Science & Technology

From left, Martin Kaczocha, Robert Rizzo, Iwao Ojima and Lloyd Trotman. Photo from SBU

By Daniel Dunaief

Pulling together experts from a variety of fields, scientists at Stony Brook University and Cold Spring Harbor Laboratory have demonstrated promise in their efforts to tackle prostate cancer in a new way.

Led by Iwao Ojima, a distinguished professor of chemistry and director of the Institute of Chemical Biology and Drug Discovery at SBU, and Martin Kaczocha, an assistant professor in the Department of Anesthesiology at SBU, the multidisciplinary team recently received a five-year, $4.2 million grant from the National Cancer Institute.

The team is following up on its preliminary success with inhibitors of fatty acid binding protein 5, or FABP5. By tamping down on this protein in prostate cancer cells grown in the lab and in mouse models of the disease, these researchers treated metastatic cancer cells.

The scientists, who received a Translational Research Opportunities Seed Grant from the Renaissance School of Medicine at Stony Brook, were pleased with the next steps in their research.

“We’re happy that the National Cancer Institute validated our target,” said Kaczocha. It will help us “move forward and expand the scope of our work.”

From left, Robert Rizzo, Iwao Ojima, Martin Kaczocha and Lloyd Trotman. Photo from SBU

To be sure, scientists are generally cautiously optimistic about the translation between basic discoveries about mechanisms involved in cancer and the ability of doctors to use these findings in future therapies. Indeed, numerous promising early efforts haven’t always led to treatments. “Many tumors develop resistance to existing therapies through a variety of mechanisms,” said Kaczocha.

Still, the researchers involved in the current study hope the findings will eventually provide another tool in the treatment of prostate cancer.

The inhibitors scientists including Lloyd Trotman, a professor at Cold Spring Harbor Laboratory, are testing “appear to work in a context where [other treatments] lose efficacy. We hope this will translate” to a setting in which the researchers test their treatment in a mouse model of prostate cancer, explained Kaczocha. One of the goals of the NCI grant is to find further validation of this benefit.

Eventually, any possible treatment that utilizes these findings would involve a combination of inhibitors and existing therapeutics, Kaczocha said.

To create a product that might target this molecule, Ojima screened more than one million commercially available compounds on a computer. Out of over 1,000 compounds designed and analyzed, he selected about 120 for chemical synthesis and biological assay.

Artificial intelligence helps dig out known matters from a huge data, but not for newly created substances. Ojima found more than 30 compounds from the ones he synthesized and tested that were more advanced than the original project.

“It’s an ongoing process,” Ojima explained, adding that he believes he will find a more efficacious inhibitor. Ojima and Kaczocha are working with Robert Rizzo, a professor in the Department of Applied Mathematics & Statistics at SBU to develop these inhibitors.

Indeed, that process involves determining the stability, bioavailability and many other factors to minimize any adverse side effects

The side effects from this treatment connect to the original focus of the scientific team. As it turns out, inhibiting FABP5 causes pain relief because it reduces the breakdown of anandamide, or AEA, which is part of the body’s natural pain relief system. The inhibitors also have anti-inflammatory properties.

“This compound’s side effect is pretty beneficial for patients,” said Ojima.

The Long Island team is continuing to pursue the use of these compounds to manage pain as well.

Indeed, Kaczocha’s mother Zofia, who has pain associated with arthritis, asks him at least once a month when his drug will be available. The NCI grant will enable him and his colleagues to continue to build on their earlier work as they hope to translate their scientific discoveries into a clinical option.

“We are continuing our original research on the use of FABP5 inhibitors for pain control,” Ojima explained in an email.

As for their work with cancer, the inhibitors are “less cytotoxic,” Ojima said, and, in animal models, have been able to kill metastatic cancer cells that have become resistant to drug treatment. He suggested that the hope of this treatment is that it can sensitize the cancer cells or tumor to other therapies, which is a “promising approach.”

So far, Ojima, Kaczocha, Trotman and colleagues have tested this treatment only on tumors that haven’t yet metastasized, and not on tumors that have spread to other organs. “Our hope is that it may have some preventive effect in the early stages” of metastasis, Ojima said.

Ojima and Kaczocha were grateful for the seed grant from the medical school, which helped push the research forward. “A seed grant is very important for basic research,” Ojima added.

Other cancers, such as breast cancer, also have over expression of the same fatty acid binding protein. While the scientists are starting with prostate cancer, they hope to expand their work to other cancers as well, once they start gathering results.

La Jolla, California-based Artelo Biosciences partnered with these researchers starting in the spring of 2018. Artelo is licensing the patents for the target as well as the patents for lead compounds. Moving any compound through the beginning of the Food & Drug Administration testing is something Artelo will eventually take over, Kaczocha said. “They will have the financing to pursue this further,” he added.

As a researcher and a pharmacologist who is involved in basic and translational studies, Kaczocha said his hope is always to develop something in his career that will help patients.

Other research groups are also developing small molecule inhibitors to reduce the prevalence or activity of fatty acid binding proteins, but these other scientists have generally not focused on the role of these proteins in cancer. Fatty acid binding protein 4, for example, has a role in metabolic disorders.

“We have a relatively unique position where we are targeting prostate cancer” by reducing the activity and effect of this protein, Kaczocha said.

Trotman, whose lab has a unique animal model of prostate cancer that is a close mimic to the progression of prostate cancer in humans, offers an advantage in their research work, added Kaczocha.

 

Robert Cushman Murphy Jr. High School (team one), from left, coach Jillian Visser, Jayden Chandool, Michael Melikyan, Michaelangelo Scialabba, Rithik Sogal, Kevin Shi and coach Emily Chernakof

On Thursday, Jan. 30 and Friday, Jan. 31, the U.S. Department of Energy’s Brookhaven National Laboratory held two back-to-back installments of the Long Island Science Bowl, a regional branch of DOE’s 30th annual National Science Bowl®. In this fast-paced question-and-answer showdown, teams of students from across Long Island were tested on a range of science disciplines including biology, chemistry, Earth science, physics, energy and math.

