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Power of 3

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From left, Patricia Wright with Pamela Reed Sanchez, President and CEO of the Seneca Park Zoo Society with the Warrior Award, a depiction of a tree growing out of rock, designed and created by artists at the Corning Museum of Glass. Photo courtesy of Amanda Lindley

By Daniel Dunaief

For only a short period of time, Patricia Wright was just a primatologist who studies the charming lemurs of Madagascar.

Now the Herrnstein Professor of Conservation Biology and Distinguished Service Professor at Stony Brook University, Wright first trekked to the island nation off the southwest coast of the African continent in 1986 to understand and study these unique primates.

Within a year, she realized she wouldn’t have much to observe and understand in a perilously short time if she didn’t also work to protect them, their habitat, and many other threatened and endangered animals and plants.

With the help of the government of Madagascar, Wright created a protected area known as Ranomafana National Park, which includes 41,500 hectares of space, keeping loggers, poachers and others from threatening to eradicate animals and plants that are unique to the country.

Between the original effort to create the national park and today, Wright has collected numerous honors and distinctions. She has won three Medals of Honor from the Malagasy government and become the first female recipient of the coveted Indianapolis Zoo Prize in 2014.

Recently, the Seneca Park Zoo in Rochester, New York named Wright its inaugural “Conservation Warrior,” providing her with a $20,000 prize in recognition for conservation work that has had a lasting, meaningful impact on species survival.

Patricia Wright with her Warrior Award from the Seneca Park Zoo.

“Dr. Wright’s early years were spent in Rochester, New York and it is fitting that the inaugural Conservation Warrior award be bestowed upon arguably the most influential conservationist to come out of the Finger Lakes region,” Pamela Reed Sanchez, President and CEO of the Seneca Park Zoo Society, explained in an email.

The newly anointed conservation warrior recently traveled to Montreal as a member of the Madagascar delegation at the fifteenth meeting of the Conference of the Parties to the Convention on Biological Diversity, or COP-15.

While she’s in Montreal, she plans to meet with conservation donors in an all-out effort to save wildlife on Madagascar, where almost all the reptiles and amphibians, half of its birds and all of its lemurs are only found on the island nation.

Wright hopes to raise $250 million for the country and $50 million for Centre ValBio (CVB), the research station she created in Ranomafana in 2003 and that employs 80 Malagasy staff. CVB has developed a conservation network around CVB that includes work with 75 villages.

Drew Fellman, who directed and wrote the Island of Lemurs documentary, encouraged donors to support Wright’s efforts. Wright and CVB are at the “front line of defense and anyone who cares [about] wildlife and endangered species should lend them a hand,” Fellman wrote in an email. He described how some species of lemurs are down to fewer than 10 individuals and “without conservation, there will be nothing left to research.”

In areas where conservation isn’t a priority, the region has lost habitat and biodiversity. In the northern areas of Madagascar, loggers and timber exporters reduced rainforest areas to grasslands, she said.

In the bigger picture, Wright said Madagascar needs funding immediately as the country is “closer to the brink of extinction with so many more species.” Saving plants and animals in Madagascar extends beyond committing to the protection and stewardship of vulnerable creatures. It also could provide benefits for people.

“So many lemur species are close relatives [to humans] and contain genetic information” about Alzheimer’s, diabetes and other conditions, she said. Additionally, creatures like bamboo lemurs regularly eat large quantities of cyanide, which would kill humans. Understanding how they can tolerate such high quantities of cyanide could provide an antidote.

The forests in the national park, which might otherwise attract loggers, prevent erosion, silting and landslides, she explained.

The benefit of a research stations like CVB extend beyond gathering information and conducting experiments.

In a recent correspondence in Nature Communications, lead author Timothy Eppley, a postdoctoral fellow at San Diego Zoo Wildlife Alliance along with three other scientists including Wright, argues that field research stations “are on the front line of biodiversity conservation, acting as no-take zones that rewild surrounding ecosystems.”

In the correspondence, Eppley and his colleagues said that these stations are “invisible” in global environmental policy, despite their importance in conservation.

“Our point in the paper is that this has not been given any conservation attention,” said Wright. “Nobody is funding us for doing conservation” even though these sites are “conservation engines. We should be given recognition and more conservation money.”

Eppley, who leads SDZWA’s lemur conservation program, added that the Nature correspondence didn’t include any of the data the group collected.

While Eppley cautioned in an email sent from Madagascar that it’s difficult to generalize about conservation efforts at field stations, he said many have some conservation initiatives or projects, or that some element of their research includes a strong conservation component.

“Without the conservation piece, all other research will eventually disappear: we need the ecosystem and animals to exist in the first place,” he explained.

Eppley suggested that scientists often approach conservation initiatives that they can test on a small scale and then, if they are effective, find the best way of scaling up those initiatives for entire protected areas, landscapes, countries or broader geographic regions.

As for the honor Wright received from the Seneca Park Zoo, Eppley believes such recognition dovetails with their recent correspondence piece in Nature Communications.

Wright “founded CVB and has been tirelessly building it into a globally recognized field research station,” he wrote.

Bringing international recognition to the work being done at CVB “highlights the overall importance of field research stations and why they need to be included in global environmental policy frameworks,” Eppley added.

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Luisella Lari. Photo from BNL

By Daniel Dunaief

Some day, physicists and members of the public who benefit from their discoveries may be happy that Luisella Lari had limited musical and sports talent.

Lari, who grew up in Torino, Italy, tried numerous sports and instruments, especially with her parents’ encouragement.

Luisella Lari studies continuous feature drawings of the Electron Ion Collider. Photo from BNL

After gamely trying, Lari blazed her own trail, which has led her to become Project Manager and senior scientist for the Electron Ion Collider, a one-of-a-kind nuclear physics research facility at Brookhaven National Laboratory. BNL won the rights to construct the EIC, which the lab will plan and develop over the course of the next decade, from the Department of Energy in 2020.

By using a 2.4 mile circumference particle collider, physicists will collide polarized electrons into ions with polarized protons to answer a host of questions about the nature of matter. They will gather information about the basic building blocks of nuclei and how quarks and gluons, the particles inside neutrons and protons, interact dynamically through the strong force to generate the fundamental properties of these particles, such as mass and spin.

Lari, who joined the EIC effort on October 3rd, described her role, which includes numerous meetings, calls and coordinating with multinational and multi-state teams, as a “dream job.”

“I’m so excited to be a part of a project that can help the next generation of physicists,” Lari said. “It’s my turn to participate in the construction” of the cutting edge facility. BNL is coordinating with numerous other labs nationally, including the Thomas Jefferson National Accelerator in Virginia, an internationally on the project.

