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Camila dos Santos. Photo courtesy of CSHL

By Daniel Dunaief

Pregnancy and lactation can alter genes in specific mammary cells, which may have implications in a defense against cancer.

In mouse models, mice that became pregnant at a young age have so-called epigenetic changes that survive for the animal life span and some of those are linked to a decrease in breast cancer.

In a recent study published in Cell Reports, Cold Spring Harbor Associate Professor Camila dos Santos and her graduate student Amritha Varshini Hanasoge Somasundara found that a protein involved in mammary cells in mice, called CD1d, boosts the immune system after a full pregnancy cycle, protecting it against breast cancer.

“Our research demonstrated that increased levels of CD1d in breast cells serve as a signal to recruit higher numbers of specialized immune cells” called natural killer T-cells, or NKT, “to come and reside within the breast tissue after pregnancy,” dos Santos explained in an email. These NKTs are part of mechanisms that reduce breast cancer risk after pregnancy.

Dos Santos would like to understand the molecular changes that occur from pregnancy and hopes one day to adapt them in the form of a vaccination or pill to decrease the risk of breast cancer.

To be sure, numerous questions about the process of using the immune system to prevent cancer remain, which means that the development of such a preventive pill requires considerable additional research.

Dos Santos has spent the last eight years developing model systems that allow her to discover pregnancy-induced changes that could lead to preventive strategies.

Enhancing the communication between epithelial and immune cells could represent a way to decrease breast cancer development and even treat cases of developed cancer.

To get to that point, dos Santos, the members of her lab, and her collaborators plan to make discoveries like this one to understand the dynamic interaction between the cascade of molecular interactions from pregnancy and the genetic and immunological reactions.

Humans have four CD1 genes, which all play a similar role in immunity. Additionally, there are several types of NKT cells, and each of them has a different immunological function, which means that any prevention or treatment that tapped into this system would need to bring the right CD1 molecule and the right NKT cells.

It is not yet clear whether enhancing CD1 signals protect women who might have a predisposition to breast cancer. Dos Santos is currently exploring this question in animals.

While dos Santos is focusing specifically on pregnancy-driven changes in the mammary gland, she acknowledged that altering CD1d levels in other organs might also decrease other types of cancer.

Dos Santos described pregnancy as being akin to turning on a light. First, during the course of gestation, pregnancy brightens that light to the top. After birth, the dimmer goes to the middle, leaving the system in a different state, which is not only more prepared for the next pregnancy but also to defend itself against alterations like cancer.

In most pregnancy mammary cells in mice, the scientists found a 10-fold increase in the abundance of NKT cells when compared to cells from an individual who had never been pregnant.

When the researchers removed the CD1d protein in mice, they found an association between the absence or low expression and the development of tumors in the breast.

Dos Santos and Hanasoge hypothesize that this protein is recruiting immune cells to monitor breast cells after pregnancy. If the epithelial cells develop cancer, the NKT cells may kill them, preventing the development and advancement of cancer.

In addition to working with mouse models of pregnancy, dos Santos is collaborating with Northwell Health to study cells from healthy women who are undergoing cosmetic surgery. They are analyzing that data, which wasn’t in this paper. 

Dos Santos is investigating several questions, including how the age at pregnancy influences breast tissue. She is creating organoids, which are three-dimensional models of breast cells that react to change in their environment

Joining a family

From left, Amritha Varshini Hanasoge Somasundara and Camila dos Santos

Amritha Varshini Hanasoge Somasundara, who has been a part of dos Santos’s lab for over two years, explained that she felt comfortable and supported instantly when she arrived. She described the atmosphere as extremely collegial and felt as if she were included in a scientific family.

Joining dos Santos’s group was “possibly the best decision I’ve ever made,” said Hanasoge. Dos Santos’s lab is a “really special place” where lab members often have lunch together and support each other’s research.

