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Power of 3

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Ramana Davuluri

By Daniel Dunaief

Ramana Davuluri feels like he’s returning home.

Davuluri first arrived in the United States from his native India in 1999, when he worked at Cold Spring Harbor Laboratory. After numerous other jobs throughout the United States, including as Assistant Professor at Ohio State University and Associate Professor and Director of Computational Biology at The Wistar Institute in Philadelphia, Davuluri has come back to Long Island. 

As of the fall of 2020, he became a Professor in the Department of Biomedical Informatics and Director of Bioinformatics Shared Resource at Stony Brook Cancer Center.

“After coming from India, this is where we landed and where we established our life. This feels like our home town,” said Davuluri, who purchased a home in East Setauket with his wife Lakshmi and their six-year-old daughter Roopavi.

Although Davuluri’s formal training in biology ended in high school, he has applied his foundations in statistics, computer programming and, more recently, the application of machine learning and deep algorithms to the problems of cancer data science, particularly for analyses of genomic and other molecular data.

Davuluri likens the process of the work he does to interpreting language based on the context and order in which the words appear.

The word “fly,” for example, could be a noun, as in an insect at a picnic, or a verb, as in to hop on an airplane and visit family for the first time in several years.

Interpreting the meaning of genetic sentences requires an understanding not only of the order of a genetic code, but also of the context in which that code builds the equivalent of molecular biological sentences.

A critical point for genetic sequences starts with a promoter, which is where genes become active. As it turns out, these areas have considerable variability, which affects the genetic information they produce.

“Most of the genetic variability we have so far observed in population-level genomic data is present near the promoter regions, with the highest density overlapping with the transcription start site,” he explained in an email.

Most of the work he does involves understanding the non-coding portion of genomes. The long-term goal is to understand the complex puzzle of gene-gene interactions at isoform levels, which means how the interactions change if one splice variant is replaced by another of the same gene.

“We are trying to prioritize variants by computational predictions so the experimentalists can focus on a few candidates rather than millions,” Davuluri added.

Most of Davuluri’s work depends on the novel application of machine learning. Recently, he has used deep learning methods on large volumes of data. A recent example includes building a classifier based on a set of transcripts’ expression to predict a subtype of brain cancer or ovarian cancer.

In his work on glioblastoma and high grade ovarian cancer subtyping, he has applied machine learning algorithms on isoform level gene expression data.

Davuluri hopes to turn his ability to interpret specific genetic coding regions into a better understanding not only of cancer, but also of the specific drugs researchers use to treat it.

He recently developed an informatics pipeline for evaluating the differences in interaction profiles between a drug and its target protein isoforms.

In research he recently published in Scientific Reports, he found that over three quarters of drugs either missed a potential target isoform or target other isoforms with varied expression in multiple normal tissues.

Research into drug discovery is often done “as if one gene is making one protein,” Davuluri said. He believes the biggest reason for the failure of early stage drug discovery resides in picking a candidate that is not specific enough.

Ramana Davuluri with his daughter Roopavi. Photo by Laskshmi Davuluri

Davuluri is trying to make an impact by searching more specifically for the type of protein or drug target, which could, prior to use in a clinical trial, enhance the specificity and effectiveness of any treatment.

Hiring Davuluri expands the bioinformatics department, in which Joel Saltz is chairman, as well as the overall cancer effort. 

Davuluri had worked with Saltz years ago when both scientists conducted research at Ohio State University.

“I was impressed with him,” Saltz said. “I was delighted to hear that he was available and potentially interested. People who are senior and highly accomplished bioinfomaticians are rare and difficult to recruit.”

Saltz cited the “tremendous progress” Davuluri has made in the field of transcription factors and cancer.

Bioinformatic analysis generally doesn’t take into account the way genes can be interpreted in different ways in different kinds of cancer. Davuluri’s work, however, does, Saltz said.

Developing ways to understand how tumors interact with non-tumor areas, how metastases develop, and how immune cells interact with a tumor can provide key advances in the field of cancer research, Saltz said. “If you can look at how this plays out over space and time, you can get more insights as to how a cancer develops and the different part of cancer that interact,” he said.

When he was younger, Davuluri dreamt of being a doctor. In 10th grade, he went on a field trip to a nearby teaching hospital, which changed his mind after watching a doctor perform surgery on a patient.

Later in college, he realized he was better in mathematics than many other subjects.

Davuluri and Lakshmi are thrilled to be raising their daughter, whose name is a combination of the words for “beautiful” and “brave” in their native Telugu.

As for Davuluri’s work, within the next year he would like to understand variants. 

“Genetic variants can explain not only how we are different from one another, but also our susceptibility to complex diseases,” he explained. With increasing population level genomic data, he hopes to uncover variants in different ethnic groups that might provide better biomarkers.

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Pixabay photo

By Daniel Dunaief

While wind is nice and effective, moving water is even more promising, especially in the future of alternative energies.

Ali Khosronejad. Photo from SBU

That’s because water is almost 1,000 times more dense than air, which means that the movement of the wet stuff due to tides or storms could produce a considerable amount of energy.

Indeed, “if we can effectively harness the energy from moving waters in our national waterways alone, it could provide enough energy to power the whole country,” said Ali Khosronejad, Assistant Professor in the Department of Civil Engineering at Stony Brook University.

Khosronejad recently received $2 million as part of a $9.7 million four-year Department of Energy grant to study and develop ways to turn the movement of water into usable energy.

“I’m very optimistic about the future of this” approach, he said.

The DOE funds, which will involve a collaboration with East Carolina University, the University of New Hampshire, and Lehigh University, is a part of the new Atlantic Marine Energy Center, for which Khosronejad is a co-director.

The funds at Stony Brook will support hiring researchers at numerous levels, from post doctoral scientists, to graduate students and undergraduates. The money will also support adding new computer modules and expanding storage at the supercomputer. 

Stony Brook will also tap into these funds to enable travel for these new hires, to help them interact in person with their collaborators from other universities.

The combined effort at these academic centers will be dedicated to researching ocean energy technology, education and outreach. 

Researchers will work in the field, the laboratory and with computers on these ocean energy projects. They will seek to use wave energy and tidal energy conversion through such efforts as wave energy converters and tidal turbine farms.

