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Daniel Dunaief

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Francis Alexander. Photo from BNL

By Daniel Dunaief

Now what? It’s a question that affects everyone from the quarterback who wins the Super Bowl — who often says something about visiting a Disney facility — to the student who earns a college degree, to the researcher who has published a paper sharing results with the scientific community.

For some, the path forward is akin to following footsteps in the snow, moving ever closer to a destination for which a path is clear. For others, particularly those developing new technology, looking to unlock mysteries, the path is more like trudging through unfamiliar terrain.

The technology at facilities like Brookhaven National Laboratory, which includes the powerful National Synchrotron Light Source II and the Center for Functional Nanomaterials, among others, enables scientists to see processes at incredibly fine scales.

While these sites offer the promise of providing a greater ability to address questions such as what causes some batteries to die sooner than others, they also cost considerable money to use, putting pressure on researchers to ask the most fruitful question or pursue research that has the greatest chance for success.

Francis Alexander. Photo from BNL

That’s where people like Francis Alexander, the deputy director of Brookhaven National Laboratory’s Computational Science Initiative, and his team at BNL can add considerable value. Alexander takes what researchers have discovered, couples it with other knowledge, and helps guide his fellow laboratory scientists to the next steps in their work — even if he, himself, isn’t conducting these experiments.

“Given our theoretical understanding of what’s going on, as imperfect as that may be, we take that understanding — the theory plus the experimental data — and determine what experiments we should do next,” Alexander said. “That will get us to our goal more quickly with limited resources.”

This approach offers a mutually reinforcing feedback loop between discoveries and interpretations of those discoveries, helping researchers appreciate what their results might show, while directing them toward the next best experiment.

The experiments, in turn, can either reinforce the theory or can challenge previous ideas or results, forcing theoreticians like Alexander to use that data to reconstruct models that take a wide range of information into account.

Alexander is hoping to begin a project in which he works on developing products with specific properties. He plans to apply his knowledge of theoretical physics to polymers that will separate or grow into different structures. “We want to grow a structure with a [particular] function” that has specific properties, he said.

This work is in the early stages in which the first goal is to find the linkage between what is known about some materials and what scientists can extrapolate based on the available experiments and data.

Alexander said the aerospace industry has “models of everything they do.” They run “complex computer simulations [because] they want to know how they’d design something and which design to carry out.”

Alexander is currently the head of a co-design center, ExaLearn, that focuses on exascale, machine-learning technologies. The center is the sixth through the Exascale Computing Project. Growth in the amount of data and computational power is rapidly changing the world of machine learning and artificial intelligence. The applications for this type of technology range from computational and experimental science to engineering and the complex systems that support them.

Ultimately, the exascale project hopes to create a scalable and sustainable software framework for machine learning that links applied math and computer science communities to create designs for learning.

Alexander “brings to machine learning a strong background in science that is often lacking in the field,” Edward Dougherty, a distinguished professor in the Department of Electrical and Computer Engineering at Texas A&M, wrote in an email. He is an “excellent choice to lead the exascale machine learning effort at Brookhaven.”

Alexander is eager to lead an attempt he suggested would advance scientific and national security work at the Department of Energy. “There are eight national laboratories involved and all the labs are on an equal level,” he said. 

One of the goals of the exascale computing project is to build machines capable of 10 to the 18th operations per second. “There’s this enormous investment of DOE” in this project, Alexander said.

Once the project is completely operational, Alexander expects that this work will take about 30 percent of his time. About 20 percent of the time, he’ll spend on other projects, which leaves him with about half of his workweek dedicated to management.

The deputy director recognizes that he will be coordinating an effort that involves numerous scientists accustomed to setting their own agenda.

Dougherty suggested that Alexander’s connections would help ensure his success, adding that he has “established a strong network of contacts in important application areas such as health care and materials.

The national laboratories are akin to players in a professional sporting league. They compete against each other regularly, bidding for projects and working to be the first to make a new discovery. Extending the sports metaphor, members of these labs often collaborate on broad projects, like players on an all-star team competing against similar teams from other nations or continents.

