Represented in this illustration is the authors’ finding that DNA hypermethylation disrupts CCCTC-binding factor (CTCF) mediated boundaries which in turn lead to aberrant interactions between an oncogene and an enhancer, driving hyperproliferation and subsequently tumorigenesis from normal OPCs. Photo by William Scavone/Kestrel Studio
Study in Cell led by Stony Brook researcher provides unique analysis in a glioma model
Gliomas are incurable brain tumors. Researchers are trying to unlock the mysteries of how they originate from normal cells, which may lead to better treatments. A new study published in the journal Cell centers on epigenetic rather than genetic changes that drive normal cells to form tumors. The work reveals the precise genes that are regulated epigenetically and lead to cancer.
Genes make us who we are in many ways and are central to defining our health. Cancer is often viewed as a disease caused by changes in our genes, thus our DNA. Epigenetics is the study of how behavior, environment, or metabolic changes can cause alterations to the way genes work. Unlike genetic changes, epigenetic changes do not change one’s DNA, and they can be reversed.
“We used tumor samples and mouse modeling to discover and functionally demonstrate the role of epigenetic alterations in gliomas,” says Gilbert J. Rahme, PhD, first author and Assistant Professor in the Department of Pharmacological Sciences at the Renaissance School of Medicine, and formerly a postdoctoral fellow at the Dana-Farber Cancer Institute in Boston. “By doing this, we discovered genes regulated epigenetically in gliomas, including potent tumor suppressor genes and oncogenes, that drive the tumor growth.”
In the paper, titled “Modeling epigenetic lesions that cause gliomas,” the research team show in the model that epigenetic alterations of tumor suppressor and oncogenes collaborate together to drive the genesis of this brain tumor.
The authors explain that “epigenetic activation of a growth factor receptor, the platelet-derived growth factor receptor A (PDGFRA) occurs by epigenetic disruption of insulator sites, which act as stop signs in the genome to prevent aberrant activation of genes. The activation of PDGFRA works in concert with the epigenetic silencing of the tumor suppressor Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) to transform a specific cell type in the brain, the oligodendrocyte progenitor cell (OPC), driving the formation of brain tumors.”
Rahme says the next step is to test whether therapies that can reverse the epigenetic changes observed in brain tumors can be helpful as a treatment.
From the shore, they can look like odd-shaped shadows with tails, moving in and out of the surf or approaching the shoreline.
Up close, they can have a collection of barnacles attached to their shells, particularly as they age.
Horseshoe crabs, who have been roaming the oceans for over 450 million years, have attracted the admiration of researchers and the dedication of volunteers around Long Island, who not only want to ensure they continue to survive, but also would like to know more about creatures that are more related to spiders and scorpions than to the crabs their names suggest.
“One of the things we’re trying to do is look at spawning in a more comprehensive way,” said Robert Cerrato, a professor in the School of Marine and Atmospheric Sciences at Stony Brook University. “We’re trying to figure out if there are specific things that [horseshoe crabs] are responding to” when they come up on the beach to lay their eggs.
A closeup of two horseshoe crabs. Photo courtesy Matthew Sclafani
Horseshoe crabs have had a steady decline in their population over the last 20 years overall. In the last three to five years, however, not much has changed in the Long Island area, scientists explained.
The population is “still very similar to where it was,” said Matthew Sclafani, senior resource educator at Cornell Cooperative Extension of Suffolk County and assistant adjunct faculty member at SBU.
Scalafani and Cerrato have worked together for well over a decade and are hoping to address a wide range of questions related to these unusual creatures that have nine eyes and blue blood.
Apart from the fascination of scientists and volunteers, the horseshoe crab provides a critical food source for shore birds like the Red Knot, which depends on these eggs during their migration.
At the same time, horseshoe crabs and their blue blood provide a key ingredient in tests of pharmaceuticals. When exposed to endotoxins, horseshoe crab blood forms clots.
The use of horseshoe crab blood to test drugs does not occur in New York, however, as companies don’t catch these creatures in the Empire State for this specific test.
Cerrato and Scalafani explained that numerous towns have also limited or banned the harvesting of horseshoe crabs to maintain their local populations.
Areas around West Meadow Beach in Old Field, for example, are closed to hand harvesting, as is Jamaica Bay and Gateway National Recreation Area.
Such policies “theoretically will allow for more eggs on the beach to hatch and for shore birds dependent on them” to find food, Sclafani said. Such closures, including some during the last two weeks in May and the first two weeks in June during the peak spawn were “significant steps for conservation,” Sclafani added.
An aerial photograph taken by a drone during a horseshoe crab survey at Pike’s Beach, Westhampton. Photo by Rory MacNish/Cornell Cooperative Extension of Suffolk County
Ongoing questions
By labeling and tracking horseshoe crabs, these researchers and a team of volunteers hope to understand whether crabs, which are capable of reproducing when they are between 8 and 10 years old, return to the same sites each year to lay their eggs.
Cerrato and Scalafani are hoping to get satellite tags they can attach to adults, so that when they come out of the water to spawn, researchers know their location.
The researchers submitted a proposal to the New York State Department of Environmental Conservation to do a pilot study with these satellite tags.
Juvenile horseshoe crabs also present unknowns, as they have a different diet and migrate at a much lower rate.
“We started to look at” crabs that are 3 to 10 years old, said Cerrato. Moriches Bay is an “important habitat” for them.
Volunteer passion
Volunteers who help count the horseshoe crabs count these creatures often until well after midnight.
Frank Chin has been wandering beaches, counting crabs for 15 years. When he was young, Chin wanted to be a forest ranger.
“I realized that forest rangers don’t make that much money, so I went to school for engineering, got a degree and worked as an engineer,” he said.