Hanasoge was drawn to Dos Santos’s mentorship and the overall lab dynamic. Scientifically, she was also interested in the immunology project, exploring NKT cells. Her main project has involved trying to characterize NKT cells further. 

Hanasoge sees plenty of opportunities to address additional questions in this field. “We don’t know if the process of lactation is causing more CD1d and increasing expression,” she said. “We are still trying to characterize what T-cell receptors are being expressed after pregnancy.”

A resident of Syosset, Hanasoge enjoys reading and said she was fascinated by science when she was growing up in Mysore, Kamataka in India. She asked her parents for a microscope when she was around seven and used it to looked at flower petals and leaves. That toy microscope, which her parents purchased from a science museum in Mumbai, is still in her parent’s house.

Hanasoge is eager to combine basic and translational work and hopes her research has a clinical benefit. She is looking forward to the next steps in her research in dos Santos’s lab.

“I learn from her every day by watching how she interacts with people she mentors, both inside the lab and out,” Hanasoge explained in an email. “Her passion and commitment to being a good mentor and her drive to ask the right questions in our research are inspiring.”

 

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Richard Leakey at the Provost's Lecture Series: "Living Off the Grid with Good Access to Energy and Water". Paleoanthropologist, politician, explorer and environmentalist, Richard Erskine Frere Leakey is chairman of the Turkana Basin Institute (TBI), and Professor of Anthropology at Stony Brook University.
Famed paleoanthropologist, conservationist and SBU professor Richard Leakey leaves a lasting legacy

By Daniel Dunaief

A revered scientist, conservationist, Kenyan, and faculty member at Stony Brook University, Richard Leakey died on Jan. 2 at the age of 77.

Leakey made several significant human fossil discoveries, wrote books and ground breaking journal articles, appeared on the cover of Time Magazine in 1977, and saved elephants and rhinoceros from poaching.

Leakey, who received honorary degrees from numerous institutions including Stony Brook, was also a professor in SBU’s Department of Anthropology in the College of Arts and Sciences and the founder of the Turkana Basin Institute in Nairobi, Kenya.

“I considered him my brother,” said former Stony Brook President Shirley Kenny, who had helped recruit Leakey to join the university and developed a close relationship with him over the course of over two decades. When she learned of his death, she was “devastated.”

The Stony Brook connection

Leakey was visiting Manhattan in 2001 when he met with Kenny and Lawrence Martin, who is the director of the Turkana Basin Institute (TBI). Eager to make a good first impression and “nervous about asking this great, incredible man to come and give a lecture,” Kenny got a manicure before the meal. “He wouldn’t have noticed if I had nails,” she laughed.

When Kenny learned that Leakey was in town to find new leg prosthetics after he lost his legs in a 1993 plane crash, the Stony Brook President asked if he had health insurance, which he didn’t. 

Richard Leakey examines fossils at the Turkana Basin Institute.

“Jewish mother that I am, I said, ‘Richard, you have to have medical insurance.’ We arranged for him to be this faculty member at Stony Brook, who came for a certain amount of time each year to give lectures and work with students, to have students work on his digs,” Kenny recalled.

Leakey, who didn’t graduate from college, was proud of his role at Stony Brook and relished the opportunity to teach, several friends and faculty members recalled. Audiences appreciated the opportunity to hear about the most recent discoveries into human origins, especially from someone with Leakey’s world-renowned reputation.

He was just a  “spellbinding public speaker,” said Martin, who first met Leakey when Martin was a graduate student in 1979. 

“When [Leakey] got an honorary degree, he had two to three minutes to make an acceptance speech,” Martin said. “There was not a sound from the moment he got up. It’s one of only two occasions when the entire student body rose to their feet and gave him a standing ovation.” The other was when famed physicist C.N. Yang received an honorary degree.

Leakey was such a draw that he gave some of his bigger talks at the Staller Center for the Arts, which had to accommodate overflow space for the audience demand.

