryl alcohols as fragments in this application of ASCC.

This approach “allows us to explore chemical space so much faster,” Homer said.

In an email, Moses suggested that the paper “demonstrates that SuFEx chemistry can be a feasible and speedy approach compared to traditional methods.”

To be sure, the products could still be a long way from concept to bedside benefit.

“It’s important to note that while the chemistry itself shows promise, the actual application in drug development is complex and can take many years,” Moses added.

The research contributed to finding compounds that may be promising in treating various conditions and represent initial findings and potential starting points for further development, Homer added.

Specifically, Homer took inspiration from the structure of combrestastatin A4 when developing microtubule targeting agents.

The chemicals he produced had good activity against drug-resistant cancer cell lines that resist other treatment options.

Homer also modified the structure of dapsone, generating a derivative with greater activity against a strain of M. tuberculosis that is otherwise resistant to dapsone. 

“Strains of bacteria develop resistance to antibiotics,” said Homer. Derivatization of antibiotic structures can generate compounds that maintain activity.

Breast cancer

In creating these compounds, Homer bolted on different commercially available fragments and developed potential nano-molar treatments that could be effective against triple-negative breast cancer.

At this point, he has evaluated two lead agents in two dimensional cell culture and against patient-derived organoids. Homer did this work in collaboration with the lab of CSHL Cancer Center director David Tuveson.

Organoids can help gauge the potential response of a patient’s tumor to various treatments.

Homer found that eight of the microtubule targeting agents were more potent than colchicine against HCT-15. This cancer cell line, he explained, is known to have upregulated efflux, which is a major cause of drug resistance in cancer cells.

His compounds maintained a similar potency between two dimensional cell lines and organoids. Often, compounds are less potent in organoids, which makes this a promising discovery.

Making molecules and screening them for function to discover lead candidates is one of the first steps in the drug discovery process, with considerable optimization and regulatory steps necessary to generate a drug for the clinic.

Promising treatments sometimes also cause cellular damage in healthy tissue, which reduces the potential benefit of any new treatment. Effective cancer drugs are selective for cancer cells over normal cells.

At this point, the molecules Homer creates involve a search for function, he said. “Once we identify the reaction, we can remake our molecule to confirm it is our compound that is causing a reaction.”

Click chemistry doesn’t necessarily lead to solutions, but it enables scientists and drug companies to create and test molecules more rapidly and with considerably less financial investment.

Click solutions

Click chemistry has affected the way Homer thinks about problems outside the lab.

“I think more about doing things quickly and how to tackle the issues we face, rather than using brute force in one direction,” he said. “We can go in lots of directions and probe. We should be looking at all sorts of baskets at once to solve the issues we have.”

Originally from Tauranga, New Zealand, Homer enjoys traveling around the country, visiting new cities and interacting with different people. A resident of Huntington, Homer is looking forward to an upcoming visit from his parents Dave and Debbie and his aunt Carol, who are making their first trip to the continental United States.

“One of my favorite things about being a scientist is that I can bring my parents out of their comfort zone,” he said. His parents live on a small lifestyle block with several sheep and chickens.

Moses lauded the contributions Homer has made to the lab, including providing mentorship to other students.

As for click chemistry, Homer appreciates how the reactions create opportunities even for those without advanced backgrounds in chemistry.

Click chemistry creates the opportunity to help non-scientists understand scientific concepts more easily.

“I can give a high school student the reagents and substrates and they can reliably make biologically active anticancer agents or antibiotics,” he said. “That helps connect science and drug discovery with the community.”

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Brookhaven Lab biologist Meng Xie and postdoctoral fellow Dimiru Tadesse with sorghum plants like those used in this study. Note that these plants are flowering, unlike those the scientists engineered to delay flowering indefinitely to maximize their accumulation of biomass. Photo by Kevin Coughlin/ BNL

By Daniel Dunaief

A traffic light turns green and a driver can make a left turn. Similarly, plants on one path can change direction when they receive a particular signal. In the case of the sorghum plant, the original direction involves growth. A series of signals, however, sends it on a different trajectory, enabling the plant to flower and reproduce, halting the growth cycle.

Brookhaven Lab biologist Meng Xie and postdoctoral fellow Dimiru Tadesse in the lab. Photo by Kevin Coughlin/ BNL

Understanding and altering this process could allow the plant to grow for a longer period of time. Additional growth increases the biomass of this important energy crop, making each of these hearty plants, which can survive in semiarid regions and can tolerate relatively high temperatures, more productive when they are converted into biomass in the form of ethanol, which is added to gasoline.

Recently, Brookhaven National Laboratory biologist Meng Xie teamed up with Million Tadege, Professor in the Department of Plant and Soil Science at Oklahoma State University, among others, to find genes and the mechanism that controls flowering in sorghum.

Plants that produce more biomass have a more developed root system, which can sequester more carbon and store it in the soil.

The researchers worked with a gene identified in other studies called SbGhd7 that extends the growth period when it is overexpressed.

Validating the importance of that gene, Xie and his colleagues were able to produce about three times the biomass of a sorghum plant compared to a control that flowered earlier and produced grain.

The plants they grew didn’t reach the upper limit of size and, so far, the risk of extensive growth  that might threaten the survival of the plant is unknown.

Researchers at Oklahoma State University conducted the genetic work, while Xie led the molecular mechanistic studies at BNL.

At OSU, the researchers used a transgenic sorghum plant to over express the flowering-control gene, which increased the protein it produced. These plants didn’t flower at all.

“This was a dramatic difference from what happens in rice plants when they overexpress their version of this same gene,” Xie explained in a statement. “In rice, overexpression of this gene delays flowering for eight to 20 days — not forever!”

In addition to examining the effect of changing the concentration of the protein produced, Xie also explored the way this protein recognized and bound to promoters of its targets to repress target expression.

Xie did “a lot of molecular studies to understand the underlying mechanism, which was pretty hard to perform in sorghum previously,” he said.