Chin found himself at a Friends of Flax Pond meeting, where Scalafani asked for help from the community.
“I foolishly raised my hand and they made me a coordinator,” joked Chin, who counts horseshoe crabs with his wife Phyllis.
Every year presents something new to Chin.
This year, he has run into people who fish late at night. Chin said the fishermen, who have permits, are cordial, but that he’s concerned they might be scaring crabs away from their usual spawning spots.
In addition to counting the crabs, Chin, who is the director of the lab in the Physics Department at SBU, also tags them. He once caught a crab seven years after he initially tagged it.
Chin, who will count crabs in the rain but not in thunderstorms, appreciates the dedication of his fellow volunteers, who not only count the crabs but will pick up garbage and bottles along the beach.
Chin plans to continue to “do it as long as I can walk down the beach.” Some day, he “hopes someone else will take over.”
A problematic atmospheric greenhouse gases, methane comes from natural gas, agriculture, and swamps.
John Mak
Recently, John E. Mak, a Professor in the School of Marine and Atmospheric Sciences at Stony Brook University worked with an international group of scientists to demonstrate a process that removes methane from the atmosphere.
A mixture of dust from the Sahara and sea spray reacts with methane to form carbon monoxide and a small amount of hydrochloric acid.
In a recent paper published in the prestigious journal Proceedings of the National Academy of Sciences, Mak, corresponding author Matthew Johnson, who is a Professor in the Department of Chemistry at the University of Copenhagen, and others showed how a novel process removes 5 percent, plus or minus 2 or 3 percent, of the methane from the atmosphere in specific areas.
“What we are showing is that some methane in the middle of the tropical Atlantic Ocean region may be removed” through this process, Mak said from the Gordon Research Conference on Atmospheric Chemistry in Sunday River, Maine.
The research validates a mechanism Mak had proposed in the late 1990’s, when he conducted studies funded by the National Science Foundation in Barbados. “When I first made the observations, I proposed that what we were seeing was a chlorine mediated removal of methane,” Mak explained.
At that time, he didn’t have the ability to make those measurements. The technology, however, has evolved over the years and researchers can now measure chlorine radical precursors such as Cl2 and other chlorine compounds.
Indeed, Maarten van Herpen, first author on the study and a member of Acacia Impact Innovation, approached Mak with a new theory and a new mechanism that he thought could explain Mak’s results from decades earlier.
“They were excited to hear that no one had solved the problem,” said Mak.
By working together through this international team, the group was able to take new measurements and utilize advances in their understanding of atmospheric processes.
‘New, but old’
Mak had conducted his studies towards the beginning of his time at Stony Brook University in the late 1990’s as a part of one of his first federally funded projects.
“It’s a little unusual for people to make use of observations so far in the past,” said Mak. “It opens up a new, but old avenue of research.”
Mak, who is conducting studies in other areas including a recent project in New York to investigate air quality and air chemistry mechanisms specific to the greater New York City region, believes the research on this PNAS paper takes him almost full circle back to this earlier work.
“There’s a feeling of satisfaction that good measurements are useful for a longer period of time,” he said.
In this study, Mak helped interpret some of the data his collaborators generated.
The reactions
The process of removing methane starts with sea spray, which is aerosolized by bubbles bursting at the contact point between the ocean and the air. The chlorine comes from that sea spray, while iron comes from the continental crust.
Saharan dust can traverse the globe, but scientists are not sure of the spatial extent of this process. They believe it could be throughout the tropical Atlantic, but it could be in other dust laden ocean regions in the Indian and Pacific Oceans as well.
That process creates what is described as a reactive chlorine species, which is on the hunt for a positively charged particle, such as one of the four hydrogen atoms attached to carbon in methane.
Once the chlorine removes a hydrogen, it creates a methyl group, or CH3, and an incredibly small amount of hydrochloric acid, or HCl, at about one part per quadrillion.
The acid, in fact, is so low that it doesn’t cause any acidification of the oceans. Ocean acidification primarily comes from the absorption of carbon dioxide gas, which reacts with seawater and eventually increases the amount of positively charged hydrogen atoms, decreasing the ocean’s pH.
Meanwhile in the atmosphere, the remaining methyl group is oxidized to carbon monoxide, which eventually becomes carbon dioxide. That is also a greenhouse gas, but is not as potent at trapping heat in the atmosphere as methane.
Now that the group has explored this process, Mak explained that the next step will involve proposing a field campaign in the tropical Atlantic with state of the art instruments.
Mak believes the journal PNAS likely found the subject matter compelling on a broader scale, particularly because this process affects weather and climate.
Outside work
When he’s not working, Mak enjoys boating and fishing. A native of Southern California, Mak is a commercial pilot, who also does some flying as a part of his research studies.
As for climate change, Mak suggested that the weather extremes from this year, which include record high temperatures in the ocean near the Florida Keys and high temperatures in areas in Arizona, are a part of a pattern that will continue.
“What we have been and will continue to observe are changes to the broad equilibrium of energy balance of the Earth ocean atmosphere system,” he explained. “There’s a lot of inertia in the system. But when you change the input by changing the forcing, you upset that equilibrium.” That, he explained, could alter the weather, which is generated as a response to differences in energy from one place to another.
This graphic shows how per unit water saving by dry cooling increases carbon emissions by each power unit globally, a significant issue for example in areas of India. Qin et al., 2023. Nature Water
Study published in Nature Water suggests integrating planning may reduce carbon emissions in the future
Water scarcity and climate change is a threat to energy security, as carbon emission reduction from water and dry cooling of power plants remains a major challenge worldwide. An international collaboration of scientists including Gang He, PhD, of Stony Brook University, used global power plant data to demonstrate an integrated water-carbon management framework that bridges the gap to coupling diverse water carbon-mitigation technologies with other methods. Their findings are detailed in a paper published in Nature Water.