On Thursday, Team One of Great Neck South Middle School garnered first place in the middle school competition, earning their school three years of consecutive wins. Team Three of Great Neck Middle School captured second place; Robert Cushman Murphy Jr. High School (team one) of Stony Brook won third place; and Commack Middle School (team one) placed fourth.

On Friday, top honors went to Great Neck South High School, who competed against 19 other teams in the high school competition. High school runners-up included Wheatley School in Old Westbury (second place); Ward Melville High School in E. Setauket (third place); and Comsewogue High School in Port Jefferson Station (fourth place). 

As first place winners, Great Neck South Middle School (team one) and Great Neck South High School have won all-expenses-paid trips to the National Finals near Washington, D.C., which will begin on April 30. They’ll be joined by the winners of all 112 regional competitions held across the country.

“The National Science Bowl® continues to be one of the premier academic competitions across the country, preparing America’s next-generation for future success in the ever-expanding fields of science, technology, and engineering,” said U.S. Secretary of Energy Dan Brouillette. “The Department of Energy is committed to fostering opportunities for our nation’s students, and we congratulate Great Neck South in advancing to the National Finals, where they will continue to showcase their talents as the top minds in math and science.”

All participating students received a Science Bowl T-shirt and winning teams also received trophies and medals, and the top four high school teams received cash awards. Prizes were courtesy of Teachers Federal Credit Union and Brookhaven Science Associates (BSA), the event’s sponsors. BSA is the company that manages and operates Brookhaven Lab for DOE.

For more information, visit https://energy.gov/science. 

Peng Zhang, center, with four of his students from his power systems class, from left, Marissa Simonelli, Ethan Freund, Kelly Higinbotham and Zachary Sola, who were selected as IEEE Power and Engergy Scholars in 2017. Photo by Mary McCarthy

By Daniel Dunaief

If Peng Zhang succeeds in his work, customers on Long Island and elsewhere will no longer lose power for days or even hours after violent storms.

One of the newest additions to the Department of Electrical and Computer Engineering at Stony Brook University, Zhang, who is the SUNY Empire Innovation associate professor, is enhancing the resiliency and reliability of microgrids that may be adaptable enough to provide energy to heat and light a home despite natural or man-made disruptions. Unlike the typical distributed energy network of most utilities around the country, microgrids are localized and can function on their own.

Peng Zhang. Photo from SBU

A microgrid is a “central theme of our research,” said Zhang, who joined Stony Brook at the beginning of September. “Even when a utility grid is down because of a hurricane or an attack, a microgrid is still able to supply the local customers” with power. He is also using quantum information science and quantum engineering to empower a resilient power grid.

Zhang expects that the microgrid and utility grid will be more resilient, stable and reliable than the current system. A microgrid will provide reliable power even when a main grid is offline. The microgrid wouldn’t replace the function of the grid in the near future, but would enhance the electricity resilience for customers when the central utility is unavailable or unstable.

Part of his motivation in working in this field comes from his own experience with a weather-related loss of power. 

Even though Zhang, who used his training in mathematics to develop an expertise in power systems, had been working on wind farms and their grid integration, he decided after Hurricane Irene and a nor’easter that he should do more research on how to restore power after a utility became unavailable.

Irene hit in August, while the nor’easter knocked out power in the winter. After the storms, Northeast Utilities, which is currently called Eversource Energy, asked him to lead a project to recommend solutions to weather-induced outages.

Zhang plans to publish a book through Cambridge University Press this year called “Networked Microgrids,” which not only includes his previous results but also presents his vision for the future, including microgrids that are self-healing, self-protected, self-reconfiguring and autonomous.

He recognizes that microgrids, which are becoming increasingly popular in the energy community, present a number of challenges for customers. For starters, the cost, at this point, for consumers can be prohibitively high.

Zhang can cut those expenses, however, by replacing hardware upgrades with software, enabling more of the current system to function with greater resilience without requiring as many costly hardware modifications.

His National Science Foundation project on programmable microgrids will last until next year. He believes he will be able to verify most of the prototypes for the programmable microgrid functions by then.

Zhang called advances in energy storage a “key component” that could improve the way microgrids control and distribute power. Energy storage can help stabilize and improve the resilience of microgrids.

He is eager to work with Esther Takeuchi, who has dual appointments at Stony Brook University and Brookhaven National Laboratory, not only on microgrid technologies but also on renewable integration in the transmission grid.

Zhang appreciates SBU’s reputation in physics, applied math, computer science and electrical and computer engineering. When he was young, he said he also heard about and saw Chen-Ning Yang, whom he described as a model and legend.

“I feel proud and honored to be working at Stony Brook where Dr. Yang taught for more than three decades,” he stated in an email.

In his lab, Zhang has six doctoral students, one visiting doctoral student and two master’s students. A postdoctoral researcher, Yifan Zhou, who worked with him at the University of Connecticut, will soon join his Long Island lab.

Zhang, who earned doctorates from Tsinghua University and the University of British Columbia, brought along a few grants from the University of Connecticut where he held two distinguished titles.

Zhang has “high expectations for the people who work for him,” Peter Luh, a board of trustees distinguished professor at the University of Connecticut, explained in an email. “However, he is considerate and helps them achieve their goals.”

Zhou, who comes from Tsinghua University, is working with him on stability issues in microgrids to guarantee their performance under any possible scenario, from a major storm to a cyberattack.

Zhang is working with Scott Smolka and Scott Stoller, both in the Computer Science Department  at Stony Brook, on resilient microgrids

“We are planning to use simulations and more rigorous methods for formal mathematical analysis of cyberphysical systems to verify resiliency properties in the presence of fault or attacks,” said Stoller who described Zhang as a “distinguished expert on electric power systems and especially microgrids. His move to Stony Brook brings significant new expertise to the university.”

The Stony Brook scientists have created an exercise in which they attack his software systems, while he tries to ensure its ongoing reliability. Zhang will develop defense strategies to guarantee the resilience and safety of the microgrids.