Alexander grew up in Ohio and wound up working at Los Alamos National Laboratory in New Mexico  for over 20 years. He came to BNL in 2017 because he felt he “had the opportunity to build something almost from the ground up.” The program he had been leading at Los Alamos was large and well developed, even as it was still growing. 

The experimental scientists at BNL have been receptive to working with Alexander, which has helped him achieve some of his early goals.

Ultimately, Alexander hopes his work increases the efficiency of numerous basic and applied science efforts. He hopes to help experimental scientists understand “what technologies we should develop that will be feasible” and “what technologies would be most useful to carry experiments out.”

have a few questions for the newly minted Supreme Court Justice, Brett Kavanaugh.

What did you learn through this process?

You will be judging legal cases from people from all walks of life, working together with the eight other Supreme Court justices to decide on cases that will determine the law of the land for everyone.

What’s it like to be the accused? In some cases, the accused will be as angry and defensive and frustrated as you were. How will you understand the legal issues of their cases? How will you consider the legal questions and how will you consider the implications for them?

Will you understand the fury some people might feel through the legal process? Will you appreciate their position, even as you use the law to guide your decision-making process?

Maybe not because you, after all, didn’t go through a trial. Well, you certainly didn’t go through a judicial trial. You endured an ordeal, you experienced a political maelstrom and you became a divisive figure, suffering through accusations you found abhorrent.

People prejudged you because of the claims women made about your behavior from years ago.

Will you be able to appreciate the implications of your decisions on the people awaiting them?

Will a process that you found impossibly difficult make you better at your job? Will you grow from this experience, the way people who take an impossible organic chemistry class where they have to memorize and learn structures, concepts and stoichiometry become better students?

People rarely ask for the suffering and hardship that comes during any process. It’s what makes movies about road trips so compelling: People have to overcome or surmount obstacles along the way to get closer to the destination — or the truth.

Will you learn about yourself and gain a new perspective on the country and all of its citizens now that you’ve made that trip?

In many jobs, we ask people to go beyond what might be their natural responses to people or circumstances. Firefighters race toward a burning building when they may want to run toward safety. The same holds true with the police, who enter unknown and potentially dangerous circumstances.

Doctors can’t look at a wound and screech, “Yuck, that’s so disgusting, get that away from me.”

In many jobs, we need to overcome our visceral responses, doing what’s asked and ignoring other parts of our experience because that’s what’s required.

In your case, the country asks you to make the best judgment for everyone, even the Democrats or those who might accuse others of sexual assault.

Will you be able to step out of a reflexive response that’s all too human to make decisions that affect the lives of everyone?

Taking a step away from Judge Kavanaugh, what have we all learned? We know the country is divided and we know people are prepared to find evidence to support whatever conclusions they have already drawn.

Can we become more judicial instead of prejudicial? Can we act the way we all hope Judge Kavanaugh will behave?

The downside of the instantaneous world in which we live is that we expect instant results. We want food as soon as we order it and we want to speak with everyone and anyone whenever we feel the urge, even if we’re driving, standing in a line or watching a movie.

Maybe what we’ll learn is that the judicial process requires time, effort and consideration. Perhaps we can be thankful that the fact-finding, questions and appeals process that accompanies trials will bring out enough information to render a verdict consistent with the law — not a political or any other personal belief.

Leila Esmailzada, kneeling, with another BeLocal team member Caroline Rojosoa (in the black argyle sweater) distribute trial briquettes. Photo courtesy of BeLocal

By Daniel Dunaief

Leila Esmailzada set out to change the world but first had to perform a task that turns many people’s stomachs: clean someone else’s vomit off the floor.

The Stony Brook University graduate student, who is in the master’s Program in Public Health, traveled to Madagascar for a second consecutive summer with the nonprofit BeLocal Group to help several teams of student engineers put into place projects designed to improve the lives of the Malagasy people.

Before they could help anyone else, however, these students, many of them recent graduates from the College of Engineering, fought off a series of viruses, including a particularly painful stomach bug.

Esmailzada said she saw cleaning the vomit off the floor as part of the big picture.

