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Power of 3

Above, Leila Esmailzada, executive director of BeLocal observes a traditional charcoal making process in Madagascar. Photo from BeLocal

By Daniel Dunaief

BeLocal has progressed from the drawing board to the kitchen. The nonprofit group, which was started by the husband and wife team of Mickie and Jeff Nagel as well as data scientist Eric Bergerson, has been working to improve and enhance the lives of people living in Madagascar.

BeLocal, which started in 2016, has sent representatives, including Laurel Hollow resident Mickie Nagel and executive director Leila Esmailzada, to travel back and forth to the island nation off the southeast coast of the African continent.

Working with Stony Brook University students who identified and tried to come up with solutions for local challenges, BeLocal has focused its efforts on creating briquettes that use biomass instead of the current charcoal and hardwood, which not only produces smoke in Malagasy homes but also comes from cutting down trees necessary for the habitat and the wildlife it supports.

Biochar briquettes reduce the amount of hardwood Malagasy residents chop down to provide fuel for cooking. Photo from BeLocal

“In the summer of 2018 we figured out that we had something that works,” said Mickie Nagel. “We had all the agricultural waste and could turn it into fuel. Our goal is to start thinking about how to bring it into communities and into the daily lives” of people in Madagascar.

In January of this year, Esmailzada partnered up with Zee Rossi to introduce the new briquettes to residents of three villages, who were interested in the BeLocal process and offered feedback.

Rossi worked in Madagascar for three years as a part of the Agricultural Food Security Advisory Section of the Peace Corps, until he recently joined the staff at BeLocal.

At this point, BeLocal has helped create four working production sites for the briquettes, all of which are on the outskirts of the Ranomofana National Park, which Stony Brook Professor Patricia Wright helped inaugurate in 1991.

The biochar briquettes solve several problems simultaneously. For starters, they reduce the amount of hardwood Malagasy residents chop down to provide fuel for cooking. The biochar briquettes are made from agricultural waste, such as corn husks and cobs, rice stalks, leaves, small sticks and even unusable waste from the production of traditional charcoal.

The briquettes also produce less smoke in the homes of the Malagasy. At this point, BeLocal doesn’t have any data to compare the particulates in the air from the briquettes.

One of the current briquette makers is generating about 2,000 of the circular fuel cells per month. As a start-up effort, this could help with several families in the villages. Nagel estimates that it takes about 12 briquettes to cook a meal for a family of four. The families need to learn how to stoke the briquettes, which are slightly different from the cooking process with the charcoal and hardwood.

Esmailzada and Rossi had planned to return to Madagascar in July, where they hoped to understand how people are using these sources of energy.

Esmailzada has taught and workshopped with the Malagasy on how to make the briquettes. Since returning to the United States, where she recently completed a master’s program in public health with a focus on community health at Stony Brook University, she was eager to see how much progress has been made.

BeLocal has continued to refine the technique for creating these briquettes. Working across the border with Stony Brook graduate student Rob Myrick, Malagasy residents have tried to char the biomass in a barrel, instead of digging a pit.

“Hopefully there will be movement” with the barrel design, Nagel said.

Myrick is working on refining the airflow through the pit, which could enhance the briquette manufacturing process.

Myrick will “work on techniques [at Stony Brook] and [Rossi] will work on the process with the villagers over there,” Nagel explained in an email. Myrick has been “such a helpful and great addition to BeLocal.”

Esmailzada and Nagel are delighted that Rossi joined the BeLocal effort.

“It’s such a natural partnership,” Esmailzada said. “He built this incredible trust with this group of really dynamic people. Having him be the liaison between us and the community really came together nicely.”

Rossi explained some of the challenges in developing a collaboration that works for the Malagasy. “One of the biggest barriers is being a foreigner,” he said. “With any new thing you present to a farmer, you have to sell yourself first. It’s really important that you connect with a farmer on a person-to-person level.”

Numerous farmers are skeptical of the ongoing commitment foreign groups will have. Many of them have experience with a foreigner or a local nongovernmental organization coming in, doing a program and “not following up,” Rossi added.

Nagel is putting together a nongovernmental organization conference to get the organizations “working on projects in the same room,” she said.

Through this effort, BeLocal hopes to create new partnerships. The organization continues to work with Stony Brook’s VIP program, which stands for vertically integrated projects.

Students from sophomore year through graduate school can continue to work on the same projects. The goal is to enable a continued commitment, which the school hopes will lead to concrete results, instead of one-year efforts that often run into obstacles that are difficult to surmount in a short period of time.

Ultimately, Nagel believes the process of building briquettes could translate to other cross-border efforts and suggested that these goals should include the kind of information crowd-sourcing that benefits from other successful projects.

BeLocal is receptive to support from Long Islanders and elsewhere.

Nagel added that projects like the briquette effort keep the context and big picture in mind.

“Helping Patricia Wright save this rain forest and the lemurs will always be a goal and we know the only way to do that is to help with alternatives to food and fuel sources, and better farming techniques so they don’t have a need to slash and burn more rain forest to add more farming fields,” Nagel said.

Peter Van Nieuwenhuizen

By Daniel Dunaief

Peter van Nieuwenhuizen was sitting at the kitchen table, paying an expensive dental bill, when he received an extraordinary phone call. After he finished the conversation, he shared the exciting news — he and his collaborators had won a Special Breakthrough Prize in Fundamental Physics for work they’d done decades earlier — with his wife, Marie de Crombrugghe.

The prize, which is among the most prestigious in science, includes a $3 million award, which he will split with Dan Freedman, a retired professor from the Massachusetts Institute of Technology and Stanford University, and Sergio Ferrara from CERN.

De Crombrugghe suggested he could use the money “for a whole new set of teeth,” if he chose.

Van Nieuwenhuizen, Freedman and Ferrara wrote a paper in 1976 that extended the work another famous physicist, Albert Einstein, had done. Einstein’s work in his theory of general relativity was incomplete in dealing with gravity.

Freedman, who was at Stony Brook University at the time, van Nieuwenhuizen and Ferrara tackled the math that would provide a theoretical framework to include a quantum theory of gravity, creating a field called supergravity.

From left, Peter van Nieuwenhuizen, Sergio Ferrara, and Dan Freedman in 1980.

After 43 years, “I didn’t expect” the prize at all, said van Nieuwenhuizen. It’s not only the financial reward but the “recognition in the field” that has been so satisfying to the physicist, who continues to teach as a Toll Professor in the Department of Physics at SBU at the age of 80.

“To have one’s work validated by great leaders has just been wonderful,” added Freedman, who worked at SBU through the 1980s until he left to join MIT. He treasures his years at Stony Brook.

Freedman believes a seminal trip to Paris, where he discussed formative ideas that led to supergravity with Ferrara, was possible because of Stony Brook’s support.

The physics trio approached the problem of constructing a way to account for gravity by combining general relativity and particle physics, which were in two separate scientific communities at the time. Even the conferences between the two types of physics were separate.

Einstein’s theory of general relativity has infinities when scientists add quantum aspects to it. As a result, it becomes an inconsistent theory. “Supergravity is not a replacement of Einstein’s theory, it is an extension or a completion if one is bold,” van Nieuwenhuizen explained.