Zhang was born in Shandong Province in China. He is married to Helen Wang, who works for a nonprofit corporation as an electrical engineer. The power couple has three sons: William, 13, Henry 10, and Benjamin, 8. They are hoping their sons benefit from the public school system on Long Island.

Zhang’s five-year goal for his work involves building an institute for power engineering, which will focus on microgrids and other future technologies. This institute could have 20 to 30 doctoral students.

An ambitious researcher, Zhang would like to be the leader in microgrid research in the country. “My goal is to make Stony Brook the top player in microgrid research in the U.S.,” he said.

Meng Yue, scientist in the Sustainable Energy Technologies Department at Brookhaven National Laboratory who has been collaborating with Zhang for over five years, anticipates that Zhang’s research will help consumers.

“As New York State has more aggressive renewable portfolio, I believe the research achievements will soon advance technologies in the power grid application,” he said.

 

Adam Singer. Photo from SBU

By Daniel Dunaief

A patient comes rushing into the emergency room at a hospital. He has numerous symptoms and, perhaps, preexisting conditions, that the staff gather together as they try to stabilize him and set him back on the path toward a healthy life.

Emergency room protocols typically involve testing for the function of major organs like the heart, even as a patient with diabetes would also likely need a blood sugar test as well.

For a specific subset of patients, hyperkalemia, in which a patient has potentially dangerously elevated levels of the element potassium, may also merit additional testing and treatment.

Adam Singer with his son Daniel. Photo by Michael Beck

In a recent study in the American Journal of Emergency Medicine, Adam Singer, a professor and vice chair for research at the Department of Emergency Medicine at the Renaissance School of Medicine at Stony Brook University, found that mortality rates were cut in half when doctors corrected for high levels of potassium.

“This study was focused on what we could do” to help patients with hyperkalemia, Singer said. “We always knew that rapid normalization was important, but we did not have the evidence except for anecdotal cases.”

Examining about 115,000 hospital visits to the Stony Brook Emergency Department between 2016 and 2017, Singer and his colleagues found that the mortality rate fell to 6.3 percent from 12.7 percent for patients whose potassium level was normalized.

Singer is “tackling a topic which is very important, which is life threatening and for which there is no clear standard,” said Peter Viccellio, a professor and vice chairman in the Department of Emergency Medicine at the Renaissance School of Medicine at SBU.

Viccellio said Stony Brook has become “more conservative over the last couple of years in treating patients with lower levels” of potassium.

One of the challenges with hyperkalemia is that it doesn’t usually come with any tell-tale symptoms. Emergency room doctors can’t determine an elevated level of potassium by looking at a patient or by hearing a list of symptoms.

Sometimes, people with hyperkalemia show weakness, nausea or vomiting, but those three conditions are also present in numerous other medical challenges.

Singer said not all the patients died directly from hyperkalemia. Most people with hyperkalemia have significant co-morbidities that put them at risk from other causes. Nonetheless, the higher level of mortality for patients above a threshold for potassium suggests that evaluating patients not only should include an awareness of the amount of this element in the blood, but also a clear set of guidelines for how to reduce it.

“This strengthens the need to call for more evidence-based studies to figure out the best and most effective therapies,” Singer said. “The higher the level of potassium, the greater the urgency for rapid correction,” he added.

Some hospitals may be using point-of-care tests and newer medications, especially new potassium binders. These treatments, however, have not been studied in large numbers yet.

As the population ages, more chronic disease patients take medicines that affect potassium levels. This, in turn, increases the risk of hyperkalemia, in part because chronic conditions like diabetes are so common. This risk extends to people who are obese and are developing diabetes.

On the positive side, Singer said some hospitals are using rapid point-of-care testing and, when they discover evidence of higher potassium, are using a new class of medications that treats the condition.

While the urgency for emergency room attendants is high enough to add potassium tests, especially for vulnerable patients, Singer does not believe that first responders necessarily need to add these tests to their evaluations on the way to the hospital. Such testing might be more urgent in rural areas, where transportation to a medical facility would take more time.

“Generally, such testing is not going to make a big difference” because patients will arrive at the hospital or medical facility before hyperkalemia becomes a contributing factor in their health, said Singer.

Changing a person’s lifestyle to lower the risk of hyperkalemia can be difficult because diets that are low in potassium are “hard to follow,” he said. Additionally diets that are low in potassium are often “lacking in other important food contents.”

Patients who are prone to hyperkalemia include people who are dehydrated, have kidney disease and missed a dialysis treatment, or are taking medications that can, as a side effect, boost the amount of potassium.

Generally, people don’t suddenly develop a high risk for hyperkalemia without any past medical history that suggests they are susceptible to it. During annual physicals, doctors customarily test for the level of potassium in the blood.

In terms of the total emergency room population, about 1 percent have higher potassium. During the years of the study, 308 patients had elevated potassium levels that remained high, while 576 had potassium levels that were high, but that were stabilized through treatment.

Higher potassium levels don’t necessarily require immediate treatment, in part because of a person who vomited several times might be getting fluids that restore the potassium balance

As director of research, Singer balances between his clinical responsibilities and his interest in conducting scientific research. When he sees an issue in the clinic, he can go back to the lab and then translate his research into clinical practice.

Viccellio said Singer is “internationally renowned” as a researcher and that he was a “superstar from day one.” 

Singer’s primary interests are in acute wound care and burns. He has recently been studying a new, minimally invasive, nonsurgical technique to remove dead tissue after burns that involves an enzymatic agent and has been involved in several promising clinical trials of this technique.

Viccellio said Singer has done “fantastic work” on cosmetic repair of facial lacerations. Viccellio also suggested that Singer was “like the Bill Belichick” of research, helping numerous other people who went on to become research directors at other institutions.

A resident of Setauket for the last quarter of a century, Singer and his wife, Ayellet, have three children. Following in his father’s footsteps, his son Daniel is finishing his residency in emergency medicine at Stony Brook. 