This image depicts simulated turbulence in a waterway where a virtual tidal farm can be installed. The Stony Brook research team will use such simulations to investigate potential renewable ocean energy options. Image from Ali Khosronejad

The wave-energy converter floats on the seawater surface and uses the energy from the up and down motion of the water surface to produce electrical energy.

Researchers around the world are working to improve the efficiency of tidal turbine farms. Khosronejad described the effort as being in its infancy.

A good portion of the current project involves finding ways to optimize the positioning and layout of turbines in tidal farms. In his team, Khosronejad will work on the development of new artificial intelligence approaches to optimize the positioning and layout of turbines in tidal farms.

Stony Brook’s role in this project will involve working with computers.

In his research group, Khosronejad will work with supercomputers. His effort involves working to develop high-fidelity mathematical models that can address sediment transport and sediment-laden flows in tidal farms. 

Scientists at the University of New Hampshire and ECU are involved in addressing environmental concerns.

In the Department of Electrical Engineering at Stony Brook, co-principal investigators Fang Luo, Associate Professor and Peng Zhang, Professor in the Department of Electrical Engineering will work with computers and laboratories for micro-grid software and hardware research, respectively.

Ali Khosronejad, right, with former graduate student Kevin Flora, who earned his PhD in 2021

Working with Lehigh University, Khosronejad is doing high fidelity simulations, to replicate what researchers in the field at the University of New Hampshire and the Coastal Studies Institute at ECU are studying.

“We validate and develop artificial intelligence for design optimization of these tidal farms,” Khosronejad explained. The goal is to optimize the design of hydrokinetic turbines in estuaries and coastal areas that can create tidal farms.

The collaboration will coordinate with the National Renewable Energy Laboratory, Sandia National Laboratories, Pacific Northwest National Laboratory, European Marine Energy Centre and Old Dominion University.

The first year of the project involves hiring, training graduates and undergraduates, setting up the foundation, and beginning the infrastructure upgrade.

“The training part is important,” Khosronejad said. “This will be the next workforce. The infrastructure will stay there for the next 10 years” so the university can use it in a host of other projects.

Khosronejad is encouraged by the financial commitment from the Department of Energy. “They understand how important it is, which is why they are investing a lot in this,” he said. Some of these tidal farms are already working in the East River, between Manhattan and Roosevelt Island.

Wind turbines

At the same time, Khosronejad is continuing a wind turbine project he started with Fotis Sotiropoulos, the former dean of the College of Engineering and Applied Sciences at Stony Brook who is now Provost at Virginia Commonwealth University.

Khosronejad is now the principal investigator on that $1.1 million project and is continuing to work with Sotiropoulos, who officially left the project but is still volunteering to participate in its research activities. The scientists are working on how to use artificial intelligence to enhance the design of wind turbines.

Computer programs can alter the angle of the blades for the offshore wind farms where they attempt to use a control system to pitch the blades automatically to reduce the wind load during highly turbulent wind flows.

Changing the angle of attack of the blade can lower the loads and save money that would otherwise go to repairing blades that cracked or developed weaknesses amid strong winds, Khosronejad said.

The researchers presented their results at the American Physical Society meeting in Phoenix just before Thanksgiving. 

The researchers are trying to balance between using the turbine to generate energy and preventing the force of the winds from damaging the system.

When wind speeds are up to 25 miles per hour, the system uses the full power of the wind to maximize energy production. At speeds above that, the turbulent wind can damage the rotor and gearbox. The blades are pitched to reduce the angular velocity, which is known as self-preservation mode. At speeds over 55 miles per hour, the turbine stops working to produce no energy and avoid significant damage to the rotors and gearbox.

Generally, such federal research projects involve sharing results publicly and with the industry sector. The goal is to share science that enables the production of reliable energy.

 

 

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From left, Daniele Rosado and Ullas Pedmale examine a sample of the model plant Arabidopsis. Photo courtesy of Ullas Pedmale

By Daniel Dunaief

Many plants are in an arms race akin to the developers of skyscrapers eager to get the most light for their prized penthouse apartments. Only, instead of trying to collect rent from well-heeled humans, these plants are trying to get the most sun, from which they create energy through photosynthesis.

Plants are so eager to get to the coveted sunlight that the part growing towards the light sends a distress signal to the roots when they are in the shade. While that might help an individual plant in the short term, it can create such shallow and ineffective roots that the plant becomes vulnerable to unfavorable weather. They also can’t get as many nutrients and water from the ground.

This is problematic for farmers, who want plants that grow in the sun, but that don’t sacrifice the development of their roots in the shade. Ullas Pedmale, Assistant Professor at Cold Spring Harbor Laboratory, is working to lend a hand.

Pedmale, who recently published research in the journal Plant Physiology, is studying the signals the shoots, or the parts of the plants either in the sunlight or the shade, send to the roots.

Pedmale and postdoctoral researcher Daniele Rosado, who is the first author on the recent paper, explored the genes that turned on in the roots of the model plant Arabidopsis and tomato plants when these plants were in the shade.

When plants are in the shade, they “prioritize shoot growth and try to outcompete the neighboring plants,” said Rosado. “That’s when root development is compromised.”

Among the genes that are active when plants are in the shade is a family of genes called WRKYs, which affect gene expression and cause stunted growth in the roots.

WRKY genes respond to stress. Keeping WRKY genes on all the time, even when a plant is in the sun, caused stunted growth of the roots. WRKY proteins turn on or off other genes.

This can be problematic for farmers, who tend to try to increase yield by putting more plants in an area. At that point, the plants shade each other, which is “bad for the root system. If we can find a way to get the roots to grow normally, we can potentially increase yield,” Rosado said.

This could also remove more carbon dioxide from the air and store it in the developing roots, helping to mitigate the effect of global warming. “Our study can give a roadmap on how to make longer, deeper roots,” Pedmale said.

At this point, researchers still don’t know how the plant transfers information about the amount of sunlight it receives in the green chloroplasts where photosynthesis occurs to the WRKY genes, which are in the nucleus.

Researchers have been studying the shade response in the shoots of plants for over five decades. They have not, however, focused as much attention on the effect of less sunlight on the roots.

“We want to tackle this problem,” Pedmale said.

WRKY genes are a generalized stress signal, which is not just involved when a plant isn’t getting enough light. They are also turned on during pathogen attacks, stress and amid developmental signals.