Amid her numerous responsibilities, Lari will ensure that effective project management systems, cost controls and project schedules are developed, documented and implemented. Core competencies of the team she is responsible for include procurement, quality and safety.

EIC applications

The EIC has numerous potential applications across a host of fields. It could lead to energy-efficient accelerators, which could lower the cost of accelerators to make and test computer chips. The EIC could also provide energetic particles that can treat caner cells and improve the design of solar cells, batteries and catalysts. The EIC may also help develop new kinds of drugs and other medical treatments.

Lari explained that she provides a review and approval of the safety evaluations performed by experts. She suggested this suits her background as she did similar work earlier in her career.

Luisella Lari on a recent vacation to Mackinac Island.

Lari has made it a priority to hire a diversified workforce of engineers, technicians and quality and safety managers who can contribute to a project that BNL will likely start constructing in 2026 and 2027.

“I am a strong supporter of building a diverse workforce at levels of the organization,” she explained in an email. “I am strongly convinced that it will add value to any work environment and in particular in a scientific community.”

Applying her experience

Lari isn’t just an administrator and a project coordinator —  she is also a physicist by training.

She earned a master’s degree in nuclear engineering from Politecnico di Torino University in Italy and a PhD in physics from the Swiss Federal Institute of Technology Lausanne in Switzerland.

Early in her professional career, Lari worked at Thales Alenia Space, an aerospace company in Turin, Italy, where she collaborated for the development of her master’s thesis. She worked for two years at the company, performing tasks that included testing internal fluid supply lines for one of the International Space Station’s pressurized modules that connects the United States, European and Japanese laboratories in orbit.

She enjoyed the opportunity to work for a “really interesting project” and still routinely uses the NASA system engineering handbook.

She also worked for about a dozen years as an applied physicist and planning officer at CERN, a particle physics lab, which is on the border between France and Switzerland near Geneva.

Lari also served as a project manager and scientist for the European Spallation Source, a neutron source under construction in Sweden. She coordinated ESS Accelerator Project budgets and ran data-driven safety analyses.

Recently, Lari was a senior manager at Fermi National Accelerator in Illinois, where she coordinated international partner contributions to the Proton Improvement Plan II, which upgraded the accelerator complex.

A need to know

When Lari was in middle school, the Chernobyl nuclear power plant melted down. As a school assignment, she had to explain what happened. At that point, she said she understood nothing, which motivated her to want to become a nuclear engineer.

She was “fascinated by nuclear energy.” When she worked at CERN, she had not been studied much about accelerator physics. She attended meetings where sophisticated discussions physics took place and was driven to learn the material.

“All my life, which started when I was a child, I wanted to understand the world around me,” she said. Her work in project management for scientific projects is also her passion, she said. “My mother would say to me when I was younger that I should choose my job in a way that I would do something I like, because I will spend half my life doing it.”

In addition to committing to understanding the physics and helping other scientists pursue their curiosity, Lari said she appreciates the opportunity to collaborate.

While Lari never became proficient in music or athletics, she enjoys dancing and is looking forward to attending Broadway musicals in New York.

She has hosted her parents at each of the places where she has worked, broadening their horizons.

As for her work, Lari recalls being impressed by the ability of the managers at the LHC to summarize complex work in a few pages and to make big picture decisions that affected so many other scientists. She became impressed and inspired “by the power of the project administrator approach,” she said. She also appreciates the opportunities to interact with experts in several fields, which gives her the chance to “better understand and learn.”

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Egypt’s coral reefs, shown here in a recent photo of the Red Sea in Egypt, remain one of the few pristine reef systems worldwide. Photo by Maoz Fine

By Daniel Dunaief

While global warming threatens most of the warm water reefs of the world, the reefs off the coast of Egypt and nearby countries are capable of surviving, and even thriving, in warmer waters.

That, however, does not mean these reefs, which live in the Northern Red Sea and the Gulf of Aqaba and are along the coastline of Egypt, Israel, Jordan and Saudi Arabia, are safe. 

Karine Kleinhaus

Indeed, several factors including unsustainable tourism, sewage discharge, coastal development, and desalination discharge threaten the survival of reefs that bring in more money than the Great Pyramids.

Recently, Karine Kleinhaus, Associate Professor at the School of Marine and Atmospheric Sciences at Stony Brook University, published a letter in the prestigious journal Science that suggested it’s time to conserve the Egyptian reefs, which constitute about 2 percent of the country’s gross domestic product.

Along with co-author Ellen Pikitch, Endowed Professor of Ocean Conservation Science at SOMAS, whe urged an expanded and fortified marine protected network. As of now, the MPAs only protect about 4 percent of Egypts’s waters.

Kleinhaus, who is President of the Red Sea Reef Foundation which supports scientific research on the reefs, also urged more effective fisheries management and enforcement and an investment in sustainable tourism practices and infrastructure that mitigates land-based pollution, such as waste-water treatment infrastructure and garbage disposal mechanisms.

Science published the letter just days before the 27th Conference of the Parties to the UN Framework Convention on Climate Change (COP27), which was held in Sharm el-Sheikh, Egypt.

During the COP27 conference, the United States Agency for International Development (USAID) committed up to $15 million to scale reef-positive blue economic growth and conservation finance in the Red Sea in partnership with the Global Fund for Coral Reefs.

Kleinhaus called the investment a “great start” in protecting a “valuable global treasure. It’s great that the US recognizes the value of this place and that the US is working to contribute to preserve it.”

Other work ahead

Kleinhaus added that considerable works lies ahead to protect one of the few reefs capable of surviving climate change. “We can’t turn the clock back right this minute on warming the oceans, [but] we can stop the conditions that are happening along the Red Sea reef,” she said.

Kleinhaus suggested that all the threats to the reefs are significant. Tourists who are not educated about the fragility of the nature they’ve come to see have damaged the reef. Scuba divers, meanwhile, smash into the reefs with their tanks or drag their regulators and other gauges over the reefs, killing or injuring them.

Kleinhaus with a grouper in Eilat.

During Covid travel restrictions, Kleinhaus heard that some parts of the reef, which would have otherwise been damaged by visitors, recovered. Raw sewage and general pollution reaching the reefs also threatens marine life, as is over fishing.

Other reefs, such as the Great Barrier Reef in Australia, have sustained damage from global warming. Kleinhaus described those reefs as a “warning that things are going to change.”

Transplanting parts of the Red Sea reef into other parts of the world to enhance temperature resilience is unlikely to work, Kleinhaus said. These reefs include a diverse ecosystem that supports it, including algae, bacteria, invertebrates and fish.

“We don’t have the scientific knowhow to transplant entire ecosystems at this time,” said Kleinhaus

Evolution of resistance

Kleinhaus explained that heat resistance in the Red Sea reefs developed through natural selection of the coral animals.

