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Power of 3

By Daniel Dunaief

This is part 2 of a two-part series.

Cancers not only compromise human health, but they can also suppress the body’s immune response. A little studied small protein called cystatin C, which is secreted by numerous cells, may render the immune system less effective in its response to tumors.

Sam Kleeman, a PhD student in Cold Spring Harbor Laboratory Assistant Professor Tobias Janowitz’s lab, recently published results in the journal Cell Genomics that demonstrate a link between elevated levels of this protease inhibitor, the suppression of the immune system, and the development of cancer.

Kleeman was able to demonstrate a potential role “Cystatin C might play in damping down the immune response to tumors,” he said.

Cystatin C is a known cysteine protease inhibitor, but the biological and organ-level relevance of this has not been characterized in detail. This protein could be one of many mechanisms by which glucocorticoids can reduce the effectiveness of the immune system.

Cystatin C could drive the progression of the disease, which could explain why Kleeman has found evidence that higher levels coordinate with worse outcomes.

Starting with the data

Pursuing an interest in data- driven research, Kleeman, who has a Bachelor of Medicine and Surgery from New College at the University of Oxford, searched the UK Biobank, which provides health data for numerous people in the United Kingdom. 

In this Biobank, Kleeman, who joined Cold Spring Harbor Laboratory in August of 2020, found that cystatin C was the best prognostic indicator of cancer deaths.

“I was a little surprised by this,” Kleeman said as he had heard of cystatin C as a marker of kidney function, but was not aware of any association with cancer mortality. Some studies had found evidence for this previously, but those were in small cohorts and were poorly understood, he explained.

A healthy kidney clears most proteins quickly, pumping it out into urine. A kidney that’s not functioning optimally, however, allows it to accumulate.

In his research, Kleeman removed cystatin C selectively in cancer cells, causing the tumors to grow more slowly. The main changes in the architecture of the tumor was that it reduced the frequency of macrophages with expression of a protein called Trem2. While the exact mechanism is not known, it’s likely that immune control of the tumor increases without cystatin C.

Kleeman also demonstrated a similar effect on the connection between levels of Covid-19 and mortality in a paper published in iScience.

The biological mechanism explaining the correlation is nuanced. Patients with higher levels of glucocorticoids can be associated with poor outcomes. It is not a simple relationship, he said, which makes causality difficult to assess.

Kleeman believes cystatin C secretion in response to glucocorticoids has context dependency. Not all cells posses inducible cystatin C secretion.

The research primarily found that only macrophages and cancer cells can secrete cystatin C in response to glucocorticoids.

He describes a “two hit” model, by which glucocorticoids plus an inflammatory stimulus recruit macrophages. The model applies to all inflammatory stores, but is co-opted in the case of cancer.

At this point, drugs aren’t available to inhibit or reduce cystatin C. Instead, Kleeman suggested that a viable research target route might involve creating a specific antibody.

Some researchers have created so-called knockout mice, which don’t have this protein. These mice can survive without it, although eliminating all cystatin C creates other problems.

Kleeman speculated that the protein could play a role in preventing significant immune reaction against sperm.

Indeed, this protein is secreted at high levels in the testes. Males without it have lower sperm function and production.

Kleeman hopes this work acts as a starting point to understand the mechanism better by which glucocorticoids modify immune response to cancer, and to investigate cystatin C as a possible therapeutic target.

Long standing partnership

As an undergraduate, Kleeman took a class with Janowitz, which kicked off a mentorship that now spans two continents.

Kleeman appreciates the comfort level Janowitz has in working on higher-risk, higher-reward topics or on ideas that haven’t already attracted considerable attention from other scientists.

“There’s a tendency in science towards group think,” Kleeman said. In the history of medicine and science, many widely accepted theories turn out to be wrong. “Patients undoubtedly benefit from a diversity of thought in science and medicine,” he explained.

When he completes his PhD, Kleeman said it would be a “dream to have a dual appointment” in which he could conduct research and work in the clinic with patients. To get there, he knows he needs to establish his research profile that includes a genuine track record of achievement while demonstrating that he can function as a reliable and effective clinician.

Kleeman’s thesis research lies outside the field of cystatin C, which started out as a curiosity and developed into the recent publication. He wanted to “understand what UK Biobank could teach us about cancer patients.” With Janowitz and Cold Spring Harbor Laboratory Professor Hiro Furukawa, Kleeman is working to understand how a specific type of cancer could cause an auto-immune disease.

A resident of Forest Hills, Kleeman lives about 45 minutes from the lab. Outside of work, he enjoys visiting national parks. He has visited 10 so far, including Yosemite National Park, Zion and Rocky Mountain National Park. 

Professionally, Kleeman feels it is a privilege to be a PhD student. He appreciates that he can explore his interests without too many restrictions and is eager to make the most of the opportunity.

From left, Sam Kleeman, Assistant Professor Tobias Janowitz, Miriam Ferrer Gonzalez and Emma Davidson. Photo by Caryn Koza/CSHL

By Daniel Dunaief

This part one of a two part series.

It’s a bit like shaking corn kernels over an open flame. At first, the kernels rustle around in the bag, making noise as they heat up, preparing for the metamorphosis.

That’s what can happen in any of the many laboratories scattered throughout Long Island, as researchers pursue their projects with support, funding and guidance from lab leaders or, in the science vernacular, principal investigators.

Sometimes, as happened recently at the benches of Cold Spring Harbor Laboratory Assistant Professor Tobias Janowitz, several projects can pop at around the same time, producing compelling results, helping advance the careers of developing scientists and leading to published papers.

PhD graduate Miriam Ferrer Gonzalez and MD/ PhD student Sam Kleeman recently published separate studies.

In an email, Janowitz suggested the work for these papers is “time consuming and requires a lot of energy.” He called the acceptance of the papers “rewarding.” 

In a two-part series, Times Beacon Record News Media will describe the research from each student. This week, the focus is on Ferrer Gonzalez. Check back next week for a profile of the work of Kleeman.

Miriam Ferrer Gonzalez

Miriam Ferrer Gonzalez. Photo by Caryn Koza/CSHL

Miriam Ferrer Gonzalez was stuck. She had two results, but couldn’t seem to figure out how to connect them. First, in a mouse model of the ketogenic diet — heavy on fats, without including carbohydrates —cancer tumors shrunk. That was the good news.

The bad news, which was even more pronounced than the good, was that this diet was not only starving the tumors, but was triggering an earlier onset of cachexia, in which bodies weaken and waste away. The cachexia overpowered the mice, causing them to die sooner than if they had a normal diet.

Ferrer, a student in residence from Spain who was conducting her research at Cold Spring Harbor Laboratory while earning her PhD at the University of Cambridge in the UK, thought the two discoveries were paradoxically uncoupled. A lower tumor burden, she reasoned, should have been beneficial.

In presenting and discussing her findings internally to the lab group, Ferrer received the kind of feedback that helped her hone in on the potential explanation.

“Finding out the mechanism by which a ketogenic diet was detrimental for both the body and the cancer was the key to explaining this uncoupling,” Ferrer explained.

The adrenal glands of mice fed a ketogenic diet were not producing the necessary amount of the hormone corticosterone to sustain survival. She validated this broken pathway when she discovered higher levels of corticosterone precursors that didn’t become functional hormones.