“Compassion really plays into being abroad for your work and for your team, because you realize that everybody came here for a shared mission,” Esmailzada said. “What happens along the way is sometimes just a result of the path that brought them here.”

Briquettes lay out to dry in Madagascar. Photo courtesy of BeLocal

Indeed, beyond Esmailzada’s compassion, her ability to continue to accomplish tasks in the face of unexpected and potentially insurmountable obstacles encouraged BeLocal, a group started by Laurel Hollow residents Mickie and Jeff Nagel and Eric Bergerson, to ask her to become the group’s first executive director.

“I can’t say enough about [Esmailzada] being so resourceful over there,” said Mickie Nagel, who visited the island nation of Madagascar the last two years with Esmailzada. “She thinks about things in a different way. You can have the best product, but if you can’t connect it to the Malagasy and understand more deeply what they need, what their concerns or wants are” the project won’t be effective.

This past summer BeLocal tried to create two engineering design innovations that had originated from senior projects at SBU. In one of them, the engineers had designed a Da Vinci bridge, borrowing a model from the famous inventor, to help villagers cross a stream on their way to the market or to school. When the makeshift bridge constructed from a log or tree got washed away or cracked, the residents found it difficult to get perishable products to the market.

The first challenge the group faced was the lack of available bamboo, which they thought they had secured months before their visit.

“When the bamboo wasn’t delivered, I figured we were now going to do research on bamboo,” Nagel explained in an email, reflecting the group’s need to react, or, as she suggests, pivot, to another approach.

When they finally got bamboo, they learned that it was cut from the periphery of a patch of bamboo that borders on a national park. Government officials confiscated the bamboo before it reached BeLocal.

“We were happy to see that law enforcement recognized and acted on the ‘gray area rules’ of conserving the national park, which shows that the hard work Madagascar is putting into conservation is actually paying off,” Esmailzada said. She eventually found another provider who could deliver the necessary bamboo a few days later. This time, an important material was cut down from a local farm.

While they had the bamboo, they didn’t know how to cure it to prepare it for construction. Uncured, the bamboo could have become a soggy and structural mess. “We did try to cure [it] a few different ways, but we really didn’t have the time needed to properly treat all of it,” Nagel said. “We didn’t anticipate the bamboo not arriving cured since it was what we had been working on for months.”

Nagel credits the bridge team with adjusting to the new circumstances, constructing two girder bridges over creeks for more market research.

The BeLocal team also worked on a project to create briquettes that are healthier than the firewood the Malagasy now use for cooking. The wood produces considerable smoke, which has led to respiratory diseases and infections for people who breathe it in when they cook.

The group produced briquettes toward the end of their summer trip and presented their technique to an audience of about 120 locals, which reflected the interest the Malagasy had shown in the process during its development.

This fall, BeLocal is working on ways to move forward with sharing the briquette technique, which they hope to refine before the new year. BeLocal wants to develop clubs at Stony Brook and at the University of Fianarantsoa in Madagascar that can work together.

While BeLocal will continue to share senior design ideas on its website (www.belocalgrp.com) with interested engineers, the group is focusing its energy on perfecting the briquettes and getting them to people’s homes in Madagascar.

Nagel admired Esmailzada’s approach to the work and to the people in Madagascar.

Esmailzada said she studied how people in Madagascar interact and tried to learn from that, before approaching them with a product or process. She believes it’s important to consider the cultural boundaries when navigating the BeLocal projects, realizing that “you are not the first priority in a lot of these villagers’ lives in general. You have to understand they won’t meet and speak with you. It’s a reasonable expectation to ask maybe three times for something before you think you can get it done.”

Esmailzada also developed a routine that allowed her to shift from one potential project to another, depending on what was manageable at any given time.

The Stony Brook graduate student is delighted to be an ongoing part of the BeLocal effort.

“I love working with an organization that has the passion and vision as large as BeLocal,” she explained. “This work is fulfilling because you are working toward the chance of improving the well-being of another person or community.”

With Washington leading the way, we have become a divided nation, bickering, fighting, shouting and disagreeing as if we’re at a competing pep rally.

What are we to do?

Perhaps we need metaphors to turn the thermostat down.