The Stony Brook professor suggested that supergravity is an extension of general relativity just as complex numbers are an extension of real numbers. He added that it’s unlikely that there are other extensions of general relativity that theoretical physicists have yet to postulate.

Supergravity is “confirmed by its finiteness,” he said, adding that it suggests the existence of a gravitino, which is a partner to the graviton or the gravity-carrying boson. At this point, scientists haven’t found the gravitino.

“Enormous groups have been looking” for the gravitino, but, so far, “haven’t found a single one,” van Nieuwenhuizen said. The search for such a particle isn’t a “problem for me. That’s what experimental physicists must solve,” he said.

The work has already had implications for numerous other fields, including superstring theory, which attempts to provide a unified field theory to explain the interactions or mechanics of objects. Even if the search for a gravitino doesn’t produce such a particle, van Nieuwenhuizen suggested that supergravity still remains a “tool able to solve problems in physics and mathematics.”

Indeed, since the original publication about supergravity, over 11,000 articles have supergravity as a subject.

Collaborators and fellow physicists have reached out to congratulate the trio on winning the Special Breakthrough Prize, which counts the late Stephen Hawking among its previous winners.

The theoretical impact of supergravity “was huge,” said Martin Roček, a professor in the Department of Physics at Stony Brook who has known and worked with van Nieuwenhuizen for decades.

Whenever interest in the field wanes, Roček said, someone makes a new discovery that shows that supergravity is “at the center of many things.”

He added that the researchers are “very much deserving” of the award because the theory “offers such a rich framework for formulating and solving problems.”

Roček, who worked as a postdoctoral researcher in Hawking’s laboratory, said other researchers at Stony Brook are “all delighted” and they “hope some of the luster rubs off.”

Van Nieuwenhuizen’s legacy, which is intricately linked with supergravity, extends to the classroom, where he has invested considerable time in teaching.

Van Nieuwenhuizen is a “wonderful teacher,” Roček said. Indeed, he received the Dean’s Award for Excellence in Graduate Teaching in 2010 based on teaching evaluations from graduate students. Roček has marveled at the way van Nieuwenhuizen prepares for his lectures, adding, “He doesn’t give deep statements and leave you bewildered. He explains things explicitly and he does a lot of calculations without being dull.”

Van Nieuwenhuizen recalled the exhilaration, and challenge, that came from publishing their paper in 1976. “We knew right away” that this was a seminal paper, he said. “The race was on to discover its consequences.”

Prior to the theory, the three could work in relative calm before the physics world followed up with more research. After their discovery, they knew the “happy, isolated life is over,” he said..

Van Nieuwenhuizen has no intention to retire from the field, despite the sudden funds from the prize, which is sponsored by Sergey Brin, Priscilla Chan, Mark Zuckerberg, Pony Ma, Yuri and Julia Milner and Anne Wojcicki.

“The idea that I would stop abhors me,” he said. “I wouldn’t know what on earth I would be doing. I consider it a privilege to give these courses, to work and be paid to do my hobby. It’s really unheard of.”

A. Laurie Shroyer File photo

By Daniel Dunaief

Annie Laurie Shroyer isn’t standing on a podium somewhere, listening to the national anthem with tears in her eyes and a hand over her heart as she mouths familiar words. She hasn’t won a Nobel Prize or some other distinction that will add to a medal count or that will rise to the top of her resume.

Shroyer is, however, standing tall in an arena that matters to her and to her colleagues, mentors and collaborators.

A professor and vice chair for research in the Department of Surgery at the Stony Brook Renaissance School of Medicine and the without compensation health science officer in the Research and Development Office at the Northport VA Medical Center, Shroyer recently learned that two of her research papers on coronary artery bypass surgery made an impressive and important list.

Her papers were ranked 8th and 28th among a review by the Journal of Cardiac Surgery of the top 11,500 papers in her field, making Shroyer one of only two senior investigators in the world with two citations in the top 50.

Researchers often work in obscurity, toiling in a lab or on a computer late into the night, analyzing data, applying for grants and receiving constructive but sometimes critical comments from peer reviewers. What many of them hope for, apart from the stability of tenure or the opportunity to provide a breakthrough discovery that alters the way other researchers or clinicians think about a disease or condition, is to make a lasting impact with their work.

In many ways, this ranking suggests that Shroyer has accomplished that with research into a surgical procedure that is increasingly common.

Shroyer is “one of the most influential cardiovascular researchers of our era,” Faisal Bakaeen, the staff surgeon and professor of surgery at the Heart and Vascular Institute in Cleveland, Ohio, explained in an email. Shroyer’s leadership in her research is “proof of her deep intellect and genius.”

Learning that her research, which Shroyer explained was interdisciplinary, collaborative and team-based, was among the most cited in the field was “really an honor,” she said. “I was very pleasantly surprised.”

Shroyer heard about the distinction from the VA Hospital, which noticed her prominent place in the realm of coronary artery bypass surgery research. She conducted one of her studies, called the ROOBY trial for Randomized On/Off Bypass, through the Northport hospital.

That research, which was published in the New England Journal of Medicine and benefited from the support of the VA Cooperative Studies Program Coordinating Center and the Research and Development Offices at the Northport and Denver VA Medical centers, compared the short-term and intermediate outcomes evaluating the impact of using a heart-lung machine versus operating on a beating heart.

That trial asked focused research questions about the comparative benefits of using the machine.

Shroyer concluded that there was “no off pump advantage” across a diversity of clinical outcomes and likened the process of performing this surgery without a pump to sewing a patch onto blue jeans while a child is walking up the stairs, making the stitching process more technically demanding.

Shroyer recognizes that some doctors prefer to do the procedure without the pump. Many of them suggest they have the surgical expertise to make the process a viable one for patients.Some patients may also have specific reasons to consider off pump procedures.

As for the second highly cited paper, Shroyer worked with the STS National Adult Cardiac Surgery Database Committee team and published that in the Annals of Thoracic Surgery. That paper identified the most important preoperative risk factors associated with major morbidities after surgery.

“This paper described a broad-based analytical approach which was originally developed in the VA” by Drs. Karl Hammermeister, Fred Grover, Guillermo Marshall and Shroyer working together, she explained in an email. Given that the Society of Thoracic Surgery’s database has subsequently been used to address other research questions, this early statistical modeling approach has attracted considerable interest.

In terms of the overall list, Shroyer expressed a few surprises. For starters, she noticed a larger than anticipated proportion of articles focused on the surgical procedure’s clinical outcomes. In her view, the topic is important, but not to the exclusion of research focused on evaluating the process of care and the structures of care. These include actions that care providers take on behalf of their patients, the actions patients take for themselves, and the nature of the environment where patients seek out care.

“Identifying the adverse outcomes post-CABG informs you that there is a problem, but clinical outcomes research doesn’t provide guidance on how to solve” the problem or problems identified, she said, adding that she hopes future research evaluates the processes and structures of care that may affect risk-adjusted clinical outcomes.

Shroyer also expected that the findings of several trials published in the New England Journal of Medicine would have ended the debate about off-pump versus on-pump benefits. The debate, however, is “still active,” she said.