To test this hypothesis, she gave mice dexamethasone, which boosted their corticosterone levels. These mice had slower growing tumors and longer lives.

Ferrer recently published her paper in the journal Cell Metabolism.

To date, the literature on the ketogenic diet and cancer has been “confusing,” she said, with studies that show positive and negative effects.

“In our study, we go deeper to explain the mechanism rather than only talking about glucose-dependency of cancer cells and the use of nutritional interventions that deprive the tumor of glucose,” said Ferrer. She believed those factors are contributing to slower tumor growth, but are not solely responsible.

Thus far, there have been case studies with the ketogenic diet shrinking tumors in patients with cancer and, in particular, with glioblastoma, but no one has conducted a conclusive clinical trial on the ketogenic diet.

Researchers have reported on the beneficial effects of this diet on epilepsy and other neurological diseases, but cancer results have been inconclusive.  For the experiments in Janowitz’s lab, Ferrer and technician Emma Davidson conducted research on mouse models.

Ferrer, who is the first author on the paper, has been working with this system for about four years. Davidson, who graduated from the College of Wooster in Ohio last year and is applying to MD and MD/PhD programs, contributed to this effort for about a year.

Next steps

From left, Emma Davidson, Assistant Professor Tobias Janowitz, Sam Kleeman and Miriam Ferrer Gonzalez. Photo by Caryn Koza/CSHL

Now that she earned her PhD, Ferrer is thinking about the next steps in her career and is considering different institutions across the country. Specifically, she’s interested in eating behavior, energy homeostasis, food intake and other metabolic parameters in conditions of stress. She would also like to focus on how hormonal cycles in women affect their eating behavior.

Originally from a small city in Spain called Lleida, which is in the western part of Catalonia, Ferrer appreciated the opportunity to learn through courses and conferences at Cold Spring Harbor Laboratory.

Until she leaves the lab in the next few months, Ferrer plans to work with Davidson to prepare her to take over the project for the next year.

The follow up experiments will include pharmacologically inducing ferroptosis of cancer cells in mice fed a ketogenic diet. They hope to demonstrate that early induction of ferroptosis, or a type of programmed cell death, prevents tumor growth and prevents the tumor-induced reprogramming of the rest of the body that causes cachexia.

These experiments will involve working with mice that have smaller and earlier tumors than the ones in the published paper. In addition, they will combine a ketogenic diet, dexamethasone and a ferroptosis inducing drug, which they didn’t use in the earlier experiments.

Janowitz has partnered with Ferrer since 2018, when she conducted her master’s research at the University of Cambridge. As the most senior person in Janowitz’s lab, Ferrer has helped train many of the people who have worked in his lab. She has found mentoring rewarding and appreciates the opportunity to invest in people like Davidson.

Ferrer, who is planning a wedding in Spain in September, is a fitness and wellness fan and has taken nutrition courses. She does weight lifting and running.

Ferrer’s parents don’t have advanced educational degrees and they supported their three children in their efforts to earn their degrees.

“I wanted to be the best student for my parents,” said Ferrer, who is the middle child. She “wanted to make my parents proud.

The hand off

Emma Davidson and Miriam Gonzalez Ferrer examine an adrenal gland sample section from a cachectic mouse. Photo by Caryn Koza/CSHL

For her part, Davidson is looking forward to addressing ways to implement further treatment methods with a ketogenic diet and supplemental glucocorticoids to shrink tumors and prevent cachexia. 

Davidson appreciated how dependable Ferrer was during her time in the lab. Just as importantly, she admired how Ferrer provided a “safe area to fail.”

At one point, Davidson had taken all the cells she was planning to use to inject in mice. Ferrer reminded her to keep some in stock.

“Open lines of communication have been very beneficial to avoid more consequential failures,” Davidson said, ”as this mistake would have been.”

Davidson developed an interest in science when she took a high school class called Principles in Biological Science and Human Body Systems. When she was learning about the cardiovascular system, her grandfather had a heart attack. In speaking with doctors, Davidson acted as a family translator, using the language she had studied to understand what doctors were describing.

Like Ferrer, Davidson lives an active life. Davidson is preparing for the Jones Beach Ironman Triathlon in September, in which she’ll swim 1.2 miles, bike 56 miles and run a half marathon. She plans to train a few hours during weekdays and even more on weekends for a competition she expects could take about six hours to complete.

Davidson started training for these events with her father Mark, an independent technology and operations consultant and owner of Exoro Consulting Group.

Longer term, Davidson is interested in medicine and research. After she completes her education, she will try to balance between research and clinical work.

 

Above, a photo of Turkana taken from a single engine plane shows the Koobi Fora spit and Lake Turkana alongside a time map. Photo from Bob Raynolds

By Daniel Dunaief

In a wide-ranging interview, Louise Leakey, Director of Public Education and Outreach for the Turkana Basin Institute and a Research Professor in the Department of Anthropology at Stony Brook University shared her thoughts on numerous topics in the field of paleontology.

Louise Leakey at the Richard Leakey Memorial Conference on June 5. Photo by John Griffin/SBU

Leakey, who earned her PhD at the University College London, suggested that the process of finding fossils hasn’t changed that much, although other options beyond scouring a landscape for fragments of the world’s former occupants may be forthcoming.

“It may very well change if we can implement machine learning with high resolution imagery, using drones,” she said. “That’s one of the things we’re looking at the moment.”

What’s really changed, however, is the accuracy field scientists have in marking where, and, importantly, when new discoveries originated, she said.

Geologists like Bob Raynolds, Research Associate at the Denver Museum of Nature & Science, have created time maps that indicate the approximate age of sediments around a fossil in some select areas of the Turkana Basin.

These maps “can be uploaded onto an iPad app for use in the field that shows you in real time where you are on the geological map,” Leakey explained. “This is a game changer for field work in the basin.”

A time map created by Bob Raynolds in collaboration with Geologic Data Systems, a Littleton, Colorado company.

The maps represent the work of many people, Raynolds explained.  Originally, teams of Master’s students used air photographs, tracing paper and ink to make a map. These students spent many weeks walking systematically on the ground and tracing the patterns on the photos.

The rugged and isolated nature of the ground in Northern Kenya makes the work done on foot difficult, Raynolds explained.

The original maps, which were made in the 1970’s, took months to make and were presented as paper copies in unpublished Master’s theses. After numerous enhancements, Raynolds, working with companies including Geologic Data Systems in Littleton, Colorado, created time maps.

The internal GPS on an iPhone enables a blue dot to indicate a person’s location on the map.

“I have worked on the maps to make a new set of derived products that are maps of the age of the rocks,” said Raynolds who created these time maps earlier this year. “The resolution of the time maps is 100,000 years” which is an “astonishingly detailed resolution for us who are accustomed to million year packages of time.”

The maps cover the entire Turkana Basin at various scales, Raynolds added.

More broadly, Bernard Wood, University Professor of Human Origins in the Center for the Advanced Study of Human Paleontology at George Washington University and the first speaker at a recent Stony Brook University conference to honor Richard Leakey, explained that dating fossils has become increasingly accurate.