Patricia Wright, Distinguished Service Professor and founder of a research station Centre ValBio at Stony Brook, recalled how a primate conservation class responded to him.

In his provocative style, Leakey would come in and say something “totally outrageous,” she recalled. The students, who might have otherwise been starstruck and been inclined to write everything he said, felt compelled to speak and would respond, saying, “Wait a second, it shouldn’t be like that.” The class would then discuss a conservation issue with Leakey, which opened up an effective dialogue.

“They loved him because he was so charming and was able to turn their minds around,” Wright said. “I loved those classes and watching him with my students.”

In the world of conservation, Leakey took unconventional approaches that proved effective. In 1989, five years after the landmark discovery of Turkana Boy, a 1.5-million-year-old fossil of one of the most complete early human skeletons, Leakey arranged the burning of 12 tons of ivory tusks in Kenya, signaling that they belonged on live animals.

“We can absolutely say that there are elephants and rhinoceros that are alive today that wouldn’t have been alive if it weren’t for Richard Leakey,” Wright said.

Words of wisdom

In addition to leading by example, Leakey dispensed valuable advice, often over food he prepared specially (more about that in the None of the Above column in this issue).

Leakey “left me with a huge gift, the gift of being confident in what I’m doing, as long I’m doing it with principles,” said Sonia Harmand, Associate Professor in Anthropology at Stony Brook. Leakey urged Harmand not to be “scared of breaking boundaries” and trying something nobody else had tried, she said. “Have faith in what you think you want to do. Never be afraid of being judged.”

Richard Leakey and Joe Biden in 2017 at the Stars of Stony Brook gala at Chelsea Piers. Photo from SBU

Harmand made a significant archaeological discovery, for which she received some skeptical comments. Leakey suggested that she consider such questions a point of pride and a reflection of the value of the work.

“You start to have enemies when you start to be famous and important,” Harmand said Leakey told her. It made her think she should be pleased that people were scrutinizing and criticizing her work. 

Wright, meanwhile, appreciated how Leakey gave her the strength to live life the way she wanted. He urged her to put in the time and effort to work on politics and networking.

Several people suggested that Leakey, who battled physical challenges throughout his life without complaint, also inspired them. “He really taught me about courage and strength,” Kenny said. “I had the kind of courage that let me take on paths I didn’t know if I could handle. He taught me physical courage.”

Indeed, Leakey displayed the kind of physical courage and belief in his convictions people typically associate with a character from a Tom Clancy novel.

In 1967, Leakey was on a Kenyan flight that had to divert because of a dust storm. Despite earlier reports that the land in the Lake Turkana region was volcanic, Leakey thought he saw sedimentary rock, which could contain fossils. He rented a helicopter and landed with only seven minutes of extra gas to spare for the return trip. When he got out of the helicopter, he found fossils. He quickly appeared at a National Geographic meeting, where he urged the group to fund the search on the east side of Turkana.

The chairman of the society told him “if you don’t find fossils, don’t bother to come back to National Geographic,” Martin said the chairman told Leakey. The findings were more than enough for the group to continue funding Leakey’s research, including on the west side of Lake Turkana, where he discovered Turkana Boy. 

Life-altering contact

For several of those who knew Leakey, the interaction was life-altering.

When he was a high school student in Nairobi, Isaiah Nengo heard a talk Leakey gave about plate tectonics and evolution.

“I was completely blown away,” said Nengo, who is now Associate Director at the Turkana Basin Institute.

As a second-year student at the University of Nairobi, Nengo attended an evolution lecture by Leakey. At that point, he was hooked, deciding to become a paleoanthropologist.

Nengo, whose parents’ education stopped around fourth grade, wrote to Leakey after he graduated from college, not expecting to hear back.

“It goes to tell you what kind of person [Leakey] was,” Nengo said. “This kid from the University of Nairobi out of nowhere writing him a letter, and he wrote back.”

Nengo, who said he heard similar stories from others in Kenya, including some who are currently colleagues at TBI, volunteered for a few months, until he got a fellowship.