To start with the obvious, perhaps we are a nation of onions. No, we don’t give everyone bad breath and, no, we don’t cause gas. We have layers, as Shrek so famously described in his eponymous movie. The surface, which everyone sees, has a layer of anger and frustration, but peel back a few of those layers and we’re filled with sympathy, empathy and concern for our friends and neighbors who, like us, are pursuing the American Dream.

Sticking with the food metaphor, perhaps we’re a kitchen stocked with incredible ingredients trucked in from all over the country. You may never have been to Idaho, but I can assure you that the simple potato in that state is remarkable for its flavor and texture.

While we have all these wonderful ingredients, perhaps we have a kitchen filled with too many cooks, who are changing recipes and oven temperatures so often that the food we’re baking will inevitably be unrecognizable and either vastly overcooked or undercooked.

Then again, perhaps we’re an enormous cruise ship in the middle of a vast ocean. We’re slowly turning but, because we’re such a huge vessel, we move and change direction at a rate that’s hard to perceive, especially when landmarks are either too far away or are masked by an enveloping fog.

Perhaps we’ve become a collection of angry bees, buzzing loudly, perceiving threats from everywhere and everyone — even inside our own honey-producing hive. Are we truly threatened from within and without, facing insurrection among the ranks of other bees, or are we surrounded by majestic purple mountains? Are we creating such cacophony that we can’t hear the birds singing around us?

We may be a batch of apples, looking suspiciously at the other fruit in the bin, wondering if any of us have turned bad, threatening the entire bunch.

Maybe we’re on a roller-coaster ride, racing up and down, screaming and shouting as we circle tracks that we fear might need repair, hoping to return to where we were so we can regain our equanimity on solid ground again.

Maybe we’ve become a boulder gathering size and momentum as it plunges down a hill. Our anger and frustration propel us forward, even as we ignore the kinds of moments and people who could, and should, unify a country. Have you been to a sporting event lately? I’m not thinking of the athletes as unifying forces.

I’m talking about the salutes to members of the military that often occur during the seventh-inning stretch in a baseball game or during a stoppage in the action in the middle of a hockey game. People throughout the stadium — those who think Trump is either a superstar or an imploding supernova — stand and cheer together, thanking these humble men and women for the sacrifice and service to our country.

Those heroes among us are the few who might do the impossible, catching the boulder or slowing it down as it cuts a path of emotional destruction through an outraged nation.

Then again, maybe the best metaphor to keep in mind amid the finger-pointing and criticism and self-doubt is the document that got us this far: the Constitution. It is the enduring net that protects the country and its citizens, even when we seem to be shadow boxing against each other on a high wire at the top of a circus tent.

Above, Mikala Egeblad works with graduate student Emilis Bružas in the Watson School of Biological Sciences. Photo from Pershing Square Soon Cancer Research Alliance

By Daniel Dunaief

For some people, cancer goes into remission and remains inactive. For others, the cancer that’s in remission returns. While doctors can look for risk factors or genetic mutations, they don’t know why a cancer may come back at the individual level.

In a mouse model of breast and prostate cancers, Mikala Egeblad, an associate professor at Cold Spring Harbor Laboratory, has found an important driver of cancer activation and metastasis: inflammation. When mice with cancer also have inflammation, their cancer is likely to become more active. Those who don’t have inflammation, or whose inflammation is treated quickly, can keep the dreaded disease in check. Cancer cells “may be dormant or hibernating and not doing any harm at all,” she said. “We speculated what might be driving them from harmless to overt metastasis.”

Egeblad cautioned that this research, which was recently published in the journal Science, is on mice and that humans may have different processes and mechanisms.

CSHL’s Mikala Egeblad. Photo from Pershing Square Soon Cancer Research Alliance

“It is critical to verify whether the process happens in humans,” Egeblad suggested in an email, which she will address in her ongoing research. Still, the results offer a window into the way cancer can become active and then spread from the lungs. She believes this is because the lungs are exposed to so many external stimuli. She is also looking into the relevance for bone, liver and brain metastases. The results of this research have made waves in the scientific community.