Indeed, plants in the shade that have turned on these signals are especially vulnerable to attacks. Caterpillars, for example, can eat most of a shaded plant because the plant is so focused on growing its shoot that its defenses are down.

When that same plant is in the sunlight, it is more effective at defending itself against caterpillars.

At this point, Pedmale doesn’t know whether these genes and signals occur across a broad species of plants beyond tomatoes and Arabidopsis. He and others are hoping to look for these genes in grasses and grains.

Pedmale is also searching for other signals between the shoot and the root. “Plants are masters of adaptation,” he said. “They might have redundant systems” that signal for roots to slow their growth while the shoots tap into the available energy to grow.

Plants may also have natural molecules that serve as brakes for the WRKY signal, preventing the shoot from taking all the available energy and rendering the plant structurally fragile.

A scientist at CSHL for five years, Pedmale came to the lab because of the talent of his colleagues, the reputation and opportunity at CSHL and the location.

Born and raised in Bangalore, India, Pedmale enjoys reading fiction and autobiographies and wood working when he’s not in the lab. He recently made a book shelf, which provides him with a chance to “switch off” from science, which, he said, is a 24-hour job. He has taken wood pieces from his workshop and brought them to PhD classes at CSHL, where he can show them plant biology and genetics at work.

Pedmale and his wife Priya Sridevi, who also works at CSHL, have a mini golden doodle named Henry.

A native of São Paulo, Brazil, Rosado is married to plant biologist Paula Elbl, who is the co-founder of a start up called GALY, which is trying to produce cotton in a lab instead of in a field.

Rosado is the first in her family to attend a public university. She has been working in Pedmale’s lab for two years and plans to continue her research on Long Island for at least another year.

Rosado knew Pedmale had worked as a post doctoral researcher in the lab of celebrated plant biologist Joanne Chory at the Salk Institute for Biological Studies. She met Pedmale at a plant conference, where she expressed an interest in his research.

Longer term, Rosado hopes her research has a broader impact.

“If I’m lucky, I’ll be able to see the fruits of my work being applied to make a difference and help feed people,” she said.

As for his work, Pedmale is eager to understand and use the signals from one part of a plant to another, given that the plant lacks a nervous system. “Once we can understand their language,” he said, “we can manipulate it to increase yield.”

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Jessica Tollkuhn Photo courtesy of CSHL

By Daniel Dunaief

They are like directors in a carefully choreographed production, instructing certain groups that become active, while giving others a five-minute break.

In the case of the human body, directors take many forms, including hormones; the same hormones that can transform adorable, sweet and well-behaved children into smelly, strong-willed teenagers.

Hormones like estrogen, testosterone and progesterone affect people at various ages and in different ways.

Recently, Cold Spring Harbor Laboratory Assistant Professor Jessica Tollkuhn and her graduate student Bruno Gegenhuber teamed up with University of California at San Francisco Herzstein Professor of Molecular Physiology Holly Ingraham to link the way estrogen in a specific area of the brain turns on particular genes.

For mice that are representative of post-menopausal women, the lower activity of a gene called melanocortin-4, or MC4R causes these mice to become less active.

By activating MC4R neurons in the ventrolateral ventromedial hypothalamic nucleus of the brain in the absence of estrogen, researchers caused a dramatic increase in physical activity and 10 percent body weight loss after one day.

Additionally, turning up the MC4R gene increased their bone density over time.

Linking the gene activated by estrogen in a part of the brain that affects how adult females use energy, the scientists provided a causative link that explains lower energy in this population.

Tollkuhn said her contribution showed that the estrogen receptor binds DNA in the presence of hormones.

The scientists published their research in the journal Nature.

“If anything, this paper is a study of how just one gene can show this exquisite behavioral response,” Tollkuhn added.

The MC4R gene is also found in the male brain, although not in the same area. Experimentally, turning up the gene also increases physical activity in males.

Numerous drugs currently target this gene in connection with increasing libido in post-menopausal women. Using these treatments for other issues, like weight gain and activity level, would require additional study.

Estrogen affects numerous other areas of the body, including some that may cause other problems. Hormone replacement therapy has contributed to the development or worsening of other cancers, such as breast cancer, although it is not clear why or how this happens.

“There’s evidence that there can be positive benefits [like bone and mental health], but also evidence that it can increase the risk of cancers,” Tollkuhn said.

Ingraham knew Tollkuhn from their overlapping research experiences at the University of California at San Diego and, later at UCSF.

Ingraham had reached out to Tollkuhn to see if the experiments in Tollkuhn’s lab could determine the link between the hormone and the MC4R gene.

“It’s always a challenge in biology to get a direct causality” because numerous factors in a living system could contribute to the development of a condition or a behavior, Tollkuhn said.

Tollkuhn suggested that the bulk of the experiments were done in Ingraham’s lab.

Ingraham recognized early on the benefit of finding these direct binding sites.

“We are saying, ‘Here is a hormone and it is acting through this molecule and it’s causing this change … that we know is really important for eliciting this behavior,” Ingraham said.

Ingraham, who worked with Tollkuhn when she was a post doctoral researcher and Tollkuhn was a graduate student in Geoffrey Rosenfeld’s lab at UC San Diego, called her colleague “really talented” and said she “spent years working this whole system out. It’s heroic and nobody else has done it.”

Ingraham sent Rosenfeld a message after the journal Nature accepted their paper, indicating his trainees had “hit pay dirt on this one.”

Ingraham hopes the paper motivates other researchers to think about entering this area and tackling this challenge, which is so important for women’s health.

“The only way we’re going to move forward for women’s health is to understand all these different facets of what estrogen is doing in the brain,” she added.

In press coverage of the research, Ingraham described the comments as falling into two categories. In the first, women suggest that they’re past menopause and have never been more active. In the second, women indicate that getting hormone replacement therapy genuinely helped them, including with brain fog.

Other scientists have sent Ingraham congratulatory emails about the paper. They have “appreciated that this had such a great molecular story,” she said.

In a broader research context, Tollkuhn is interested in determining how hormones affect the brain during sexual differentiation.

She is now focused on identifying a new repertoire that she and others can explore in future studies.

Tollkuhn’s lab is also investigating how estrogen influences brain development. She has found dozens of genes she would like to understand in the kind of detail with which she explored MC4R. Estrogen receptors also are connected to HTR1A and HTR1D, which are genes for serotonin receptors and may connect estrogen to mood.