Xie worked with protoplasts, which are plant cells whose outer wall has been removed. He inserted a so-called plasmid, which is a small piece of DNA, into their growth medium, which the plants added to their DNA.

The cells can survive in a special incubation/ growth medium, enabling the protoplasts to incorporate the plasmid.

Sorghum plant. Photo by Kevin Coughlin/ BNL

Xie attached a small protein to the gene so they could monitor the way it interacted in the plant. They also added antibodies that bound to this protein, which allowed them to cut out and observe the entire antibody-protein DNA complex to determine which genes were involved in this critical growth versus flowering signaling pathway.

The flowering repressor gene bound to numerous targets. 

Xie and his BNL colleagues found the regulator protein’s binding site, which is a short DNA sequence within the promoter for each target gene.

Conventional wisdom in the scientific community suggested this regulator protein would affect one activator gene. Through his molecular mechanistic studies, Xie uncovered the interaction with several genes.

“In our model, we found that [the signaling] is much more complicated,” he said. The plant looks like it can “bypass each [gene] to affect flowering.”

Regulation appears to have crosstalk and feedback loops, he explained.

The process of coaxing these plants to continue to grow provides a one-way genetic street, which prevents the plant from developing flowers and reproducing.

These altered plants would prevent any cross contamination with flowering plants, which would help scientists and, potentially down the road, farmers meet regulatory requirements to farm this source of biomass.

Ongoing efforts

The targets he found, which recognize the short sequence of DNA, also appears in many other flowering genes.

Xie said the group’s hypothesis is that this regulator in the form of this short sequence of DNA also may affect flowering genes in other plants, such as maize and rice.

Xie is continuing to work with researchers at OSU to study the function of the numerous targets in the flowering and growth processes. 

He hopes to develop easy ways to control flowering which might include spraying a chemical that blocks flowering and removing it to reactive reproduction. This system would be helpful in controlling cross contamination. He also would like to understand how environmental conditions affect sorghum, which is work he’s doing in the lab. Down the road, he might also use the gene editing tool CRISPR to induce expression at certain times.

Honing the technique to pursue this research took about four years to develop, while Xie and his students spent about a year searching for the molecular mechanisms involved.

Rough beginning

Xie departed from his post doctoral position at Oak Ridge National Laboratory in March of 2020, when he started working at BNL. That was when Covid altered people’s best-laid plans, as he couldn’t come to the lab to start conducting his research for about six months. 

Born in Shanxi province in China, Xie and his wife Jingdan Niu live in Yaphank and have a two-year old son, Felix Xie.

When he was growing up, Xie was interested in math, physics, chemistry and biology. As an undergraduate in Beijing, Xie started to learn more about biology and technology, which inspired him to enter this field.

Biotechnology “can change the world,” Xie said.

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Tobias Janowitz and Hassal Lee. Photo by Caryn Koza

By Daniel Dunaief

Before treatments for any kind of health problem or disease receive approval, they go through a lengthy, multi-step process. This system should keep any drugs that might cause damage, have side effects or be less effective than hoped from reaching consumers.

In the world of cancer care, where patients and their families eagerly await solutions that extend the quality and quantity of life, these clinical trials don’t always include the range of patients who might receive treatments.

Hassal Lee. Photo by Caryn Koza

That’s according to a recent big-picture analysis in the lab of Cold Spring Harbor Laboratory Professor Tobias Janowitz. Led by clinical fellow Hassal Lee, these researchers compared where clinical trials occurred with the population near those centers.

Indeed, 94 percent of United States cancer trials involve 78 major trial centers, which were, on average, in socioeconomically more affluent areas with higher proportions of self-identified white populations compared with the national average.

“We should test drugs on a similar population on which we will be using the drugs,” said Lee. In addition to benefiting under represented groups of patients who might react differently to treatments, broadening the population engaged in clinical trials could offer key insights into cancer. Patient groups that respond more or less favorably to treatment could offer clues about the molecular biological pathways that facilitate or inhibit cancer.

Janowitz suggested that including a wider range of patients in trials could also help establish trust and a rapport among people who might otherwise feel had been excluded.

The research, which Lee, Janowitz and collaborators published recently as a brief in the journal JAMA Oncology, involved using census data to determine the socioeconomic and ethnic backgrounds of patient populations within one, two and three hour driving distances to clinical trials.

The scientists suggested researchers and drug companies could broaden the patient population in clinical trials by working with cancer centers to enlist trial participants in potential life-extending treatments through satellite hospitals.

Project origins

This analysis grew out of a study Janowitz conducted during the pandemic to test the effectiveness of the gerd-reducing over-the-counter drug famotidine on symptoms of Covid-19.

Janowitz generally studies the whole body’s reaction to disease, with a focus on cancer associated cachexia, where patients lose considerable weight and muscle mass. During the pandemic, however, Janowitz, who has an MD and PhD, used his scientific skills to understand a life-threatening disease. He designed a remote clinical trial study in which participants took famotidine and monitored their symptoms.

While the results suggested that the antacid shortened the severity and duration of symptoms for some people, it also offered a window into the way a remote study increased the diversity of participants. About 1/3 of the patients in that population were African American, while about 1/4 were Hispanic.

Lee joined Janowitz’s lab in early 2022, towards the end of the famotidine study. 

“The diverse patient population in the remote trial made us wonder if commuting and access by travel were important factors that could be quantified and investigated more closely,” Janowitz explained.

Lee and Janowitz zoomed out to check the general picture for cancer clinical trials.

To be sure, the analysis has limitations. For starters, the threshold values for travel time and diversity are proof of concept examples, the scientists explained in their paper. Satellite sites and weighted enrollment also were not included in their analysis. The cost other than time investment for potential clinical trial participants could present a barrier that the researchers didn’t quantify or simulate.

Nonetheless, the analysis suggests clinical trials for cancer care currently occur in locations that aren’t representative of the broader population.

The work “leveraged freely available data and it was [Lee’s] effort and dedication, supported by excellent collaborators that we had, that made the study possible,” Janowitz explained.

Since the paper was published, Cancer Center directors and epidemiologists have reached out to the CSHL scientists.