During the last Ice Age, the Red Sea got cut off from the Indian Ocean, which meant the temperature climbed and the sea didn’t have any rivers emptying into it. When the Ice Age ended, waters rose into the Red Sea that carried coral from the Indian ocean. The coral that survived had to be tolerant of heat and salt.

“That is the working hypothesis as to why the corals in the northern Red Sea are resilient,” Kleinhaus explained in an email. “They were selected to tolerate hotter water than where they live now.” She called this resilience a “lucky break” for the reefs.

Unusual path

Kleinhaus, who grew up in Westchester, New York, followed an unusual path into marine research.

After attended medical school in Israel at Tel Aviv Medical School, she practiced briefly as an obstetrician in New York. From there, she was the divisional vice president for North America for an Israeli biotechnology company.

Egypt’s coral reefs, shown here in a recent photo of the Red Sea in Egypt, remain one of the few pristine reef systems worldwide. Photo by Maoz Fine

Kleinhaus was reading about the effect of heatwaves and global warming on coral reefs. Upset that they were dying, she decided to make a career change and earned her master’s degree in Marine Conservation and Policy at Stony Brook’s School of Marine and Atmospheric Sciences.

The common thread in her career is that she was working on cell therapy using cells from the placenta, which is an extension of her obstetrics career. Nowadays, she studies reproduction in corals.

Like humans, corals have the hormones estrogen, progesterone and testosterone. Unlike humans, reefs are hermaphrodites and can switch back and forth between genders. Kleinhaus is exploring the relationship between hormones and the stages of reproduction in coral.

Numerous species of coral spawn once a year within 20 minutes of each other. Their reproduction is tied to the moon cycle. Kleinhaus has collected over two and a half years of data and plans to publish those results in a scientific journal.

She started diving in 1993 and said she enjoys seeing the colors, the shapes, the fish, turtle, octopuses, dolphin and barracuda. Invertebrates and sponges also contribute to the “overwhelming and glorious” experience of visiting reefs.

Down the road, she’d like to collect information from the COP27 conference and write a follow-up piece that would include more deep research about policies and conditions of the reef.

The point of the letter was to “highlight that this has to be protected and it’s a serious interest to everybody in Egypt.”

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From left to right, physician assistants Michelle Rosa and Katherine Malloy, Dr. David Fiorella and Dr. Jason Mathew visit Joseph Annunziata in his hospital bed. Photo from Stony Brook Medicine

By Daniel Dunaief

Joseph “Bob” Annunziata, a resident of Kings Park, wants you not to be like him.

An army veteran, Annunziata urges residents and, in particular, other veterans, to pay attention to their medical needs and to take action when they find out they have a problem. 

A self-described “tough guy” who grew up in Bay Ridge, Brooklyn, Annunziata put off medical care for a partially blocked left carotid artery and it caused a medical crisis.

“My brother and sister vets, if you got a pain or the doctor tells you to do something, do it,” he said. “It almost cost me my life. I don’t want that to happen to anyone else.”

Joseph Annunziata at his 80th birthday party

Annunziata, 80, was driving to the supermarket on Veterans Day when his right hand became limp and he was slurring his speech. Knowing he was in trouble, he turned the car around and drove 10 minutes to the Northport VA Medical Center.

The doctors evaluated him and rushed him to Stony Brook University Hospital, which is well equipped to handle stroke-related emergencies and is the only hospital in the state named one of America’s 100 Best Hospitals for Stroke Care for eight years in a row. 

Several doctors evaluated Annunziata, including by Dr. David Fiorella, Director of the Stony Brook Cerebrovascular Center and Co-Director of the Stony Brook Cerebrovascular and Comprehensive Stroke Center, and Jason Mathew, stroke neurologist.

“We identified that there was a severe blockage in the left side of his brain,” said Dr. Mathew. “If blood flow is not returned to this area, the patient is at risk for a larger area of stroke.”

Indeed, a larger stroke could have caused right side paralysis and could have robbed Annunziata of his ability to speak or worse.

Performing emergency surgery could protect endangered brain cells, but also presented some risk. If not removed carefully and completely, the clot in the carotid artery could travel into the brain or the stroke could expand over time due to a lack of sufficient blood flow to the left side of the brain.

Time pressure

Stony Brook doctors discussed the particulars of the case together and explained the situation to Annunziata, who could understand what they were describing and respond despite symptoms that threatened to deteriorate.

The hospital, which does between 200 and 250 interventional stroke treatments per year and handles many more strokes than that annually, has a group of health care specialists who can provide accessible information to patients who are not experts in the field and who need to make an informed decision under time pressure.

Stony Brook has become adept at “conveying this complex information in a time-sensitive way,” Dr. Fiorella said. In those cases for which surgery is the best option, each minute that the doctors don’t open up a blood vessel reduces the benefits and increases the risk of longer-term damage.

Stony Brook sees about one to two of these kinds of cases per month. As a whole, the hospital, which is a large referral center, sees numerous complex and unusual cerebrovascular cases of all types, Dr. Fiorella said.

Annunziata and the doctors decided to have the emergency surgery.

Dr. Fiorella used a balloon guiding catheter, which is a long tube with a working inner lumen that has a soft balloon on the outside of it that is designed to temporarily block flow. He deploys these occlusion balloons in most all stroke cases. 

The particular way he used it in these complete carotid occlusions is unique. The balloon guiding catheter makes interventional stroke procedures more efficient, safer, and the outcomes better, according to data for thrombectomy, Dr. Fiorella said. 

The occlusion balloon enabled Dr. Fiorella to control blow flow the entire time, which makes the procedure safer. The surgery took under an hour and involved a small incision in Annunziata’s right wrist.

Joseph Annunziata with his girlfriend Rosemarie Madrose

After the surgery, Annunziata was able to speak to doctors and call Rosemarie Madrose, his girlfriend of five and a half years. “He came out talking,” said Madrose. “I could understand him. I was relieved.” Four days after the emergency operation, Annunziata, who also received post operative care from Dr. Yuehjien Gu, Neurocritical Care Unit Director, left the hospital and returned to his home, where he spent the next morning preparing a welcome meal of a scrambled egg and two slices of toast.

The doctors attribute Annunziata’s quick recovery to a host of factors. Getting himself to the hospital as soon as symptoms started saved precious minutes, Dr. Fiorella said, as “time is brain.” He also advised against driving for people having stroke-like symptoms, which can include slurred speech, numbness, weakening of the arm or leg and loss of vision in one eye.

Dr. Fiorella urged people to call for help or to get a ride in an ambulance. Stony Brook has two mobile stroke unit ambulances, which are equipped with technology to assess patients while en route, saving time and alerting doctors in the hospital to patients who might need immediate attention and intervention.