The first dates of fossils in the KBS Tuff, which is an ash layer in the Koobi Fora Formation east of Lake Turkana, was estimated within 260,000 years of a specific date. Using improved methods, a study published this year has reduced that range to 600 years.

Publishing pace

In the meantime, the pace of publishing has slowed considerably.

“There’s so much more material” that can serve as a frame of reference for new discoveries, Leakey said. “The rate of publication is frustratingly slow for some of these specimens.” This contrasts dramatically with the experience of Leakey’s father Richard.

When the elder Leakey submitted his letters or paper to the prestigious journal Nature, the late editor John Maddox never sent them out for review. “[Maddox] explained that he couldn’t see the point, because they concerned fossils so recently discovered” that few had seen them, Wood explained in his presentation.

Louise Leakey also differed from Richard in earning her bachelor’s degree and PhD, while her father dropped out of high school and never received any additional formal education.

Wood suggested that, next to marrying Meave, the elder Leakey described leaving school as one of the best decisions he’d ever made.

For his daughter, though, Leakey “encouraged me to go and do that,” Louise Leakey said. The education helped “in terms of being able to be [principal investigator] on grant applications,” she said.

Leakey suggested it was a “real privilege to be able to spend time” earning her PhD. She also found that the educational experience gave her the opportunity to “stand on my own two feet” in her research.

Like her father, Louise Leakey is concerned about conservation and declining biodiversity. When she was younger, she saw areas that were teeming with wildlife. On a recent three-hour drive, she only saw a golden jackal and a dik-dik, which is a type of small antelope, compared with the much wider variety of creatures she would have seen decades ago, such as Grévy’s zebra, Burchell zebra, lesser kudu, ostriches, warthogs, topi, gerenuk, oryx and, possibly lions and cheetah. 

She attributes this decline to hunting as some have exterminated these species as result of competition for grazing areas and hunting the animals for meat. Record droughts are also threatening their survival.

Leakey is working with the next generation to get “kids to care about nature” so they can “think about what they’re doing and the real impact it has.”

In addition to preserving biodiversity, Leakey remains passionate about studying the past, which could help the current and future generations tackle climate change. “We might be able to learn lessons” from those who survived during such challenging conditions, she said.

Leakey is able to maintain her involvement and commitment to numerous efforts by working with talented collaborators.

“If you don’t have teams to really hold it together, you can’t do any of it,” she said.

Ali Khosronejad in front of the Santa Maria Cathedral, which is considered the first modern cathedral in Madrid.

By Daniel Dunaief

An approaching weather front brings heavy rains and a storm surge, threatening to inundate homes and businesses with dangerous water and potentially undermining critical infrastructure like bridges.

Once officials figure out the amount of water that will affect an area, they can either send out inspectors to survey the exact damage or they can use models that take time to process and analyze the likely damage.

Ali Khosronejad

Ali Khosronejad, Associate Professor in the Department of Civil Engineering at Stony Brook University, hopes to use artificial intelligence to change that.

Khosronejad recently received $550,000 from the National Science Foundation (NSF) for four years to create a high-fidelity model using artificial intelligence that will predict the flood impact on infrastructure.

The funds, which will be available starting on June 20, will support two PhD students who will work to provide an artificial intelligence-based program that can work on a single laptop at a “fraction of the cost of more advanced modeling approaches,” Khosronejad said during an interview in Madrid, Spain, where he is on sabbatical leave under a Fulbright U.S Senior Scholar Award. He is doing his Fulbright research at Universidad Carlos III de Madrid.

Stony Brook University will also provide some funding for these students, which will help defray the cost of expenses related to traveling and attending conferences and publishing papers.

In the past, Stony Brook has been “quite generous when it comes to supporting graduate students working on federally funded projects,” Khosronejad explained and he hopes that continues with this research.

Khosronejad and his students will work with about 50 different flooding and terrain scenarios, which will cover about 95 percent of extreme flooding. These 50 possibilities will cover a range of waterways, infrastructure, topography, and coastal areas. The researchers will feed data into their high fidelity supercomputing cluster simulations to train artificial intelligence to assess the likely damage from a flood.

As they build the model, Khosronejad explained that they will collect data from floods, feed them into the computer and test how well the computer predicts the kind of flooding that has can cause damage or threaten the stability of structures like bridges. Over the next four years, the team will collect data from the Departments of Transportation in California, Minnesota and New York.

Nearly six years ago, his team attempted to use algorithms available in ChatGPT for some of his AI development. Those algorithms, however, didn’t predict flood flow prediction. He tried to develop new algorithms based on convolutional neural networks. Working with CNN, he attempted to improve its capabilities by including some physics-based constraints.

“We are very enthusiastic about this,” Khosronejad said. “We do think that this opportunity can help us to open up the use of AI for other applications in fluid mechanics” in fields such as renewable energy, contaminant transport predictions in urban areas and biological flow predictions, among others.

Planners working with groups such as the California Department of Transportation could use such a program to emphasize which infrastructure might be endangered.

This analysis could highlight effective mitigation strategies. Artificial intelligence can “provide [planners and strategists] with a tool that is not that expensive, can run on a single laptop, can reproduce lots of scenarios with flooding, to figure out which infrastructure is really in danger,” Khosronejad said.

Specifically, this tool could evaluate the impact of extreme floods on bridge foundations. Floods can remove soil from around the foundation of a bridge, which can cause it to collapse. Civil engineers can strengthen bridge foundations and mitigate the effect of future floods by using riprap, which is a layer of large stones.

This kind of program can reduce the reliance on surveying after a flood, which is expensive and sometimes “logistically impossible and unsafe” to monitor areas like the foundations of bridges, Khosronejad said. He plans to build into the AI program an awareness of the changing climate, so that predictions using it in three or five years can provide an accurate reflection of future conditions.

“Floods are getting more and more extreme” he said. “We realize that floods we feed into the program during training will be different” from the ones that will cause damage in subsequent years.

Floods that had a return period of every 100 years are now happening much more frequently. In one or two decades, such a flood might occur every 10 years.

Adding updated data can allow practitioners to make adjustments to the AI program a decade down the road, he suggested. He and his team will add data every year, which will create a more versatile model.

What it can’t do

While the AI programs will predict the damage to infrastructure from floods, they will not address storm or flood predictions.

“Those are different models, based on the movement of clouds” and other variables, Khosronejad said. “This doesn’t do that: if you give the program a range of flood magnitudes, it will tell you what will happen.”

High fidelity models currently exist that can do what Khosronejad is proposing, although those models require hundreds of CPUs to run for five months. Khosronejad has developed his own in house high fidelity model that is capable of making similar predictions. He has tested it to examine various infrastructures and used it to study various flooding events. These models are expensive, which is why he’s trying to replace them with AI to reduce the cost while maintaining fidelity.

AI, on the other hand, can run on a single CPU and may be able to provide the same result, which will allow people to plan ahead before it happens. The NSF approved the single principal investigator concept two months ago.

Khosronejad has worked with Fotis Sotiropoulos, former Dean of the College of Engineering and Applied Sciences at Stony Brook and current Provost at Virginia Commonwealth University, on this and other projects.

The two have bi-weekly discussions over the weekend to discuss various projects.