Thermal electric power generation uses substantial amounts of freshwater primarily for cooling of power plants, amounting to 40 to 50 percent of the total water withdrawal in the U.S. and 40 percent in Europe. Meanwhile, power generation accounted for approximately 36 percent of the energy-related carbon dioxide (CO2) emissions across world economies in 2019. The authors note that consequently, the power sector has a high dependence on freshwater resources and demonstrates intrinsic water-carbon interconnections that have critical implications on reliable electricity output and energy security, particularly under climate change.
In “Global assessment of the carbon-water tradeoff of dry cooling for thermal power generation,” they conclude such integrated planning is crucial to address the complex interactions between water and energy systems. The team constructed a global unit-level framework to assess the impact of dry cooling—a vital water mitigation strategy—alongside alternative water sourcing and carbon capture and storage (CCS) under different scenarios.
According to He, a co-author and Assistant Professor in the Department of Technology and Society at Stony Brook University, the research team collected unit-level power plant data, which included basic power generation unit information such as fuel and engine types, installed capacity, cooling technologies and other details. Then they estimated carbon emissions and water withdrawal based on what is known of emission factors at plants and water intensity by the cooling technologies, fuel types and local meteorology.
He says that from their global data the CO2 emission and energy penalty from dry cooling units were found to be location and climate specific, and ranged from 1 to 15 percent of power plant output. Additionally, efficiency losses were high under climate changes scenarios.
On a positive note, the team discovered potentially promising solutions to alleviate water scarcity around the power plants – such as increasing accessibility to wastewater and brine water that can provide viable alternatives to dry cooling and reduce energy and CO2 penalties.
Additionally, He and coauthors concluded that CCS emerged as a valuable tool to offset CO2 emission tradeoffs associated with dry cooling, especially when alternative water sourcing alone is insufficient in certain power plant regions.
However, He stresses that the issue is complicated globally, as CCS could demand more energy and thus more emissions, and wastewater could be useful but has its limitations and may not be available near some power plants.
The authors are concerned about the potentially increasing water-carbon tradeoffs with dry cooling. They write: “Facing increasing water concerns, dry cooling has been and may continually be promoted as an emerging freshwater mitigation technique in some major economies in the next few decades along with renewable energy transitions.”
He says the research leading to the paper underscores the urgency of integrated power sector planning in the face of dual water-carbon challenges and “highlights the importance of considering climate-specific factors and interconnected systems to achieve sustainable energy solutions.”
The work was led by Dr. Yue Qin of Peking University. He’s research contributing to the paper findings is supported by the Global Energy Initiative at the ClimateWorks Foundation.
Maurizio Del Poeta is taking another approach to battling fungal infections that can be deadly, particularly for people who are immunocompromised.
Maurizio Del Poeta. Photo from SBU
A Distinguished Professor at Stony Brook University in the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University, Del Poeta has made progress in animal models of various fungal infections in working on treatments and vaccines.
After receiving an additional $3.8 million from the National Institutes of Health for five years, Del Poeta is expanding on some findings that may lead to a greater understanding of the mechanism that makes some fungal infections problematic.
The Stony Brook Distinguished Professor is studying “what makes people susceptible to fungal infections,” he said. “It’s something I’m really passionate about.”
Del Poeta explained that researchers and medical professionals often focus on the people who get sick. Understanding those people who are not developing an infection or battling against a fungus can provide insights into ways to understand what makes one population vulnerable or susceptible and another more resistant.
Expanding such an approach outside the realm of fungal infections could also provide key insights for a range of infections in the future.
Indeed, the awareness of specific signals for other infections could help protect specific populations, beyond those who had general categories like underlying medical conditions, who might be more vulnerable amid any kind of outbreak.
“It’s possible that the study we are doing now with fungi could stimulate interest” in other areas of infectious disease, Del Poeta said.
He suggested that this was “pioneering work” in terms of fungal infections. At this point, his lab has produced “strong preliminary data.”
An important drug treatment side effect as a signal
This investigation arises out of work Del Poeta had done to understand why some people with multiple sclerosis who took a specific drug, called fingolimid, developed fungal infections during their drug treatment.
Del Poeta observed that the drug inhibits a type of immunity that involves the movement of lymphocytes from organs into the bloodstream.
Fingolimid mimics a natural lipid, called a sphingolipid. Del Poeta showed that this sphingolipid is important to contain the fungus Cryptococcus neoformans in the lung. When its level decreases, the fungus can move from the lung to the brain.
Indeed, Fingolimid mimics sphingosin-1-phosphate (S1P) and binds to several S1P receptors.
Del Poeta believes that the pathway between S1P and its receptor regulates the immunity against Cryptococcus. Blocking a specific receptor is detrimental for the host and may lead to reactivation of the fungus.
Putting a team together
Nathália Fidelis Vieira de Sá. Photo by Futura Convites studio
Del Poeta has been working with Iwao Ojima, a Distinguished Professor and the Director of the Institute of Chemical Biology and Drug Discovery in the Department of Chemistry at Stony Brook, to create compounds that energize, instead of block, the target of fingolimid.
Del Poeta has recruited two scientists to join his lab in this effort, each of whom has educational experience in nursing.
Nathália Fidelis Vieira de Sá, who is a registered nurse at the Federal University of Minas Gerais and a chemistry technician at Funec- Contagem City, will join the lab as a technician in the second week of September.
Fidelis Vieira de Sá, who currently lives in her native Brazil, is an “expert on collecting and analyzing organs for mice,” explained Del Poeta in an email.