“This study is fantastic,” declared Zena Werb, a professor of anatomy and associate director for basic science at the Helen Diller Family Comprehensive Cancer Center at the University of California in San Francisco. “When [Egeblad] first presented it at a meeting six months ago, the audience was agog. It was clearly the best presentation of the meeting!”

Werb, who oversaw Egeblad’s research when Egeblad was a postdoctoral scientist, suggested in an email that this is the first significant mechanism that could explain how cancer cells awaken and will “change the way the field thinks.”

Egeblad credits a team of researchers in her lab for contributing to this effort, including first author Jean Albrengues, who is a postdoctoral fellow. This group showed that there’s a tipping point for mice — mice with inflammation that lasts six days develop metastasis.

Egeblad has been studying a part of the immune system called neutrophil extracellular traps, which trap and kill bacteria and yeast. Egeblad and other researchers have shown that some cancers trick these NETs to aid the cancer in metastasizing.

In the new study, inflammation causes cancer cells that are not aggressive to develop NETs, which leads to metastasis. The traps and enzymes on it “change the scaffold that signals that cancer should divide and proliferate instead of sitting there dormant,” Egeblad said.

To test out her theory about the role of enzymes and the NETs, Egeblad blocked the cascade in six different ways, including obstructing the altered tissue scaffold with antibodies. When mice have the antibody, their ability to activate cancer cells after inflammation is prevented or greatly reduced, she explained.

The numbers from her lab are striking: in 100 mice with inflammation, 94 developed metastatic cancer. When she treated these mice with any of the approaches to block the inflammation pathway, 60 percent of them survived, while the remaining 40 percent had a reduced metastatic cancer burden in the lungs.

If inflammation is a key part of determining the cancer prognosis, it would help cancer patients to know, and potentially treat, inflammation even when they don’t show any clinical signs of such a reaction.

In mice, these NETs spill into the blood. Egeblad is testing whether these altered NETs are also detectable in humans. She could envision this becoming a critical marker for inflammation to track in cancer survivors.

The epidemiological data for humans is not as clear cut as the mouse results in Egeblad’s lab. Some of these epidemiological studies, however, may not have identified the correct factor.

Egeblad thinks she needs to look specifically at NETs and not inflammation in general to find out if these altered structures play a role for humans. “We would like to measure levels of NETs and other inflammatory markers in the blood over time and determine if there is a correlation between high levels and risk of recurrence,” she explained, adding that she is starting a study with the University of Kansas.

Werb suggested that inflammation can be pro-tumor or anti-tumor, possibly in the same individual, which could make the net effect difficult to determine.

“By pulling the different mechanisms apart, highly significant effects may be there,” Werb wrote in an email. Other factors including mutation and chromosomal instability and other aspects of the microenvironment interact with inflammation in a “vicious cycle.”

In humans, inflammation may be a part of the cancer dynamic, which may involve other molecular signals or pathways, Egeblad said.

She has been discussing a collaboration with Cold Spring Harbor Laboratory’s Doug Fearon, whose lab is close to hers.

Fearon has been exploring how T-cells could keep metastasis under control. Combining their approaches, she said, cancer might need a go signal, which could come from inflammation, while it also might need the ability to alter the ability of T-cells from stopping metastasis.

In her ongoing efforts to understand the process of metastasis, Egeblad is also looking at creating an antibody that works in humans and plans to continue to build on these results. “We now have a model for how inflammation might cause cancer recurrence,” she said. 

“We are working very actively on multiple different avenues to understand the human implications, and how best to target NETs to prevent cancer metastasis.”

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After living in our new house in Charlotte, North Carolina, for a few weeks, we were delighted to receive an invitation to a block party to meet our neighbors.

Up to that point, we’d only seen and spoken with one neighbor. She and her family welcomed us to the area, offered an air-conditioning reference and shared the garbage pickup schedule.

The morning of the upcoming gathering, my wife and I took a walk through the neighborhood. We admired the landscaping and architecture of nearby homes. We moved off the sidewalk as runners passed us. We trotted up one lawn to clear space for a biker whose steering wheel seemed to be pulling left and right.

Most of the people in cars waved as they passed, a regular occurrence here, even when they didn’t know us.