Sotiropoulos was “very happy” when Khosronejad told him he received the funds. Although he’s not a part of the project, Sotiropoulos will “provide inputs.”

Sotiropoulos has “deep insights” into fluid mechanics. “When you have him on your side, it always pays off,” Khosronejad said.

Chengfeng Yang Photo by Zhishan Wang

By Daniel Dunaief

This is part two of a two-part series.

As Erin Brockovich (the real life version and the one played by Julia Roberts in the eponymous movie) discovered, some metals, such as hexavalent chromium can cause cancer in humans.

Chengfeng Yang and Zishan Wang

Environmental exposure to a range of chemicals, such as hexavalent chromium, benzo(a)pyrene, arsenic, and others, individually and in combination, can lead to health problems, including cancer.

In March, Stony Brook University hired Chengfeng Yang and Zhishan Wang, a husband and wife team to join the Cancer Center and the Pathology Departments from Case Western Reserve University.

The duo, who have their own labs and share equipment, resources and sometimes researchers, are seeking to understand the epigenetic effect exposure to chemicals has on the body. Yang focuses primarily on hexavalent chromium, while Wang works on the mechanism of mixed exposures.

Last week, the TBR News Media highlighted the work of Wang. This week, we feature the work of Yang.

————————————–

When he was young, Chengfeng Yang was using a knife to make a toy for his younger brother. He slipped, cutting his finger so dramatically that he almost lost it. Doctors saved his finger, impressing him with their heroic talent and inspiring him to follow in their footsteps.

Indeed, Yang, who earned an MD and a PhD from Tongji Medical University, is focused not only on answering questions related to cancer, which claimed the life of his mother and other relatives, but also in searching for ways to develop new treatments.

A Professor in the Department of Pathology at the Renaissance School of Medicine at Stony Brook University and a member of the Stony Brook Cancer Center, Yang has his sights set on combatting cancer.

“Our research always has a significant clinical element,” said Yang. “This is related to our medical background.”

He is interested in studying the mechanism of cancer initiation and progression and would like to develop new strategies for treatment.

Yang and his wife Zhishan Wang recently joined the university from Case Western after a career that included research posts at the University of Pennsylvania, Michigan State University, and the University of Kentucky.

The tandem, who share lab resources and whose research staffs collaborate but also work independently, are focused specifically on the ways exposures to carcinogens in the environment cause epigenetic changes that lead to cancer.

Specifically, Yang is studying how hexavalent chromium, a metal commonly found in the environment in welding, electroplating and even on the double yellow lines in the middle of roads, triggers cancer. It is also commonly used as a pigment to stain animal leather products.

Yang is focused mainly on how long cancer develops after exposure to hexavalent chromium.

People can become exposed to hexavalent chromium, which is also known as chromium 6, through contaminated drinking water, cigarette smoking, car emissions, living near superfund sites and through occupational exposure.

Yang has made important findings in the epigenetic effect of metal exposure. His studies showed that chronic low-level chromium six exposure changed long non-coding RNA expression levels, which contributed to carcinogenesis. Moreover, his studies also showed that chronic low level exposure increased methylation, in which a CH3 group is added to RNA, which also contributed significantly to chromium 6 carcinogenesis.

“It is now clear that metal carcinogens not only modify DNA, but also modify RNA,” Yang explained. Metal carcinogen modification of RNAs is an “exciting and new mechanism” for understanding metal carcinogenesis.

By studying modifications in RNA, researchers may be able to find a biomarker for the disease before cancer develops.

Yang is trying to find some specific epigenetic changes that might occur in response to different pollutants.

Stony Brook attraction

Yang was impressed with the dedication of Stony Brook Pathology Chair Ken Shroyer, whom he described as a “really great physician scientist. His passion in research and leadership in supporting research” helped distinguish Stony Brook, Yang said.

Yang is confident that Stony Brook has the resources he and Wang need to be successful, including core facilities and collaborative opportunities. “This is a very great opportunity for us, with strong support at the university level,” he said.“We plan to be here and stay forever.”

Yang is in the process of setting up his lab, which includes purchasing new equipment and actively recruiting scientists to join his effort.

“We need to reestablish our team,” he said. “Right now, we are trying to finish our current research project.”

He hopes to get new funding for the university in the next two to three years as well. After he establishes his lab at Stony Brook, Yang also plans to seek out collaborative opportunities at Cold Spring Harbor Laboratory, which is “very strong in RNA biology,” he added.

A return home

Returning to the Empire State brings Yang full circle, back to where his research experience in the United States started. About 23 years ago, his first professional position in the United States was at New York University.

Outside of work, Yang likes to hike and jog. He is looking forward to going to some of Long Island’s many beaches.

He and Wang live in an apartment in South Setauket and are hoping to buy a house in the area. The couple discusses science regularly, including during their jogs.

Working in the same area provides a “huge opportunity” for personal and professional growth, he said.

Yang suggested that his wife usually spends more time training new personnel and solving lab members’ technical issues. He spends more time in the lab with general administrative management and support. Wang has “much stronger molecular biology skills than I have,” Yang explained in an email, whereas he has a solid background in toxicology.

Growing up, Yang said he had an aptitude in math and had dreamed of becoming a software engineer. When he applied to college, he received admission to medical school, which changed his original career path.

Once he started running his own experiments as a researcher, he felt he wanted to improve human health.“Once humans develop disease, in many cases, it’s very expensive to treat and [help] people recover,” he said. “Prevention could be a more cost effective way to improve health.”

Zhishan Wang. Photo from Chengfeng Yang

By Daniel Dunaief

This is part one of a two-part series.

As Erin Brockovich (the real life version and the one played by Julia Roberts in the eponymous movie) discovered, some metals, such as hexavalent chromium can cause cancer in humans.

Chengfeng Yang and Zhishan Wang

Environmental exposure to a range of chemicals, such as hexavalent chromium, benzo(a)pyrene, arsenic, and others, individually and in combination, can lead to health problems, including cancer.

Recently, Stony Brook University hired Chengfeng Yang and Zhishan Wang, a husband and wife team to join the Cancer Center and the Pathology Departments from Case Western Reserve University in Ohio.

The duo, who have their own labs and share equipment, resources and sometimes researchers, are seeking to understand the epigenetic effect exposure to chemicals has on the body. Yang focuses primarily on hexavalent chromium, while Wang works on the mechanism of mixed exposures. 

In part one, TBR News Media highlights the work of Wang. Next week, we will feature the efforts of Yang.

——————————-

In certain areas and specific job sites, people can be exposed to environmental pollutants.

Sometimes, the introduction of a metal or element can cause cancer after long term exposure. The effect of another carcinogen can be synergistic in triggering disease, triggering a stronger progression of cancer than an individual exposure alone.

Zhishan Wang, who joined Stony Brook in March and is a Professor of Research in the Department of Pathology, is trying to understand what changes this mixed exposure creates at a molecular level.

“If we find out some gene or pathway change, we can try to intervene,” said Wang, who is a member of the Stony Brook Cancer Center and earned MD and PhD degrees from her native China.

Among the many possible environmental triggers, Wang chose to study arsenic, which is common in rock soil and water and is present in some places in drinking water.