Five years from now, Shroyer anticipates changes in the list. She hopes these high impact journals will include evaluations of novel treatments and surgeon-based characteristics, which may influence risk-adjusted outcomes.

Shroyer is pleased with the collaborators who have worked with her, as well as with the information from which she has drawn her conclusions.

“This high level of citation represents a tribute to the entire VA ROOBY trial team as well as to the STS Adult Cardiac Surgery Database and National Database Committees’ members,” she said. “In addition to terrific collaborators, I feel very blessed to have had several great mentors,” which includes Gerald McDonald and Fred Grover.

She also appreciates that she has had appointments at Stony Brook and at the Northport VA Medical Center that support her research projects.

By Daniel Dunaief

Screws can’t be the best and only answer. That was the conclusion neurosurgeon Daniel Birk at the Stony Brook Neurosciences Institute came to when he was reconsidering the state-of-the-art treatment for spinal injuries. The screws, which hold the spine in place, create problems for patients in part because they aren’t as flexible as bone.

That’s where Stony Brook University’s College of Engineering and Applied Sciences, headed by Fotis Sotiropoulos, plans to pitch in. Working with Kenneth Kaushansky, dean of Stony Brook University’s Renaissance School of Medicine, the two Stony Brook leaders have been immersed in uniting their two disciplines to find ways engineers can improve medical care.

Fotis Sotiropoulos

The two departments have created the Institute for Engineering-Driven Medicine, which will address a wide range of medical challenges that might have engineering solutions. The institute will focus on developing organs for transplantation, neurobiological challenges and cancer diagnostics.

The institute, which already taps into the medical and engineering expertise of both departments, will move into a new $75 million building at the Research and Development Park, in 2023.

The original investment from New York State’s Economic Development Council was for an advanced computing center. The state, however, had given Buffalo the same funds for a similar facility, which meant that former Stony Brook President Sam Stanley, who recently became the president of Michigan State University, needed to develop another plan.

Sotiropoulos and Kaushansky had already created a white paper that coupled engineering and medicine. They developed a proposal that the state agreed to fund. In return for their investment, the state is looking for the development of economic activity, with spin-off companies, jobs, new industries and new ideas, Kaushansky said.

The two leaders are developing “a number of new faculty recruits to flesh out the programs that are going in the building,” Kaushansky added.

Sotiropoulos, who has conducted research in the past on blood flow dynamics in prosthetic heart valves, believes in the potential of this collaboration. “This convergence of engineering and medicine is already doing what it was intended to do,” he said. Clinicians can get “crazy sci-fi ideas, talk to engineers and figure out a way to make it happen.”

In addition to spinal cord support, researchers in engineering and medicine are working on developing algorithms to make decisions about surgical interventions, such as cesarean sections. 

A recent project from principal investigator Professor Petar Djurić, chair of SBU’s Department of Electrical and Computer Engineering, and Gerald Quirk, an obstetrician and gynecologist at Stony Brook Medicine, recently received $3.2 million from the National Institutes of Health. The goal of the project is to use computer science to assist with the decisions doctors face during childbirth. A potential reduction in C sections could lower medical costs. 

“This is a fantastic example of this type of convergence of engineering and medicine,” said Sotiropoulos.”

Dr. Kenneth Kaushansky. Photo from SBU

While the building will host scientists across a broad spectrum of backgrounds, researchers at Stony Brook will be able to remain in their current labs and coordinate with this initiative. Combining all these skills will allow researchers to apply for more grants and, Stony Brook hopes, secure greater funding.

“For a number of years now, the [National Institutes of Health have] really favored interdisciplinary approaches to important medical problems,” Kaushansky said. “Science is becoming a team sport. The broader range of skills on your team, the more likely you’ll be successful. That’s the underlying premise behind this.”

The notion of combining medicine and engineering, while growing as an initiative at Stony Brook, isn’t unique; more than a dozen institutions in the country have similar such collaborations in place.

“We’re relatively early in the game of taking this much more holistic approach,” said Kaushansky, who saw one of the earlier efforts of this convergence when he was at the University of California at San Diego, where he worked with the Founding Chair of the Department of Bioengineering Shu Chien. 

The Stony Brook institute has created partnerships with other organizations, including Albert Einstein College of Medicine and Montefiore Medical Center.

“The more clinical people we engage, the better it is for the institute,” Sotiropoulos said.

As for the bionic spine, Kaushansky has familial experience with spinal injuries. His mother suffered through several spinal surgeries. “There’s a need for much, much better mechanical weight-bearing device that will help people with back problems,” he said.

At this point, Stony Brook has gone two-thirds of the way through the National Science Foundation process to receive a $10 million grant for this spinal cord research. Sotiropoulos suggested that a bionic spine could be “a game changer.”

While the institute will seek ways to create viable medical devices, diagnostics and even organs, it will also meet the educational mandate of the school, helping to train the next generation of undergraduate and graduate students. The school already has a program called Vertically Integrated Projects, or VIPs, in place, which offers students experiential learning over the course of three or four years. The effort combines undergraduates with graduates and faculty members to work on innovative efforts.

“These projects are interdisciplinary and are all technology focused,” Sotiropoulos said. “We bring together students” from areas like engineering, computer science and medicine, which “go after big questions,” and that the VIP efforts are structured to unite engineers and doctors-in-training through the educational process.

Through the institute, Stony Brook also plans to collaborate with other Long Island research teams at Cold Spring Harbor Laboratory and Brookhaven National Laboratory, Sotiropoulos said, adding that the scientists are “not just interested in doing blue sky research. We are interested in developing services, algorithms, practices, whatever it is, that can improve patient care and costs.”

Indeed, given the translational element to the work, the institute is encouraging a connection with economic development efforts at Stony Brook, which will enable faculty to create spin-off companies and protect their ideas. The institute’s leadership would like to encourage the faculty to “create companies to market and take to market new products and developments,” said Sotiropoulos.

Photos from SBU

Kedar Kirane Photo from SBU

By Daniel Dunaief

Some day, a collection of soldiers in the Army may be sleeping in a bunker near an explosion. Their lives may depend on the ability of their bunker to crack, rather than fracture and collapse.

Kedar Kirane, an assistant professor in the Department of Mechanical Engineering at Stony Brook University, recently received a $359,000 grant from the Army Research Office’s Young Investigator Program to develop a computational model to predict the fracturing behavior of woven textile composites under dynamic loading, such as blasts and other impact loads.

In his work, Kirane hopes to develop a model for how composite materials fracture.

Kedar Kirane. Photo courtesy of Mechanical Engineering/Stony Brook University

Ralph Anthenien, the division chief for mechanical sciences in the U.S. Army Research Office, described the process of granting these awards as “very selective.”

The program supports “innovative breakthroughs,” he said. Part of the charter is to fund “high risk research, which won’t have a 100 percent chance of success,” but could provide a way forward for research.

Ultimately, the hope in the work the Army funds is to “protect soldier’s lives and protect Army systems,” Anthenien continued. The research should “make everything for the Army better.”

Kirane suggested that this research could also have implications in civilian life, such as to predict automotive crashworthiness. While it’s possible to consider fractures and cracks at the atomic scale, he said he is focusing on the macro level because the structures he is studying are so large.