Searching for clinical research

After Lee, who was born in Seoul, South Korea and moved to London when she was five, completed her MD and PhD at the University of Cambridge, she wanted to apply the skills she’d learned to a real-world research questions.

She found what she was looking for in Janowitz’s lab, where she not only considered the bigger picture question of clinical trial participation, but also learned about coding, which is particularly helpful when analyzing large amounts of data.

Lee was particularly grateful for the help she received from Alexander Bates, who, while conducting his own research in a neighboring lab in the department of Neurobiology at the MRC Laboratory of Molecular Biology in Cambridge, offered coding coaching.

Lee described Bates as a “program whiz kid.”

A musician who enjoys playing classical and jazz on the piano, Lee regularly listened to music while she was in the lab. Those hours added up, with Spotify sending her an email indicating she was one of the top listeners in the United Kingdom. The music service invited her to an interview at their office to answer questions about the app, which she declined because she had moved to the United States by then.

The top medical student at Cambridge for three years, Lee said she enhanced her study habits when she felt unsure of herself as a college student.

She credits having great mentors and supportive friends for her dedication to work.

Lee found pharmacology one of the more challenging subjects in medical school, in part because of the need to remember a large number of drugs and how they work.

She organized her study habits, dividing the total number of drugs she needed to learn by the number of days, which helped her focus on studying a more manageable number each day.

Lee will be a resident at Mt. Sinai Hospital later this year and is eager to continue her American and New York journey.

As for the work she did with Janowitz, she hopes it “really helps people think about maintaining diversity in clinical trials using data that’s already available.”

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From left, Juan Jimenez and Sanjaya Senanayake in front of CO2 and Methane Conversion Reactor Units in the Chemistry Division at Brookhaven National Laboratory. Photo by Kevin Coughlin/BNL

By Daniel Dunaief

If we had carbon dioxide glasses, we would see the gas everywhere, from the air we, our pets, and our farm animals exhale to the plumes propelled through the smokestacks of factories and the tail pipes of gas-powered cars.

Juan Jimenez. Photo by Kevin Coughlin/BNL

A waste product that scientists are trying to reduce and remove, carbon dioxide is not only a part of the photosynthesis that allows plants to convert light to energy, but it also can be a raw material to create usable and useful products.

Juan Jimenez, a postdoctoral researcher and Goldhaber Fellow at Brookhaven National Laboratory, has been working with carbon dioxide for the last 10 years, in his undergraduate work at CUNY City College of New York, for his PhD at the University of South Carolina and since he arrived at BNL in 2020. 

Jimenez contributed to a team led by engineers at the University of Cincinnati to create a way to improve the electrochemical conversion of this greenhouse gas into ethylene, which is an important ingredient in making plastics as well as in manufacturing textiles and other products.

University of Cincinnati Associate Professor Jingjie Wu recently published work in the journal Nature Chemical Engineering in which they used a modified copper catalyst to improve the electrochemical conversion of carbon dioxide into ethylene.

“I’m always looking out to collaborate with groups doing cutting edge research,” explained Jimenez, who spearheaded the research at the National Synchrotron Lightsource II. “Since the work on CO2 is a global concern we require a global team” to approach solutions.

Jimenez is fascinated with carbon dioxide in part because it is such a stable molecule, which makes reacting it with other elements to transform it into something useful energy intensive.

A modified copper catalyst helped convert more carbon dioxide, which breaks down into two primary carbon-based products through electrocatalysis, into ethylene, which has been called the “world’s most important chemical.”

“Our research offers essential insights into the divergence between ethylene and ethanol during electrochemical CO2 reduction and proposes a viable approach to directing selectivity toward ethylene,” UC graduate student Zhengyuan Li and lead author on the paper, said in a statement.

A previous graduate student of Wu, Li helped conduct some of the experiments at BNL.

This modified process increases the selective production of ethylene by 50 percent, Wu added.

The process of producing ethylene not only increases the production of ethylene, but it also provides a way to recycle carbon dioxide.

In a statement, Wu suggested this process could one day produce ethylene through green energy instead of fossil fuels.

Jimenez’s role

Scientists who want to use the high-tech equipment at the NSLS-II need to apply for time through a highly competitive process before experimental runs.

Jimenez led the proposal to conduct the research on site at the QAS and ISS beamlines.

Several of the elements involved in this reaction are expensive, including platinum, iridium, silver and gold, which makes them prohibitively expensive if they are used inefficiently. By using single atoms of the metal as the sites, these scientists achieved record high rates of reaction using the least possible amount of material.

The scientists at BNL were able to see the chemistry happening in real time, which validated the prediction for the state of the copper.

Jimenez’s first reaction to this discovery was excitement and the second was that “you can actually take a nap. Once you get the data you’re looking for, you can relax and you could shut your eyes.”

Working at NSLS-II, which is one of only three or four similar such facilities in the United States and one of only about a dozen in the world, inspires Jimenez, where he appreciates the opportunity to do “cutting edge” research.

“These experiments are only done a few times in the career of the average scientist,” Jimenez explained. “Having continuous access to cutting edge techniques inspires us to tackle bigger, more complicated problems.”

In the carbon dioxide research, the scientists drilled down on the subject, combining the scope of what could have been two or three publications into a single paper.

Indeed, Nature Chemical Engineering, which is an online only publication in the Nature family of scientific journals, just started providing scientific papers in the beginning of this year.

“Being part of the inaugural editions is exciting, specifically coming from a Chemical Engineering background” as this work was published along with some of the “leading scientists in the field,” said Jimenez.

New York state of mind

Born in Manhattan, Jimenez lived in Queens near Jamaica until he was 11. His family moved into Nassau County near the current site of the UBS Arena.

During his PhD at the University of South Carolina, Jimenez spent almost a year in Japan as a visiting doctoral student, where he learned x-ray absorption spectroscopy from one of the leading scientists in the field, Professor Kiyotaka Asakura. Based in Hokkaido University in Sapporo, Japan, Jimenez enjoyed touring much of the country.