“People living in high exposure areas to arsenic and [who] are also cigarette smokers have a significantly higher risk of lung cancer,” she said.

Arsenic can cause three different kinds of cancer: skin, bladder and lung cancer. For skin cancer, Wang explained that direct contact can lead to the kind of irritation that promotes the disease. 

As the heavy metal works its way through the body, parts of it get excreted through the urine system, which means that bladder cells come into contact with it as well.

For a long time, scientists knew arsenic exposure through drinking water caused lung cancer. The underlying mechanism for the development of that cancer was not well understood. 

Wang’s lab studies the mechanism by which arsenic and benzo(a)pyrene (or BAP) co-exposure increases lung cancer risk. Exposure to arsenic alone causes cancer, but it takes a long time in animal models. Arsenic and BPA co-exposure significantly increases lung cancer risk.

Wang’s study showed that co-exposure increases lung tumor burden and malignancy. She plans to continue to study the mechanism of how arsenic and BAP co exposure increases lung cancer risk.

“That’s our big goal: to try to find some useful method to prevent this tumor from happening,” she said.

Wang believes the cancer cells caused by the mixed exposure increases the number of cancer stem cell-like cells, which could mediate therapeutic resistance.

Wang explained that generating the mouse model took considerable time and effort. She tried to find the exposures during particular windows of time that lead to cancer.

“By using this model, we can do a lot of data analysis” including single cell analysis and can determine which cluster or pathway will change.

Choosing SBU

Wang suggested she and her husband chose Stony Brook for several reasons. The couple would like to help the University earn a National Cancer Institute (NCI) designation, which would give scientists the ability to compete for ambitious, well-funded, multidisciplinary efforts.

Both Wang and Yang “lead NCI-funded research programs that will enhance the [Cancer Center’s] eligibility for NCI designation,” explained Kenneth Shroyer, chair of the Pathology Department at Stony Brook.

Shroyer, who described both researchers as “highly competitive candidates with the potential to enhance the status of any cancer center,” is looking forward to working with his newest recruits.

Wang is eager to use the tissue bank at Stony Brook, which Shroyer explained has also attracted other cancer research scientists recruited to the Renaissance School of Medicine at Stony Brook.

The new scientists also hope to tap into the expertise at nearby Cold Spring Harbor Laboratory, which has become one of the leading centers in creating organoids. 

In the early years of her training during her MD and PhD years in China, Wang developed her technical skills. Through her career, she has worked on several genes that play important roles in carcinogenesis. Down regulation of the gene known as SOCS3, for suppressor of cytokine signaling 3, plays an important role in arsenic and BAP co-exposure caused lung tumorigenesis.

Early in their careers, Wang worked in her husband’s lab for seven years until she received her own research funding.

Outside of work, Wang enjoys playing badminton and ping pong. She also cooks every day. She and her husband bring her home cooked meals to work.

When she was in high school, Wang had ambitions to become a writer. Her teachers regularly read her work out loud to the class.

Her father, who was a lawyer, had encouraged her to join the legal profession. She had heard that people called others “smart” when they joined the fields of Science, Technology, Engineering and Mathematics. “I want people to call me smart,” she said, so she changed her career and went to medical school at Tongji Medical University where she earned top scores. 

Her father had a stroke, surviving afterwards for seven years. When she was in medical school, Wang hoped to learn ways to help him. Wishing she could have done more, she pursued clinical research in the lab. She passed the tests to become a practicing physician in the United States, but she was more inspired to work as a scientist.

As for her work at Stony Brook University, Wang appreciates the beauty of Long Island. She hopes this is their “last move,” as they continue their careers.

John Moses. Photo courtesy of CSHL

By Daniel Dunaief

It sounds like something straight out of a superhero origin story.

With resistance to widely used drugs becoming increasingly prevalent among bacteria, researchers and doctors are searching for alternatives to stem the tide.

That’s where shape shifting molecules may help. Cold Spring Harbor Laboratory Professor of Organic and Click Chemistry John Moses and his team have attached the drug vancomycin to a molecule called bullvalene, whose atoms readily change position and configuration through a process called a thermal sigmatropic rearrangement as atoms of carbon break and reform with other carbon atoms.

The combination of the bullvalene and vancomycin proved more effective than vancomycin alone in wax moth larva infected with vancomycin resistant Enteroccoccus bacteria.

“Can I make a molecule that changes shape and will it affect bacteria? That was the question,” Moses said. The promising early answer was, yes!

Moses believes that when the bullvalene core is connected to other groups like vancomycin, the relative positions of the drug units change, which likely change properties related to binding.

The urgency for novel approaches such as this is high, as drug resistant bacteria and fungi infect about 2.8 million people in the United States per year, killing about 35,000 of them. 

In his own life, Moses said his father almost died from a bacterial infection five years ago. Vancomycin saved his father’s life, although the infection became resistant to the treatment. Other drugs, however, conquered the resistant strain.

“We need to work hard and develop new antibiotics, because, without them, there will be a lot more misery and suffering,” Moses explained.

To be sure, an approach like this that shows promise at this early stage with an insect may not make the long journey from a great idea to a new treatment, as problems such as dosage, off target effects, toxicity, and numerous other challenges might prevent such a treatment from becoming an effective remedy.

Still, Moses believes this approach, which involves the use of click chemistry to build molecules the way a child puts together LEGO blocks, can offer promising alternatives that researchers can develop and test out on a short time scale.

“We shouldn’t be restricted with one set of ideas,” Moses said. “We should keep testing hypotheses, whether they are crazy or whatever. We’ve got to find alternative pathways. We’re complementary” to the standard approach pharmaceutical companies and researchers take in drug discovery.

Looking to history, Moses explained that the founders of the Royal Society in 1660 followed the motto “nullius in verba,” or take nobody’s word for it. He believes that’s still good advice in the 21st century.

The shape shifting star

Moses has described this bullvalene as a Rubik’s Cube, with the parts moving around and confounding the bacteria and making the drug more effective.

The CSHL scientist and his team don’t know exactly why shape shifting makes the drug work in this moth model.

He speculated that the combination of two vancomycin units on either side of a bullvalene center is punching holes in the cell wall of the bacteria.

Moses is eager to try to build on these encouraging early developments. “If you can make it, then you can test it,” he said. “The sooner the better, in my opinion.”

Moses acknowledged that researchers down the road could evaluate how toxic this treatment might be for humans. It didn’t appear toxic for the wax moth larvae.

Welcoming back a familiar face

Adam Moorhouse
Photo by Rebecca Koelln

In other developments in his lab, Moses recently welcomed Adam Moorhouse back to his team. Moorhouse, who serves as Chemistry Data Analyst, conducted his PhD research in Moses’s lab at the University of Oxford.

Moorhouse graduated in 2008 and went on to work in numerous fields, including as an editor for the pharmaceuticals business and for his own sales consultancy. In 2020, he had a motorcycle accident (which he said was his fault) in which he broke 16 bones and was hospitalized for a while. During his recovery, he couldn’t walk.

At the time, he was working in the intense world of sales. After the accident, Moorhouse decided to build off his volunteer work with disabled children and become a high school teacher. After about 18 months of teaching, Moorhouse reconnected with Moses.