My wife believes I alert the canines in the area that I am a “dog person.” A golden retriever and a black Labrador spotted me from across the street and stared, causing their owner to stop and wait as they watched us disappear up the block.

A friendly man with a small dog stopped and chatted. He asked if we were residents and if we were attending the block party that evening. When we told him we moved here with our kids, he asked what brought us down.

“Work,” we said.

“Oh,” he said, turning to me. “Did you get a job with one of the banks?”

“No, my wife did,” I replied, directing his attention to her.

He was embarrassed and immediately apologized for assuming I had landed a job that required us to relocate. We reassured him it was fine and we kept walking.

I am proud of my wife and her professional accomplishments. I also recognize, even in a world where people regularly discuss equal opportunity, that we are still far from situations in which people can’t assume anything about the roles husbands and wives play when they meet a couple.

Later that evening, with our children in tow, we walked the few blocks to the party, waving politely at a man who almost certainly carried a beer the same way 20 years ago when he was in college, although his clothing, like ours, was probably a few sizes smaller. Maybe that’s an unfair assumption, too?

When we arrived on a tree-lined cul-de-sac, we noticed that most of the children were considerably younger than our pair, who snarled about an early exit.

After urging them to stay, we made some selections in the crowd and broke the social ice. Consistent with our experience since our arrival, we found people who came originally from Long Island, New York and New Jersey.

We chatted with a proud father, who pointed to his high school senior and proclaimed her the best athlete in her entire school.

“You must be in public relations,” I said.

He and his daughter laughed.

“That guy over there,” he said, pointing to a house.

“Yes?” I replied.

“He is a neurosurgeon who works with football players. His attends games and he does concussion protocol.”

“Really?” I asked.

“The players are supposed to say ‘spaghetti’ when they see him after a hard hit. They get hit so hard that they say things like ‘ham’ or ‘bologna’ because they can’t remember the first concussion word,” he offered.

Our children, despite their initial disappointment, found contemporaries that night and are cellphone buddies with the kids on the block. We received restaurant recommendations and local service provider referrals, while we also will recognize a few of the people who exchange pleasant waves on and off the block.

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The emails, text messages and calls came from all over the country. In the days leading up to Hurricane Florence’s arrival in North Carolina, friends and family shared good wishes for my family, who had moved to the Tar Heel State during the summer.

Preparing for the storm, we were under the impression that we were leaving the typical path of hurricanes when we moved this far west to Charlotte, which is more than 200 miles from the coast.

As the tone and urgency to prepare for the hurricane from meteorologists and politicians reached a peak, people lined up outside supermarkets, waiting to park their cars and navigate their overflowing carts through crowded aisles for their list of must-haves.

Clearly, water and bread were on every list, as the shelves at the 24-hour supermarket didn’t have a drop of bottled water. The only remaining bread was a cranberry concoction that sat on an otherwise bare shelf, examined closely perhaps by a desperate shopper and discarded at a rakish angle, a lone bread crumb telling the tale of the hurricane hurry.

Gas stations brought the same crowds, as drivers were as anxious as they would be on Long Island to gather fuel before trucks might be delayed and gas lines could grow.

People often referred to 1989, when Hurricane Hugo ripped through Charlotte.

Two days before the hurricane reached the area, the public schools closed despite the clear skies and the relatively calm winds. Several of the schools transformed into shelters for residents of the city and for those fleeing from points further east.

The day before the storm, a local bank teller told me about a nearby store that received a new water shipment. The parking lot for this rare find was as empty as the shelves were full of fresh water.

On the day of the hurricane, the forecast for the area called for squalls and heavy rains through much of the day. We stared outside, judging how far the trees bent over and how hard the sheets of rain were blown into our windows. Did we dare go out, especially when we didn’t know areas of local flooding all that well?

I called the local bagel store, where the man who answered the phone said the store planned to remain open through the afternoon.

We looked at trees that provide shade for us in a typical day and are homes for all manner of songbirds to see if we could figure out which of our arboreal friends were the most dangerous — and vulnerable — in the storm.