He said Leakey helped fund a post-baccalaureate one-year program in the United States.

“The best gift you could get is the gift of knowledge,” Nengo said. “From [Leakey], I got the gift of knowledge, which changed the trajectory of my life.”

Like others who were prepared to change their lives after interacting with Leakey, Harmand had been in a comfortable job at the Centre National de la Recherche Scientifique in France when Leakey suggested she join Stony Brook and the Turkana Basin Institute in 2011. “I’m not sure I would have taken” the job, but for Leakey. The work was only supposed to last a couple of years, but she never left.

“He marked my life forever and my career forever,” Harmand said. “We also had a very deep friendship” that extended to the next generation, as her nine-year-old daughter Scarlett has forged a connection with Leakey’s granddaughter Kika, whose mother Samira is the daughter of Richard and Meave Leakey.

With three daughters, including Louise Leakey, who conducts field research at Turkana Basin institute, Leakey was a strong advocate for women.

Women are “equally capable as men and for him, this was not even a question,” Harmand said.

A passion for Kenya

In addition to being pleased with his connection to Stony Brook University, Leakey, who accepted the ceremonial key to a French city in his first language of Swahili, was a proud Kenyan. He set out to employ, train, include and inspire Kenyans in research projects and encouraged the children of staff members to come see the fossils, Martin said.

Leakey also helped raise money from people who traveled to Kenya to support educational fellowships. He contributed to the construction of maternity clinics on either side of Lake Turkana so women could give birth in safe, sterile conditions with electric light, Martin added.

Kenyans recognized Leakey when he traveled and appreciated his contribution to the country.

“We were driving to his farm, when we got stopped,” Martin said. “Everybody knew him and wanted to shake his hand and say hello. He was a local hero who was seen as a Kenyan doing things for his fellow Kenyans,” Martin said.

Harmand recalled one of the last times she spoke with him; he reiterated his passion for his home country.

Leakey made it clear “how important it is to involve Kenyans in what we do,” Harmand said. “We are training the next generation of human origin scientists in Kenya. He is the son of Kenya.”

A passion for science

While Leakey had a genuine interest in a variety of fields, he was, at his core, a scientist. Nengo called him a “polymath” who knew a great deal about a wide range of scientific subjects.

In one of her final conversations with Leakey, Wright said he took her aside after a meal she described as “exquisite” and asked her about bones she’d found in Madagascar.

The conventional wisdom about human origins in the island nation was that humans had come from Borneo 2,000 years ago.

In the middle of Madagascar, however, Wright had found bones from hippos and birds that had cut marks from humans that dated back 10,000 years.

Leakey told her that she “had to find those people,” she recalled. “You will be letting down all of Madagascar if you don’t find their origins.”

Wright said that conversation, which had its intended effect, was “emblematic of his burning desire to know and to learn about hominid history and the burning desire to collect and assemble pieces of history.”

Birthday presents

Leakey, who gave so much of himself to so many people, didn’t like receiving gifts, Martin said, but he welcomed receiving cheese, wine or cooking tools, including pots and pans.

When Leakey reached his 70th birthday, Martin asked him what he planned to do to celebrate. He had scheduled a sailing trip, but he wasn’t sure if he could pull together a crew. Martin offered to be a part of his crew for a journey that lasted over a week aboard a 38-foot catamaran.

Leakey’s daughters Samira and Louise joined Martin as deck hands, giving Richard Leakey the opportunity to take the helm during his journey along the coast of Kenya near his home in Lamu.

“When he was steering the boat, it was the only time he wasn’t challenged by his disabilities,” Martin said. “He didn’t need his feet. Driving wasn’t particularly easy. When he was sitting in the catamaran, it didn’t heel; it went fast, and he could steer the boat. Watching him, I had the sense that he felt completely free.”