“It’s nice getting here and thinking about chemistry and thinking about ideas and communicating those ideas,” Moorhouse said.

He has hit the ground running, contributing to grants and helping to translate intellectual property into commercial ventures.

The chance to work on projects that get molecules into humans in the clinic was “really exciting,” Moorhouse said. “I’m back to try and support that.”

Moorhouse will be working to procure funding and to build out the business side of Moses’s research efforts.

“Where I’d like to lend a hand is in driving ongoing business discussions,” Moorhouse said. He wants to “get these small molecules into the clinic so we can see if they can actually treat disease in humans.” The vehicle for that effort eventually could involve creating a commercial enterprise.

Like Moses, Moorhouse is inspired and encouraged by the opportunity for small operations like the lab to complement big pharmaceutical companies in the search for treatments.

Moses believes the work his lab has conducted has reached the stage where it’s fundable. “We’ve done something that says, ‘we checked the box,’” he said. “Let’s find out more.”

Currently living on campus at CSHL, Moorhouse appreciates the opportunity to do some bird watching on Long Island, where some of his favorites include woodpeckers, herons, egrets, robins and mockingbirds.

He is tempted to get back on a motorcycle and to return to mountain biking.

As for his work, Moorhouse is excited to be a part of Moses’s lab.

“Back in my PhD days, [Moses] was always an idea machine,” Moorhouse said. “The aim is to move ideas to the clinic.”

 

Lucas Cheadle with two pieces of artwork in his office, from left by Porferio Tirador 'Gopher' Armstrong, a Cheyenne-Caddo native from Oklahoma and Oklahoma Kiowa artist Robert Redbird. Photo by Austin Ferro

By Daniel Dunaief

Cold Spring Harbor Laboratory Assistant Professor Lucas Cheadle knows a thing or two about under represented groups in the field of Science, Technology, Engineering and Mathematics.

Of Chickasaw, Choctaw and Cherokee lineage, Cheadle, who was born in Ada, Oklahoma, was recently named one of 31 inaugural Howard Hughes Medical Institute’s (HHMI) Freeman Hrabowski scholars.

Lucas Cheadle. Photo by Steve Ryan/ AP Images for HHMI

The first scholars in this highly competitive and unique program, which drew 1,036 applicants, will receive funding that will last at least five years and could get as much as $8.6 million each for their promising early research and for supporting diversity, equity and inclusion in their labs.

“This is the first time a program of this type and magnitude has been attempted,” said HHMI Vice President and Chief Scientific Officer Leslie Vosshall. The scholars are “doing things that set them in the top one percent in creativity and boldness and we are certain we are going to have really healthy, inclusive, diverse labs.”

Vosshall said the scholars, which include scientists from 22 institutions, including Columbia, Harvard, Duke, Cornell, Princeton, the University of Pennsylvania, and Massachusetts Institute of Technology, hit it “out of the park” in their science and diversity efforts.

HHMI, which has committed $1.5 billion for Freeman Hrabowski Scholars, will award about 30 of these select scholarships every other year for the next 10 years, supporting promising scientists who can serve as mentors for under represented groups while also creating a network of researchers who can provide advice and collaborations.

The first group of scientists to receive this support is “diverse in such a way that it reflects the U.S. population,” Vosshall said.

The program is named after Freeman Hrabowski, who was born in Birmingham, Alabama and was president of the University of Maryland, Baltimore County, from 1992 to 2022. Hrabowski, who was arrested during the civil rights movement, created a tutoring center in math and science for African Americans in high school and college and helped create the Meyerhoff Scholars Program.

Cheadle was celebrating the December holidays in Oklahoma when he learned he was a semifinalist, which was “really surprising and exciting,” he recalled. Becoming an HHMI scholar is “amazing” and “very validating,” he said.

Bruce Stillman, President and CEO of CSHL, suggested that HHMI recognition is “a prestigious achievement” and, in a email, wrote that he was “pleased that [Cheadle] was included in the list of remarkable scientists.”

Stillman predicted that Cheadle’s passion about increasing diversity in science would have a “major influence” on CSHL.”

Scientific questions

Cheadle appreciates how HHMI funds the scientist, not individual projects. With this unrestricted funding, which includes full salary and benefits and a research budget of about $2 million over the first five years and eligibility to participate in HHMI capital equipment purchasing programs, Cheadle and other scholars can pursue higher-risk, higher-reward projects.

“If I have a crazy idea tomorrow, I can do that with this with funding,” Cheadle explained.

Cheadle, who joined CSHL in August of 2020, studies the way the immune system shapes brain development, plasticity and function. He also seeks to understand how inflammatory signals that disrupt neural circuit maturation affect various disorders, such as autism.

Last September, Cheadle and his lab, which currently includes six postdoctoral researchers, two PhD students, one master’s student, a lab manager and two technicians, published a paper in Nature Neuroscience that showed how oligodendrocyte precursor cells, or OPCs, help shape the brain during early development.

Previously, scientists believed OPCs produced cells that surrounded and supported neurons. Cheadle’s recent work shows that they can play other roles in the brain as well, which are also likely instrumental in neural circuit construction and function.

When young mice raised in the dark received their first exposure to light, these OPCs engulfed visual processing circuits in the brain, which suggested that they helped regulated connections associated with experience.

With this new position and funding, Cheadle also plans to explore the interaction between the development of nerves in the periphery of the brain and different organs in the body, as well as how immune cells sculpt nerve connectivity.

He is not only studying this development for normal, healthy mice, but is also exploring how these interactions could explain why inflammation has arisen as such an important player in neurodevelopmental dysfunction.

Stillman explained that Cheadle’s work will “have broad implications.”

A talented, balanced team

Cheadle is committed to creating a balanced team of researchers from a variety of backgrounds.

“As principal investigators,” Cheadle said, “we have to actively work to have a diverse lab.”

He has posted advertisements on women’s college forums to garner more applications from women and under represented groups. He has also adopted a mentorship philosophy that focuses on inclusivity. 

Cheadle explained that he hopes to be adaptable to the way other people work. Through weekly lab meetings, mentorship arrangements and reciprocal interactions, he hopes to provide common ground for each aspiring scientist.

He recognizes that such goals take extra effort, but he feels the benefits outweigh the costs.

During annual events, Cheadle also leans in to the cultural diversity and differences of his staff. He hosts a pre-Thanksgiving pot luck dinner, where everybody brings a food item that’s important and close to them. 

Last year, he made pashofa out of cracked corn that his stepmom sent him from the Chickasaw Nation in Oklahoma. Pashofa is a traditional meat and corn Chickasaw dish. Other lab members brought tropical beverages common in Brazil.

In terms of diversity in science, Cheadle believes such efforts take years to establish. Through an approach that encourages people from different backgrounds to succeed in his lab, Cheadle hopes to share his thoughts and experiences with other researchers.

Cheadle last summer hosted a Chickasaw student on campus to do research. He is working with the Chickasaw Nation to expand that relationship.

As for the Freeman Hrabowski scholars, Vosshall said all HHMI wants to do is “allow everybody to do science.-

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HHMI Chief Scientific Officer Vosshall celebrates benefits of diversity in science

By Daniel Dunaief

It’s not one or the other. She believes in both at the same time. For Leslie Vosshall, Vice President and Chief Scientific Officer at Howard Hughes Medical Institute, science and diversity are stronger when research goals and equity work together.