For her part, Fidelis Vieira de Sá is thrilled to join Del Poeta’s lab at Stony Brook. “I’m very excited,” she said in an email. She is eager to get started because the research is “of such great relevance to public health” and is occurring at such a “renowned institution.”
Fidelis Vieira de Sá believes this is a public health issue that could have a positive impact on people with immunodeficiency conditions who need effective treatment so they live a better, longer life. When she was a peritoneal dialysis nurse, she had a few patients who had fungal infections.
“This is very serious and challenging, detection is difficult, and the life expectancy of these patients drops dramatically with each episode of infection,” she explained.
Fidelis Vieira de Sá, who has never lived outside Brazil, is eager for new experiences, including visiting Central Park, the Statue of Liberty, Times Square, and the One World Trade Center Memorial.
As for the work, she hopes that, in the near future, Del Poeta will “be able to explain this mechanism deeply and to develop new drugs that will act on this receptor.”
Dr. Marinaldo Pacífico Cavalcanti Neto
Dr. Marinaldo Pacífico Cavalcanti Neto, who is an Assistant Professor at Federal University of Rio de Janeiro, will be arriving at Stony Brook University on August 6. Dr. Neto earned his bachelor of science in nursing and has a PhD in biochemistry from the Medical School of Ribeirão Preto at the University of São Paulo.
Del Poeta described Dr. Neto as an “expert on animal handling and genotyping,”
Dr. Neto recognizes the burden of fungal infections around the world and hoped to work with someone with Del Poeta’s credentials and experience in immunology and infection.
Understanding how cells eliminate infection, how cells might have a lower capacity to control an infection, and looking for how cells respond to treatments such as fingolimid could be a “great strategy to understand why these are so susceptible,” he said.
While Dr. Neto’s background is in immunology, he hopes to learn more about molecular biology.
Unlike Fidelis Vieira de Sá, Dr. Neto, who will live in Centereach, has worked previously in the United States. He has experience at the National Institutes of Health and at the University of California at San Diego and has been attending Del Poeta’s lab meetings from a distance for about a month.
Dr. Neto, whose interest in science increased while he watched the TV show Beakman’s World while he was growing up, is eager to work in an area where he can apply his research.
He appreciates that his work may one day “be used in the generation of protocols in a clinic.
John Hill, a distinguished physicist who is widely recognized as a world leader in x-ray scattering research, has been named deputy director for science and technology (DDST) at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, effective July 1.
Hill’s appointment comes after an international search that began in March 2022, when current DDST Robert Tribble announced his plans to step down after eight years in the position.
“John Hill offers vision, institutional knowledge, and a track record of sound leadership,” said JoAnne Hewett, who was named the next director of Brookhaven Lab in April. “I look forward to working with him and the entire Brookhaven Lab community at the forefront of science.”
Jack Anderson is serving as interim director until Hewett joins the Lab later this summer.
In his new position, Hill will work closely with Hewett, the Lab’s science leaders, and the Brookhaven Science Associates (BSA) Board of Directors and its committees in charting the Laboratory’s future research directions (BSA, a partnership between Stony Brook University and Battelle, manages and operates the Lab on behalf of the DOE Office of Science). More than 2,600 scientists, engineers, technicians, and professionals at Brookhaven are currently working to address challenges in nuclear and high energy physics, clean energy and climate science, quantum computing, artificial intelligence, isotope research and production, accelerator science and technology, and national security.
“I am incredibly excited to be taking on this role,” said Hill who is a resident of Stony Brook. “Brookhaven Lab has a long history of carrying out world-leading science for the benefit of the Nation and I am honored to be chosen to help lead the Lab as we continue that tradition and seek to answer some of the most important scientific questions facing the world today.”
Hill, a long-time employee of Brookhaven Lab, joined its Physics Department as a postdoc in 1992. He progressed through the ranks and has been director of the National Synchrotron Light Source II (NSLS-II), a DOE Office of Science User Facility located at Brookhaven, since 2015.
NSLS-II is one of the most advanced synchrotron light sources in the world. It produces ultra-bright x-rays for researchers to study materials for advances in energy, quantum computing, medicine, and more.
In addition, Hill has served as deputy associate laboratory director for energy and photon sciences since 2013. He also chaired Brookhaven Lab’s COVID-19 science and technology working group and represented Brookhaven as a member of DOE’s National Virtual Biotechnology Laboratory, a consortium comprising all 17 national laboratories working to address challenges in the fight against COVID-19.
Hill’s research has focused on using resonant elastic and inelastic x-ray scattering to study magnetic and electronic phenomena. He has authored more than 120 articles published in peer-reviewed journals and has been recognized with both a Presidential Early Career Award and a DOE Young Independent Scientist Award. He was elected a fellow of the American Physical Society. Brookhaven Lab awarded Hill its Science and Technology Award—one of the Lab’s highest accolades—in 2012.
Hill earned a Ph.D. in physics from the Massachusetts Institute of Technology. He earned his bachelor’s degree in physics from Imperial College in London.
——————————–
Brookhaven celebrated its 75th anniversary in 2022 and is home to seven Nobel Prize-winning discoveries and countless advances. Its 5,322-acre site attracts scientists from across the country and around the world, offering them expertise and access to large user facilities with unique capabilities. Each year, Brookhaven hosts thousands of guest researchers and facility users—in-person and virtually—from universities, private industry, and government agencies. The Lab’s annual budget is approximately $700 million, much of which is funded by the DOE and its Office of Science.
Brookhaven National Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit science.energy.gov.
Follow @BrookhavenLab on social media. Find us on Instagram, LinkedIn, Twitter, and Facebook.