A resident of Middle Island, Jimenez likes to run and swim. He enjoys cooking food from all over the world, including Spanish, Indian and Japanese cuisines.

As a scientist, he has the “unique luxury” of working with an international audience, he said. “If you are having lunch and you see someone eating amazing Indian food, you can talk to them, learn a bit about their culture, how they make their food, and then you can make it.”

As for his work, Jimenez explains that he is drawn to study carbon dioxide not just for the sake of science, but also because it creates a “pressing environmental need.”

He has also been looking more at methane, which is another potent greenhouse gas that is challenging to activate.

Ideally, at some point, he’d like to contribute to work that leads to processes that produce negative carbon dioxide use.

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From left, Mikala Egeblad and Xue-Yan He. Photo from Constance Brukin

By Daniel Dunaief

They both have left Cold Spring Harbor Laboratory, but the innovative research they did on Long Island and that they continue to do, is leaving its mark.

From left, Mikala Egeblad and Xue-Yan He at the American Association for Cancer Research (AACR) annual meeting in New Orleans, Louisiana in 2022. Photo from Xue-Yan He

When Xue-Yan He was a postdoctoral researcher in the lab of Mikala Egeblad, who was Associate Professor at CSHL, the tandem, along with collaborators, performed innovative research on mice to examine how stress affected the recurrence and spread of cancer in a mouse model.

In a paper published in late February in the journal Cancer Cell, He, who is currently Assistant Professor of Cell Biology & Physiology at Washington University School of Medicine in St. Louis, discovered that stress-induced neutrophil extracellular traps (NETs), which typically trap and kill bacteria, trigger the spread of cancer.

“The purpose of our study is to find out what stress does to the body” of an animal model of cancer, said He.

The data in mice demonstrated that targeting NETs in stressed animals significantly reduced the risk for metastases, He explained, suggesting that reducing stress should help cancer treatment and prevention. The researchers speculate that drugs preventing NET formation can be developed and used as new treatments to slow or stop cancer’s spread.

To be sure, this finding, which is encouraging and has generated interest among cancer scientists and neurobiologists, involved a mouse model. Any potential application of this research to the diagnosis and treatment of people will take considerably more effort.

“I want to stress that the evidence for the link between stress, NETs, and cancer is from mouse studies,” Egeblad explained. “We will need to design human studies to know for sure whether the link also exists for humans.”

Still, Egeblad hopes that eventually reducing stress or targeting NETs could be options to prevent metastatic recurrence in cancer survivors. “One major challenge is that a cancer diagnosis by itself is incredibly stressful,” she explained. The results of these experiments have attracted considerable attention in the scientific community, where “there is a lot more to learn!” 

Three part confirmation

When she was a postdoctoral researcher, He removed neutrophils from the mice using antibodies. Neutrophils, which are cells in the immune system, produce the NETs when they are triggered by the glucocorticoid stress hormone.

She also injected an enzyme called DNAse to destroy NETs in the test mice. The former CSHL postdoctoral researcher also used genetically engineered mice that didn’t respond to glucocorticoids.

With these approaches, the test mice developed metastasis at a much lower rate than those that had intact NETs. In addition, chronically stressed mice who didn’t have cancer had NETs that modified their lung tissue.

“Stress is doing something to prepare the organs for metastasis,” said He.

Linda Van Aelst, CSHL Professor and a collaborator on the study, suggested that this work validates efforts to approach mental health in the context of cancer.

“Reducing stress should be a component of cancer treatment and prevention,” Van Aelst said in a statement.

After He removed the primary tumor in the mouse models, the stressed mice developed metastatic cancer at a four-fold higher rate than the mice who weren’t stressed but who also previously had cancer.

The CSHL scientists primarily studied breast cancer for this work.

He appreciated the help and support from her colleagues at CSHL. “To really understand the mechanism” involved in the connection between stress and cancer, “you need a mouse model in the lab, an expert in neuroscience and an expert in the cancer field,” she said.

As a neuroscientist, Van Aelst offered suggestions and comments and helped He conduct behavioral tests to determine a mouse’s stress level. The work for this project formed the focus ofHe’s postdoctoral research, which started in 2016 and ended in 2023.

The link between stress and cancer is receiving increasing attention in the scientific community and has attracted attention on social media, He said.

CSHL “provided a great environment to perform all these experiments,” said He. The numerous meetings CSHL hosts and the willingness of principal investigators across departments made the lab “one of the best places” for a postdoctoral scientist.

“If you need anything from a neural perspective or a technical perspective, you can always find a collaborator” at CSHL, He added.

Born and raised in Nanjing, China, He enjoyed living on Long Island, visiting vineyards and trying to explore every state park. In the harbor, He caught blue crabs while her husband Chen Chen, who was a postdoctoral researcher at CSHL in the lab of Camila dos Santos, went fly fishing at Jones Beach.

In her current research, where she manages a lab that includes a senior scientist, a postdoctoral researcher and an undergraduate, He is extending the work she did at CSHL to colorectal cancer, where she is also analyzing how stress affects the spread of cancer.

“When you’re stressed, you can develop gastrointestinal problems, which is why I wanted to switch from breast cancer to colorectal cancer,” she said.

Extensions of the work

As for context for the research at CSHL, Egeblad wrote that doctors treating patients where the known risk of recurrence is high might use NETs in the blood as a biomarker.

The scientists think cancers that tend to metastasize to the liver, lung or spleen are the strongest candidates to determine the effect of NETs and stress on cancer.

“We have not seen any effects of targeting NETs for metastasis to the bone or the brain in our mouse model and similarly, the studies that have linked NETs to metastasis in human patients have mostly been cancer that has spread to the liver or the lung,” Egeblad said.

Egeblad appreciated the “fantastic job” He did on the work and described her former researcher as being “fearless.”

“She found that stress increased metastasis early in her project but it was a lot of work to discover it was the NETs that were responsible and to conduct studies to ensure that the results were applicable to different types of cancer,” Egeblad explained.