While Singer was born in Philadelphia and lived in Israel for part of his life, including during medical school, he has roots on Long Island. His grandparents originally lived in Ronkonkoma. Singer Lane in Smithtown, which was named after his realtor grandfather Seymour Singer, includes the one-room schoolhouse where Walt Whitman was a schoolmaster. 

As for his work on hyperkalemia, Singer is pleased with the way he and his colleagues at Stony Brook have contributed to an awareness of the dangers of this condition. “We are identifying these patients and treating them,” he said.

 

Dave Jackson. Photo from CSHL

By Daniel Dunaief

Just as humans have competing impulses — should we eat or exercise, should we wait outside in the rain to meet a potential date or seek shelter, should we invest in a Spanish tutor or a lacrosse coach — so, too, do plants, albeit not through the same deliberate abstract process.

Working with corn, Dave Jackson, a professor at Cold Spring Harbor Laboratory, has discovered that the gene Gß, (pronounced Gee-Beta,) balances between the competing need to grow and to defend itself against myriad potential threats.

By looking at variations in the gene, Jackson and his postdoctoral fellows, including Qingyu Wu and Fang Xu, have found that some changes in Gß can lead to corn ears with more kernels. The results of this work, which were published in the Proceedings of the National Academy of Sciences last month, suggest that altering this gene may eventually increase the productivity of agricultural crops.

Indeed, the study of this gene included an analysis of why some mutations are lethal. An overactive Gß gene turns the corn brown and kills it. This occurs because the gene cranks up the immune system, causing the plant to attack itself.

Other scientists have found mutations in this gene in plants including arabodopsis and rice.

“We are the first to figure out why the mutations are lethal in corn,” Jackson said. “That’s also true in rice. Rice mutations were made over a decade ago and they also caused the plants to die. Nobody knew why. The main puzzle was solved.”

Dialing back this immune response, however, can encourage the plant to dedicate more resources to growth, although Jackson cautions that the research hasn’t reached the point where scientists or farmers could fine tune the balance between growth and defense.

“We are not there yet,” he said. “That’s what would be possible, based on this knowledge.”

Even in the safer environment of an agricultural field, however, plants can’t abandon all efforts at defense.

“Plants need some defense, but probably much less than if they were growing in the wild,” he said.

By altering the balance toward growth, Jackson is looking at mutations that make more stem cells, which can produce flowers and, eventually kernels. The next steps in this research will not likely include scientists in Jackson’s lab. Qingyu Wu plans to move on to a research position in China. 

Penelope Lindsay. Photo by Patricia Waldron

A prolific plant scientist and mentor, Jackson has seen several of his lab members leave CSHL to pursue other opportunities. Recently, he has added three new postdoctoral researchers to his team: Thu Tran, Jae Hyung Lee and Penelope Lindsay.

Jackson plans to use single-cell sequencing in his future research. Using this technique, scientists can find regulatory relationships between genes and monitor cell lineages in development. Jackson described this approach as an “amazing new technology” that’s only been around for a few years. He hopes to use this technique to find new leads into genes that control growth.

Lindsay, who is joining the lab this month, would like to build on her experience as a plant biologist by adding computational expertise. A graduate of the Boyce Thompson Institute in upstate Ithaca, where she was working on the symbiotic relationship between some plants and a specific type of fungi in the soil, Lindsay would also like to work on single-cell sequencing. She plans to continue to study “how specific genotypes produce a phenotype” or how its genes affect what it becomes.

Jackson’s lab’s focus on the undifferentiated cells of the meristem appealed to Lindsay.

Lindsay first met Jackson a few years ago, when he was giving a talk at Cornell University. It was there, fittingly enough, that she had learned about the work that led to the current paper in the Proceedings of the National Academy of Sciences about growth versus defense.

“I was really impressed with the techniques and with the connection to basic research,” Lindsay said. She was excited to learn how Jackson and his students took biochemical approaches to understand how this signaling pathway affected development.

Cold Spring Harbor Laboratory also intrigued Lindsay, who was interested to join a facility that encouraged collaborations among labs.

Born in New York City, Lindsay spent some of her time in upstate New York before moving to Florida, where she also attended college.

Surrounded by family members who have found outlets for their creativity through art — her mother, Michelle Cartaya, is an artist who takes nature photos and her father, Ned Lindsay, remodels homes — she initially attended New College of Florida in Sarasota expecting to pursue a degree in English. Once in college, however, she found excellent scientific mentors, who encouraged her to pursue research.

As a graduate student, Lindsay was greatly intrigued by the signaling pathway between plants and the symbiotic relationship with arbuscular mycorrhizal fungi. During her graduate work, she studied a mutated version of a plant that lacked a signaling protein that encourages this collaboration. When she added considerable amount of the protein to the plant, she expected to restore the symbiosis, but she found the exact opposite.

“The amount of the protein is critical,” she said. “If you have too much, that’s a bad thing. If you don’t have enough, it’s also bad. It’s like Goldilocks.”

A new resident of Huntington, Lindsay, who was a disc jockey for a community radio station in Ithaca and makes electronic music using synthesizers and computers, is looking forward to starting her work at Cold Spring Harbor Laboratory and to living near New York City.

Lindsay continues to find plants fascinating because they “get everything they need” while living in one place their entire lives. “They have so many sophisticated biochemical pathways to protect themselves,” she said.

Saket Navlakha

By Daniel Dunaief

Plants have to solve challenges in their environment – without a brain or the kind of mobility mammals rely on to survive – through strategies and computations that keep them alive and allow them to reproduce.

Intrigued by plants and by the neurobiology that affect decisions or behavior in a range of other organisms, Associate Professor Saket Navlakha recently joined Cold Spring Harbor Laboratory to study the processes a range of organisms use.

“Biological systems have to solve problems to survive,” said Navlakha. “The hope is that by studying these algorithms, we can inspire new methods for computer science and engineering and, at the same time, come up with new ways to predict and model behaviors of these systems.”