These mobile units, which are available from 8 a.m. to 8 p.m., have helped reduce death and disability for stroke and have cut down the length of stays in the hospital.

People or family and friends who are observing someone who might be having a stroke can call 911 and indicate that the patient is having stroke-like symptoms. The emergency operator will alert the mobile stroke unit of a possible case if the unit is available and the patient is in range.

Helping a veteran

The doctors involved in Annunziata’s care were well aware of the fact that they were treating a veteran on Veterans Day.

“Oftentimes, we think about how we can give back more than just a thank you” to people like Annunziata, who “risked his life and helped his country the way he could,” said Dr. Mathew. “I’m helping him the way I can help.”

Dr. Fiorella added that he thought it was “wonderful” to “help someone who’s given so much to our country on Veterans Day.”

Army origin

Annunziata explained that he wound up in the Army through a circuitous route.  “We watched all the war movies” when he was young and wanted to join the Marines, he said.

When he went to enlist in 1962, he was told there was a two and a half year wait. He and his young friends got the same reception at the Air Force, Navy and the Army. As they were leaving the Army building on Whitehall Street, he and his friends ran into a sergeant with numerous medals on his uniform. The sergeant urged them to go back up the hallway and enter the first door on the right and indicate that they wanted to expedite the draft. About a week later, Annunziata was drafted and got a 15 cent token in the mail for a train trip to Wall Street.

After basic training at Fort Dix, he was stationed in Greenland, where Annunziata operated a radar at the top of a mountain for two years. He participated in drills in which he had to catch American planes flying overhead.

Fortunately, he said, even during the height of the Cold War and just months after the Cuban Missile Crisis, Annunziata never spotted a Russian threat, even though the base was just 20 minutes from Russian air space.

Having gone through emergency surgery that likely saved his life, Annunziata urges residents to pay attention to any medical needs on their radar.

Dr. Fiorella was amazed at how quickly Annunziata expressed concern for his fellow veterans during his recovery.

“One of the first things he talked about was, ‘How can I use what happened to me to help other vets?’” Dr. Fiorella said.

Annunziata’s girlfriend Madrose, who is grateful that the procedure saved his life, said he “didn’t listen to me. He knew he had to do this. I kept saying, ‘When are you going to do it?’ He said, ‘I will, I will, I will.’ He learned the hard way.” She added that they both know he is “extremely lucky.”

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Daniel Knopf and Josephine Aller. Photo by John Griffin/Stony Brook University

By Daniel Dunaief

The ocean often serves as an enormous reflecting pool, showing a virtual image of migrating and water birds soaring on the wind, planes carrying people across continents, and clouds in multiple layers sporting various shades of white to grey.

Those clouds have more in common with the ocean below than just their reflection. In fact, some of the ice nucleating particles that help form the clouds come directly from the phytoplankton in the water below.

Daniel Knopf, Professor of Atmospheric Chemistry at Stony Brook University, and Josephine Aller, microbial oceanographer in the School of Marine and Atmospheric Sciences at Stony Brook University, have been teaming up to study the effect of sea spray aerosols on cloud formation in the ocean for 15 years.

Recently, the duo published a paper in the journal Science Advances, in which they simulated sea spray aerosols in laboratory tanks to reflect ocean conditions. They found that organic compounds released by marine microorganisms become ice nucleating particles.

“We performed ice formation experiments in our lab using particles generated from our tanks to determine under which conditions (of temperature and relative humidity) they form ice,” Knopf explained in an email. 

During specific temperature and relative humidity conditions, these sea spray aerosols, which are released when bubbles at the surface containing the materials burst or when wind carries them from the ocean into the air, initiate ice crystal formation.

Previous studies revealed that the water contains organic material from biological activity, but the researchers could not identify the specific type of nuclei.

“The current study closes this gap and identifies polysaccharides and proteinaceous matter” as the ice nucleating particles, Knopf explained.

Through work in the lab, Knopf and Aller showed that the particles produce ice crystals through two different pathways under typical atmospheric conditions. Ice can form either by water vapor onto the aerosolized particles or from liquid aerosol droplets.

From x-rays to climate models

Aller and Knopf explored the composition of individual particles using x-ray microscopy technology at the synchrotron light source at the Lawrence Berkeley National Laboratory in California. 

After digitally marking particles, the researchers transferred the particles to the x-ray microscope to determine their shape and composition.

“This allowed us to unambiguously examine the ice nucleating SSA particles and compare their organic signature with reference spectra of organic/ biogenic matter,” Knopf wrote.

Aller added that the research provides a clear picture of the conditions necessary for freezing.

“This study not only identifies the ice nucleating agent, but also provides the first holistic parameterization to predict freezing from SSA particles,” she said in a statement. “This new parameterization includes immersion freezing, as the INP is engulfed in a liquid, usually water, and the deposition ice nucleation where ice forms on the INP without any visual water.”

The parameterization can be applied in cloud-resolving and climate models to determine the climatic impact of ice crystal containing clouds, Aller added.

This type of modeling can help with climate models of the polar regions, which is heating at a rate faster than other parts of the world.

At this point, Knopf said the Stony Brook researchers have collaborated with scientists at NASA GISS who work on climate models to improve the understanding of mixed-phase clouds.

“We will make use of the newly developed ice formation parameterization in cloud-resolving models and compare the results to observations,” Knopf wrote. “Those results, ultimately, will be useful to improve climate models.”

Competition in the clouds

As for any surprises, Knopf added that it is “astonishing how biological activity in surface waters can be related to cloud formation in the atmosphere.” Additionally, he was amazed that the organic matter that nucleated the ice was similar independent of the water source.

Spectroscopically, the ice showed the same features, which allowed the researchers to combine the various data sets.

This means that different parts of the ocean do not need local freezing parameterization, which makes modeling the impact of oceans on cloud formation easier.

While sea spray aerosols can and do act as ice nucleating particles, the Stony Brook scientists added that other airborne particles also contribute to the formation of clouds. A heterogeneous mix of particles creates a competition among them for activation. Dust and certain fly ash serve as more efficient ice nucleating particles compared to sea spray aerosols.

During periods when sufficient water vapor is in the area, the sea spray aerosols can also be activated. When these organic particles do not become a part of clouds, they form supercooled droplets or float around as interstitial aerosols and get transported to other areas, Knopf explained.

As for the impact of global warming, Knopf suggested that such increases may first change the microorganisms’ activity and breakdown of chemical species in the ocean surface waters. “How this impacts the source of sea spray aerosols and ice nucleating particles, we do not know that yet,” he said.