“If you start looking at the atomic scale, it would be impossible because we don’t have the kind of computing power we would need” to convert that into buildings, bridges or other structures, Kirane said.

He is exploring the rates of loading for these fiber composite materials and would like to understand how these objects hold up in response to a blast or a projectile hitting it, as opposed to a more gradual progression of stressors.

Kirane will not conduct any of the laboratory work that explores the fracturing and reaction of the materials. Instead, he will use public data to calibrate and verify his model. The grant supports only the development of the model, not the performance of any physical experiments.

While materials are manufactured with different procedures, he is focused on how the materials fracture, crack and branch. The work is “more of a fundamental study rather than an applied study for a particular material,” he said.

One of the areas of focus in Kirane’s research involves analyzing the branching of cracks during fracture. As the cracks branch, they multiply, causing the material to break into multiple pieces.

The speed at which load builds on an object determines its reaction. A slow buildup typically causes one crack to form, while a more rapid load can cause a single crack that can branch and rebranch to produce multiple cracks.

“Being able to model this is complicated,” Kirane said. “The more it fractures, the more energy it can dissipate.” Ultimately, he would like his model to provide the Army with an idea of how much load a structure can withstand before the developing defects compromises its integrity.

In other projects, Kirane’s work will try to extrapolate from studies of smaller objects up to much larger manufactured structures. Ideally, he’d gain a better understanding of how to extend the information up to the scale at which people live.

He starts with objects that are of various dimensions, at 10 by 10 millimeters and then doubles and quadruples the size to determine the effect on their resilience and strength. There are mechanics-based scaling laws to extrapolate the structure strength to larger sizes, Kirane explained. It depends on the material and its fracturing behavior.

“That is the use of having a model: you can do some experiments in the lab, develop the model, calibrate it, use the model to predict the response and the scaling correctly,” he said.

Kirane explained that he usually tries to get data from a published journal, especially from sources where he knows the principal investigators produce reliable research. 

Indeed, sometimes the models can suggest problems with the data.“There is some back and forth” between the bench researchers and the scientific modelers, he said.

Kirane, who joined Stony Brook two years ago, has two doctoral students in his lab, one master’s student and several undergraduates. 

A resident of Westbury, he commutes about an hour back and forth. He enjoys visiting Jones Beach and appreciates the proximity to New York City. 

Raised in Pune, India, Kirane speaks English, Hindi and Marathi, which is his native language. During his schooling, which was in English, he not only pursued his interest in science but also played a percussion instrument called the tabla and was a gymnast. He says he can’t do any of the gymnastics routines from his youth today, although he does practice yoga and his gymnastics training helps. 

As for his future work, he hopes to start collaborating with scientists at Brookhaven National Laboratory, where he’d like to conduct some research at the National Synchrotron Light Source II. He’d like to understand how rocks fracture at the atomic scales.

In his own life, Kirane said he doesn’t recognize failures but sees any result that falls short of his hopes or expectations as a learning opportunity. “If something doesn’t go as planned, it’s an opportunity to retry,” he explained.

Indeed, in Kirane’s research, scientists call the process of fracturing “failure,” but that judgment depends on the context. When structures are “supposed to be sacrificial and dissipate energy by fracturing,” he said, then that “fracturing is good and not equal to failure.”

 

Timothy Glotch. Photo from BNL

By Daniel Dunaief

Several Stony Brook University scientists are studying the health effects of lunar dust on the human body. The accompanying article describes a recent $7.5 million, five-year award that the researchers, led by Tim Glotch in the Department of Geosciences, recently won from the National Aeronautics and Space Administration. See below for email exchanges with some of the other researchers.

Fifty years after astronauts Neil Armstrong and Buzz Aldrin left those fateful first footprints on the moon, a team of scientists is hoping to ensure the safety of future astronauts who remain on the moon for longer periods of time.

Led by Tim Glotch, a professor in geosciences at Stony Brook University, the research team was awarded $7.5 million in funds over five years from the National Aeronautics and Space Administration. The funding will begin this fall. The goal of the multinational team, which includes researchers from Brookhaven National Laboratory, NASA Johnson Space Center, the American Museum of Natural History, among many others, is to explore the health effects of lunar dust.

Different from the dust on Earth, which tends to be more rounded and small, where the sharp edges have been weathered away, lunar dust has jagged edges because the lack of atmosphere prevents the same erosion.

The group, whose work is called the Remote, In Situ, and Synchrotron Studies for Science and Exploration 2 (or RISE2) will determine the effects on exposure on cell death and genetic damage.

Glotch’s team will follow up on an earlier five-year effort that just concluded and will coordinate with seven research groups that received similar funding from the space agency.

Astronauts who were on the moon for a matter of hours sometimes developed a respiratory problem called lunar hay fever, which came from the introduction of these particles into their lungs. In preparing for missions to the moon, asteroids or other planets, NASA is preparing for considerably longer term voyages, which could increase the intensity and accumulation of such dust.

At the same time, NASA is working on dust mitigation strategies, which will hopefully prevent these particles from becoming a problem, Glotch explained.

Joel Hurowitz, an assistant professor in the Department of Geosciences at SBU, is leading the reactivity study. He will take simulated minerals that are common on the moon and put them in simulated lung fluids. He and the RISE2 team may be able to provide a better understanding of the risks and preclinical symptoms for astronauts.

Hurowitz is working with Hanna Nekvasil, a professor and the director of undergraduate studies in the Department of Geosciences at SBU. Nekvasil is synthesizing pure minerals in the lab, which are analogs to the materials people would encounter on the moon.

“One of the problems we counter when trying to assess the toxicity of lunar materials to astronauts is that Earth materials” don’t have the same structure or properties, explained Nekvasil in an email. “For this reason, we plan to make new materials under conditions that more closely simulate the conditions under which the materials formed at depth and were modified at the lunar surface.”

On the medical school side, the researchers will use human lung and brain cell cultures and mouse lung cells to see how the minerals and regolith affects cell viability and cell death, Glotch said.

Nekvasil explained that the research team will also explore the effects of the function of mitochondria, which can have acute and long-term health effects.

Stella Tsirka, a professor in pharmacological sciences at Stony Brook, is leading the cytotoxicity studies and will continue to look at what happens to the lungs and the central nervous system when they are exposed to lunar dust. “What we see is some transient increase in inflammatory markers, but, so far, we have not done chronic exposures,” Tsirka said. The new study will aim to study chronic exposure.

Bruce Demple, a professor in pharmacological sciences at the Renaissance School of Medicine at SBU, is leading the genotoxicity efforts.

In addition to the jagged pieces of lunar dust, astronauts also may deal with areas like the dark spots on the moon, or lunar mare, which has minerals with higher amounts of iron, which can lead to the production of acidity in the lungs.

Ideally, the scientists said, NASA would design airlock systems that remove the dust from spacesuits before they come into the astronaut’s living spaces. The work on RISE2 will help NASA “understand just how big a health problem these astronauts will face if such engineering controls cannot be put into place, and develop reasonable exposure limits to the dust,” Hurowitz explained in an email.

The most likely landing spot for the next exploration is the south pole, which is the largest impact basin in the solar system. That area may have clues that lead to a greater understanding of the chronology of events from the beginning of the solar system.