From left, graduate students Thomas Reilly and Hanxiao Wu with Weisen Shen. Wu and Shen are holding two of the 183 sensors they will place in the Antarctic. The team is shipping the sensors in the black container, which will travel through Port Hueneme, California and New Zealand before reaching the South Pole. Photo by Maeve McCarthy/ Angela Gruo
By Daniel Dunaief
While it’s easy to see and study materials in valleys or on the tops of bare mountains, it’s much more difficult to know what’s beneath 2.7 kilometers of ice. Turns out, that kind of question is much more than academic or hypothetical.
At the South Pole, glaciers sit on top of land that never sees the light of day, but that is relevant for the future of cities like Manhattan and Boston.
The solid land beneath glaciers has a strong effect on the movement of the ice sheet, which can impact the melting rate of the ice and sea level change.
Weisen Shen, Assistant Professor in the Department of Geosciences at Stony Brook University, recently received over $625,000 over the course of five years from the National Science Foundation to study the unexplored land beneath the East Antarctic Ice Sheet at the South Pole.
The subglacial water and hydrosystems, together with geology such as sediment or hard rocks, affect the dynamics and contribute to the movement speed of the ice sheet.
Once Shen provides a better understanding of the material beneath the ice, including glacial water, he can follow that up with other researchers to interpret the implications of ice sheet dynamics.
“We can predict better what’s the contribution of the Antarctic ice sheet to the sea level change” which will offer modelers a way to gauge the likely impact of global warming in future decades, he said.
Using seismic data
Starting this November, Shen and graduate students Siyuan Sui, Thomas Reilly and Hanxiao Wu will venture for two months to the South Pole with seismic monitors.
By placing 183 seismic nodes and installing an additional eight broad-band seismic stations, Shen and his team will quantify the seismic properties and, eventually, use them to infer the composition, density and temperature structure of the crust and the uppermost mantle.
The temperature when they place these monitors will be 10 to 30 degrees below 0 degrees Fahrenheit. They will need to do some digging as they deploy these sensors near the surface.
While the South Pole is believed to be geologically stable, signs of sub-glacial melting suggest the crust may bear a higher concentration of highly radioactive elements such as uranium, thorium and potassium.
Those natural elements “produce heat all the time,” said Shen.
The process and analysis of seismic waves works in the same way it would for the study of a prism. Looking at the refraction of light that enters and leaves the prism from various angles can help researchers differentiate light with different frequencies, revealing clues about the structure and composition of the prism.
Earth materials, meanwhile will also cause a differentiation in the speed of surface waves according to their frequencies. The differentiation in speeds is called “dispersion,” which Shen and his team will use to quantify the seismic properties. The area has enough natural waves that Shen won’t need to generate any man-made energy waves.
“We are carefully monitoring how fast [the seismic energy] travels” to determine the temperature, density and rock type, Shen said.
The water beneath the glacier can act like a slip ’n slide, making it easier for the glacier to move.
Some large lakes in Antarctica, such as Lake Vostok, have been mapped. The depth and contours of sub glacier lakes near the South Pole, however, are still unclear.
“We have to utilize a lot of different methods to study that,” said Shen.
The Stony Brook researcher will collaborate with colleagues to combine his seismic results with other types of data, such as radar, to cross examine the sub ice structures.
The work will involve three years of gathering field data and two years of analysis.
Educational component
In addition to gathering and analyzing data, Shen has added a significant educational component to the study. For the first time, he is bringing along Brentwood High School science teacher Dr. Rebecca Grella, A PhD graduate from Stony Brook University’s Ecology and Evolutionary Biology program, Grella will provide lectures and classes remotely from the field.
In addition to bringing a high school teacher, Shen will fund graduate students at Stony Brook who can help Brentwood students prepare for the Earth Science regents exam.
Shen is working with Kamazima Lwiza, Associate Professor in the School of Marine and Atmospheric Sciences at Stony Brook, to bring Earth Science, including polar science, to schools in New York City and on Long Island with a bus equipped with mobile labs.
Lwiza, who is the Principal Investigator on the EarthBUS project, will work together with Shen to build a course module that includes a 45-minute lecture and exhibition.
Shen feels that the project will help him prepare to better educate students in graduate school, college, and K-12 in the community.
He feels a strong need to help K-12 students in particular with Earth Science.
As for students outside Brentwood, Shen said he has an open door policy in which the lab is receptive to high school and undergraduate students who would like to participate in his research all year long.
Once he collects the first batch of data from the upcoming trip to the South Pole, he will have to do considerable data processing, analysis and interpretation.
While Shen is looking forward to the upcoming field season, he knows he will miss time in his Stony Brook home with his wife Jiayi Xie, and his four-and-a-half year old son Luke and his 1.5 year old son Kai.
“It’s a huge burden for my wife,” Shen said, whose wife is working full time. When he returns, he “hopes to make it up to them.”
Shen believes, however, that the work he is doing is important in the bigger picture, including for his children.
Record high temperatures, which are occurring in the United States and elsewhere this summer, will “definitely have an impact on the dynamics of the ice sheet.” At the same time, the Antarctic ice sheet is at a record low.
“This is concerning and makes [it] more urgent to finish our work there,” he added.
It’s almost easier to figure out what makes Earth unique among the planets than it is to list the ways humans are unique among Earth’s inhabitants. Earth is, after all, the only blue planet, filled with water from which humans, and so many other creatures, evolved. It is also the only planet on which seven enormous plates deep beneath the surface move. These unique features have led scientists to expect certain features that give Earth its unique geological footprint.
Not so fast.
According to a recent paper in the high-profile journal Nature in which Timothy Glotch, Professor of Geosciences at Stony Brook University, was a co-author, the moon has a vast swath of over 50 kilometers of granite in the Compton-Belkovich Volcanic complex, which is on the its far side.