The particular species of planktonic communities may change, as differences in nutrient levels could select for cyanobacteria over the normal mix of algal groups. That could cause a change in the exudates produced.

Locally, Knopf and Aller are working with Chris Gobler, Professor in the School of Marine and Atmospheric Sciences at Stony Brook, in Lake Agawam in Southampton, which is prone to harmful algal blooms. The Stony Brook scientists are working to understand if the toxins produced by these algae are becoming airborne in sufficient mass.

“It may imply a health-related issue when aerosolized and one is close to the source,” Knopf explained. “There won’t be toxic clouds due to dilution and aerosol mass constraints.”

Knopf and Aller hope to continue to develop these models by combining their lab work with field data.

“This is an ongoing process,” Knopf said. “The more data we acquire, the more accurate the parameterization should become.”

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Ke Jian Liu

By Daniel Dunaief

Ke Jian “Jim” Liu, who arrived at Stony Brook University in late July, plans to help build effective, interdisciplinary research teams.

Ke Jian Liu

Most recently at the University of New Mexico, Liu joins Stony Brook as a Professor in the Renaissance School of Medicine’s Department of Pathology and Associate Director of Basic Science at the Stony Brook Cancer Center.

“In my mind, Stony Brook, research wise, is outstanding,” Liu said in an interview. “The quality of the faculty is excellent.”

Liu will rely on the team building experience he honed while serving as Distinguished Professor in the Department of Pharmaceutical Sciences and Associate Dean for Research in the College of Pharmacy at the University of New Mexico. He also worked for eight years at Dartmouth Medical School, where he focused on developing larger collaborations.

“I really enjoy working with people and building teams,” Liu said.

In a note announcing Liu’s arrival, Kenneth Shroyer, chair in the Department of Pathology, recognized Liu’s multidisciplinary approaches in his research. Shroyer explained that Liu has used techniques ranging from chemical to biochemical to biophysical, and from the molecular and cellular level to animal models, to answer specific biological questions.

Shroyer wrote that Liu would focus on opportunities for grant development within several programs. 

At the Cancer Center, Liu said he plans to continue the effort to help Stony Brook earn National Cancer Institute designation.

To achieve that designation, Stony Brook will need to continue to provide outstanding medical care, demonstrate community engagement and highlight what makes Stony Brook different from everyone else, he said.

“It takes a village to do that,” Liu said.

He praised the efforts of current Cancer Center Director Yusuf Hannun, who recently announced his plans to step down as head of the center, triggering a nationwide search for a replacement.

Liu said an ideal candidate for that position would have clinical experience.

Player coach

With a busy research effort and lofty leadership goals, Liu explained that he’s able to tackle numerous challenges at once.

“I consider myself a player coach,” he said. “I enjoy research. I have my own research grant and am working with my students and post docs.”

Liu typically maintains a lab with five to six people at different levels. His research has two branches, cancer and stroke, that most people likely consider unrelated, but for which he has found connections.

“People always think, ‘Cancer is cancer and stroke is stroke and they are two entirely different diseases,” Liu  said. As a basic researcher, however, he looks at the cells and the molecules involved in both conditions.

“At a molecular level, a molecule doesn’t care where it is,” he said. “When a disease develops, the biological fundamental process is the same. For me, it’s interesting to look at [whether] certain processes that occur in the brain also occur in cancer.”

Liu’s cancer research focuses specifically on the molecular processes that become carcinogenic when metals like arsenic enter people’s bodies. A well-described poison in numerous murder mysteries, arsenic can contaminate drinking water, get incorporated into crops like rice, or can appear in fruit juices.

When metal enters the body, it doesn’t just cause damage everywhere. It has to find a certain molecular target with which to interact.

What Liu and researchers in his lab have discovered is that the target for arsenic is often the same pathways the body uses in zinc. A transition metal, zinc provides an important element as a part of transcription factors that are critical in biological processes.

Arsenic, however, replaces zinc, which is “one of the major mechanisms for carcinogenesis,” Liu said.

Fortunately for residents of Long Island, arsenic isn’t as prevalent as it is in the midwest and the southwest.

“Long Island doesn’t have too much arsenic in drinking water,” Liu said, although people are still exposed to it through fruit juices, rice and other products.

Arsenic also causes vascular disease issues and anemia. People who develop these other conditions in response to arsenic are also at higher risk to develop cancer. The specific types of cancers arsenic causes are lung, skin and bladder cancer.

“Arsenic is the dirty bomb” in the body as it creates multiple problems, Liu said. “Arsenic interacts with those key zinc molecules.” 

Overlap between stroke and cancer

In highlighting the overlaps between the two fields of research, Liu related how the brain has one of the highest concentrations of zinc in the body.

When people have strokes, their brain cells have oxidative stress, which causes a flood of zinc into the brain tissue that also damages cells.

“We are trying to understand how zinc is released and how zinc causes damage to the brain,” Liu said.

Stroke and cancer also have molecular overlaps regarding oxygen. In a stroke, a blood clot causes a blockage of blood flow. Without oxygen, a situation called hypoxia, neurons start to die.

By contrast, a tumor grows in a hypoxic environment, using energy from sugars like glucose, rather than relying on oxygen for its growth.

Liu emphasized the importance of continuing to provide oxygen to brain regions around a clot even before trying to remove the clot or restore blood flow.

A goal for his 100th year

Originally from Beijing, China, Liu and his wife Jiao Ding enjoy traveling. Their daughter Sarah Liu is a resident at Vermont Medical Center and their son Evan Liu is a PhD student at Stanford.

An avid tennis player who plays the sport at least twice a week, Liu is looking forward to attending his first U.S. Open next year.

He and his former tennis partner in New Mexico joked that their goal is to be in the top 20 in the United States when they are 100 years old.

Liu chose the American name “Jim” because it sounds similar to the second syllable of his given name, Ke Jian.

“If people can’t pronounce your name, they shy away,” he said. He believes it’s important to “make yourself adaptable.”

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Arkarup Banerjee. Photo ciourtesy of CSHL

By Daniel Dunaief

Brain cells don’t always have easily discovered roles, the way various instruments do in an orchestra.

Sometimes, different cells share a function, making it possible to perform various tasks or to process information from the environment, while other times, different cells play their own part in making it possible for an organism to optimize its circuitry to act and react on the world.

So it is for the tufted and mitral cells of land based vertebrates, which are part of the olfactory system, sending signals to the brain about the odors and triggering thoughts about moving towards a desired food or away from the scent of a predator. In many studies, the names have been used interchangeably, as scientists were not sure how to separate them.

Florin Albeanu. Photo courtesy of CSHL

Researchers have spent considerable time studying mitral cells, which project into a region of the brain called the piriform cortex. These cells are nicely organized into one layer, which makes them easy to identify and are bigger in size compared to tufted cells.