“I hope future missions will help answer questions about the timing and processes through which the moon formed and evolved,” Deanne Rogers, an associate professor of geosciences at SBU, explained in an email. Rogers, who also participated in the first RISE research effort and is married to Glotch, will conduct thermal infrared spectral imaging and relate the spectral variations to chemistry and mineral variations in surface materials.

Additionally, the south pole holds volatile elements, like ice deposits. Finding ice could provide other missions with resources for a future settlement on the moon. Water on the moon could provide hydration for astronauts and, when split into its elements, could create hydrogen, which could be used for fuel, and oxygen, which could create air.

In addition to working with numerous scientists, including coordinating with the other current NASA research efforts, Glotch is pleased that RISE2 continues to fund training for undergraduates and graduate students.

The current effort is also coordinating with the School of Journalism at Stony Brook. Science journalism classes will involve writing stories about the research, profiling the scientists and going into the field for two weeks.

Glotch, who thought seriously about becoming an astronaut until he was about 23 years old, explained that he is pleased that there appears to be a “real push to go back to the moon. I have hoped to see a new human mission to the moon or beyond since I was a kid.”

————————————————————————————————Q & A with Associate Professor of Geosciences Deanne Rogers:

What role will you play in this work? Is this similar to the contribution you made to the original RISE project?

My contribution is very similar to my role in in the original RISE project. I will be participating in Theme 2, conducting thermal infrared spectral imaging and relating the spectral variations to chemistry and mineral variations in surface materials. A major new component is developing rapid analysis algorithms and pipelines, and evaluating strategies for how to best organize and integrate the various data sets.

How much of your research time will you dedicate to RISE2?
About 15% of my research time. But there will be a graduate student who will be doing the heavy lifting (collecting, processing and analyzing the data, correlating the data with surface materials and chemistry, developing the processing algorithms).
Have you and Tim spent considerable time discussing RISE2 and did you go through numerous drafts of the proposal?
Yes.
Will you also be involved in working with undergraduates and graduate students, as well as journalism school students, through the RISE2 efforts?
Yes, I will be mentoring undergrads and grads and working with the journalism students.
Are you excited to be a part of efforts to ensure the safety of astronauts on future extended trips to the moon, asteroids and/or other planets?
Yes, I am honored and excited.
Is it especially exciting/ compelling to be working on a  NASA funded effort around the 50th anniversary of the first steps on the moon?
Yes!
Are there scientific questions you hope future lunar missions answer? Do you think future expeditions will help ask new research questions?
Yes. I hope future missions will help answer questions about the timing and processes through which the moon formed and evolved to its present state. I am also interested in hydrogen sources and hydrogen mobility on the moon. History shows that we always end up with new questions whenever we send a mission to answer existing questions.

Q and A with Assistant Profess or Geosciences Joel Hurowitz:

Will you be working with Hanna Nekvasil to take minerals she produced and put them in simulated lung fluid. Is that correct? Is this simulated lung fluid a novel concept or have other research efforts taken a similar approach to understanding the effect of exposure to elements or chemicals on the lungs?

Yes, I will be working with Hanna.  Our plan is to produce a suite of high-fidelity lunar regolith simulant materials in her laboratory, characterize them extensively to ensure that they are a good chemical and mineralogical match to the different types of soil on the Moon, and then assess how toxic they are.  Some of those toxicity experiments will involve immersing the materials she creates in simulated lung fluid and assessing what chemical reactions take place between the solid regolith simulants and the lung fluid.  Other experiments will be done in collaboration with our partners in the Stony Brook medical school, and will involve, e.g., assessing how cells, DNA, and lung tissue react to these regolith simulants.  These experiments build on work that has been done by the previous iteration of RISE (1.0), but have the added benefit that we can apply the lessons learned for assessing toxicity from our first round of research, as well as making use of this new suite of very high-fidelity simulants.

Does this work have the potential to provide future missions with early warning signs of exposure, while also generating potential solutions to lunar dust driven lung damage?

This is a question that is probably better posed to our medical school colleagues on the team, Stella Tsirka and Bruce Demple.  They could speak in a much more informed way about what types of signals we might be able to recognize from, e.g., a blood test, that an astronaut is beginning to show signs of a toxicological response to regolith.

Ultimately, I think that the best solution to lunar dust driven lung damage is to engineer the exposure problem away – NASA needs to design airlock systems that remove regolith from spacesuits before they come into the astronaut’s living spaces.  Our work will help NASA to understand just how big a health problem these astronauts will face if such engineering controls cannot be put into place, and develop reasonable exposure limits to the dust.

Is there considerable excitement at Stony Brook about the RISE2 effort? Do you have, if you’ll pardon the pun, high hopes for the research and do you think this kind of effort will prove valuable for astronauts on future long term missions to the moon, asteroids or other planets?
Absolutely – we couldn’t be more excited about all of the new research we’ll be able to perform as part of RISE 2.0, in so many areas, including better understanding the origin of the Moon and asteroids from remote and laboratory analyses, and learning how to live safely and explore efficiently on the surfaces of these solar system bodies.
 Are there novel elements to the work you’re doing?
To me, the real novelty of our part of the RISE 2.0 research lies in the combination of really disparate areas of expertise to produce a very useful research outcome for NASA.  Our team combines the expertise of: (1) geologists who understand the conditions deep within the Moon that result in the formation of the rocks and regolith that are present there today, thus enabling us to better simulate the properties of lunar soil, (2) geochemists who understand how to execute experiments between fluids and soil materials to extract the maximum information about potentially toxic compounds that result from that interaction, and (3) medical scientists who can take the geological materials we make in our labs and apply them to relevant biological materials that are the best models to understand the toxic effect of lunar soil on astronauts.  It’s a truly cross-disciplinary approach that few other groups are taking.
Could this approach also have implications for people working in areas like coal mines or regions where particulates cause lung damage?
Yes – absolutely.  So much of the science we are performing is actually grounded (if you’llpardon the pun) in earlier work that has been done to understand diseases like coal miners lung, silicosis, and asbestosis.  We’re building on that foundation of research and taking it off-Earth to understand if astronauts have to be as worried about their lung health as someone donning a mining hat and heading underground.
Given that it’s been 47 years since the last manned trip to the moon, is it exciting to contribute to efforts that will allow for future safe and extended trips back to the moon?
Of course!  These issues really need to be sorted out if we’re going to ensure that the astronauts traveling to moons, asteroids, and other planets are safe, and I’m really happy to be a part of that effort.
Are there specific geologic questions you hope future missions to the moon answer? Will future samples lead to new questions?
I think one of the biggest questions that future missions that return samples from the Moon can address will relate to the timing of formation of the largest impact basins on the Moon and whether or not they record evidence for a cataclysmic “spike” in the rate of meteorite impacts in the early history of the inner Solar System.  So much of our current thinking about when life on Earth (or anywhere else in the inner Solar System) arose is tied to the idea that it must have happened after this cataclysmic “late heavy bombardment”, and yet, we aren’t completely sure whether this spike actually happened.  If it didn’t, it might force us to rethink what conditions were like on the surface of the Earth early in its geological history and when life could’ve first began.
How much of your time (as a percentage of your research time) will you dedicate to the RISE2 work?