 

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Sean Clouston. Photo by Rachel Kidman

By Daniel Dunaief

The same wind that powers sailboats, makes kites dart through the air, and causes flags to flutter can make being outdoors in a group safer, particularly during the pandemic.

While public health officials have suggested that being outdoors with others amid the pandemic is safer than remaining inside, the strength of the wind can affect the level of protection provided by wide open spaces.

That’s the conclusion Sean Clouston, Associate Professor in the Program in Public Health and the Department of Family, Population and Preventive Medicine at the Renaissance School of Medicine at Stony Brook University, reached after studying public health data from 96,000 cases of COVID in Suffolk County from March 16, 2020 to December 31, 2020.

By combining public health data with the daily reports from the National Oceanic and Atmospheric Administration, Clouston found that days in which the temperature was between 60 and 84 degrees Fahrenheit and in which the wind was about 5 miles per hour or less had higher COVID-19 transmission than those days in which the wind speed was faster.

This kind of study, which was recently published in the journal BMC Infectious Disease, might affect the guidance policy makers provide to reduce the risk of COVID transmission during outdoor gatherings.

“If you’re imaging yourself as a policy maker and you want to contain COVID, what do you do?” Clouston asked rhetorically. Vaccines and masks are established tools. Ensuring airflow is higher might also be important, he suggested.

Indeed, amid the early days of the pandemic in 2020, public officials closed parks in Suffolk County for a while and eventually reopened them.

An alternative could be to provide access to parks where wind speed is also protective, or to reduce the use of parks where social distancing is difficult and where wind speed is lower.

At the same time, residents might want to protect themselves by putting out fans in their backyard or some other airflow devices to keep the flow of air moving during a social gathering, reducing the chance of transmitting the virus. People might want to avoid using tents that reduce the flow of air around them.

Additionally, people could eat out at restaurants where the airflow is stronger. 

Diners can search for places where the air “moves around, so the outdoor experience is as protective as possible,” Clouston said. He recognized that the data had some variability between when people who went outside might have contracted COVID. The air flow could increase and then decrease and the average length of time from exposure to symptoms and testing could differ between people.

“Any time we deal with humans, this is the problem,” Clouston said. Researchers can’t control for everything. Instead, they have to assume people make decisions in a consistent, but variable, way.

The larger data set, with close to 100,000 cases, enabled Clouston and his colleagues to average out the effects of the time when people reported their positive COVID tests.

For numerous cases, people had a good idea where and how they contracted COVID. Even when they were at outdoor events, such as a barbecue, some people had indoor parties where they ate together.

In addition, merely being outdoors didn’t reduce the risk if people were standing in the equivalent of stale air, where wind couldn’t reach them and help carry viral particles away from others who attended these events.

Being outside if the air isn’t moving is similar to being indoors in a space with a very large ceiling and a wide space between walls, he explained. It is safer than a small room, but it is not inherently safe on its own.

As for air circulation indoors, Clouston said people have suggested that moving air in buildings could reduce the spread of the virus.

Testing the effects of having HEPA filters or air filtration systems run continuously in hospitals  compared to areas that don’t have such units could reveal the benefit of having these air flow systems. Some studies have been done on this, although more work is ongoing, he said. 

Clouston suggested that other environmental conditions could also impact the transmissibility of the virus. The heat index, for example, might explain why wind speed might be important.

The heat index “might diminish the effect or make it stronger,” Clouston said. “It can push people indoors.”

Clouston worked on this study with Stony Brook colleagues in the Department of Family, Population and Preventive Medicine Assistant Professor Olga Morozova and Professor Jaymie Meliker. The team has worked with the Suffolk County Department of Health since 2020 on different aspects of COVID modeling.

Clouston was surprised that the research revealed a threshold model wind speed. He was also surprised to see that the speed was so low. “You only need a little airflow,” he explained.

The Stony Brook scientist looked at where the positive cases were located by zip code. The summer distribution and the spatial distribution was somewhat unclear, he said.