Mitral cells, which have been the celebrated stars of the olfactory system, are easier to see and sort out than their nasal cousins, the tufted cells which, by contrast, are slightly smaller.

Recently, two scientists at Cold Spring Harbor Laboratory, Florin Albeanu, an Associate Professor, and Arkarup  Banerjee, an Assistant Professor, published a study that suggested there’s more than meets the eye, or, maybe, the nose, with these tufted cells.

Tufted cells, it turns out, are better at recognizing smells than mitral cells and are critical for one of two parallel neural circuit loops that help the brain process different odor features, according to a study the scientists published in the journal Neuron at the end of September.

“People had assumed mitral cells were very good at” differentiating odor, but “tufted cells are better,” Albeanu said. “How they interact with each other and what the mitral cells are computing in behaving animals remains to be seen.”

Albeanu and Arkarup, who had performed his PhD research in Albeanu’s lab before returning to CSHL in 2020, exposed mice to different odors, from fresh mint to bananas and at different concentrations. They chose these compounds because there are no known toxic effects. The scientists also screened for compounds that elicited strong responses on the dorsal surface of the olfactory bulb that they could access using optical imaging tools.

It is hard to distinguish mitral and tufted cells when doing recordings. Optical imaging, however, enabled them to see through layers and shapes, if they were recording activity in a particular type of cell.

So, Albeanu asked rhetorically, “why is this exciting?”

As it turns out, these two types of cells project to different regions of the brain. Mitral cells travel to the piriform cortex, while tufted cells travel to the anterior olfactory nucleus.

It appears at this point that tufted cells are more likely to share information with other tufted cells, while mitral cells communicate with other mitral cells, as if the olfactory system had two parallel networks. There may yet be cross interactions, Albeanu said.

Mitral cells may be part of a loop that helps enhance and predict smells that are important for an animal to learn. Tufted cells, however, appear superior to mitral cells in representing changes in odor identity and intensity. By flagging the tufted cells as sources of olfactory information, the researchers were able to suggest a different combination of cells through which animals detect smells.

“A large fraction of people in the field would expect that mitral cells and the piriform complex are representing odor identity more so than the tufted cells and the anterior olfactory nucleus, so this is the surprise,” Albeanu explained in an email. Thus far, the reaction in the research community has been positive, he added. 

Throughout the review process, the researchers encountered natural skepticism.

“It remains to be determined how the findings we put forward hold when mice are engaged in odor trigger behavior” as odors are associated with particular meaning such as a reward, an lead to specific actions,” Albeanu explained. “This is what we are currently doing.”

Albeanu added that a few different streams of information may be supported by tufted and mitral cells, depending on the needs of the moment.

Arkarup Banerjee. Photo ciourtesy of CSHL

The study that led to this work started when Banerjee was a PhD student in Albeanu’s lab. Albeanu said that a postdoctoral fellow in his lab, Honggoo Chae, provided complementary work to the efforts of Banerjee in terms of data acquisition and analysis, which is why they are both co-first authors on the study.

For Banerjee, the work with these olfactory cells was an “echo from the past,” Albeanu added. 

As for where the research goes from here, Albeanu said future questions and experiments could take numerous approaches.

Researchers are currently looking for markers or genes that are expressed specifically and differentially in mitral or tufted cells and they have found a few potential candidates. While some markers have been found, these do not sharply label all mitral only versus all tufted cells only.

One of the confounding elements to this search, however, is that these cells have subtypes, which means that not every mitral cell has the same genetic blueprint as other mitral cells.

Another option is to inject an agent like a virus into the piriform cortex and assess whether boosting or suppressing activity in that region in the midst of olfaction alters the behavioral response.

Additionally, researchers could use tools to alter the activity of neurons during behavior using optogenetic approaches, inducing or suppressing activity with cell type specificity and millisecond resolution.

Albeanu would like to test speculation about the roles of these cells in action, while a mice is sampling smells he presents.

By observing the reactions to these smells, he could determine an association between rewards and punishment and anything else he might want to include.

The upshot of this study, Albeanu said, is that an objective observer would have much less trouble extracting information about the identity and intensity of a smell from a tufted cell as compared with a mitral cell.

Tufted cells had been “slightly more mysterious” up until the current study.

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Mercy Baez. Photo by Joseph Rubino/ BNL

By Daniel Dunaief

She is a greeter, a corporate concierge, a facilitator, a point of contact for people traveling thousands of miles, a Spanish translator, an important contact in case of emergencies, and whatever else visitors need.

While Mercy Baez, who was promoted to User Program Coordinator for the National Synchrotron Lightsource II and the Laboratory for BioMolecular Structure at Brookhaven National Laboratory early in October, wears many hats, one of the only ones she doesn’t wear is scientist, although that doesn’t keep her from appreciating and taking pride in the research conducted at the Department of Energy facility.

“We’re helping them and they are helping the world,” Baez said.

BNL has a steady stream of users who apply for time at the various research facilities at the national laboratories. 

Baez is specifically responsible for providing a wide range of support and services to the NSLS II and the LBMS. Users, which is how BNL describes potential visiting scientists who conduct research at the lab’s facilities, submit proposals to her office, which then distributes them to a proposal review panel.

When visiting scientists learn that their work, which includes monitoring batteries as they function and searching for fine structural sites in the molecular battle against pathogens, has earned a high enough score to receive coveted time on the lab’s instruments, they prepare for their visit by interacting with Baez and her current team of four by getting registered and approved for access.

Baez offers soup to nuts guidance that often also includes helping users literally find soup, nuts and numerous other items. Baez ensures that users take any necessary training courses, provides guidance regarding registering for on site access to BNL, provides information on the steps or items necessary when they arrive, helps find nearby hotels, coordinate travel to and from the lab and, if necessary, secures places to stay if they miss their planes, get snowed in or have other unforeseen changes in their schedules.

As of October 1st, visitors also have to have some type of active shooter training to access the lab’s facilities. Currently, users are required to take five training courses. Last week, the lab decided to incorporate active shooter training into one of these other training courses.

The lab has always had routine emergency training courses and drills for lab employees. With the changing times and current events, the lab is looking to equip users for such emergencies. The lab hopes never to have to use this training, but if such an event occurs, staff and users will know how to handle such a situation.

In addition to training to help users prepare to visit the facility, Baez provides visitors with a host of on site facilities, including adaptors in case they are using European electronics that don’t connect with the outlets, laptops in case the computer a scientist brought isn’t working, conference rooms for impromptu meetings, and dorm rooms for a respite while running time-intensive experiments.