While the two researchers have gone to different institutions and are leading other lab efforts, Egeblad said she’d be happy to collaborate with her former student, who shares the same sense of humor.

Egeblad recalled how He ended her talks by telling the audience that her results showed that Egeblad should give her a “long vacation.”

“I think indeed that she has deserved one after all this work!” Egeblad offered.

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Georgios Moutsanidis, Photo by Ram Telikicherla

By Daniel Dunaief

In the best of times, water provides a serene background, offers an escape from searing summer heat, serves as a livelihood for the fishing industry, and supports a range of aquatic life that shimmers just below the surface.

In the worst of times, that same water can threaten communities that line coasts, bringing a powerful surge of destructive force that takes lives and destroys homes, buildings and infrastructure.

Recently, Georgios Moutsanidis, Stony Brook University Assistant Professor in the department of Civil Engineering, received a $500,000, five-year Faculty Early Career Development grant from the National Science Foundation to conduct research that could increase the resilience of coastal structures.

Rigoberto Burgueño, who is the chairman of the Civil Engineering department and who helped recruit Moutsanidis to Stony Brook in 2020, is pleased with the recognition from the NSF.

It is “one of the highest achievements for an individual investigator in terms of their potential as future leaders in their field and future mentors and teachers,” Burgueño said. The prestige from the award “will provide opportunities and bigger audiences to communicate his findings and his work.”

Amid climate change, the need for efforts to improve resilience from a range of water-driven forces increases, as rising sea levels encroach on coastlines and stronger storms driven by higher ocean temperatures threaten buildings and infrastructure.

“What we are trying to do with this project is to develop state-of-the-art computational tools that engineers and other researchers will use to incorporate in their work and study the resilience of structures against extreme hydrodynamic events” such as storm surges and tsunamis, said Moutsanidis.

Engineers, city planners and builders have used what Moutsanidis described as mostly outdated empirical models to test the resilience of structures. Moutsanidis, however, hopes to enhance those models by taking a physics-based numerical approach to understanding the damage a surge of water could do to various structures.

Moutsanidis is using established and well-known equations. He will contribute to solving them more accurately and efficiently.

Other models “could simulate water hitting a structure, but they were unable to capture the detailed response of the structure, with cracks, fractures, fragmentation and collapse,” Moutsanidis said. He hopes the new computational methods he will develop will predict the type and extent of damage more accurately.

The model he plans to create, with the help of graduate students he will hire who will use new high-performance computers he expects to use the funds to purchase, can address site-specific features of an area that would affect the likely speed, amount and force of any water surge.

Burgueño described Moutsanidis as being “at the forefront of very advanced computational simulations that take into account interactions of water with a structure.”  

By generating better estimates of the actual loads imposed on a structure, “we will be better prepared as engineers to either strengthen existing structures or to design future ones better,” Burgueño said.

Checking his work

While the information he’s using to construct these models relies on physics and deploys established equations, the Stony Brook Assistant Professor and his students will perform verification and validation. They will compare their results with existing experimental data and other computational approaches.

In addition, Moutsanidis’s lab will conduct experiments in a flume, which is a water tank in which he can vary the amount and speed of water approaching models of coastal communities. With a high-speed camera, he can evaluate how these simulated structures respond. In buildings that might collapse or fracture, he can test a slightly different fortified design, run a similar analysis and determine if the modifications led to a better outcome.

At this point, Moutsanidis has completed a proof of concept article in the journal Engineering with Computers, where he demonstrated the idea and the equations he’s solving. He hopes to produce a useful package that engineers and the public can use within the next four to five years, which he will release through an open source platform such as GitHub.

Moutsanidis is “very eager to start this work” as storm surges, flooding and tsunamis threaten coastal communities every year.

Larger context and other projects

In the bigger picture, Moutsanidis seeks to use computational methods and software to solve problems of engineering driven by physics. He has also worked in the aerospace community, studying the interaction of solids with hypersonic flow.

The goal is to “design more efficient aerospace vessels” that can withstand high temperatures and pressure as they travel five times the speed of sound or more, he said. The temperature is so high that the air undergoes a chemical reaction.

Moutsanidis has also worked with the impact of blast waves on structures, simulating the response to the shock wave or blast.

The goal is to make structures “more resilient or resistant to extreme events” such as a terrorist attack or an accident that triggers an explosion.

From Karditsa to Queens

Born and raised in a small town in the center of Greece called Karditsa, Moutsanidis is the son of two engineers. “In my early childhood, I was influenced by them, but I chose a different engineering path,” he said.

Moutsanidis, who completed postdoctoral research at Brown University before joining Stony Brook, lives in Queens. 

Moutsanidis is impressed with the students at Stony Brook, whom he described as “very engaged.” As for his work, he explained that his field is “quite competitive” and he was surprised and pleased to receive this award.

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Cold Spring Harbor Laboratory neuroscientist Arkarup Banerjee is using singing mice, like the one shown here, to understand how our brains control timing and communication. Photo by Christopher Auger-Dominguez

By Daniel Dunaief

Animals don’t have clocks, telling them when and for how long to run on a treadmill, to eat whatever they catch or to call to each other from the tops of trees or the bottom of a forest.

Arkarup Banerjee

The Alston’s singing mouse, which lives in Costa Rica, has a distinctive call that people can hear and that, more importantly, conveys meaning to other members of the species.

Using equipment to monitor neurons when a mouse offers songs of different length, Cold Spring Harbor Assistant Professor Arkarup Banerjee showed that these unusual rodents exhibit a form a temporal scaling that is akin to stretching or relaxing a rubber band. This scaling suggests that their brains are bending their processing of time to produce songs of different lengths.

“People have shown this kind of time stretching phenomenon in monkeys,” said Banerjee. It was unexpected and surprising that the same algorithm was used in the rodent motor cortex to control the flexibility of a motor pattern and action during vocalization.

Using recordings of neuronal activity over many weeks, Banerjee focused on a part of the mouse brain called the orofacial motor cortex (or OMC). He searched for differences in songs with particular durations and tempo.