The spread of COVID was distributed by population size and density. Population size and density are likely more important than alterations in microclimate in the summer.

The analysis is important for places when and where outdoor exposures are most common, he explained.

“This may be true in the summer on Long Island or in the winter in southern states like Louisiana when outdoor activities are more comfortable,” he wrote in an email.

Clouston has several ongoing projects. He has papers discussing the role of social inequalities and COVID, a paper looking at clinical risk factors for COVID at Stony Brook Hospital, and one describing the initial wave of COVID in World Trade Center responders.

He would like to look at the effect of outdoor protests during 2020 on the spread of COVID, which would require data on attendance at those events and at the ones in New York City.

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Graduate student John Yuen wearing an N95 mask for fit testing after the mask was disinfected via dry heat. Photo from SBU
Study details published in PLOS ONE could serve as a guide to practical, safe reuse of N95s.

Entering a third year of the COVID-19 pandemic and the latest infection surge nationwide comes with many challenges. One of those is for a continued adequate supply of masks, including the often used N95 respirator masks for healthcare and other settings. A study led by Stony Brook University researchers discovered that a readily available method using dry ovens can be used to disinfect N95s for reuse, in settings where new masks may not be available. Their findings are published in PLOS ONE.

To combat any shortages of N95 masks during the pandemic, many institutions were forced to search for other alternatives to protect health care providers and their patients. While some studies have evaluated the impact of various methods of decontamination on how  well masks filter viral-sized particles, this study adds to such research and also addresses the equally important concept of maintaining proper mask fit after decontamination.

“Our study demonstrated that treatment of N95 face masks using dry heat was sufficient to inactivate COVID-19, while preserving the ability of these masks to filter aerosolized particles for potentially exposed workers,” summarizes Kenneth Shroyer, MD, PhD, lead author and the Marvin Kushner Professor and Chair of Pathology at the Renaissance School of Medicine at Stony Brook University.

Since heat is potentially more readily accessible than other methods of decontamination in many healthcare facilities, the researchers used dry heat sterilization to disinfect the masks. They also used X-ray diffraction, Raman spectroscopy, contact angle, and electron microscopy collected at the Center for Functional Nanomaterials—a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Brookhaven National Laboratory—to test for changes in the material of N95 masks post decontamination.

By contrast, other methods for disinfection, including treatment with hydrogen peroxide vapor, may be equally effective in specially equipped facilities but are usually not available in most hospitals or outpatient clinical care facilities.

Dr. Shroyer and colleagues also tested autoclaving, which is widely available in most hospitals and is a proven method of sterilization but found that this caused the fit of the respirator onto the user’s face to fail. Thus, the researchers ruled out autoclaving as a safe method to decontaminate N95 masks.

The research involved experts from the School of Medicine, the College of Engineering and Applied Sciences, the College of Arts and Sciences, the Institute for Electrochemically Stored Energy, and the School of Marine and Atmospheric Sciences (SoMAS), along with colleagues in the Interdisciplinary Science Department and the Center for Functional Materials at Brookhaven National Laboratory.

For additional details about the initial studies that served as the foundation for this study – which was launched during the first wave of the pandemic in April 2020 – see this story.

Dr. Shroyer emphasizes that the findings from the study highlight the importance of both optimal disinfection and mask fit and suggest that when no other decontamination alternatives are available, N95 masks can be reused after dry heat treatment to ensure the safety of health care workers.

 

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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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Enyuan Hu (front) and Peter Khalifah, two of the principal investigators for battery research projects that just received funding from the Department of Energy, at NSLS-II's X-ray Powder Diffraction beamline.

The U.S. Department of Energy (DOE) announced $209 million in funding for 26 new laboratory projects focusing on electric vehicles (EV), advanced batteries, and connected vehicles. Scientists from DOE’s Brookhaven National Laboratory will play key roles in two EV battery projects—one aimed at understanding and improving materials for battery anodes and cathodes and another to guide the design of safer electrolytes. The funding comes from the DOE’s Office of Energy Efficiency and Renewable Energy (EERE).