It will vary from year to year.  Early on, I’ll be heavily invested in starting the program of research up, but then starting in 2021, I’ll hand off some of my duties in order to work on mission operations on the Mars 2020 rover mission.  I’m the deputy principal investigator for one of the instruments that is flying aboard that rover, so the year 2021 is going to be consumed with my Mars-related work.  As things start to settle down a bit on Mars (in 2022), I’ll be able to return to my RISE research.  It’ll be really exciting to see how much progress will have been made by that time, but I’ll be planning to keep tabs on the RISE research even when I’m spending more time on the Mars 2020 mission.

Q & A with Hanna Nekvasil, Director of Undergraduate Studies and Professor of Geosciences:

Will you be synthesizing pure minerals in the lab, which are analogs to the materials  astronauts would encounter on the moon?

One of the problems that we encounter when trying to assess the toxicity of lunar materials to astronauts, is that Earth materials make poor analogs, as we know from the materials brought back to Earth from the Apollo missions.  For this reason we plan to make new materials under conditions that more closely simulate the conditions under which the materials formed at depth and were modified on the lunar surface. For this work we use the experimental equipment that we normally use to simulate the processes that form and modify igneous rocks on Earth modified for the special low oxygen conditions of the Moon.  The materials produced will simulate more closely both the compositional and textural characteristics of dust that we expect will be encountered in future manned lunar missions.
Will Joel Hurowitz use these minerals to expose them to lung fluids? 
The RISE4E team will expose cells to the new lunar regolith simulants and assess the molecular effects to understand the cytotoxic and genotoxic potential of the new, more relevant simulants. Beyond the cell-killing and DNA-damaging capacity of the materials, we will also examine their effects on the function of mitochondria: dysfunction in that organelle can have both acute and long-term health effects.
Are you excited to be a part of an effort that may one day help ensure the safety of astronauts who spend considerable time on a lunar habitat? 
I am very excited about this and I think that the diverse team that we have assembled has great potential to really move our understanding of the potential toxicity of lunar materials forward.
Is there a specific question or mission objective you hope future trips to the moon addresses?
My greatest hope is that we encounter a diverse set of new rocktypes as each new rocktype will provide a wealth of information on the origin and evolution of the Moon’s surface and interior.

Wellington Rody. Photo by John Griffin/Stony Brook University

By Daniel Dunaief

Straightening teeth involves moving, changing and reconfiguring the bone and the gums that hold those teeth in place. While the gums and bone adapt to the suddenly straight teeth, the roots may encounter unusual stress that makes them more prone to deterioration.

That’s not particularly welcome news for hormone-riddled teenagers who are maneuvering through the minefield of adolescence with a mouth full of metal. Fortunately, however, significant root damage that threatens the health and stability of teeth occurs in only about 5 percent of the cases of people with braces.

Wellington Rody. Photo by John Griffin/Stony Brook University

The challenge for people whose roots resorb in response to orthodonture is that most patients don’t show signs of problems until the process is well under way.

Wellington Rody Jr., the chair of the Department of Orthodontics and Pediatric Dentistry at the Stony Brook University School of Dental Medicine, hopes to change that.

Rody, who joined the staff at Stony Brook last May, received a $319,000 grant from the National Institute of Dental and Craniofacial Research to find biomarkers that may show early signs of periodontal disease and dental resorption.

Rody explained that he is “searching for noninvasive markers of root destruction.” Once orthodontists start moving teeth around, a major side effect can be that roots are compromised, to varying degrees. It’s a “common side effect with everybody that wears braces,” but it is usually minor with no clinical relevance.

Currently, the only way to discover root destruction from braces is through X-rays or CT images. “The problem is that when we find those things, as a clinical orthodontist, sometimes, it’s already too late,” Rody said.

Since biomarkers of bone destruction and root destruction may overlap, the focus of his research is to search for biomarkers that can differentiate between the two processes and find the markers that are more specific to root destruction. A few biomarkers of root destruction have been proposed, but there aren’t enough studies to validate those markers. 

Rody will be searching for markers in both saliva and gum fluid. He anticipates that a panel of biomarkers may be more successful than trying to focus on one marker only.

If the markers, which Rody has been developing in collaboration with Shannon Holliday, at the Department of Orthodontics at the University of Florida, and Luciana Shaddox, from the Department of Periodontology at the University of Kentucky, are effective, they will likely provide guidance to clinicians so that high-risk patients may have their treatment plan adapted to prevent further damage.

The type of molecules Rody is searching for include proteins, lipids, metabolites and RNAs. He has been using proteomics, but in this NIH grant, he received enough funding to extend the analysis to other molecules.

According to Rody, there are many predisposing factors for bone loss in the literature. Predisposing factors for root destruction in the dentition also exist but are not well validated.“Genetics definitely plays a major role,” but as far as he is concerned “there is not genetic testing that is 100 percent reliable.”

Until he discovers a reliable biomarker, Rody, who maintains a clinical practice at Stony Brook about one and a half days a week, suggests taking follow-up X-rays after initiating orthodontic treatment, to make sure the “roots are behaving properly,” he said.

A patient who develops serious root destruction may need active monitoring. If the resorption is severe enough, orthodontists typically recommend stopping treatment for a period of one to five months, which is called a “holiday,” and then resume treatment. 

Wellington Rody on vacation in California with his family. Photo from W. Rody

It is only recommended if the patient shows signs of moderate or severe root destruction. Another option is to interrupt treatment early and accept some compromises in the final results 

“We try to get the patient out of braces as soon as possible” in cases of severe root resorption, Rody explained.

Rody has been working in this area since 2014. He received initial funding from the American Association of Orthodontists Foundation. He started by simulating bone and root destruction in a lab and looking for different molecular signatures between the two processes and has already published articles that highlight these differences.

The current NIH study will allow for the search for potential biomarkers. If the group finds them, the next step would be to try to validate them through a process that is expensive and requires large trials.

Ultimately, if and when he finds those biomarkers, Rody said he can use them in a noninvasive way to closely monitor a patient with periodic X-rays. He also might adjust the treatment regime to make sure the patient receives positive results without compromising the prognosis for his or her teeth in the longer term.

Rody believes orthodontics are worth the risk of root resorption, as patients who develop this side effect will likely keep their teeth for many years if not for their whole lives, even with some reduction in their roots.

“Considering all the benefits that orthodontic treatment can bring, in terms of function and cosmetics, it’s still justifiable” but the patient and his or her parents need to understand the risks and benefits associated with braces, he said. 

The teeth that are typically affected by root resorption are the upper front teeth.

Originally from Vitória in Brazil, which is six hours by car north of Rio de Janeiro, Rody lives in Port Jefferson with his wife, Daniela, and their 14-year-old daughter, Thais. 

As for his research, Rody explained that a major goal is to “detect the process [of root resorption] before it becomes severe.” If he does, he will be able to “revise the course of treatment and make sure we don’t allow destruction” of roots and the potential consequences for teeth to reach a high level.