Banerjee had set up a system in which he played back the recordings of Alston’s singing mice to his test subjects, who then responded to those songs. Mice generally respond with songs that are variable durations compared to when they sing alone.

These mice can adjust duration and tempo of these 10-second long songs while engaged in social communication.

People “do that all the time,” said Banerjee. “We change the volume of how loud we are speaking and we can change the tempo.”

The mice showed some vocal flexibility similar to other animals, including people.

These mice are singing the same song, with varying rhythms over shorter or longer periods of time. It is as if the same person were to sing “Happy Birthday” in 10 seconds or in 15 seconds.

Banerjee would like to know what is it in the mouse’s brain that allows for such flexibility. He had previously shown that the motor cortex is involved in vocal behavior, which meant he knew of at least one region where he could look for clues about how these rodents were controlling the flexibility of their songs.

By tracking the firing pattern of neurons in the OMC, he was able to relate neural activity to what the mice were doing in real time.

Neural activity expands or contracts in time, almost as if time is running faster or slower. These animals are experiencing relative time when it comes to producing their songs as they change their songs through a wide range of durations.

Pre-song activity

Even before an animal sings, Banerjee speculates its brain could be preparing for the sounds it’s going to make, much as we think of the words we want to say in a conversation or our response to a question before we move our mouths to reply or type on a keyboard to respond.

Songs also track with intruder status. An animal in a home cage sings a shorter song than an animal brought into a new cage.

Vocalizations may scale with social rank, which might help attract mates or serve other social purposes.

Females in the lab, which presumably reflect similar trends in the wild, tend to prefer the male that produces a longer song with a higher tempo, which could reflect their physical fitness and their position in the social hierarchy, according to research from Steve Phelps, Professor at the University of Texas at Austin in the Department of Integrative Biology.

Applications

While it’s a long way from the research he’s conducting to any potential human application, Banerjee could envision ways for these studies to shed light on communication processes and disorders.

The motor cortex in humans and primate is a larger region. Problems in these areas, from strokes or injuries, can result in aphasia, or the inability to articulate words properly. Banerjee plans to look at stroke models to see if the Alston’s singing mouse might provide clues about potential diagnostic or therapeutic clues.

“There are ways we can use this particular system to study cognitive deficits that show up” during articulation deficits such as those caused by strokes, said Banerjee.  While he said scientists know the parts list of the brain regions involved in speaking, they don’t yet know how they all interact.

“If we did, we’d have a much better chance of knowing where it fails,” Banerjee  explained. A challenge along this long process is learning how to generalize any finding in mice to humans. While difficult, this is not an impossible extrapolation, he suggested.

An effective model

Banerjee built a model prior to these experiments to connect neural activity with behavior.

“We had an extremely clear hypothesis about what should happen in the neural domain,” he said. “It was pretty gratifying to see that neurons change the way we predicted given the modeling.”

When the paper first came out about eight months ago in the scientific preprint bioRxiv, it received considerable attention from Banerjee’s colleagues working in similar fields. He went to India to give three talks and gave a recent talk at Emory University.

Outside of the lab, Banerjee and his wife Sanchari Ghosh, who live in Mineola, are enjoying watching the growth and development of their son Ahir, who was born a year and a half ago.

“It’s fascinating as a neuroscientist to watch his development and to see how a tiny human being learns about the world,” Banerjee said.

As for his work with this compelling mouse, Banerjee credited Phelps and his post doctoral advisor at New York University, Michael Long for doing important work on this mouse and for encouraging him to pursue research with this species. Long is a co-corresponding author on the paper. “It’s very gratifying to see that the expectation of what we can do with this species is starting to get fulfilled,” said Banerjee. “We can do these interesting and complex experiments and learn something about vocal interactions. I’m excited about the future.”

——————————————————-

SCIENCE ON SCREEN

The Cinema Arts Centre, 423 Park Ave., Huntington continues its Science on Screen series with a mind-expanding exploration of the mysteries of language and communication, featuring a lecture and Q&A with neuroscientist Arkarup Banerjee, of Cold Spring Harbor Laboratory, and a rare big-screen showing of Denis Villeneuve’s profound 2016 drama ARRIVAL on Tuesday, March 26 at 7 p.m..

Dr. Banerjee’s work explores the theme of decoding messages and touches on the fundamental assumptions of reality which are unpacked in the film. Discover how every species and culture’s unique symbols and codes shape our understanding of the world around us, and uncover the intriguing ways in which our brains navigate the limits and possibilities of language.

Tickets are $16, $10 members. To purchase in advance, visit www.cinemaartscentre.org. 

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A snail eating colubrid snake, Dipsas indica, from Peru.
Pascal Title with a semi-arborial colubrid snake, Chironius multiventris, from Peru.
A tree boar, Corallus hortulamus, which is an ambush predator, in Peru.
Pascal Title with a neotropical colubrine snake at the Los Amigos field station in Peru.
A false boa eating a lava lizard. Photo by Ivan Prates, University of Michigan
A CT scan of a cat-eyed snake that shows a frog (the blue skeleton) in its digestive tract. Photo by Ramon Nagesan, University of Michigan Museum of Zoology
An emerald tree boa in the amazonian rainforest, a specialized predator of small mammals. Photo by Dan Rabosky
an eyelash pitviper from the new world tropics. Photo by Alejandro Arteaga
Graham’s crayfish snake, a harmless semiaquatic species from central Noth America that feeds on crayfish. Photo by Tristan Schramer
A defensive display by a western ring necked snake native to the western United States. Photo by Alison Davis-Rabosky
A cat eyed snake in the Amazonian rainforest. Photo by Alison Davis-Rabosky

By Daniel Dunaief

Eating machines even more focused than teenagers approaching a stocked refrigerator, snakes slither towards foods other animals assiduously avoid.

In a recent and extensive study of snakes using the genetics, morphology and diet of snakes that included museums specimens and field observations, a team of scientists including Pascal Title, Assistant Professor in the Department of Ecology & Evolution at Stony Brook University, showed that the foods skin-shedding creatures eat as a whole is much broader than the prey other lizards consume.