Navlakha, who has a doctorate in computer science from the University of Maryland College Park and conducted postdoctoral research at Carnegie Mellon University’s Machine Learning Department, focuses on the “algorithms of nature,” in which organisms evolved ways to solve problems that enhance the likelihood of their survival.

In his first three months at CSHL, Navlakha plans to do an interview tour, speaking with researchers who study cancer, molecular biology, neurology and plants.

While his primary areas of focus have been on plants and neurobiology, he appreciates that the internationally recognized research facility presents “new opportunities” for him and a lab in which he intends to hire four to six scientists over the next two years.

Adam Siepel, the chair of the Simons Center for Quantitative Biology and professor at the Watson School of Biological Sciences at Cold Spring Harbor Laboratory, led the recruitment of Navlakha.

In an email, Siepel wrote that Navlakha “immediately struck us as an ideal candidate for the center” in part because he is a “free thinker with an eye for interesting and important problems in biology.”

Navlakha believes processes and strategies that foster survival spring from a set of principles that helps them thrive and adapt. In 2018, when he was at the Salk Center for Integrative Biology, he wrote a piece for Wired magazine about species extinction. “By not preserving [species that become extinct], we are losing out on interesting ideas that evolution gave them to survive,” he said.

Even amid these losses, however, Navlakha recognizes the lessons computer scientists and engineers like him can learn. Through losses and failures, humans can understand the limitations of algorithms that only allowed a species to survive up to a point, as conditions pushed its algorithms past a tipping point.

At its core, Navlakha’s approach to these algorithms includes the idea that biological systems perform computations. He originally studied brains because they are “such an elegant computer, doing all kinds of things that modern, human-made computers can’t do,” he said.

When he was at the Salk Institute, he spoke with colleagues in plant biology who told him about research that examined how plants modify their shape amid a changing environment, which is what triggered his interest in plants.

One of the themes of his work involves understanding trade-offs. Doing well in one task typically means doing worse in another. He likened this analysis to investing in stocks. An investor can put considerable funds into one stock, like Apple, or diversify a portfolio, investing less money per stock in a variety of companies from different sectors.

“We’ve been studying how plants hedge” their bets, he said. The hedge in this description bears no relation to a collection of plants at the edge of a property.

A plant can create one huge seed that might survive a drought or other environmental threat, or it can diversify the types of seeds. “We’re really interested in understanding these trade-offs, how they hedge, and what kind of strategies” they employ, he said.

Ziv Bar-Joseph, a professor of computer science at Carnegie Mellon University who has known Navlakha for over eight years, suggested Navlakha has “deep insights.” 

In an email, Bar-Joseph described Navlakha’s biggest achievement as his work that shows how the brain uses a computational method to store and retrieve smells. 

“This work both solved an important mystery about how the brain functions and informed us on novel usages of an important computational method, thus contributing to both areas,” Bar-Joseph explained.

Navlakha doesn’t have a typical laboratory filled with beakers, pipettes or plants growing under various conditions. He relies on wet labs to provide data that he then interprets and analyzes as a part of the Simons Center for Quantitative Biology. While his training is in computer science, he has shown a talent for experimental research as well. 

Bar-Joseph recalled how Navlakha performed experiments and analysis. In a short time, Navlakha “was able to master very involved techniques and obtained very good results.” 

Navlakha explained that the work he does colors the way he sees the world. “People walk by plants without paying attention to the incredible computations that they’re doing to keep us on this planet,” he said. “Computation is the basis of life.”

A resident of Great Neck, Navlakha recently married Sejal Morjaria, an infectious disease physician at Sloan Kettering, who works with patients who have cancer. The couple met through an online dating app when he was in San Diego and she lived in New York. They chatted for a while without any expectation of seeing each other, until he traveled to Washington, D.C                                 for a conference.

Navlakha enjoys playing numerous sports, including tennis and basketball. He also played hockey. He and Morjaria participate in yoga classes together.

Navlakha, who grew up in Miami, Florida, said he had to readjust to life on Long Island after living in Southern California for several years. “San Diego makes you weak,” he joked.

In his work, Navlakha hopes to bring together two fields in a different way.

Given the importance of computations, Navlakha appreciates a corollary to the concept proposed by Rene Descartes’ “I think, therefore I am.” For Navlakha, “I compute, therefore I am” describes processes he studies among animals and plants.

the U.S. Department of Energy awarded a 10-year multi-billion project to build a new electron-ion collider at Brookhaven National Laboratory in Upton. Provide photo from Brookhaven National Lab

By Daniel Dunaief

Through answers to basic questions, scientists develop new technology that changes the world, leading to medical breakthroughs, energy applications and national security devices.

That’s the theory behind the U.S. Department of Energy’s decision last week to award a 10-year project that will cost between $1.6 billion and $2.6 billion to build a new electron-ion collider at Brookhaven National Laboratory in Upton. 

For the scientists, the discoveries will flow from answers to questions about the nature of visible matter.

“The big science we’re excited about, the hundred-year-old questions, are things like where does the mass of a proton come from,” said Robert Tribble, the deputy director for science and technology at Brookhaven National Laboratory and a nuclear physicist. The EIC is like a microscope to look at quarks and gluons, he explained.

With support from numerous New York State and Long Island leaders, BNL recently won a competition against Thomas Jefferson National Accelerator in Virginia to build an electron-ion collider. Members of the Jefferson Accelerator, as well as over 1,000 scientists from 30 nations, will partner with BNL staff to conceptualize and build the new collider, which will be the most advanced ever constructed.

In addition to understanding atomic nuclei, we will be able to generate a better view of the universe writ large [with discoveries from the EIC].”

Robert Tribble

“We do not understand very dense matter that exists in the universe in objects like neutron stars and black holes,” Tribble explained in an email. “In addition to understanding atomic nuclei, we will be able to generate a better view of the universe writ large [with discoveries from the EIC].”

Over the next decade, the construction of the new EIC will employ 4,000 people, said Doon Gibbs, the laboratory director at BNL. That number represents the workforce that will, at one time or another, contribute to the construction of this new facility. 