Maureen O’Leary wraps fossils during an expedition in Mali. Photo by Eric Roberts

By Daniel Dunaief

Mali is filled with challenges, from its scorching hot 125 degree temperatures, to its sudden rainstorms, to its dangers from militant and terrorist-sponsored groups.

The current environment in the landlocked country in West Africa makes it extraordinarily difficult to explore the past in a region that includes parts of the Sahara Desert, but that, at one point millions of years ago, was part of a waterway called the Trans-Saharan Seaway.

Maureen O’Leary, professor of anatomical sciences at the Renaissance School of Medicine at Stony Brook University, led three expeditions to Mali, in 1999, 2003 and 2008, collecting a wide array of fossils and geological samples from areas that transitioned from an inland seaway that was about 50 meters deep on average to its current condition as a desiccated desert.

Maureen O’Leary and Eric Roberts with Mali guards. Photo from Maureen O’Leary

On her third trip, O’Leary quickly left because she decided the trip was too dangerous for her and the scientific team. Rather than rue the lack of ongoing access to the region, however, O’Leary pulled together an international team of researchers from Australia, the United States and Mali to look more closely and categorize the information the research teams had already collected from the region.

“We made the most of a bad situation,” O’Leary said. “It is a silver lining, to some degree.”

Indeed, O’Leary and her collaborators put together a paper for the June 28 issue of the Bulletin of the American Museum of Natural History that is over 170 pages and contains numerous images of fossils, as well as recreations of a compelling region during a period from 100 million to 50 million years ago. This time period coincided with one of the five great prehistoric extinction events, during the Cretaceous-Paleogene boundary.

O’Leary characterized some of the more exciting fossil finds from the region, which include the first reconstruction of ancient elephant relatives and large predators such as sharks, crocodiles and sea snakes.

The size of some of these creatures far exceeds their modern relatives. For example, O’Leary’s scientific colleagues estimate that a freshwater catfish was about 160 centimeters in length, which is four times the total size of a modern catfish. The larger catfish dovetails with similar observations the researchers had made about sea snakes in 2016 and 2017. They started to knit this trend into a preliminary hypothesis in which a phenomenon known as island gigantism may have played a role in selecting for these unusually large creatures.

“Species become bigger in these environments,” O’Leary said, suggesting that other scientists have made similar observations. “It’s not clear what causes that kind of selection.”

Above, some of the species that lived in and around the TransSaharan Seaway, including an extinct species of crocodile. Illustrated by Lucille Betti-Nash/ Department of Anatomical Sciences, Stony Brook University.

 

In addition to studying vertebrate and invertebrate fossils, scientists including Eric Roberts at James Cook University in Australia looked at the geology of the region. Roberts helped name and describe many of the formations in the area. This provides context for the lives of creatures who survived in an environment distinctly different from the modern milieu of the Sahara Desert.

Roberts, who is a part of the Sedimentary Geology & Paleontology Research Group that has nicknamed themselves Gravelmonkeys, explained that his initial efforts in Mali came from the fieldwork over a course of weeks when he explored the rock sequences and took copious notes on them.

He suggested that the region still represents a geoscience frontier, in part because it is so difficult to get to, takes serious logistics to do fieldwork and is hard to maintain research.“Over many years, I have worked with collaborators on the project to analyze the samples in many different ways and especially to compare our notes and analytical results with descriptions of rocks and geological formations in other parts of the Sahara and further afield in Africa to understand how they are different and how they correlate,” he said.

O’Leary suggested that the paper provides some context for climate and sea level changes that can and have occurred. During the period she studied, the Earth was considerably warmer, with over 40 percent of today’s exposed land covered by water. Sea levels were about 300 meters higher than current levels, although the Earth wasn’t home to billions of humans yet or to many of the modern day species that share the planet’s resources.

Robert Voss, the editor-in-chief of the series at the American Museum of Natural History, praised the work for its breadth. “This was an unusually large and multidisciplinary author team, as appropriate for the broad scope of the report,” he explained .

“Seldom is such a large geographic area so poorly known paleontologically, so there was a unique opportunity here to break new ground and establish a broad framework for future work,” he added.

Voss described O’Leary as a “force of nature” who “responds constructively to peer reviews.” Roberts, too, appreciated the effort O’Leary put into this work.

O’Leary “drove the entire process and product,” which was only possible with someone of her “vision to wrangle so much science from so many different scientists into one place,” he offered in an email.

Roberts is very pleased with the finished product and added that it is “something that I will be proud of for the rest of my career. This took a lot of effort over the years and it great to see the end product.”

O’Leary said that much of the literature for the science in Mali was in French, which had kept it a bit below the radar for scientific discourse, which tends to be in English.

Indeed, O’Leary was able to facilitate conversations among the many people involved in this project because French was the common denominator language. She studied French at the Holton-Arms School in Bethesda, Maryland. “When I was sitting in my high school French class, I didn’t think it would come in so handy to be fluent in French” in her career, O’Leary said. “It was helpful as a female leader in this situation to be able to speak for [myself], whether speaking to other Americans or collaborating or working with guards.”

O’Leary plans to look at different projects in the United States, including in Puerto Rico, and in Saudi Arabia next. “We now have this synthetic story for Mali [and will be] building out from this to other areas. I anticipate a large time to ramp up to study areas like deposits in Nevada.”

Gábor Balázsi. Photo from SBU

By Daniel Dunaief

Take two identical twins with the same builds, skill sets and determination. One of them may become a multimillionaire, a household name and the face of a franchise, while the other may toil away at the sport for a few years until deciding to pursue other interests.

What causes the paths of these two potential megastars to diverge?

Gábor Balázsi, an associate professor in biomedical engineering at Stony Brook University, asked a similar question about a cellular circuit in the hopes of learning more about cancer. He wanted to know what is it about the heterogeneity of a cancer cell that makes one susceptible to treatment from chemotherapeutic drugs and the other resistant to them. Heterogeneity comes from molecular differences where the original causes may be subtle, such as two molecules colliding or a cell being closer to the tumor’s surface, while the consequences can create significant differences, even among cells with the same genes.

In research published this week in the journal Nature Communications, Balázsi used two mammalian cell lines that were identical except that each carried a different synthetic gene circuit that made one more heterogeneous than the other. He subjected the two cell lines, which would otherwise perform the same function, to various levels of the same drug to determine what might cause one to be treatable and the other to become resistant. 

Through these mammalian cells, Balázsi created two circuits, one of which kept the differences between the cells low, while the other caused larger differences. Once inserted in the cell, these gene circuits created uniform and variable populations that could serve as models for low and high heterogeneity in cancer.

Working with Kevin Farquhar, who recently graduated from Balázsi’s lab, and former Stony Brook postdoc Daniel Charlebois, who is currently at the Department of Physics at the University of Alberta, Balázsi tried to test how uniform versus heterogeneous cell populations respond to treatment with different drug levels. 

Using the two synthetic gene circuits in separate but identical cell lines, the Stony Brook scientists, with financial support from the National Institutes of Health and the Laufer Center for Physical and Quantitative Biology at SBU, could re-create high and low stochasticity, or noise, in drug resistance in two cell lines that were otherwise identical.

While the work is in its preliminary stages and is a long way from the complicated collection of genes responsible for various types of cancer, this kind of analysis can test the importance of specific processes for drug resistance.