Usually formed from plate tectonics of water bearing magma, the presence of this granite, which appears in greater quantities around the Earth, is something of a planetary mystery.
“Granites are extremely rare outside of Earth,” said Glotch. “Its formation process must be so different, which makes them interesting.”
The researchers on this paper, including lead author Matt Siegler, a scientist at the Planetary Science Institute, suggest a range of possibilities for how the granite formed. Over three billion years ago, the moon, which, like the Earth, is over 4.5 billion years old, had lava that erupted to form the Compton-Belkovich Volcanic Complex, or CBVC. Researchers think most volcanic activity on the moon ended about two billion years ago.
This illustration shows the Compton-Belkovich Volcanic Complex (CBVC) on the Moon’s far side and the boxed area indicated a large granite zone, which could not be picked up by topography. Image courtesy of Matthew Siegler/Planetary Science Institute/Nature
The magma formed as a result of a melting of a small portion of the lunar mantle. Melting could have been caused by the addition of water or the movement of hot material closer to the surface. Scientists are not completely sure about the current nature of the lunar core.
As for the granite, it might have come from fractionation, in which particles separate during a transition from different phases, in this case from a hot liquid like magma to a solid.
Additionally, the presence of granite could suggest that some parts of the moon had more water than others.
“There are other geochemical arguments you could make,” Glotch said. “What we really need are to find more samples and bring them back to Earth.”
The analysis of granite on the moon came from numerous distant sources, as well as from the study of a few samples returned during the Apollo space missions. The last time people set foot on the moon was on the Apollo 17 mission, which returned to Earth on Dec. 19, 1972.
A 10-year process
The search and study of granite on the moon involved a collaboration between Glotch and Siegler, who have known each other for about 18 years. The two met when Glotch was a postdoctoral researcher and Siegler was a graduate student.
In 2010, Glotch published a paper in the journal Science in which he identified areas that have compositions that are similar to granite, or rhyolite, which is the volcanic equivalent.
Since that paper, Glotch and others have published several research studies that have further characterized granitic or rhyolitic materials, but those are “still relatively rare,” Glotch said.
Long distance monitoring
Led by Siegler and his postdoctoral researcher Jiangqing Feng, the team gathered information from several sources, including microwave data from Chinese satellites, which are sensitive to the heat flow under the surface.
The team also used the Diviner Lunar Radiometer Experiment, which is a NASA instrument on the Lunar Reconnaissance Orbiter, that measures surface temperatures.
Part of the discovery of the silicic sites on the moon comes from the identification of the element thorium, which the Lunar Prospector Gamma Ray Spectrometer found. Similar to uranium or plutonium, thorium is radioactive and decays.
Another piece of data came from the Grail mission, which measures the lunar gravity field.
Glotch suggested that the study involved a “daisy chain of observations.” In his role, he tried to identify sites that might be rich in granite, while Siegler applied new data to these areas to learn more about the underground volcanic plumbing.
In addition to doing long distance monitoring, Glotch engages in long distance recreational activities. The Stony Brook professor is preparing for a November 11th run in Maryland that will cover 50 miles. He expects it will take him about 10 or 11 hours to complete.
Looking at other planets
By analyzing granite on the moon, which could reveal its early history, geologists might also turn that same analysis back to the Earth.
“Can we use the results of this study to take a more nuanced view of granite formations on Earth or other bodies in our solar system?” Glotch asked. “We can learn a lot, not just about the moon, but about planetary evolution.”
NASA is planning a DAVINCI+ mission to Venus in the coming decade, while a European mission is also scheduled for Venus. Some researchers have suggested that Venusian terrains, which are referred to as Tesserae, might be granitic.
“If Venus has continent-like structures made of granite, that’s interesting, because Venus does not appear to have plate tectonics either,” Glotch said.
Closer to Earth, some upcoming missions may offer a better understanding of lunar granite. The first is a small orbiter called Lunar Trailblazer that will have sensitive remote instruments. The second is a part of NASA’s Commercial Lunar Payload Services program, which will include a small lander and rover that will land on the Gruithuisen Domes.
Conference in Italy
In the shorter term, Glotch and Siegler plan to attend the 10th Hutton Symposium in Italy.
Glotch is eager to discuss the work with researchers who are not planetary scientists to “get their take on this.”
He is excited by the recent planetary decadal survey, which highlighted several priorities, which include lunar research.
In his opinion, Glotch believes the survey includes more high priority lunary science than in previous such surveys.
Countries including India, China, Israel and Japan have a renewed national interest in the moon. South Korea currently has an orbiter at the moon.
All this attention makes the moon a “really good target for U.S. science to maintain our leadership position, as well as providing a tool for geopolitical cooperation,” Glotch added.
From left, Sam Kleeman, Assistant Professor Tobias Janowitz, Miriam Ferrer Gonzalez and Emma Davidson. Photo by Caryn Koza/CSHL
Sam Kleeman at Lake Tahoe
Sam Kleeman in front of a sequoia grove at Yosemite.
By Daniel Dunaief
This is part 2 of a two-part series.
Cancers not only compromise human health, but they can also suppress the body’s immune response. A little studied small protein called cystatin C, which is secreted by numerous cells, may render the immune system less effective in its response to tumors.
Sam Kleeman, a PhD student in Cold Spring Harbor Laboratory Assistant Professor Tobias Janowitz’s lab, recently published results in the journal Cell Genomics that demonstrate a link between elevated levels of this protease inhibitor, the suppression of the immune system, and the development of cancer.
Kleeman was able to demonstrate a potential role “Cystatin C might play in damping down the immune response to tumors,” he said.
Cystatin C is a known cysteine protease inhibitor, but the biological and organ-level relevance of this has not been characterized in detail. This protein could be one of many mechanisms by which glucocorticoids can reduce the effectiveness of the immune system.