“President Biden’s Administration wants to make it easier for millions of American families and businesses to make the switch to electric vehicles,” said Secretary of Energy Jennifer M. Granholm in a DOE statement announcing the funding. “By developing smarter vehicle batteries, we can make these technologies cheaper and more accessible, while positioning America to be become a global leader of EV infrastructure production and clean energy jobs.”

Brookhaven Lab will be involved in projects aimed at understanding and refining the materials that make up all major components of batteries [https://www.energy.gov/science/doe-explainsbatteries]—the anode (negative electrode), cathode (positive electrode), and the electrolyte that shuttles charged ions from one electrode to the other as electrons move in the opposite direction through an outside circuit to provide power. (For rechargeable batteries, like the ones in electric vehicles, the whole system runs in a reversible manner, allowing for repeated charge and discharge cycles.)

Both Brookhaven projects will make use of research capabilities at two Brookhaven Lab user facilities, which operate with funding from the DOE Office of Science: the National Synchrotron Light Source II [https://www.bnl.gov/nsls2/about-NSLS-II.php] (NSLS-II), which produces extremely bright x-rays for studying a wide range of materials, and the Center for Functional Nanomaterials [https://www.bnl.gov/cfn/] (CFN), home to a suite of electron microscopes [https://www.bnl.gov/cfn/facilities/microscopy.php] and nanoscale fabrication tools [https://www.bnl.gov/cfn/facilities/nanofabrication.php]. These facilities give scientists access to information about the atomic-level structure and chemical properties of battery materials, including under operating conditions. Scientists can use what they learn from these characterization studies to fine-tune and test new material designs with the goal of improving and optimizing performance. These two projects will be carried out by scientists in Brookhaven Lab’s Chemistry Division.

Battery500 Phase 2

As partners in “Battery500 Phase 2,” which is led by DOE’s Pacific Northwest National Laboratory (PNNL), a team of Brookhaven scientists will conduct studies to identify battery electrode materials with increased energy density. Such materials could reduce the size and weight of batteries used in electric vehicles and/or extend the vehicle’s driving distance for a given battery weight with better safety characteristics. Identifying lower-cost materials is another primary goal.

The total budget of Battery500 Phase 2 is $75M for the next 5 years. It is a renewal of funding for the original Battery500 Consortium, which was established in 2016 [https://www.bnl.gov/newsroom/news.php?a=111858].

Under the new funding arrangement, Brookhaven Lab will receive $1.3 million per year for the next five years. Brookhaven chemist Xiao-Qing Yang will serve as the general coordinator for the Battery500 Phase 2 consortium and as Brookhaven Lab’s point of contact. Brookhaven associate chemist Enyuan Hu is another principal investigator (PI) for this project. And Peter Khalifah, another Brookhaven PI, who holds a joint appointment at Stony Brook University, will serve as one of the two leaders of a cross-cutting thrust on materials characterization within the Consortium.

“Our team has made important discoveries over the past five years during Battery500 phase 1, which resulted in increased funding for Brookhaven and an increased project-leadership role for Battery500 Phase 2,” said Yang. “We are quite excited to be a member of this great consortium and confident in the success of this Phase 2 project.”

As an example of the success of the original Battery500 funding initiative, the Brookhaven team, working in collaboration with colleagues at PNNL and elsewhere, provided important insight into the electrochemical surface reactions of lithium metal anodes [https://www.bnl.gov/newsroom/news.php?a=117633]—one of the key components being explored to fulfill the energy density sought by Battery500. They also identified the failure mechanisms of these lithium metal anodes [https://www.bnl.gov/newsroom/news.php?a=118736] after long-term cycling. In addition, the team uncovered evidence that high voltage charging can induce strain and crack [https://www.bnl.gov/newsroom/news.php?a=114414]ing in nickel-rich cathode materials, and developed exceptionally sensitive methods for quantifying defects [https://www.bnl.gov/newsroom/news.php?a=116984] associated with disorder across atomic sites. Results from these last two studies are guiding the design of improved cathodes.