“Only in the last decade or so have we come to realize how much heterogeneity (genetic and nongenetic differences) can exist within a tumor in a single patient,” Patricia Thompson-Carino, a professor in the Department of Pathology at the Renaissance School of Medicine at SBU, explained in an email. “Thinking of cancer in a single patient as several different diseases is a bit daunting, though currently, this heterogeneity and its direct effects on how the cancer behaves remains poorly understood.”

Indeed, Thompson-Carino added that she believes Balázsi’s work will “shed light on cancer cell responses to therapy. With the rise in cancer therapies designed to specific targets and the resistance that emerges in patients on these therapies, I think [Balázsi’s] work is of extremely high value” which may help with the puzzle of how nongenetic or epigenetic heterogeneity affects responses to treatment, she continued.

In the future, researchers and clinicians may look to develop new ways of biomarker analysis that considers the variability, rather than just the average level of a biomarker.

Balázsi suggested that looking only at the variability of cells is analogous to observing an iron block sinking in water. Someone might conclude that all solids sink in liquids. Similarly, scientists might decide that cellular variability always promotes drug resistance from observations when this happens. To gain a fuller understanding of the effect of variability, however, researchers need to equalize the averages. They then need to explore what happens at various levels of drug treatment.

Current therapies do not target heterogeneity. If such future treatments existed, doctors and scientists could combine ways of treating heterogeneity with attacking cancer, which might work in the short term or prevent cancer from recurring.

Balázsi suggests his paper is a part of his attempt to address three different areas. First, he’d like to figure out how to categorize patients better, including the variability of biomarkers. Second, he believes this kind of analysis will assist in creating future combinations of treatments. By understanding how the variability of cancer cells contributes to its reaction to therapies, he might help create a cocktail of treatments, akin to the effort that helped with the treatment of HIV in the lab.

Third, he’d like to obtain cancer samples and allow them to evolve in a lab, where he can check to see how they respond to treatment levels and administration scheduling. This effort could allow him to determine the optimal drug combination and dosing for a patient.

For the work that led to the current Nature Communications paper, Balázsi explored how mammalian cells respond to various concentrations of a drug. Over 80 percent of the genes in these cells are also present in human cells, so the mechanisms he discovered and conclusions he draws should apply to human cancer cells as well.

He concluded that cells with more heterogeneity, where the cells deviate more from the average, resist drugs better when the drug level is high. These same cells, show greater sensitivity when the drug is low.

Balázsi recognizes that the work he’s exploring is a “complex problem” and that it requires considerable additional research to understand and appreciate how a therapy might kill one cancer cell, while the same treatment in the same environment doesn’t have the same effect on a genetically identical cell.

Ela Elyada. Photo by Giulia Biffi

By Daniel Dunaief

They have the ability to call the body’s armed forces. They may interact with the immunological foot soldiers and, then, somehow, inactivate them, allowing the destructive cancer they may aid and abet to continue causing havoc.

This is one hypothesis about how a newly discovered class of fibroblasts may play a role in the progression of pancreatic cancer.

Ela Elyada, a postdoctoral fellow in David Tuveson’s lab at Cold Spring Harbor Lab, partnered up with Associate Professor Paul Robson at the Jackson Laboratory in Farmington, Connecticut, to find a new class of fibroblast in pancreatic cancer.

This cell, which they called antigen-presenting cancer-associated fibroblasts (or apCAFs) had the same kind of genes that are usually found in immune cells. Cells with these genes have signals on their surface that present antigens, or foreign parts of viruses and bacteria to helper T-cells. Elyada and Robson showed that the apCAFs can use their immune cell genes to present peptides to helper T-cells.

With the apCAFs, the researchers hypothesize that something about the immunological process goes awry, as the T-cells show up but don’t engage.

Elyada and Robson suspect that the activation process may be incomplete, which prevents the body’s own defense system from recognizing and attacking the unwelcome cancer cells.

While she was excited about the potential of finding a different type of cell, Elyada needed to convince herself, and the rest of the scientific community, that what she’d found was truly original, as opposed to a scientific mirage.

“We spent hours and hours trying to understand what is different in this type of cell,” Elyada said. “Like everything new you find, as a scientist, you really question yourself, ‘Is it real? Is it an artifact of the single cell?’ It was really important for me to do everything I could from every angle to make sure they were not macrophages that looked like fibroblasts or cancer cells that looked like fibroblasts.”

After considerable effort, Elyada was sure without a doubt that the group had found fibroblasts and that these specific cells, which typically are involved in connective tissue but which pancreatic cancer uses to form a shell around it, contained these immunological genes.

She sees these cells in different experiments from other people inside and outside the lab, which further supports her work and found the apCAFs in mice and human pancreatic ductal adenocarcinoma, which is the fourth leading cause of cancer-related deaths in the world.

The fibroblasts, which are not cancerous, play an unclear role in pancreatic cancer. 

Elyada explained that single-cell sequencing enables scientists to look at individual cells, instead of at a whole population of cells. Scientists “have started to utilize this method to look at differences between cells we thought were the same,” she said. “It’s useful for looking at the fibroblast population. Scientists have appreciated that there’s probably a lot of heterogeneity,” but they hadn’t been able to describe or define it as well without this technique.

The results of this research, which was a collaboration between Elyada, Robson and others, were recently published in the journal Cancer Discovery. Robson said it was a “great example of how [single-cell RNA sequencing] can be very useful in revealing new biology, in this case, a new subtype of cancer-associated fibroblast.”

Earlier work in the labs of Robson and Tuveson, among others, have shown heterogeneity within cancer-associated fibroblast populations. These often carry a worse prognosis.

“We are very interested in continuing to explore this heterogeneity across tumor types and expect we will continue to find new subtypes and, although we have yet to confirm, would expect to see other solid tumor types to contain apCAFs,” Robson said.

“We still need to work hard to reveal their function in the full animal, but if they turn out to be tricking the immune cells, they could be a target for different immune-related inhibition methods,” explained Elyada.

The newly described fibroblast cells may be sending a signal to the T-cells and then either trapping or deactivating them. Elyada and Robson both said these results, which they developed after working together since 2016, have led to numerous other questions. They want to know how they work, what the mechanisms are that allow their formation, what signals they trigger in T-cells and many other questions.

Elyada is working with Pasquale Laise in Andrea Califano’s lab at Columbia University to gather additional information that uses this single-cell sequencing data.

Laise has “a unique way of analyzing [the information] to look at how the sequencing can predict if proteins are active or not active in a cell,” she said. Laise is able to predict the activity of transcription factors according to the expression level of their known target.

Elyada may be able to use this information to understand the source cell from which the fibroblasts are coming.

Originally from Israel, Elyada has been working as a postdoctoral researcher in Tuveson’s lab for about six years. She lives in Huntington Village with her husband Gal Nechooshtan, a postdoctoral researcher at Cold Spring Harbor Laboratory’s Woodbury complex. The couple has two daughters, Maayan, who is 10, and Yael, who is 8.

Elyada hopes to return to Israel next year, where she’d like to secure a job as a professor and build on the work she’s done at CSHL.“I definitely want to keep working on this. This would hopefully be a successful project in my future lab.”