Leslie Vosshall. Photo by Frank Veronsky

That’s the mission of the new and unique HHMI Freeman Hrabowski Scholars program. HHMI this week named 31 inaugural scholars as a part of an effort designed to support promising scientists who provide opportunities to mentor historically under represented groups in research.

Cold Spring Harbor Laboratory Assistant Professor Lucas Cheadle was among the 31 scientists who became HHMI scholars (see related story above), enabling him to receive financial support for the next five years and up to $8.6 million for the next decade.

In an interview, Vosshall said the “special sauce of this group” of scientists who distinguished themselves from among the 1,036 who applied was that they excel as researchers and as supporters of diversity. Bringing in people who may not have had opportunities as scientific researchers not only helps their careers but also enables researchers to take creative approaches to research questions.

“When you bring in people from the ‘out group’ who have been historically excluded, they have an energy of getting into the playing field,” she said. That innovation can translate into successful risk taking.

As an example, Vosshall cited Carolyn Bertozzi, a chemist at Stanford University who shared the 2022 Nobel Prize in Chemistry for helping to develop the field of bioorthogonal chemistry, which involves a set of reactions in which scientists study molecules and their interactions in living things without interfering with natural processes.

Her lab developed the methods in the late 1990’s to answer questions about the role of sugars in biology, to solve practical problems and to develop better tests for infectious diseases. “This scrappy band of women chemists tried this crazy stuff” which provided “massive innovations in chemical biology,” Vosshall said. Mainstream science often solidifies into a groove in which the same thing happens repeatedly. “Innovation comes from the edges,” she added.

In her own to hire staff in her lab, Vosshall has taken an active approach to find candidates from under served communities. “People who have pulled themselves up have worked so hard to get to where they are,” she said. “It’s important to dig deeper to find talent everywhere.”

Keeping away from the off-ramp

The number of under represented groups in science has improved over the last few decades. Indeed, when Vosshall joined Rockefeller University, where she is the Robin Chemers Neustein Professor, she couldn’t count 10 women faculty. Now, 23 years later, that number has doubled.

The number of people in under represented groups in graduate programs has increased. The problem, Vosshall said, is that they “take the off-ramp” from academic science” because they don’t always feel “welcome in the labs.” Supporting diversity will keep people in academic science, who can and will make important discoveries in basic and translational science.

As a part of the Freeman Hrabowski program, HHMI plans to survey people who were trainees in these labs to ask about their mentoring experience. By tracking how developing scientists are doing, HHMI hopes to create a blueprint for building diversity.

HHMI has hired a consultant who will analyze the data, comparing the results for the results and career trajectories. The research institute will publish a paper on the outcome of the first cohort. Researchers in this first group will not only receive money, but will also have an opportunity to interact with each other to share ideas.

New approach

When Vosshall earned her PhD, she considered an alternative career. She bought a training book for the Legal Scholastic Aptitude Test and considered applying to law school, as she was “fed up with how I was treated and fed up with science”

Nonetheless, Vosshall, who built a successful scientific career in which she conducts research into olfactory cues disease-bearing insects like mosquitoes seek when searching for humans, remained in the field.

To be sure, Vosshall and HHMI aren’t advocating for principal investigators to hire only people from under represented groups. The promising part of this scholarship is that HHMI found it difficult to get the final number down to 31, which “makes me optimistic that the [scientific and mentorship] talent is out there,” she said. Over the next decade, HHMI plans to name about 30 Freeman Hrabowski scholars every other year. If each lab provides research opportunities across different levels, this will help create a more diverse workforce in science, which, she said, benefits both prospective researchers and science.

 

James Rossie conducting field work at Lake Turkana. Photo by Susanne Cote

By Daniel Dunaief

Dead men might not tell tales but fossilized apes and the soil around them may change a narrative. That’s what happened recently when a large collaboration of researchers gathered clues from an ape fossil in Moroto, Uganda that lived 21 million years ago and from a detailed analysis of the soil.

James Rossie in his lab. Photo by Emily Goble

 

Scientists have long thought apes started climbing upright, which is an important evolutionary step, all those years ago to reach fruit in a habitat dense with trees. Recent evidence from two publications in the journal Science, however, suggest that the habitat included grassland and woodlands.

James Rossie, Associate Professor in the Department of Anthropology at Stony Brook University, studied the teeth of the fossil, called Morotopithecus, to determine what this ancient ape ate.

“The important thing about the teeth of Morotopithecus is a shift towards folivory” or leaf eating, Rossie said. “The surface of the molars were elongated with well-developed crests” which indicate that this primate consumed leaves rather than fruit.

By contrast, molars of animals that eat fruit are more rounded. Additionally, carbon isotope dating of the enamel suggest that they fed on water-stressed plants. This discovery and analysis changes not only the narrative of this particular ape species, but also of the evolutionary progression and habitat of primates.

A rendering of ancient apes foraging in trees. Image courtesy of Corbin Rainbolt

This analysis indicated that apes lived in areas of open woodlands, where there were patches of trees separated by stretches of grassland about 10 million years earlier than scientists originally believed. During the miocene period, they would have had to evade predators such as Simbakubwa, an extinct carnivore that was larger than a lion.

“It was very unexpected that an ape with upright, versatile climbing abilities was living in a seasonal woodland with open, grassy patches, rather than in a closed tropical forest,” said Laura MacLatchy, a Professor in the Department of Anthropology at the University of Michigan and the leader on the study.

“The findings have transformed what we thought we knew about early apes, and the origins for where, when and why they navigate through the trees and on the ground in multiple different ways,” Robin Bernstein, Program Director for Biological Anthropology at the National Science Foundation, said in a statement. “The effort outlines a new framework for future studies regarding ape evolutionary origins.”

The fossils Rossie and his colleagues examined including the lower part of a face, the palate, upper teeth, a couple of vertebrae, the lower jaw, and a complete femur. It’s unclear if these fossils came from one individual or from a collection of apes. With considerable wear and tear on the teeth of the upper jaw, the owner of those bones was an adult, Rossie said.

The mandible of an ancient ape with the left molar enlargement inset. Photo by Laura MacLatchy

By studying the bones as puzzle pieces that fill in a narrative, researchers concluded that the smaller, thick femur, or thigh, bone helped the ape climb quickly and effectively up the trunks of trees.

The longer legs of a human push us away from trees, making it harder to climb, while the shorter, sturdy legs of an ape enable it to get closer to the trunk and reach lower branches quickly. 

Apes that fed on leaves would likely have had larger bodies to accommodate the need for a longer digestive tract. A heavier animal that navigated through trees would run the risk of falling to the ground if their weight caused a branch to break.

By climbing upright, apes could distribute their weight more evenly over several branches, enabling them to maneuver through the trees to the leaves while reducing the strain they put on any one branch.

In a second paper published together as a part of this analysis, soil researchers studied the environment at Moroto and at several other sites of similar age across eastern Africa.  These soil scientists determined that the early habitat included forests and grasslands.