Studies in scientific literature have shown that numerous psychiatric and neurological conditions have sex differences in terms of their impacts on men and women.

“We have these pieces and we can try to put together this puzzle,” Tollkuhn said. “We can try to understand why this would be the case. The long term goal is to figure out why there is a greater increase in [certain diseases] in men or women, which could lead to the development of better treatment.”

Tollkuhn is also interested in understanding the progression of neurodegenerative conditions like Alzheimer’s, which is twice as likely in women as in men. The symptoms for this disease develops more rapidly in post menopausal women, who typically have a more precipitous decline in estrogen than older men do in their levels of testosterone.

“I’m interested in what hormone receptors are doing in the brain,” she said.

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From left, CSHL’s Bruce Stillman, Double Helix Medal recipients Leonard Schleifer and Reggie Jackson, Chair of the CSHL Board of Trustees Marilyn Simons, and Double Helix Medal recipient George D. Yancopoulos. Photos by Constance Brukin
Above, NYC Mayor-elect Eric Adams speaks at the 16th Annual Double Helix Medals dinner with CSHL President and CEO Bruce Stillmanon and television journalist Lesley Stahl. Photos by Constance Brukin
The guests, including scientists from CSHL, and the honorees shared stories and hors d’oeuvres beneath the dinosaurs at the Museum of Natural History. Photo by Tobias Janowitz
Above, NYC Mayor-elect Eric Adams speaks at the 16th Annual Double Helix Medals dinner with CSHL President and CEO Bruce Stillmanon and television journalist Lesley Stahl. Photos by Constance Brukin
Double Helix Medal recipient George Yancopoulos takes a selfie with CSHL President and CEO Bruce Stillman, Regeneron Chairman of the Board P. Roy Vagelos, Double Helix Medal recipients Leonard Schleifer and Reggie Jackson, and Chair of the CSHL Board of Trustees Marilyn Simons. Photo by Constance Brukin
Dinner was served under the Blue Whale at the Natural History Museum. Photo by Sara Roncero-Menendez
CSHL Trustee Robert W. Lourie, CSHL President and CEO Bruce Stillman, and County Executive Steve Bellone. Photo by Constance Brukin
From left, Assistant Professor Tobias Janowitz, Professor Leemor Joshua-Tor, Assistant Professor Peter Koo, and Professor Linda Van Aelst. Photo by Constance Brukin
Dessert at the awards dinner was caramel tart dessert with chocolate ganache and vanilla ice cream. Photo by Sara Roncero-Menendez

By Daniel Dunaief

This November, Cold Spring Harbor Laboratory celebrated baseball’s Mr. October.

The research facility that specializes in studying cancer, neuroscience, quantitative and plant biology hosted its 16th annual Double Helix Medals dinner at the Museum of Natural History on Nov. 17.

The evening, which was emceed by television journalist Lesley Stahl, honored Hall-of-Famer Reggie Jackson, as well as Leonard Schleifer and George Yancopoulos, the founders of Regeneron, the pharmaceutical company that has provided a life-saving antibody treatment for COVID-19.

The evening, which featured a dinner beneath the blue whale at the museum, raised a record $5 million for research.

“When we were standing in the hall of dinosaurs at the museum, it was fantastic,” said CSHL President and CEO Bruce Stillman. “It was one of the first events where people went out like the old days” prior to the pandemic.

Stillman said guests had to have received their COVID vaccinations to attend the celebration.

In addition to establishing a career as a clutch hitter in the playoffs, Reggie Jackson has dedicated considerable energy through his Mr. October Foundation to improve education around the country.

“His Mr. October foundation complements and parallels the DNA Learning Center programs, particularly now that we’ve opened a large DNA Learning Center in downtown Brooklyn that is serving underserved students in lab-based science,” said Stillman.

In his acceptance speech, Jackson said he found it “significant” that he received an honor for his educational efforts off the baseball field.

Yancopoulos, meanwhile, described his roots as the son of first generation immigrant parents from Greece. Yancopoulos highlighted the need for more funding in research and suggested that science helped pull the world through the pandemic. Yancopoulos said the National Institutes of Health should increase its budget 10-fold to meet the research and clinical needs of the population.

“Biotechnology offers the promise of really solving some of the most difficult problems that we face if we want our citizens to live not only longer, but healthier lives,” Schleifer said in a statement.

Mayor-elect Eric Adams, meanwhile, gave a speech about his vision for the future of the city which included, after some prompting from Stillman, increasing science in the education system.

The Double Helix gala, which started in 2006 when the lab honored the late boxer Muhammed Ali, raises money that goes into CSHL’s operating budget to support research and education.

This year, the donations included a generous gift from Astros owner Jim Crane, who introduced his friend Jackson.

Stillman helps direct the funds raised through the dinner to support scientists who are making what he termed “breakthrough discoveries.”

Many of the most significant discoveries come through philanthropic support, Stillman said, which makes it possible for researchers to design high-risk, high-reward experiments.

CSHL Chair of the Board of Trustees Dr. Marilyn Simons, a previous winner, attended the festive evening.

Senior leadership at the lab chooses the honorees. Stillman said CSHL already has two honorees for the event next year.

Previous honorees include actor Michael J. Fox, basketball legend Kareem Abdul-Jabbar, actor and science educator Alan Alda, and newscasters including Tom Brokaw and Katie Couric.

“It is a really spectacular list,” Stillman said. The winners, who receive a medal, have all contributed in some significant way to science or to science education.

The dinner provides an opportunity for supporters of the mission of CSHL, which has had eight Nobel Prize winners work at the lab during their careers, to invite others to hear about research at the lab.

“It was a very inspiring evening,” Stillman said.

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Above, DeLorenzo (in blue) at a Multiple Sclerosis benefit in which she and a group of friends climbed the stairs at Rockefeller Center. Photo from C. DeLorenzo

By Daniel Dunaief

Her colleagues highlight the joy, passion and optimism she brings to her work, which can be the opposite of the way people she is eager to help feel. 

Dr. Christine DeLorenzo, Professor of Psychiatry and Biomedical Engineering at Stony Brook University, studies depression.

A disease with numerous symptoms that likely has a wide range of causes, depression presents an opportunity for Dr. DeLorenzo to bring not only a relentless energy to her work, but also an engineer’s perspective.