In the next five years, the Brookhaven team will continue their efforts to develop and deploy sensitive characterization techniques that can illuminate the changes that occur in lithium metal anodes, metal oxide and sulfur cathodes, and new electrolytes during their use in rechargeable batteries. These efforts will help understand and overcome the factors limiting the performance of this exceptionally high energy density class of batteries and will accelerate the rate at which this technology can become commercially viable.

Solid state electrolytes

Another Brookhaven team, led by Enyuan Hu, will spearhead a new project to study solid state battery electrolytes. Electrolytes allow negatively and positively charged ions to flow between a battery’s anode and cathode. Most of today’s EV batteries use organic liquid electrolytes, which are highly volatile and flammable.

“Solid state batteries are intrinsically safer and have potentially higher energy density than conventional liquid-electrolyte-based batteries,” Hu said.

The Brookhaven team (one of 17 projects just awarded funding for studying solid state electrolytes under the new announcement) will conduct research on ceramic-polymer composite solid-state electrolytes. The total funding for this 5-year project is $2.5 million, including $300K per year for Brookhaven Lab and $200K per year for collaborators from Harvard and the University of California, Irvine.

This project leverages the electrolyte expertise within the Chemistry Division of Brookhaven Lab, the advanced characterization tools available at NSLS II and CFN, the ceramic and polymer expertise at Harvard and UC Irvine, and the established long-term collaboration among the three institutions.

“These important projects will help advance the development of electric vehicle batteries,” said Alex Harris, director of Brookhaven Lab’s Energy Sciences Directorate and acting chair of the Lab’s Chemistry Division. “We are grateful for the sustained funding for both the specific battery research projects and for the user facilities that enable the fundamental scientific studies that will push these technologies forward.”

U.S. Senator Kirsten Gillibrand (NY), in the DOE statement, said, “I am proud to have fought for this vital DOE funding to bring innovation home to New York State and our world-class Brookhaven National Laboratory. This investment is a down payment on a greener, more prosperous future for all of us, and I look forward to supporting more of these projects in the future.”

Brookhaven National Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit science.energy.gov. [https://www.energy.gov/science/]

Follow @BrookhavenLab on Twitter [http://twitter.com/BrookhavenLab] or find us on Facebook [http://www.facebook.com/BrookhavenLab/].

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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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'Explore' Photo from Vanderbilt Museum

The Suffolk County Vanderbilt Museum’s Reichert Planetarium, 180 Little Neck Road, Centerport has just premiered its newest show, Explore, which is showing Friday and Saturday nights at 9 p.m. and Saturdays and Sundays at 4 pm.

Explore is an odyssey to the planet Mars, seen through the lens of human history and scientific development. This visually stunning fulldome film begins with a look at how scholars and scientists throughout the ages used the sky as a clock and calendar to measure the passage of time. Their charts and star catalogs informed the modern science of astronomy.

Dave Bush, director of the Charles and Helen Reichert Planetarium, said “This is a planetarium show not to miss. We’ve presented dozens of original fulldome films, but this is one of the finest productions ever made available to our audiences. We are thrilled to have this new program on our 60-foot dome. It’s truly an immersive masterpiece.”

Once an object of mystery, the red planet may one day become a second home for humankind. Take an adventurous journey from ancient Mesopotamia to modern space exploration! Experience the fascinating history of astronomy, geocentric and heliocentric models, the laws of planetary motion, and discover the principles of orbital maneuvers which enable satellites and space travel.

The 45-minute show is recommended for ages 14 and up. Tickets are $16 adults, $15 seniors and students.

Purchase Tickets

For more information, call 631-854-5579 or visit www.vanderbiltmuseum.org.

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