BNL hosts employee resource groups including the African American Advancement Group, the Asian Pacific American Association, the Brookhaven Veterans Association, Brookhaven Women in Science, the Early Career Resource Group, the Pride Alliance and the Hispanic Heritage Group. Baez said the lab tries to involve users and visitors in as many cultural and social events as possible, which include outings to dinners, plays and cultural virtual cooking classes.

In September, Baez participated in the Port Jefferson Dragon Boat Race Festival which the Asian Pacific  American Association sponsored. 

Baez, whose mother is from Puerto Rico and whose father is from Ecuador, is a member of the Hispanic Heritage Group.

A people person

A member of the user offices since 2003, Baez had recently been responsible for coordinating conferences, workshops, and training courses, including financial and logistical aspects of the events for NSLS-II and the LBMS. She had been functioning as the user program coordinator since January, when Gretchen Cisco retired. Baez feels fortunate to have worked with Cisco since she joined NSLS in 2005.

A self-described “people person,” Baez said she loves the opportunity to interact with scientists from all over the world. She particularly appreciates the chance to get to know about other cultures and has added destinations to her travel itinerary from speaking with visitors. She is hoping to travel to Morocco and Peru next year and is hoping to travel to Japan and a few other countries in the near future.

Coming from a Latina family that tends to be loud and outspoken and whose family gatherings often includes more than 30 people, she has learned to speak in a softer voice, particularly with people from other cultures or backgrounds.

She also has a tendency to speak quickly and has learned to slow the pace down so visitors who haven’t interacted with her can understand what she’s saying.

A resident of Medford, which is a ten-minute drive from the lab, Baez has a son Xzavier and a granddaughter Francesca. She is excited for the upcoming arrival of her second granddaughter in November.

When she’s not at the lab, she uses her leisure time to go hiking, fishing and camping.

With her then teenage son in tow, she went to the jungle of Belize for a survival course, where they learned how to catch their own food, build shelters, and harpoon fish. She also learned which plants are safe to eat and which are poisonous.

While her work responsibilities can be hair-raising, particularly in emergencies, she “loves the feeling that I was able to help a scientist, whether to get him or her on site or in an emergency,” she said. Knowing that she’s a part of making all this science happen makes her day and job rewarding, she said.

Baez has had some requests from scientists who have wanted cultural foods, such as Turkish or vegan dishes, that might be harder to find, particularly during off hours.

Around Thanksgiving each year, some visitors have asked if they can hunt wild turkeys at BNL, which is located within the Pine Barrens and has turkeys and deer wandering on site. She has told those users that the lab does not allow hunting.

Hunting aside, Baez said she is “here to help [users] do what they need to do.”

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From left, K. Barry Sharpless and John Moses. Photo from CSHL

By Daniel Dunaief

K. Barry Sharpless changed John Moses’s life. And that’s before Moses even started working as a postdoctoral researcher in Sharpless’s lab.

When Moses, who is the first chemist to work at Cold Spring Harbor Laboratory in its 132-year history, was earning his PhD in chemistry at Oxford, he read an article that Sharpless co-authored that rocked his world.

Nicknamed the “click manifesto” for introducing a new kind of chemistry, the article, which was published in Angewandte Chemie in 2001, was “one of the greatest I’ve ever read,” Moses said, and led him to alter the direction of his research.

Moses walked into the office of the late chemist Sir Jack Baldwin at Oxford, who was Moses’s PhD advisor, and announced that Sharpless, a colleague of Baldwin’s at the Massachusetts Institute of Technology, was the only chemist he wanted to work with in the next phase of his career.

Baldwin looked at Moses and said, in a “very old-fashioned gangster English, ‘That shows you’ve got some brains,’” recalled Moses.

Sharpless was important not only to Moses’s career, but also to the world.

Recently, Sharpless, who is the W.M. Kepp Professor of Chemistry at Scripps Research, became only the fifth two-time recipient of the Nobel Prize.

Sharpless will share the most recent award, which includes a $900,000 prize, with Carolyn R. Bertozzi, the Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences at Stanford University, and Morten P. Meldal, professor at the University of Copenhagen, for the invention of a type of chemistry that has implications and applications from drug discovery and delivery, to making polymers, to developing anti cancer treatments.

The way click chemistry works is that chemists bring together catalysts and reagents, often attached to sulfur or carbon, that have a high level of specific attraction for each other. The click is like the sound a seat belt makes when secured, or the click a bike helmet lock makes when the two units are connected.

Scientists have often described the click reaction as being akin to LEGO blocks coming together, with an exact and durable chemical fit.

Natural product synthesis is generally challenging and often requires complex chemistries that are not always selective. This type of chemistry can produce side reactions that create unwanted byproducts and require purification.

Click reactions, by contrast, are selective and reliable and the products are generally easy to purify. Sometimes, purification is as simple as a water wash.

“It’s a democratization of synthetic chemistry,” Moses said.

Moses said biologists have performed click reactions. Chemists have developed click tablets that can be added to a reaction to create a plug and play system.

Moses described the reactions in click chemistry as “unstoppable” and suggested that they are part of a “domino rally” in which a latent build up of reactivity can create desired products with beneficial properties.

Moses, who arrived at CSHL in 2020, has collaborated with several researchers at the famed lab. He is submitting his first collaborative paper soon with Dr. Michael Lukey, who also started in 2020 and performed his PhD at Oxford, and Dr. Scott Lyons. He is also working on a New York State Biodefense funded project to create shape shifting antibiotics that can keep up with drug resistance pathogens. 

He has collaborated with Cancer Center Director David Tuveson to develop a new ligand to target a protein important in pancreatic cancer. Moses said they have a “very exciting” lead compound.

Early resistance

While the Nobel Prize committee recognized the important contribution of this approach, the concept met with some resistance when Sharpless introduced it.

“When [Sharpless] submitted this, the editor called colleagues and asked, ‘Has Barry gone crazy?’” Moses said.

Some others in the field urged the editor to publish the paper by Sharpless, who had already won a Nobel Prize for his work with chirally catalyzed oxidation reactions.

Still, despite his bona fides and a distinguished career, Sharpless encountered “significant resistance” from some researchers. “People were almost offended by it” with some calling it “old wine in new bottles,” Moses said.

In 2007, Moses attended a faculty interview at a “reasonably good” university in England,. where one of his hosts told him that click chemistry is “just bulls$#t!”

Moses recognized that he was taking a risk when he joined Sharpless’s lab. Some senior faculty advised him to continue to work with natural product synthesis.

In the ensuing years, as click chemistry produced more products, “everyone was using it and the risks diminished quickly,” Moses added.

Unique thought process

So, what is it about Sharpless that distinguishes him?

Moses said Sharpless’s wife Janet Dueser described her husband as someone who “thinks like a molecule,” Moses said.