“Engineering is all about examining a complex problem and thinking, ‘I bet we can fix that,’” explained Dr. DeLorenzo in an email. “Biomedical engineering takes it to a new level.”

Indeed, Dr. DeLorenzo specializes in brain imaging, using positron emission tomography, among other techniques, to understand and differentiate the factors that might contribute to depression and to develop ways to treat specific subtypes of the mental health disease.

Dr. Ramin Parsey, who mentored Dr. DeLorenzo and is professor and Della Pietra Chair of Biomedical Imaging at Stony Brook, believes she will help define the subtypes of depression by imaging the brain.

For Dr. DeLorenzo, the abundance of discussion in the popular and scientific literature that currently attributes the progression of depression to a host of causes, from eating the wrong foods to not exercising enough to not getting the right amount of sleep, doesn’t offer much clarity.

“We see a million articles about what causes depression and they don’t all agree,” said Dr. DeLorenzo. “Depression is caused by a bunch of different things, which is not all that helpful when you’re the person suffering.”

In her brain studies, Dr. DeLorenzo has looked at inflammation and neurotransmitter systems. The goal of her work is to find “whatever is outside the normal range in the person with depression and treat” that potential cause, she said. High levels of inflammation might suggest an anti-inflammatory treatment.

When people receive a major depressive disorder diagnosis, they often are prescribed a selective serotonin reuptake inhibitor, or SSRI. This enables the neurotransmitter serotonin to remain in the brain for a longer period of time.

“It’s great that it works in a subset of people” for whom it is effective, Dr. DeLorenzo said. “We would like to know beforehand if we give this medication will it work for you, specifically.”

In one of her studies, Dr. DeLorenzo uses positron emission tomography, or PET scans, to search for signs of inflammation. She is looking for translocator proteins, which is a marker of inflammation. Reactive glial cells in the brain, which are an important supporting part of the nervous system that don’t have axons and dendrites like nerve cells, increase the production of these proteins during some depression and other disorders.

The level of these translocator proteins increase in glial cells when the brain is having an inflammatory response, which likely occurs in a subtype of depression as well as in other diseases.

Dr. DeLorenzo has a PET tracer that sticks to that protein and that gives off a signal to the camera, which enables her to quantify the inflammation.

At this point, she and her collaborators, including co-Principal Investigator Dr. Parsey and Dr. Stella Tsirka, Professor of Pharmacological Sciences at Stony Brook, are recruiting a collection of patients with depression. They are testing the idea that people with higher inflammation are better treated with an anti-inflammatory. They are using PET to see who has high or low inflammation prior to treatment. During the study, the researchers will determine if those with the highest inflammation had the best response.

Dr. Tsirka’s lab uses animal models to understand mechanisms of disease and experiment on treatment, while Dr. DeLorenzo uses neuro-imaging in human patients to understand and treat pathology.

“Our preclinical results certainly support the idea of the neuro-inflammation hypothesis of depression” and suggest potential ways to interfere with the process in preclinical models, Dr. Tsirka explained in an email.

Dr. Tsirka, who has been working for Dr. DeLorenzo for over three years, described her colleague as “enthusiastic, rational creative and hard working” and believed imaging could provide a way to verify efficient treatment of depression.

By understanding the biology of the brain, Dr. DeLorenzo hopes to address a range of questions that might affect the disease.

In other work, Dr. DeLorenzo is exploring the possibility that a disruption in glutamate leads to circadian and mood dysfunction in a subtype of depression.

In some studies with glutamate, researchers assessed mood before and after sleep deprivation. They found that sleep deprivation provided an antidepressant effect in about 40 percent of patients with Major Depressive Disorder.

A healthy person would typically become tired and angry after staying awake for 36 straight hours. Some people with this form of depression, however, see an improvement in their mood after staying up for so many hours.

“Something about sleep deprivation causes an antidepressant effect in some people,” Dr. DeLorenzo said. “We don’t know what that is.”

The antidepressant effect can be short lived, although about 10 percent of people have benefits that last as long as a few weeks.

To be sure, Dr. DeLorenzo cautioned that no one is “advocating just doing sleep deprivation” or even a continuous cycle of partial sleep deprivation.

Born and raised in Bay Ridge, Brooklyn, Dr. DeLorenzo earned her undergraduate and Master’s Degrees at Dartmouth College. She earned her PhD from Yale University, where she started her brain imaging work.

When Parsey left Columbia to join Stony Brook in 2012, Dr. DeLorenzo moved with him, even though her commute from Queens was three hours each way.

“She never complained” about her travels, Dr. Parsey marveled. In fact, Dr. DeLorenzo uses the commuting time to read papers and prepare emails.

Dr. Parsey admired Dr. DeLorenzo’s dedication to teaching and mentoring students in her lab. In her first summer, she took on 17 interns. “This is the kind of stuff that nobody else I know does,” Dr. Parsey marveled.

As for her work, Dr. DeLorenzo believes understanding sub-categories of mental health will follow the same pattern as cancer research. “Back in the day, we used to say, ‘Someone has cancer or a tumor.’ Now, we say that that tumor has this genetic marker, which is what we’re going to target when we treat it.”

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Three long-finned pilot whales. Photo by Andrew Sutton/ Shutterstock
From left, Lesley Thorne, Eleanor Heywood and Julia Stepanuk. Photo by Julia Stepanuk
Lesley Thorne on a research ship in the Antarctic. Photo from Lesley Thorne
Lesley Thorne in the Antarctic. Photo from Lesley Thorne
Lesley Thorne with black-browed albatross in the Falkland Islands. Photo from Lesley Thorne

By Daniel Dunaief

Long-finned pilot whales can’t stand the heat, so they are heading north.

Amid increases in ocean temperatures caused by global warming, long-finned pilot whales have moved the center of their range to the north, according to a 25-year study Lesley Thorne, Assistant Professor in the School of Marine and Atmospheric Sciences at Stony Brook University and Janet Nye, Associate Professor at the University of North Carolina Institute of Marine Sciences and Adjunct Professor of SoMAS, recently published in the journal Scientific Reports.

What’s more, these whales are swimming farther north despite the fact that some of their prey, including fish and invertebrates such as squid, aren’t shifting as far north, while others are moving into deeper offshore waters.

That could have broad ecological consequences for both regions, as whales may head towards areas to compete against other predators for the same prey, while some fish populations in deeper waters offshore may increase, putting pressure on the creatures that live in those areas.