At the same time, the range of an individual snake’s diet tends to be narrower, marking individual species as more specialized predators, a paper recently released for the cover of the high-profile journal Science revealed.

“If there is an animal that can be eaten, it’s likely that some snake, somewhere, has evolved the ability to eat it,” Dan Rabosky, senior author on the paper and curator at the Museum of Zoology and Professor of Ecology and Evolutionary Biology in the College of Literature, Science and the Arts at the University of Michigan, explained in a statement.

The research, which explored the genetics and diets of snakes, suggested that snakes evolved up to three times faster than lizards, with shifts in traits associated with feeding, locomotion and sensory processing.

“This speed of evolution has let them take advantage of new opportunities that other lizards could not,” Rabosky added. “Fundamentally, this study is about what makes an evolutionary winner.”

No singular physical feature or characteristic has enabled snakes to specialize on foods that are untouchable to other animals.

“It seems to be a whole suite of things” that allows snakes to pursue their prey, Title speculates.

One unique aspect of many advanced snakes is that they have more mobile elements in their skulls. Rock pythons can stretch their jaw around enormous prey, making it possible for them to swallow an entire antelope. Garter snakes, meanwhile, can eat Pacific newts that have a high concentration of a neurotoxin. Snakes also can eat slugs and snails that have evolved a defensive ability to secrete toxins.

A change to textbooks

Title, who is the co-lead and first author on the paper, suggested that the comprehensive analysis of snakes, particularly when compared with lizards, will likely change the information that enters textbooks.

“I think the analysis of lizard and snake diets in particular could potentially enter herpetology textbooks because diet is such a fundamental axis of natural history and because the visuals are so clear,” Title said. He doesn’t believe an analysis of dietary resolution that encompasses snakes and lizards has been shown like this before.

With a few exceptions, the majority of lizards eat terrestrial arthropods. Snakes have expanded into eating not only invertebrates, but also aquatic, terrestrial and flying vertebrates.

“They have absolutely evolved the ability to prey on semi-aquatic and aquatic prey,” said Title.

Title and his collaborators gathered considerable amounts of sequence data from GenBank. They also collected data from samples and specimens in the literature.

“Our dataset involves specimen-based data from museum collections that span the globe over the better part of the last century,” he explained.

The project started with the realization that several authors were generating high-quality sequence data for separate projects from biodiversity hotspots for lizards and snakes, such as in Australia, Brazil and Peru. The researchers realized that combining their data provided unprecedented coverage.

After Title completed his PhD at the University of Michigan, he took a leading role in building the phylogeny and conducting many of the analyses.

Indeed, the list of coauthors on this study includes 19 other scientists from the United States, the United Kingdom, Australia, Brazil and Finland.

As for his work, Title is broadly interested in the ecological/ environmental/ geographic/ evolutionary factors that lead to different species richness. He is not restricted to lizards and snakes.

“I do think snakes are unbelievable,” he said. “I’ve seen sidewinder rattlesnakes flip segments of their body forward across the sand in California, I’ve seen snakes climb straight up trees and walls, I’ve seen long, skinny snakes carefully navigate tree branches, and I’ve seen semi-aquatic snakes swim with their head above water. It’s mesmerizing.”

‘Snakes are cool’

Co-lead author Sonal Singhal, Assistant Professor in Biology at California State University, Dominguez Hills, met Title when she was a PhD student and he was an undergraduate at the University of California, Berkeley.

Singhal is excited that readers can “learn cool facts about snakes from our paper,” she explained. “Research papers don’t always inspire a sense of wonder in the reader.” She hopes people “walk away from this study thinking that snakes are cool.”

Singhal suggested that Title is leading a group of collaborators to create a package that will enable other researchers to download the data from this paper quickly and easily and use it in their own work.

As a whole, snakes are moving around in their diet space at a much more rapid clip than lizards in general, Title suggested.

While snakes have evolved rapidly over short periods of time, it’s unclear how these creatures are responding to changes in the environment on smaller time scales, such as through what’s currently occurring amid climate change.

The scale, Title explained, is different, with climate changes affecting the world over decades and centuries, while snake evolution, particularly regarding specialized diets, transpired over the course of millions of years.

Grad school encounter

Title, who lives in East Setauket, met his wife Tara Smiley when both of them were graduate students.

An Assistant Professor in the Department of Ecology & Evolution at Stony Brook University, Smiley is a paleoecologist specializing in small mammals.

The couple enjoys taking their son Micah, who is almost three years old, on camping trips and spending time outdoors.

As for the paper scoring the coveted spot on the cover of Science, Title suggested the exposure validates “that lizards and snakes, and their natural history, are inherently intriguing to all sorts of people, regardless of whether or not they are trained biologists.”

He hopes the work will not only inspire young scientists to learn more about snakes and lizards, but also to seek to quantify and explore the different axes of biodiversity and to “appreciate the value of supporting natural history museum collections.”

———————————————————————————–Within a day of snake research published on the cover of Science last week, reports surfaced about the discovery of what may be the largest snake in the world. Scientists from the University of Queensland found a northern green anaconda in the Ecuadorian Amazon that was close to 21 feet long.

Pacal Title, Assistant Professor in the Department of Ecology & Evolution at Stony Brook University and first author on the recent Science paper, offered his thoughts in an emailed question and answer exchange about the anaconda, which was not a part of his recent research.

TBR: Is this a particularly compelling find?

Title: This is compelling as it provides an example of broadly distributed, large species of snakes having pretty significant genetic differentiation. There are quite a few examples, both within snakes and in other groups, where populations look superficially similar, but turn out to have been genetically independent of one another for quite a long time.

TBR: How does a discovery of what might be the largest snake in the world fit into the context (if at all) of your research? Does this species validate the radiative speciation you described?

Title: It shows that the number of known snake species is likely to be an under-estimate, although this is likely to be true for most groups out there. This fits well into the perspective that snakes have incredibly high global species diversity.

TBR: Do you have any guesses as to what the diet of this snake could be?