Cystatin C could drive the progression of the disease, which could explain why Kleeman has found evidence that higher levels coordinate with worse outcomes.
Starting with the data
Pursuing an interest in data- driven research, Kleeman, who has a Bachelor of Medicine and Surgery from New College at the University of Oxford, searched the UK Biobank, which provides health data for numerous people in the United Kingdom.
In this Biobank, Kleeman, who joined Cold Spring Harbor Laboratory in August of 2020, found that cystatin C was the best prognostic indicator of cancer deaths.
“I was a little surprised by this,” Kleeman said as he had heard of cystatin C as a marker of kidney function, but was not aware of any association with cancer mortality. Some studies had found evidence for this previously, but those were in small cohorts and were poorly understood, he explained.
A healthy kidney clears most proteins quickly, pumping it out into urine. A kidney that’s not functioning optimally, however, allows it to accumulate.
In his research, Kleeman removed cystatin C selectively in cancer cells, causing the tumors to grow more slowly. The main changes in the architecture of the tumor was that it reduced the frequency of macrophages with expression of a protein called Trem2. While the exact mechanism is not known, it’s likely that immune control of the tumor increases without cystatin C.
Kleeman also demonstrated a similar effect on the connection between levels of Covid-19 and mortality in a paper published in iScience.
The biological mechanism explaining the correlation is nuanced. Patients with higher levels of glucocorticoids can be associated with poor outcomes. It is not a simple relationship, he said, which makes causality difficult to assess.
Kleeman believes cystatin C secretion in response to glucocorticoids has context dependency. Not all cells posses inducible cystatin C secretion.
The research primarily found that only macrophages and cancer cells can secrete cystatin C in response to glucocorticoids.
He describes a “two hit” model, by which glucocorticoids plus an inflammatory stimulus recruit macrophages. The model applies to all inflammatory stores, but is co-opted in the case of cancer.
At this point, drugs aren’t available to inhibit or reduce cystatin C. Instead, Kleeman suggested that a viable research target route might involve creating a specific antibody.
Some researchers have created so-called knockout mice, which don’t have this protein. These mice can survive without it, although eliminating all cystatin C creates other problems.
Kleeman speculated that the protein could play a role in preventing significant immune reaction against sperm.
Indeed, this protein is secreted at high levels in the testes. Males without it have lower sperm function and production.
Kleeman hopes this work acts as a starting point to understand the mechanism better by which glucocorticoids modify immune response to cancer, and to investigate cystatin C as a possible therapeutic target.
Long standing partnership
As an undergraduate, Kleeman took a class with Janowitz, which kicked off a mentorship that now spans two continents.
Kleeman appreciates the comfort level Janowitz has in working on higher-risk, higher-reward topics or on ideas that haven’t already attracted considerable attention from other scientists.
“There’s a tendency in science towards group think,” Kleeman said. In the history of medicine and science, many widely accepted theories turn out to be wrong. “Patients undoubtedly benefit from a diversity of thought in science and medicine,” he explained.
When he completes his PhD, Kleeman said it would be a “dream to have a dual appointment” in which he could conduct research and work in the clinic with patients. To get there, he knows he needs to establish his research profile that includes a genuine track record of achievement while demonstrating that he can function as a reliable and effective clinician.
Kleeman’s thesis research lies outside the field of cystatin C, which started out as a curiosity and developed into the recent publication. He wanted to “understand what UK Biobank could teach us about cancer patients.” With Janowitz and Cold Spring Harbor Laboratory Professor Hiro Furukawa, Kleeman is working to understand how a specific type of cancer could cause an auto-immune disease.
A resident of Forest Hills, Kleeman lives about 45 minutes from the lab. Outside of work, he enjoys visiting national parks. He has visited 10 so far, including Yosemite National Park, Zion and Rocky Mountain National Park.
Professionally, Kleeman feels it is a privilege to be a PhD student. He appreciates that he can explore his interests without too many restrictions and is eager to make the most of the opportunity.
From left, Sam Kleeman, Assistant Professor Tobias Janowitz, Miriam Ferrer Gonzalez and Emma Davidson. Photo by Caryn Koza/CSHL
By Daniel Dunaief
This part one of a two part series.
It’s a bit like shaking corn kernels over an open flame. At first, the kernels rustle around in the bag, making noise as they heat up, preparing for the metamorphosis.
That’s what can happen in any of the many laboratories scattered throughout Long Island, as researchers pursue their projects with support, funding and guidance from lab leaders or, in the science vernacular, principal investigators.
Sometimes, as happened recently at the benches of Cold Spring Harbor Laboratory Assistant Professor Tobias Janowitz, several projects can pop at around the same time, producing compelling results, helping advance the careers of developing scientists and leading to published papers.
PhD graduate Miriam Ferrer Gonzalez and MD/ PhD student Sam Kleeman recently published separate studies.
In an email, Janowitz suggested the work for these papers is “time consuming and requires a lot of energy.” He called the acceptance of the papers “rewarding.”
In a two-part series, Times Beacon Record News Media will describe the research from each student. This week, the focus is on Ferrer Gonzalez. Check back next week for a profile of the work of Kleeman.
Miriam Ferrer Gonzalez
Miriam Ferrer Gonzalez. Photo by Caryn Koza/CSHL
Miriam Ferrer Gonzalez was stuck. She had two results, but couldn’t seem to figure out how to connect them. First, in a mouse model of the ketogenic diet — heavy on fats, without including carbohydrates —cancer tumors shrunk. That was the good news.