“We know that different species are responding in different ways to climate change,” Thorne said. “That will impact all the dynamics” including food webs and competition. 

Climate change may change the predator-prey dynamics in unexpected ways, Nye explained in an email. “We know that it would be wrong to assume that all species would shift at the same rate in response to changing environmental patterns, but this is one of a growing number of papers to illustrate that the rate at which individual species” in different feeding groups changes can be different, which alters the way ecosystems function.

Nye explained that researchers don’t yet have a good sense of how such mismatches would affect productivity of fisheries or the ecosystem as a whole, but they are “working on answering those questions with food web models and climate models.”

To be sure, Thorne indicated that the researchers would need considerably more data to validate any ecological conclusions, as they only looked at one species of whale and four main prey species.

“Understanding the specifics of the broader implications for a location would require looking at a range of important predator and prey species and assessing how the strength of interactions” might be affected by their responses to climate change, she said.

According to Thorne, this study and others suggested that species characteristics such as body size, mobility, thermoregulatory strategy and longitudinal range, in addition to the speed of change in the climate, can help predict the responses of marine species to climate change.

Whales such as the long-finned pilot whale examined in this study are challenging to observe because they have wide geographic ranges, could be difficult to track, and spend most of their time underwater, where they are difficult to see or track.

Additionally, even people with considerable maritime experience sometimes have difficulty differentiating between the long finned pilot whale and the short finned pilot whale, which are different species.

To address the central range of these long-finned pilot whales, Thorne and Nye used two data points: strandings, when whales strand on land, and bycatches, when people catching other fish with bottom trawls also bring up these whales in their nets.

Bycatches occur in part because pilot whales and other cetaceans depredate fishing gear, removing fish from fishing lines or trawls, which presents an easier meal than searching for food themselves. These whales, however, sometimes get caught in the nets themselves. 

People in the fisheries business sometimes use acoustic deterrents to keep the whales away. These efforts, however, can backfire, as the whales hear these sounds as something akin to a dinner bell and head for nets that could inadvertently trap them.

Strandings data is useful for looking at trends in the distribution of cetaceans because networks provide standardized observations throughout the coastline, dating back for decades.

Thorne is in the process of looking at strandings data more broadly. Her team is also looking at strandings of odontocete, or toothed whale, species along the east coast of the United States more broadly. She will also examine whether short-finned pilot whales, which are adapted to warmer waters, show similar trends.

“We are already examining the strandings data and testing our hypothesis that fish species may be shifting both horizontally (latitudinally or north-south) and/or shifting vertically (in depth),” Nye wrote. “I suspect that are doing a bit of both.”

Strandings represented about two thirds of the data in this study, while bycatch constituted the rest.

The shift in the central range represents a fairly dramatic geographic change in the center of the whale range and was considerably higher than that observed for their prey species.

Nye, who worked at Stony Brook from 2012 to 2020, said she was “shocked” that pilot whales were shifting much faster than the fish species, mostly because she knows how much the distribution of many species has changed over the last half century in the northeastern United States.

Whales are heading in the opposite direction that Thorne took in her career path. Thorne grew up in Kingston, Ontario and did her undergraduate work at the University of Guelph. She earned her PhD from Duke University and started as a lecturer at Stony Brook and was offered a tenure track position three years later.

During college. Thorne spent three years at the Huntsman Marine Science Center on the Bay of Fundy. Seeing the impact of the tides in the bay and taking field courses was “amazing,” she said. She first started working with whales at a research station on Grand Manan Island in the Bay of Fundy in future years.

Married to Bernd Distler, who is a surface materials engineer, Thorne and her husband have a four-year- old daughter Annika and two-year- old daughter Franka.

As for what her work tells her about the changing world, Thorne said it was sobering to see first hand the rapid changes in temperature occurring in the Northeast and, specifically, in New York.

This kind of study, along with others that highlight the increases in temperature, should be “more than enough information” to encourage action, she said.

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David McCandlish, center, with postdoctoral researchers Anna Posfai and Juannan Zhou. Photo by Gina Motisi, 2020/ CSHL

By Daniel Dunaief

If cancer were simple, scientists would have solved the riddle and moved on to other challenges.

Often, each type of the disease involves a combination of changes that, taken together, not only lead to the progression of cancer, but also to the potential resistance to specific types of treatment.

Using math, David McCandlish, Assistant Professor at Cold Spring Harbor Laboratory, is studying how the combination of various disruptions to the genome contribute to the development of cancer.

McCandlish recently published a study with colleagues at Cold Spring Harbor Laboratory in the journal Proceedings of the National Academy of Sciences.

David McCandlish. Photo by Gina Motisi, 2020/CSHL

The research didn’t explore any single type of cancer, but, rather applied the method looking for patterns across a range of types of cancers. The notion of understanding the way these genetic alterations affect cancer is a “key motivating idea behind this work,” McCandlish said.

So far, the method has identified several candidates that need further work to confirm.

“Cancer would be a lot easier to treat if it was just one gene,” said Justin Kinney, Associate Professor at CSHL and a collaborator on the work. “It’s the combination that makes it so hard to understand.”

Ultimately, this kind of research could lead researchers and, eventually, health care professionals, to search for genetic biomarkers that indicate the likely effect of the cancer on the body. This disease playbook could help doctors anticipate and head off the next moves with various types of treatments.

“This could potentially lead to a more fundamental understanding of what makes cancer progress and that understanding would very likely open up new possibilities in cancer treatments,” Kinney said.

To be sure, at this point, the approach thus far informs basic research, which, in future years, could lead to clinical improvements.

“We are working on this method, which is very general and applicable to many different types of data,” McCandlish said. “Applications to making decisions about patients are really down the road.”

McCandlish described how he is trying to map out the space that cancer evolves in by understanding the shape of that space and integrating that with other information, such as drug susceptibility or survival time.

“We are trying to ask: how do these variables behave in different regions of this space of possibilities?” he said.

McCandlish is making this approach available to scientists in a range of fields, from those scientists interpreting and understanding the effects of mutations on the development of cancer to those researchers pursuing a more basic appreciation of how such changes affect the development and functioning of proteins.

“This is accessible to a wide array of biologists who are interested in genetics and, specifically in genetic interactions,” said McCandlish.