The new EIC will expand on the technology of the Relativistic Heavy Ion Collider, which has been operating since 2000 and will stop running experiments in 2024. Indeed, part of the appeal of BNL as a site for this new facility arose out of the ability to extend the resources by building a new electron storage ring and electron accelerator elements.

Researchers will collide electrons and protons and numerous atomic nuclei to study the strong nuclear force. These collisions will reveal how the subunits of protons and neutrons in the nucleus, namely the quarks and gluons, come together to help generate mass in visible matter.

The staff at BNL is “delighted and excited” that the site for the EIC will be on Long Island, said Gibbs. “Our design has the capability of using many existing technologies and extending them farther than they’ve been before.”

Indeed, even the conception of the EIC has led to some new scientific breakthroughs, some of which the lab and its partners will share with the public in the next few weeks.

While the application of research at the EIC will likely lead to breakthroughs in fields including materials science, researchers at BNL are excited about basic questions about the nature of nuclear matter.

A typical experiment at the EIC will likely follow the same pattern as it has with RHIC, in which hundreds of researchers from around the world collaborate to understand physics properties. In the next few years, researchers will develop a detailed design before they start construction.

“We love challenges at BNL, we like building big machines. We’re good at it. We have a whole class of staff who, in particular, are experts at this kind of activity and they are pretty excited.”

Doon Gibbs

Gibbs said the facility has a strong handle on the safety features of the new collider, which will build on the protocols and designs developed at the RHIC as well as with the National Synchrotron Light Source II, also at the lab in Upton.

“We love challenges at BNL,” Gibbs said. “We like building big machines. We’re good at it. We have a whole class of staff who, in particular, are experts at this kind of activity and they are pretty excited.”

Area politicians are also excited about discoveries in basic science, translational benefits in areas like medicine and the expected boost to the local economy.

“Establishing the electron-ion collider on Long Island might be focused on particles, but it will add some serious mass — nearly $1 billion worth — to the local economy,” U.S. Sen. Chuck Schumer (D) said in a statement. BNL has the “talent, the technology and the track record to make the most of this national project.”

Schumer believes this project will guarantee that BNL continues to be a “world class research facility for the next generation.”

U.S. Rep. Lee Zeldin (R-Shirley) praised the leadership at BNL.

“I congratulate BNL Director Doon Gibbs for leading this exceptional organization and all of its scientists who have worked incredibly hard every step of the way to make this possible, and can’t wait to see what they do next,” Zeldin said in a statement.

 

Donghui Zhu

By Daniel Dunaief

About 5 percent of people who suffer from Alzheimer’s disease have a genetic mutation that likely contributed to a condition that causes cognitive declines.

That means the vast majority of people with Alzheimer’s have other risk factors.

Donghui Zhu, an associate professor of biomedical engineering in the Institute for Engineering-Driven Medicine who joined Stony Brook University this summer, believes that age-related decline in the presence of the element magnesium in the brain may exacerbate or contribute to Alzheimer’s.

Donghui Zhu

The National Institutes of Health believes the former associate professor at the University of North Texas may be on the right track, awarding Zhu $3.5 million in funding. Zhu believes magnesium helps prevent the loss of neurons, in part because of the connection between this element, inflammation and the development of Alzheimer’s.

Numerous other factors may also contribute to the development of Alzheimer’s. Diabetes, lifestyle, a specific sleep cycle and low exercise levels may all play a role in leading to cognitive declines associated with Alzheimer’s, Zhu said.

According to some prior research, people with Alzheimer’s have a lower level of free magnesium in their body and in their serum levels than people who don’t suffer from this disease, he added.

In the short term, he aspires to try to link the magnesium deficiency to neuronal inflammation and Alzheimer’s disease.

Zhu plans to use some of the funds from the grant, which will run for the next five years, on animal models of Alzheimer’s. If his study shows that a lower level of magnesium contributes to inflammation and the condition, he would like to add magnesium back to their systems. Magnesium acts as an antioxidant and an anti-inflammatory agent.

“If we supply a sufficient amount of magnesium, can we slow down or reverse the process of this disease?” Zhu asked. “We hope it would.”

Any potential cognitive improvement in animal models might offer a promising alternative to current treatments, which often only have limited to moderate effects on patient symptoms.

In the longer term, Zhu would like to contribute to an understanding of why Alzheimer’s disease develops in the first place. Knowing that would lead to other alternative treatments as well.

“I don’t think my group or we alone can solve this puzzle,” he said. “We are all trying to chip in so the scientific community can have an answer or solution for the public.”

Like people with many other diseases or disorders, any two people with an Alzheimer’s diagnosis don’t necessarily have the same causes or type of the progressive disorder.

Women represent two-thirds of the Alzheimer’s population. Zhu said this isn’t linked to the longer life span for women, but may be more of a by-product of the change in female hormones over time.

In his research, he plans to study female and male animal models separately, as he looks to understand how the causes and progression of the disease may differ by gender.

In the human population, scientists have linked drug addiction or alcoholism with a higher risk of developing Alzheimer’s. He plans to perform additional studies of this connection as well.

“It’s the consensus in the community that alcohol addiction will increase the risk of developing Alzheimer’s disease,” Zhu said. People who consume considerable alcohol have reduced blood flow to the brain that can endanger or threaten the survival of blood vessels.

“This is another topic of interest to us,” he added.

Zhu is collaborating with other experts in drug addiction studies to explore the link with Alzheimer’s. 

In his research, he hopes to link his background in biology and engineering to tackle a range of translational problems. 

Stefan Judex, a professor and interim chair in the Department of Biomedical Engineering at Stony Brook, is excited about the potential for Zhu’s work.

Zhu is “a fast rising star in the field of biomaterials and fills a gap in our department and the university,” Judex explained in an email. “He is well-equipped to apply his unique research skills to a number of diseases, ultimately aiding in preventing and treating those conditions.”