The bad news, which was even more pronounced than the good, was that this diet was not only starving the tumors, but was triggering an earlier onset of cachexia, in which bodies weaken and waste away. The cachexia overpowered the mice, causing them to die sooner than if they had a normal diet.
Ferrer, a student in residence from Spain who was conducting her research at Cold Spring Harbor Laboratory while earning her PhD at the University of Cambridge in the UK, thought the two discoveries were paradoxically uncoupled. A lower tumor burden, she reasoned, should have been beneficial.
In presenting and discussing her findings internally to the lab group, Ferrer received the kind of feedback that helped her hone in on the potential explanation.
“Finding out the mechanism by which a ketogenic diet was detrimental for both the body and the cancer was the key to explaining this uncoupling,” Ferrer explained.
The adrenal glands of mice fed a ketogenic diet were not producing the necessary amount of the hormone corticosterone to sustain survival. She validated this broken pathway when she discovered higher levels of corticosterone precursors that didn’t become functional hormones.
To test this hypothesis, she gave mice dexamethasone, which boosted their corticosterone levels. These mice had slower growing tumors and longer lives.
Ferrer recently published her paper in the journal Cell Metabolism.
To date, the literature on the ketogenic diet and cancer has been “confusing,” she said, with studies that show positive and negative effects.
“In our study, we go deeper to explain the mechanism rather than only talking about glucose-dependency of cancer cells and the use of nutritional interventions that deprive the tumor of glucose,” said Ferrer. She believed those factors are contributing to slower tumor growth, but are not solely responsible.
Thus far, there have been case studies with the ketogenic diet shrinking tumors in patients with cancer and, in particular, with glioblastoma, but no one has conducted a conclusive clinical trial on the ketogenic diet.
Researchers have reported on the beneficial effects of this diet on epilepsy and other neurological diseases, but cancer results have been inconclusive.For the experiments in Janowitz’s lab, Ferrer and technician Emma Davidson conducted research on mouse models.
Ferrer, who is the first author on the paper, has been working with this system for about four years. Davidson, who graduated from the College of Wooster in Ohio last year and is applying to MD and MD/PhD programs, contributed to this effort for about a year.
Next steps
From left, Emma Davidson, Assistant Professor Tobias Janowitz, Sam Kleeman and Miriam Ferrer Gonzalez. Photo by Caryn Koza/CSHL
Now that she earned her PhD, Ferrer is thinking about the next steps in her career and is considering different institutions across the country. Specifically, she’s interested in eating behavior, energy homeostasis, food intake and other metabolic parameters in conditions of stress. She would also like to focus on how hormonal cycles in women affect their eating behavior.
Originally from a small city in Spain called Lleida, which is in the western part of Catalonia, Ferrer appreciated the opportunity to learn through courses and conferences at Cold Spring Harbor Laboratory.
Until she leaves the lab in the next few months, Ferrer plans to work with Davidson to prepare her to take over the project for the next year.
The follow up experiments will include pharmacologically inducing ferroptosis of cancer cells in mice fed a ketogenic diet. They hope to demonstrate that early induction of ferroptosis, or a type of programmed cell death, prevents tumor growth and prevents the tumor-induced reprogramming of the rest of the body that causes cachexia.
These experiments will involve working with mice that have smaller and earlier tumors than the ones in the published paper. In addition, they will combine a ketogenic diet, dexamethasone and a ferroptosis inducing drug, which they didn’t use in the earlier experiments.
Janowitz has partnered with Ferrer since 2018, when she conducted her master’s research at the University of Cambridge. As the most senior person in Janowitz’s lab, Ferrer has helped train many of the people who have worked in his lab. She has found mentoring rewarding and appreciates the opportunity to invest in people like Davidson.
Ferrer, who is planning a wedding in Spain in September, is a fitness and wellness fan and has taken nutrition courses. She does weight lifting and running.
Ferrer’s parents don’t have advanced educational degrees and they supported their three children in their efforts to earn their degrees.
“I wanted to be the best student for my parents,” said Ferrer, who is the middle child. She “wanted to make my parents proud.
The hand off
Emma Davidson and Miriam Gonzalez Ferrer examine an adrenal gland sample section from a cachectic mouse. Photo by Caryn Koza/CSHL
For her part, Davidson is looking forward to addressing ways to implement further treatment methods with a ketogenic diet and supplemental glucocorticoids to shrink tumors and prevent cachexia.
Davidson appreciated how dependable Ferrer was during her time in the lab. Just as importantly, she admired how Ferrer provided a “safe area to fail.”
At one point, Davidson had taken all the cells she was planning to use to inject in mice. Ferrer reminded her to keep some in stock.
“Open lines of communication have been very beneficial to avoid more consequential failures,” Davidson said, ”as this mistake would have been.”
Davidson developed an interest in science when she took a high school class called Principles in Biological Science and Human Body Systems. When she was learning about the cardiovascular system, her grandfather had a heart attack. In speaking with doctors, Davidson acted as a family translator, using the language she had studied to understand what doctors were describing.
Like Ferrer, Davidson lives an active life. Davidson is preparing for the Jones Beach Ironman Triathlon in September, in which she’ll swim 1.2 miles, bike 56 miles and run a half marathon. She plans to train a few hours during weekdays and even more on weekends for a competition she expects could take about six hours to complete.
Davidson started training for these events with her father Mark, an independent technology and operations consultant and owner of Exoro Consulting Group.
Longer term, Davidson is interested in medicine and research. After she completes her education, she will try to balance between research and clinical work.
That process creates what is described as a reactive chlorine species, which is on the hunt for a positively charged particle, such as one of the four hydrogen atoms attached to carbon in methane.
When he’s not working, Mak enjoys boating and fishing. A native of Southern California, Mak is a commercial pilot, who also does some flying as a part of his research studies.
Prev