The main advance in this research is to take a framework called maximum entropy estimation  and improve its flexibility by using math to capture more of the underlying biological principals at work. Maximum entropy estimation is based on the idea of inferring the most uniform distribution of behaviors or outcomes with the least information that’s compatible with specific aspects of experimental observations.

Using this philosophy, scientists can derive familiar probability distributions like the bell curve and the exponential distribution. By relaxing these estimates, scientists can infer more complicated shapes.

This more subtle approach enhances the predictive value, which captures the distributions of data better, McCandlish explained. “We’re trying to capture and model cancer progression in a new and more expressive way that we hope will be able to tell us more about the underlying biology.”

The idea for this paper started when McCandlish, Kinney and  Jason Sheltzer, a former fellow at Cold Spring Harbor Laboratory and a current Assistant Professor of Surgery at Yale School of Medicine, discussed the possibilities after McCandlish attended a talk by Wei-Chia Chen, a post doctoral researcher in Kinney’s lab.

Chen will continue to pursue questions related to this effort when he starts a faculty position in the physics department at National Chung Cheng University in Taiwan this spring.

Chen will use artificial intelligence to handle higher dimensional data sets, which will allow him “to implement effective approximations” of the effect of specific combinations of genetic alterations, Kinney said.

Kinney believes teamwork made this new approach, which the high-impact, high-profile journal PNAS published, possible.

“This problem was an absolutely collaborative work that none of us individually could have done,” Kinney said. He described the work as having a “new exploratory impact” that provides a way of looking at the combination of genomic changes that “we haven’t had before.”

Working at Cold Spring Harbor Laboratory, which McCandlish has done since 2017, enables collaborations across different disciplines.

“We have this quantitative biology group, we also have people working on neuroscience, cancer, and plant biology,” McCandlish added.

McCandlish is also currently also working with Professor Zachary Lippman and his graduate student Lyndsey Aguirre to understand how multiple mutations interact to influence how the fruit on tomato plants develop.

“The idea is that there are these huge spaces of genetic possibilities where you can combine different mutations in different ways,” McCandlish explained. “We want to find those key places in that space where there’s a tipping point or a fork in the road. We want to be able to identify those places to follow up or to ask what’s special about this set of mutations that makes it such a critical decision point.”

A native of Highland Park, New Jersey, McCandlish was interested in math and science during his formative years. 

As for the work, McCandlish appreciates how it developed from the way these collative researchers interacted.

“This would never have happened if we weren’t going to each other’s talks,” he said.

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Qingyun Li. Photo by Xuecheng Chen

By Daniel Dunaief

Qingyun Li has a plan for carbon dioxide.

The newest hire in the Department of Geosciences at Stony Brook University, Li, who is an assistant professor, is a part of a team exploring carbon capture and storage.

“My work is expected to help reduce the amount of carbon dioxide released into the atmosphere,” Li said. It will “help people find ways to promote carbon dioxide mineralization for safer carbon dioxide storage” below the ground. While her work will help promote carbon storage, it doesn’t include capturing and transporting the gas.

By selecting sites carefully, researchers can store carbon dioxide for geologically long periods of time.

While carbon sequestration occurs on the scale of kilometers, Li often works on a minuscule level, at the nanometer to centimeter scale. Smaller scale alterations affect properties such as the permeability of the rock formation.

Li is trying to predict nucleation of a certain mineral in her computer models. She has done that for carbonate minerals, which could be what carbon dioxide becomes after it is stored in geologic formations.

A similar process of nucleation occurs in clouds, when fine particles form the nuclei around which gases condense to form water or ice.

Li used a small angle x-ray scattering synchrotron to explore important details about each particle. This technique, which doesn’t look directly at the particles, reveals through data analysis the particle’s shape, size and surface morphology and, eventually, the rate at which nucleation occurs.

For carbon dioxide sequestration, the minerals that provide nucleation start at the nanoscale, which give them a high specific surface area.

“That matters for later reactions to generate carbonate minerals,” Li said. “That’s one reason we care about the nanoscale phenomenon. The bulk minerals are generated starting from the nanoscale.” 

A larger surface area is necessary in the beginning to lead to the next steps.

Li’s work involves exploring how carbonate starts to form. Her earlier efforts looked at how calcium carbonate forms in the aqueous or water phase.

Carl Steefel, Head of the Geochemistry Department at the Lawrence Berkeley National Laboratory in California, worked with Li during her PhD research at Washington University in St. Louis. Steefel believes her research will prove productive.

“She has an approach to science that combines that one-of-its-kind capabilities for studying nucleation with a deep understanding of modeling and how these open systems involving flow and transport work,” Steefel said. “The combination of these unique capabilities, in nucleating and in understanding reactive transport modeling, will put her a very good position.”

As of now, Li plans to study carbon sequestration in natural gas formations in shale, which has nanometer sized pores. The particles can change the permeability of the rock.

Some companies, like British Petroleum and ExxonMobil, have started to explore this method as a way to reduce their carbon footprint.

While geologic carbon sequestration has shown promising potential, Li believes the process, which she said is still feasible, could be decades away. She said it may need more policy support and economic stimuli to come to fruition.

Part of the challenge is to incorporate such carbon sequestration in the established market.

Scientists working in this field are eager to ensure that the stored carbon dioxide doesn’t somehow return or escape back into the atmosphere.

“People are actively investigating possible leakage possibilities,” Li wrote in an email. “We try to design new materials to build wells that resist” carbon dioxide deterioration.

Controlling pressure and injection rates could prevent various types of leaks.

In her earlier studies, Li explored how cement deteriorates when contacted with carbon dioxide-saturated brine. She hoped to find cracks that had self-healing properties. Other studies investigated this property of concrete.

It’s possible that a mineral could form in a fracture and heal it. In natural shale, scientists sometimes see a fracture filled with a vein of carbonate. Such self healing properties could provide greater reassurance that the carbon dioxide would remain stored in rocks below the surface. Li hopes to manage that to inhibit carbon dioxide leakage.

The assistant professor grew up in Beijing, China, studied chemistry and physics in college. She majored in environmental sciences and is eager to apply what she learned to the real world.

For her PhD, Li conducted research in an engineering department where her advisor Young-Shin Jun at Washington University in St. Louis was working on a project on geologic carbon dioxide sequestration. 