In addition to his work on Alzheimer’s, Zhu also pursues studies in several other areas, including nano-biomaterials, biodegradable or bio-resorbable materials, regenerative medicine for cardiovascular and orthopedic applications, and drug delivery device and platforms

During his doctoral studies and training at the University of Missouri in Columbia, he focused on dementia and neuron science, while his postdoctoral research at the University of Rochester involved engineering, where he did considerable work on tissue engineering and biomaterials.

Zhu decided he had the right training and experience to do both, which is how he picked up on tissue engineering, regenerative medicine and neuroscience.

“They are not totally exclusive to each other,” he said. “There are many common theories or technologies, methods and models we can share.”

Adults don’t generate or create new neurons. He hopes in the future that an engineering approach may help to reconnect neurons that may have lost their interaction with their neighbors, in part through small magnesium wires that can “help guide their reconnection,” which is, he said, a typical example of how to use biomaterials to promote neuro-regeneration.

In his lab, he works on the intersection between engineering and medicine. The interdisciplinary and translational nature of the research attracted him to the new Institute for Engineering-Driven Medicine at Stony Brook.

He described Stony Brook as the “total package for me” because it has a medical school and hospital, as well as an engineering department and entrepreneurial support.

He has already filed numerous patents and would like to form start-up companies to apply his research.

Judex wrote that he is “incredibly pleased and proud that Dr. Zhu joined” Stony Brook and that it is “incredible that he received this large grant within the first few months since his start.”

In his career, Zhu would like to contribute to new treatments.

“Some day,” he said, he hopes to “put a real product on the market.”

 

Nicholas Gladman with a harvest of sorghum at Cornell University’s Long Island Horticultural Research Lab in Riverhead. Photo by Sendi Mejia

By Daniel Dunaief

When people buy a bag of potato chips, they often find that half of the bag is filled with air. The same is true of a sorghum plant, which produces livestock feed and is converted into ethanol, part of many gases that power cars.

Nicholas Gladman

In a typical sorghum plant, half of the flowers become grain, while the other half remain infertile. As the world grapples with food shortages and scientists seek ways to increase the yield of a wide array of plants, researchers at Cold Spring Harbor Laboratory wondered whether they could increase that yield.

Building on previous work done in the lab of Doreen Ware, an adjunct professor at CSHL, postdoctoral fellow Nicholas Gladman characterized a mutation for a single gene that lowered the level of a hormone. The effect of the lower hormone, or jasmonic acid, at a specific time and place within plant development doubled the fertility of the sorghum plant.

“When we don’t have a functional version of this enzyme, it releases this form of development that wouldn’t normally occur,” Gladman said. “You get increased fertility in flowers.”

The gene they studied is called MSD2. The researchers published their work in International Journal of Molecular Sciences. Another gene, MSD1, which Ware’s lab characterized in 2018, is a likely regulator for MSD2. Other genes may also serve as regulators of MSD2, Gladman said. Disruptions in either gene leads to altered flower development and seed production.

Gladman’s postdoctoral research adviser Zhanguo Xin collaborated on the work. Xin, who is a research molecular biologist at the United States Department of Agriculture’s Agricultural Research Service, explained that Gladman characterized the mutants, identified the interaction between MSD1 and MSD2 and identified the regulatory sequences of MSD1.

This research could extend to other cereal crops, which have the same conserved sets of genes that affect their growth and fertility.

A concern in altering any gene resides in the overall effect on the health of the plant. Creating a super plant that falls over and dies in a slight wind, can’t fend off common infections, or requires a perfect blend of soil would likely offset the benefit of the increased fertility. Plant geneticists would like to ensure any mutation doesn’t make the plant less viable in the long run.

“Sometimes there can be a trade off between an agriculturally beneficial genetic change by introducing other detrimental effects,” Gladman explained in an email. “Optimally, plant geneticists will try to ensure the side effects of any mutation are insignificant to farmers; sometimes, this is more difficult and the downsides may not always present themselves at the early stages of lab investigation.”

This particular gene is narrowly and spatially expressed within the plant, Gladman said, and the researchers haven’t been able to identify or quantify the effect of this gene on anything else other than flowers and floral architecture.

The gene and the hormone would be a concern if it were expressed more broadly and at high levels throughout other plant tissues, but that doesn’t seem to be the case, he said.

The researchers have looked at other tissues, such as the leaf and stem, and have found that MSD2 is expressed in low levels in these other areas. Plants that have the MSD2 mutation do not demonstrate any noticeable differences in growth compared to nonmutants in the field or in greenhouse conditions. If this mutated gene had an agricultural benefit, farmers would likely crossbreed a plant that had this gene with an elite sorghum hybrid line

Ideally, the benefits of the increased fertility would combine with benefits of all the genetic components of the hybrid lines as well. The way the researchers involved in this study produced this more fertile version of sorghum is an “acceptable type of breeding for organic or conventional farming,” Gladman said.

While the plant increases the grain number per seed head, it doesn’t necessarily produce greater overall yield in part because the seeds are smaller. Researchers haven’t been able to confirm that yet in a field condition, although they hope that’s the case.

Gladman was grateful for the opportunity to work in Ware’s lab and to collaborate with Xin. The effects of disrupting similar genes in maize and Arabidopsis, which is a plant in the mustard family that scientists often use in genetic studies, influences flower fertility.

He said researchers in Ware’s lab can perform additional developmental analysis. The researchers in Ware’s lab may seek additional collaborators for other analyses down the road as well.

“How this particular pathway is triggered and cross-communicates with other developmental pathways is very complex, but influences so much about traits that control grain production and yield that it is essential for further investigations,” he explained.

Gladman arrived at Cold Spring Harbor Laboratory in 2017. Prior to conducting research on Long Island, he finished his doctorate at the University of Wisconsin at Madison, where he worked on Arabidopsis. He decided he wanted to get more involved with crop species and explored research opportunities at United States Department of Agriculture labs. He was working with Xin in Lubbock, Texas, before transitioning to Cold Spring Harbor Laboratory.

Gladman has been delighted by the “wonderful place to learn,” where he is surrounded by “people who are always willing to talk and engage and collaborate.”