Title: The article describes anaconda diets as generally consisting of terrestrial vertebrate prey, despite the species being semi-aquatic.

TBR: What, if any, predators might pursue this snake?

Title: Jaguars have been known to prey on anacondas.

TBR: What scientific, life history, genetic or other questions would you address, if any, about this species?

Title: Now that the green anaconda is being considered as two separate species, all morphological, ecological and natural history attributes will need to be re-examined to evaluate whether or not the two species actually differ along any of these axes.

TBR: Is the ongoing attention snakes receive positive for the study of snakes?

Title: It is great that snakes are receiving positive attention. Such new studies are essential for conservation, and for the study of biodiversity and ecosystems.

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From left, Prerana Shrestha, Sunghoon Kim (Postdoc), Andrew Gallagher (Research Support Specialist), Miura Traficante (SOAR Fellow, Summer undergrad researcher), Keith Yeung (Undergraduate researcher), Matthew Dickinson (PhD student), Saheed Lawal (PhD student), and Olivia Tabaka (MS student)

By Daniel Dunaief

An increasingly complex time filled with extreme stressors such as man-made and natural disasters creates conditions that can lead to post traumatic stress disorder.

PTSD, which can cause anxiety even amid safer conditions, can have adverse effects on the ability to enjoy life.

Prerana Shrestha

Stony Brook University Assistant Professor Prerana Shrestha, who joined the Department of Neurobiology and Behavior at the Renaissance School of Medicine in 2021, recently received a four-year $2.2 million grant from the National Institute of Mental Health to study the molecular mechanisms underlying stabilization of emotional memories in the brain, which is relevant for PTSD.

“Her work will help us understand how the brain stores these traumatic memories,” said Alfredo Fontanini, chair of the Department of Neurobiology and Behavior. “The tools she has developed really are making possible a series of experiments that, before, were impossible to think about.”

Shrestha hopes to develop a druggable target that could “block a key machine inside neurons that are relevant for traumatic emotional memories,” she explained.

Using a mouse model, Shrestha plans to understand the neural signature at the level of molecules, neurons, and neural circuits, exploring the creation and stabilization of these potentially problematic memories and emotional reactions through a multi-disciplinary study.

Shrestha has developed and applied chemogenetic tools to block a key part of the memory process inside neurons that store traumatic emotional memories.

By developing tools to explore neural circuits in particular areas of the brain, Shrestha can help scientists understand the molecular mechanism involved in PTSD, Fontanini said.

‘From the ground up’

In humans, memories from traumatic events are over consolidated, creating an excessive avoidance behavior that can be a debilitating symptom.

“We are trying to understand the neurological basis for why these memories are so robust,” Shrestha said. She is looking at “what can we do to understand the mechanism that supports these memories from the ground up.”

With her chemogenetic tools, Shrestha can block protein synthesis in specific neuron populations in a time period of a few hours. She is developing new tools to improve the precision of blocking the protein synthesis machinery from hours to minutes.

Shrestha is trying to weaken the salient emotional memory while leaving all other processes intact.

The Stony Brook Assistant Professor said she has methods to create a targeted approach that limits or minimizes any off target or collateral damage from inhibiting the synthesis of proteins.

“Up until now, whenever scientists wanted to study the role of the synthesis of new proteins in memory formation” including those involved in the formation of aberrant memories such as those in PTSD, they had to “use drugs which would manipulate and affect protein synthesis everywhere in the brain,” said Fontanini.

The plan over the next four years is to understand and develop molecules to target cells in the prefrontal cortex, which, Shrestha said, is like the “conductor of an orchestra,” providing top-down executive orders for the brain.

She is focusing on neurons that interact specifically with the amygdala, which is the emotional center of the brain, exploring what happens in these streams of information between brain regions.

By increasing or reducing protein synthesis in the prefrontal cortex, Shrestha can see an enhanced or diminished avoidance response in her mouse experiments.

She is interested in how a memory is stabilized, and not as much in what is involved in its retrieval.

Shrestha works with inbred mice that are more or less genetically identical. Her experimental group has the transgenic expression of the chemogenetic tool to block protein synthesis and receive a drug after learning that triggers the tool to block the machinery from making new proteins.

When she introduces the inhibitor of protein synthesis, she found that the wave involved in stabilizing what the animal previously learned is finite in time.

Using a drug to block protein synthesis within an hour alters future behavior, with the animal showing little or no fear. Blocking protein synthesis after that hour, however, doesn’t affect the fear response.

In the first year of the grant, which started in December, Shrestha would like to send out some papers for publication based on the research her team members — postdoctoral researcher  Sunghoon Kim and graduate student Matthew Dickinson —  has already done. She also hopes to use some of the funds from this grant to hire another postdoctoral researcher to join this effort.

She has data on how the regulators of ribosomes are recruited in the prefrontal cortex, which stabilizes memories.

In other preliminary data, she has identified neurons in the prefrontal cortex that project into the amygdala that are selectively storing information for recent parts of emotional memory.

To be sure, while this research offers a potential window into the mechanisms involved in forming emotional memories in a mouse model, it is an early step before even considering any new types of diagnostics or treatment for humans.

Nepal roots

Born and raised in Kathmandu, Nepal, Shrestha received a full scholarship to attend Bates College, in Maine, where she majored in biological chemistry. She received a Howard Hughes Medical Institute fellowship for an internship at Harvard Medical school during her junior year. While preparing for a pre-medical track, she “got spoiled after getting a taste of research in my junior year,” she said. “The idea of trying something new for the first time and seeing how things work was so cool.”

Shrestha lives about eight miles west of Stony Brook and is married to Sameer Maskey, the founder and CEO of an advanced machine learning company called FuseMachines Inc. They have a nine-year old daughter and a two-year-old son.

As for her ongoing work, Shrestha is eager to combine her expertise with those of people from different backgrounds.  “It’s a fascinating time to combine molecular approaches,” she said. 

Fontanini, who helped recruit Shrestha, has been impressed with the work she’s done.

“She’s on an outstanding trajectory,” he said.

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