In her post doctoral research at SLAC National Accelerator Laboratory, which is operated by Stanford University, Li explored mineral reactions in shale, extending on the work she did on mineral reactions in concrete as a graduate student. She sought to understand what happens after hydraulic fracturing fluids are injected into shale. These reactions can potentially change how easily the mix of gas and oil flow through a formation.

With Stony Brook building a lab she hopes is finished by next spring, Li plans to hire one graduate student and one post doctoral researcher by next fall.

She is teaching a course related to carbon sequestration this semester and is looking for collaborators not only within geoscience but also within material science and environmental engineering.

Li is looking forward to working with other researchers at the National Synchrotron Lightsource 2 at Brookhaven National Laboratory, which provides beamlines that can allow her to build on her earlier research.

Li and her husband Xuecheng Chen, who are renting an apartment in South Setauket and are looking for a home close to campus, have a three-year old son and an 11-month old daughter.

Outside the lab, Li enjoys quality time with her family. A runner, Li also plays the guzheng, which she described as a wooden box with 21 strings.

Steefel, who wrote a letter to Stony Brook supporting Li’s candidacy to join the Geosciences Department, endorsed her approach to science.

“She’s very focused and directed,” Steefel said. “She’s not running the computer codes as black boxes. She’s trying to understand what’s going on and how that relates to her experiments and to reality.”

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Above, an AI-Grid prototype that is being built by the research team. Image courtesy of Stony Brook Power Lab

By Daniel Dunaief

The Department of Energy is energized by the possibility of developing and enhancing microgrids.

What are microgrids? They are autonomous local power systems that have small, independent and often decentralized energy sources. Often, they use renewable energy, like wind or solar power, although some use natural gas or diesel.

The DOE’s dedication to developing these microgrids may cut costs, create efficiencies and enhance energy reliability.

Peng Zhang. Photo from SBU

Peng Zhang, SUNY Empire Innovation Professor in the Department of Electrical and Computer Engineering at Stony Brook University, is leading a diverse team of researchers and industry experts who received $5 million of a $50 million investment the DOE recently made to developing, enhancing and improving microgrid technology.

Bringing together these energy experts, Zhang hopes to use artificial intelligence to create a usable, reliable and efficient source of energy, particularly during periods of power outages or disruption to the main source of energy.

“The traditional microgrid operation is based on models and human operators,” Zhang said. “We developed this data-driven or AI-based approach.”

Artificial intelligence can enhance the safety and reliability of microgrids that can receive and transmit power.

One of the objectives of the systems Zhang and his collaborators are developing will include protecting the power supplies against faults, accidents from natural disasters and cyberattacks.

“This project led by Professor Zhang is a great example demonstrating the impact of this novel research on essential infrastructure that we rely on daily,” Richard Reeder, Vice President for Research at Stony Brook University, said in a statement.

Zhang said he has verified the methods for this AI-driven approach in the lab and in a simulation environment.

“Now, it’s time to demonstrate that in more realistic, microgrid settings,” he said. He is working with microgrid representatives in Connecticut, Illinois and New York City. His team will soon work with a few representative microgrids to establish a more realistic testing environment.

The urgency to demonstrate the feasibility of this approach is high. “We need to kick the project off immediately,” said Zhang, whose team is recruiting students, postdocs, administrative staff and technicians to meet a two-year timeline.

The group hopes AI-grids can be used in different microgrids around the country. If the platform is generic enough, it can have wide applications without requiring significant modifications.

While operators of a microgrid might be able to know the ongoing status, they normally are not able to respond to contingencies manually. “It’s impossible for the operator to know the ongoing status” of power sources and power use that can change readily, Zhang explained. “That’s why we had to rely on a data driven approach.”

Additionally, end users of electricity don’t necessarily want their neighbors to know about their power needs. They may not want others who are using the same microgrid system to know what appliances or hardware are in their homes.

Instead, the system will rely on the data collected within each microgrid, which reflects the behavior at different intervals. Those energy needs can change, as people turn on a TV or unplug a wind turbine.

At the same time, the power system load and generation need to remain in balance. Microgrids that produce more energy than the system or end users need can send them to a utility grid or to neighboring microds or communities. If they don’t send that energy to others who might use it, they can lose some of that energy.

Power needs to be balanced between supply and demand. Storage systems can buffer an energy imbalance, although the cost of such storage is still high. Researchers in other departments at Stony Brook and Brookhaven National Laboratory are pursuing ways to improve efficiencies and reduce energy storage costs.

Balancing energy is challenging in most microgrids, which rely on intermittent and uncertain renewable energy sources such as sunlight. In this project, Zhang plans to connect several microgrids together into a “mega microgrid system,” that can allow any system with a surplus to push extra energy into one with a deficiency.

Microgrids aren’t currently designed to replace utilities. They may reduce electricity bills during normal operations and can become more useful during emergencies when supplies from utilities are lower.

While artificial intelligence actively runs the system, people are still involved in these programmable microgrids and can override any recommendations.

In addition to having an alarm in the event that a system is unsafe or unstable, the systems have controllers in place who can restore the system to safer functioning. The programming is flexible enough to change to meet any utility needs that differ from the original code.

In terms of cybersecurity, the system will have three lines of defense to protect against hacking.

By scanning, the system can localize an attack and mitigate it. Even if a hacker disabled one controller, the control function would pop up in a different place to replace it, which would increase the cost for the attacker.

Stony Brook created a crypto control system. “If an attacker got into our system, all the information would be useless, because he would not understand what this signal is about,” Zhang said.

While he plans to publish research from his efforts, Zhang said he and others would be careful in what they released to avoid providing hackers with information they could use to corrupt the system.

For Zhang, one of the appeals of coming to Stony Brook, where he arrived two years ago and was promoted last month to Professor from Associate Professor, was that the university has one of the best and best-funded microgrid programs in the country.

Zhang feels like he’s settled into the Stony Brook community, benefiting from interacting with his neighbors at home and with a wide range of colleagues at work. He appreciates how top scholars at the Massachusetts Institute of Technology, Harvard and national labs have proactively approached Stony Brook to establish collaborations.

Zhang is currently discussing a Phase II collaboration on a microgrid project with the Navy, which has funded his research since his arrival. “Given the federal support [from the Navy], I was able to recruit top people in the lab,” he said, including students from Columbia and Tsinghua University.

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