A resident of Greenlawn, Gladman enjoys hiking along the Hudson and in the Adirondacks. He credits a high school biology class he took in Grandview Heights High School in Columbus, Ohio, with instilling in him and his three brothers an appreciation and love of science. He particularly enjoyed a unit on the “genetics of disease” that inspired him to pursue a career in the sciences.

As for his work, Gladman is excited to be a part of research that may, one day, increase the productivity of crop species. He said thoughts about food shortages are “a constant concern and driver of our research.”

 

Interns Nylette Lopez (rear) and Stephanie Taboada characterize catalysts as they attempt to convert carbon dioxide and methane into synthesis gas this past summer at Brookhaven National Laboratory. Photo from BNL.

By Daniel Dunaief

This article is part two in a two-part series.

Local medical and research institutions are aware of the challenges women face in science and are taking steps to ensure that women receive equal opportunities for success in science, technology, engineering and mathematics (or STEM). Times Beacon Record News Media reached out to members of each institution and received an overview of some initiatives.

Brookhaven National Laboratory 

The Department of Energy-funded research facility has created a number of opportunities for women, including Brookhaven Women in Science. This effort has been active for over four decades and its mission, according to Peter Genzer, a BNL spokesman, is to support the development of models, policies and practices that enhance the quality of life for BNL employees and emphasize the recruitment, hiring, promotion and retention of women.

BWIS offers annual awards, outreach events and various networking opportunities in the lab and community, while the lab’s Talent Management Group partners with BWIS to bring classes and speakers to discuss issues specific to women.

In October, the group hosted Kimberly Jackson, a vice chair and associate professor of chemistry and biochemistry at Spelman College, who gave a talk titled “Realigning the Crooked Room in STEM.”

The Leona Woods Distinguished Postdoctoral Lectureship Award at BNL, meanwhile, celebrates the scientific accomplishments of female physicists, physicists from under-represented minority groups and LGBTQ physicists and to promote diversity and inclusion. BNL awarded the lectureship this year to Kirsty Duffy, a fellow at Fermi National Accelerator Laboratory.

For the past five years, BNL has also partnered with a local chapter of Girls Inc., which helps to “encourage young women towards careers” in STEM, Genzer explained in an email.

BNL has also collaborated with the Girl Scouts of Suffolk County to organize a new patch program that encourages Girl Scouts to work in scientific fields. As of September, county Girl Scouts can earn three new Brookhaven Lab patches, and the lab hopes to extend the program nationwide across the Department of Energy complex.

BNL also provides six weeks of paid time off at 100 percent of base pay for a primary caregiver after birth or adoption and one week of full pay for a secondary caregiver. BNL is exploring plans to enhance support for primary and secondary caregivers, Genzer said.

Cold Spring Harbor Laboratory

Cold Spring Harbor Laboratory has taken several recent steps as part of an ongoing effort to encourage gender diversity.

In October, a group of four CSHL administrators traveled to the University of Wisconsin in Madison to discuss mentoring. The goal was to train them on how to design and deliver mentoring training regularly to the faculty, postdocs and graduate students on campus, said Charla Lambert, the diversity, equity and inclusion officer for research at CSHL. The first version of the training will occur next spring. The ultimate goal is to ensure the research environment at CSHL emphasizes good mentoring practices and is more inclusive for all mentees.

CSHL has also hosted a three-day workshop in leadership practices for postdoctoral researchers and junior faculty since 2011. The workshop, which is run through the Meetings & Courses Program, trains about 25 postdoctoral researchers and junior faculty each year and has about one per year from CSHL, addresses how to hire and motivate people, while providing constructive feedback.

Lambert said family-friendly policies were already a part of CSHL policies, which include a child care facility. Members of the faculty receive extra funding when they travel to conferences to provide additional child care.

Lambert, who is a program manager for extramural Meetings & Courses overseeing diversity initiatives, has worked to get the demographic data for participants centralized, analyzed and used in developing policies. She believes this kind of data centralization is an area for potential improvement in the research division, where she is working to ensure an equitable distribution of resources among CSHL scientists.

Throughout her nine-year career at CSHL, Lambert said she has worked with the meetings and courses division to make sure the 9,000 scientists who visit the facility each year include women as invited speakers. She also works to reach course applicants from a wide range of institutions, including outside of prestigious research schools.

Ultimately, Lambert is hoping to help change the culture of science among the researchers with whom she interacts from a wide range of institutions. She feels that those people who leave the STEM fields because something about the culture of science didn’t work for them represent a “huge loss” to the field and creates a “survivorship bias.”

Stony Brook University 

For Stony Brook, gender diversity is “very important,” said Latha Chandran, the vice dean for Academic and Faculty Affairs at the Stony Brook University Renaissance School of Medicine. 

Chandran said more men entered the field of medicine 14 years ago. That has completely changed, as women have outnumbered their male counterparts in medicine for the last three or four years.

Chandran cited a number of statistics to indicate changes at the medical school. For starters, women faculty constituted 38 percent of the total in 2011. This April, that number climbed to 48.1 percent. That puts Stony Brook in the top 79th percentile of medical schools in terms of female representation.

While the overall numbers are higher, women are still underrepresented in the top tiers of the medical school, as 18 percent of the department chairs are women. She hopes more women can lead departments and that they can serve as role models that others can aspire to follow.

As for harassment, Chandran said Stony Brook was above the national mean in 2011. For almost all categories, Stony Brook is now below the national mean.

In 2011, Stony Brook created We Smile, which stands for We can Eradicate Student Mistreatment in the Learning Environment. The goal of this program is to educate people about harassment and to ensure that any mistreatment is reported. Through this effort, Stony Brook medical students are aware of the policies and procedures surrounding reporting.

Stony Brook is also addressing any bias in admission procedures by prospective applicants, who receive a standardized scenario to address with an admissions officer. In 2025, admissions officers will not have any information about the qualifications of the individual and will evaluate his or her response during interviews only based on response to scenarios.

Stony Brook University has almost finalized its search for a chief diversity candidate. Chandran expects that the medical school will “continue to make progress.”