For Moses, Sharpless developed his understanding of chemistry in a “way that I’ve never seen anyone else” do.

Moses credits Dueser, who he described as “super smart,” with coining the term “click chemistry” and suggested that their partnership has brought together his depth of knowledge with her ability to provide context.

Moses believes Sharpless “would admit that without [Dueser], his career would have been very different! In my opinion, [Dueser] contributed immeasurably to click chemistry in so many ways.”

Indeed, click chemistry won a team prize from the Royal Society of Chemistry last year in which Dueser was a co-recipient.

As for what he learned from working with a now two-time Nobel Prize winner, Moses said “relinquishing control is very powerful.”

Moses tells his research team that he will never say “no” to an innovative idea because, as with click chemistry, “you never know what’s around the corner.”

Moses said Sharpless is a fan of the book “Out of Control” by Kevin Kelly, the co-founder of Wired Magazine. The book is about the new biology of machines, social systems and the economic world. Sharpless calls Kelly “Saint Kevin.”

On a personal level, Sharpless is “humble and a nice person to talk to” and is someone he would “want to go to a pub with.”

Moses believes Sharpless isn’t done contributing to chemistry and the world and anticipates that Sharpless, who is currently 81 years old, could win another Nobel Prize in another 20 years.

An inspirational scientist, Sharpless ” is “that kind of person,” Moses said.

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Peter Westcott, on right, in the lab with technicians Zakeria Aminzada, on left and Colin McLaughlin, center. Photo by Steven Lewis

By Daniel Dunaief

When Peter Westcott was growing up in Lewiston/Auburn, Maine, his father Johnathan Harris put the book “Human Genome” on his bed. That is where Westcott, who has a self-described “obsessive attention to detail,” first developed his interest in biology.

Westcott recently brought that attention to detail to Cold Spring Harbor Laboratory, where he is an assistant professor and Cancer Center member. He, his wife Kathleen Tai and their young children Myles and Raeya moved from Somerville, Massachusetts, where Westcott had been a postdoctoral fellow at the Koch Institute of Integrative Cancer Research at the Massachusetts Institute of Technology.

Westcott will take the passion and scientific hunger he developed and honed to the famed lab, where he plans to continue studies on colon cancer and the immune system.

“A lot of things attracted me to Cold Spring Harbor Laboratory,” said Westcott who had been to the lab during conferences, joining three Mechanisms and Models of Cancer meetings, and appreciated that the small size of the lab encourages collaboration and the sharing of ideas across disparate fields.

At this point, Westcott, who purchased a home in Dix Hills and started on campus on September 1st, has two technicians, Zakeria Aminzada and Colin McLaughlin working with him. He will be taking on a graduate rotation student from Stony Brook University soon and would also like to add a postdoctoral researcher within about six months. He plans to post ads for that position soon. 

Research directions

Westcott said his research has two major research directions.

The first, which is more translatable, involves looking at how T cells, which he described as the “major soldiers” of the immune system, become dysfunctional in cancer. These T cells balance between attacking unwanted and unwelcome cells relentlessly, disabling and destroying them, and ignoring cells that the body considers part of its own healthy system. When the T cells are too active, people develop autoimmunity. When they aren’t active enough, people can get cancer.

“Most cancers, particularly the aggressive and metastatic ones, have disabled the immune response in one way or another, and it is our focus to understand how so we can intervene and reawaken or reinvigorate it,” he explained.

During cancer development, T cells may recognize that something on a tumor is not healthy or normal, but they sometimes don’t attack. Depending on the type of genetic program within the T cells that makes them tolerant and dysfunctional, Westcott thinks he can reverse that.

A big push in the field right now is to understand what the genetic programs are that underlie different flavors of dysfunction and what cell surface receptors researchers can use as markers to define T cells that would allow them to identify them in patients to guide treatment.

Westcott is taking approaches to ablate or remove genes called nrf4a 1, 2 and 3. He is attacking these genes individually and collectively to determine what role they play in reducing the effectiveness of the body’s immune response to cancer.

“If we knock [some of these genes] out in T cells, we get a better response and tumors grow more poorly,” he said.

Westcott is exploring whether he can remove these genes in an existing T cell response to cause a regression of tumor development. He may also couple this effort with other immunotherapies, such as vaccines and agonistic anti-CD40 antibody treatment.

As a second research direction, Westcott is also looking more broadly at how tumors evolve through critical transitions. Taking an evolutionary biology perspective, he hopes to understand how the tumors start out as more benign adenoma, then become malignant adenocarcinoma and then develop into metastatic cancer. He is focusing in particular on the patterns of mutations and potential neoantigens they give rise to across the genome, while concentrating on the immune response against these neoantigens.

Each tumor cell is competing with tumor cells with other mutations, as well as with normal cells. “When they acquire new mutations that convey a selective advantage” those cells dominate and drive the growth of a tumor that can spread to the rest of the body, Westcott said.

Using a mouse model, he can study tumors with various mutations and track their T cell response.

T cells tend to be more effective in combating tumors with a high degree of mutations. These more mutated tumors are also more responsive to immunotherapy. Westcott plans to study events that select for specific clones and that might shift the prevalence, or architecture, of a tumor.

Some of the work Westcott has done has shown that it is not enough to have numerous mutations. It is also important to know what fraction of the cancer cells contain these mutations. For neoantigens that occur in only a small fraction of the total cells in the tumor, the T cell responses aren’t as effective and checkpoint blockade therapy doesn’t work.

He wants to understand how the T cell responses against these neoantigens change when they go from being subclonal “to being present in most or all of the tumor cells,” he explained. That can occur when a single or few tumor cells acquire a selective advantage. His hypothesis is that these selective events in tumor progression is inherently immunogenic. \

By exploring the fundamental architecture of a tumor, Westcott hopes to learn the mechanisms the tumor uses to evade the immune system.

Ocean breeze

As Westcott settles in at CSHL, he is excited by the overlap between what he sees around the lab and the Maine environment in which he was raised.

“Looking out the window to the harbor feels like New England and Maine,” he said. “It’s really nostalgic for me. Being near the ocean breeze is where I feel my heart is.”

Before his father shared the “Human Genome” book with him, Westcott was interested in rocks and frogs. In high school, his AP biology teacher helped drive his interest in the subject by encouraging discussions and participation without requiring her students to repeat memorized facts. The discussions “brought to life” the subject, he said.

As for his work, Westcott chose to study colon cancer because of its prevalence in the population. He also believes colon cancer could be a model disease to study all cancers. By understanding what differentiates the 12 percent of cases that are responses to immunotherapy from the remainder that don’t respond as well to such approaches, he hopes to apply these lessons to all cancer.

“There is a huge, unmet need,” he said.

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