Cooperative work

Rossie believes the work of numerous scientists over a long period of time not only represents a paradigm shift in thinking about ape evolution and the environment in Africa, but also in the way scientists across a wide range of expertise collaborate.

James Rossie conducting field work at Lake Turkana. Photo by Susanne Cote

The researchers who trained Rossie and his colleagues were more competitive and guarded, he said. They didn’t share information with each other about their findings and wanted other researchers to learn about their findings through journal publications.

“We decided to take a different strategy” about a dozen years ago, he said. “It occurred to us that these separate silo attempts to reconstruct these environments were incompatible, with different methods and strategies. We couldn’t put it together into a coherent picture.”

By working together with the same methods, the scientists had comparable data and developed a coherent picture. Such broad collaborations across a range of fields required a “bit of a leap of faith,” he added. The scientists knew and trusted each other.

Indeed, Rossie and MacLatchy have known each other since the early 2000s when MacLatchy first asked Rossie to study other fossils.

Bringing numerous researchers across a range of expertise was a “game theory experiment,” Rossie added. Researchers could have published smaller papers about each site more quickly, but chose to combine them into the more meaningful synthesis.

MacLatchy suggested that the work on this project that involved sharing data across multiple sites, as well as joining forces in a range of expertise, makes it possible to reconstruct habitats with much greater detail.

“We are also able to obtain a regional perspective, which is not possible if interpretations are based on individual fossil sites,” she said. “I’d like to think this kind of collaboration will become standard.”

A resident of Centerport, Rossie is a hockey fan and is pulling for the Islanders.

He enjoys studying teeth because a single tooth can provide considerable information about an animal’s place among other species and about its strategies for getting and processing food.

His professional studies have come full circle. As a college junior at St. Lawrence University, he attended a field school run by Harvard University and the National Museum of Kenya at Lake Turkana. Almost every moment of that experience made him more eager to pursue paleontology as a career.

“As fate would have it, my field project is now centered on an area on the west side of Lake Turkana that I first visited back in 1995,” he explained.

The Turkana Basin Institute serves as his home base during the field season and he is grateful for their ongoing logistical support.

As for future work, Rossie is studying the fossils of at least four different species of apes in Lake Turkana in Kenya.

Michael French in front of a mobile radar antenna.

By Daniel Dunaief

Michael French

 

When he was in elementary school in Hamden, Connecticut, Michael French was several miles away from an event that would shape his life. A tornado touched down, causing extensive damage, knocking out power lines and injuring 40 people. The violent storm was traumatizing, causing him to hide in the closet during routine summer storms.

By the time French attended college at Cornell University, these powerful and potentially devastating storms had become an “interest and fascination,” he said, leading him to major in atmospheric sciences.

After graduating from college, he received an offer from Professor Howard Bluestein at the University of Oklahoma (OU) for a master’s program. A consultant for the movie Twister starring Helen Hunt and Bill Paxton, Bluestein was one of the first to put a weather radar on the back of a truck to collect data in severe storms and tornadoes. French also earned his PhD at OU.

These days, French, who is an Associate Professor in the School of Marine and Atmospheric Sciences at Stony Brook University, spends parts of his time traveling to places in the southeast in trucks with unique and emerging instrumentation, typically Doppler weather radar, gathering data about severe thunderstorms and tornadoes.

French has seen about 25 tornadoes. The closest he’s come to these violent storms is about a kilometer away, which occurred in 2004. When he’s conducting research, he is more concerned about lightning, which frequently occurs around thunderstorms that produce tornadoes.

When he’s collecting data, French has to get out of the truck to stow the antenna among other tasks. “Automatically, that means you’re in danger,” French said. “There’s nothing you can do about it, except try to minimize your time” outside. Two or three times when he was earning his PhD, lightning struck within a quarter of a mile of his location.

Better sampling

In his research, French described himself as a “pure observationalist.”

A main theme of his research is whether the nationwide network of fixed-site radar can be used by forecasters to predict whether a thunderstorm will produce a tornado and, if it does, how likely it is to be a significant or violent storm. 

French is also interested in exploring what leads to tornado dissipation and whether forecasters can use radar analysis to make dissipation predictions.

Looking at time scales of 30 seconds or fewer, he studies how tornadoes evolve, including how they tilt, how their intensity changes with height, and their motion. He can estimate these characteristics with phased-array radar technology, in which the beam of the radar is steered electronically.

Scientists like French can tap into archived data from a network of 160 radars stationed throughout the country. He would like to use information from the past 10 to 15 years to analyze hundreds of supercell thunderstorms to find commonalities among those that produce tornadoes and those that don’t.

“Ideally, in the future, such information, to the extent it exists, can be leveraged by forecasters to better assess the likelihood of a storm producing a tornado,” French explained.

Many of his ideas for research projects come from reading the results of papers from colleagues who use computer models to simulate storms and tornadoes. In a model, the scientists can control conditions like temperature and humidity. French thinks about ways to verify the findings using observational data.

Funded by the National Oceanic and Atmospheric Administration, French participates in the Propagation, Evolution and Rotation in Linear Storms field experiment (called PERiLS). 

Running from February through May in the southeast, the experiment studies tornadoes within a different type of storm, referred to as squall lines. The tornadoes that form in these storms persist or form overnight, often hitting while people are sleeping and are unprepared to protect themselves.

He is working with Stony Brook Professor Pavlos Kollias in using mobile phased array radar to collect data over short time scales of these squall lines when they’re producing tornadoes.

In areas where people live in mobile homes, these squall line tornadoes can lift the home, damaging homes and threatening the lives of people as they sleep.

Exciting findings

French uses a radar called dual polarization, which provides information about the size, shape, orientation and type of precipitation. He is interested in whether this technology can identify differences in storms to predict the formation of tornadoes.

In dual polarization, there are a few signatures of storms that hold some promise of differentiating between those that produce tornadoes and those that don’t.

Working with an algorithm to identify the ZDR column, which is a proxy for the size of the updraft, developed by Darrel Kingfield at the National Center for Atmospheric Research, French analyzed 200 supercell storms and found that the ZDR column was larger in storms that produce stronger tornadoes and was smaller or nonexistent in storms that did not.

Forecasters don’t have a way yet to automate the size of the ZDR column in real time.

In an email, Bluestein suggested that French’s studies, including on how tornadoes dissipate, can “contribute to improved short term forecasting.”

Bluestein, who has seen over 100 tornadoes, also suggested that two papers from French that related drop size distributions estimated from polarimetric radar data in supercells were “original and rather novel. This work has implications for estimating the intensity of pools of cool air in storms, which can be related to tornado formation.”

Dinner table conversations

A resident of Stony Brook, French lives with his wife Jennifer, who is a hydrometeorologist at Vieux & Co. The couple met when they were at the University of Oklahoma. 

French said his wife, who storm chased when she was in Oklahoma, knows the safety measures he uses to mitigate the risks. 

While French studies these storms because of their destructive power and the need to understand more about how and where they will form, he also has an appreciation for them.

At a distance, when these storms aren’t impacting people and when he can’t hear the roar of the wind, French describes tornadoes as a “wonder of nature” that have an “aesthetic element to them that is really astounding.”

As for his childhood concern about these storms, French feels that he “ultimately channeled [his fear] in a positive way.”