Eager to get fresh food and to leave the house before it was impossible, we drove around a few downed branches to the store, where we made the mistake of shopping when we were hungry and in provision mode.

When our teenage children awoke, we triumphantly presented the food. They seemed mildly impressed.

We still had electricity until Sunday afternoon, up until the time when we learned that schools would be closed for another day, as trees were removed from the area and power companies restored energy.

The calls and emails from outside the state continued to come in, as supportive friends continued to check to see how we were doing.

Even as other areas of the state dealt with unprecedented flooding, strong winds and tornadoes, we considered ourselves fortunate only to have lost a few trees and power for a day.

As with the response to Hurricane Sandy, our new neighbors in Charlotte offered advice. We may have moved to a fresh environment, but we were heartened by the support from up close and afar in the face of nature’s fury.

By Daniel Dunaief

We have to walk before we can learn to run. It’s a common metaphor that suggests learning new skills, like playing the bassoon, requires a comfort level with notes and scales before taking on complex compositions.

As it turns out, the expression also applies literally and evolutionarily to the part of our anatomy that is so instrumental in enabling us to walk and, eventually, run — the foot.

Carrie Mongle. Photo courtesy of SBU

Carrie Mongle, a doctoral candidate in the Interdepartmental Doctoral Program in Anthropological Sciences at Stony Brook University, recently joined a host of other researchers, including former SBU scientist Peter Fernandez and current clinical assistant professor in biomedical sciences at Marquette University, in a study on the evolution of bones in the foot that made the transition to a bipedal lifestyle possible.

Published in the journal Proceedings of the National Academy of Sciences (PNAS), the work by Fernandez, Mongle and other collaborators explored the forefoot joints of ancient hominins, looking at primitive primates from as far back as 4.4 million years ago.

By comparing the toe joint shapes of fossil hominins, apes, monkeys and humans, they were able to find specific bony shapes in the forefoot that are important in the development of bipedal locomotion — or walking on two feet.

“This study demonstrates that early hominins must have been able to walk upright for millions of years, since the 4.4-million-year-old fossil Ardipithecus ramidus, but that they did not fully transition to a modern walk until much later, perhaps in closer relatives within our own group, Homo,” Mongle explained in an email.

While modern humans are most pronounced in doming, a few primates that walk on the ground have similar foot biomechanics to bipedalism and have similar morphologies in their toes. Those, however, aren’t expressed exactly the same way because their toe bones look different from hominins generally, she explained.

Like the drawings so often associated with a knuckle-walking ancestor that transition to a familiar outline of a person walking, the foot also went through various stages of development, balancing between the need to grasp onto objects like tree limbs and an efficient ability to walk, and then run.

“The foot is a complex assemblage of bones, so it makes sense that not all of them would have changed at exactly the same time,” Mongle suggested. “Our study supports the hypothesis that the transition to bipedalism was a gradual, mosaic process.”

Mongle got involved in this study after discussions with Fernandez, who was at SBU two years ago when the work began. Fernandez suggested to her that, “If we team up together, we can combine our interests and answer some questions about this feature,” she recalled.

Fernandez and Mongle found this dome shape developed in the foot bone even as this early fossil still maintained the ability to grasp tree limbs or other objects.

Fernandez and several other researchers involved in the study collected the data from the fossils, while Mongle, who focuses on cranial morphology and teeth in her own research, performed the evolutionary modeling. “My role in this research was in analyzing and explaining the evolutionary models, which allowed us to reveal the timing and sequence of events that produced the modern human forefoot,” she explained.

As for her doctoral research, Mongle is broadly interested in updating the hominin family tree. She uses mathematical models to look at variations in the fossil record. She is currently studying a cave in South Africa, where researchers have been recovering fossils since the 1930s.The cave has a considerable number of teeth that are all blended together from a period of between 2.5 million and 3 million years ago.

The teeth could tell a more complete story about how human ancestors divided up the food and local resources available to them. If different species were in the same space, they might have divided up into different groups to relieve competitive stress.

Frederick Grine, the chairman in the Department of Anthropology at SBU, offered a strong endorsement of Mongle’s research.“I have no doubt whatever that her work on the cranium and the dentition will provide invaluable insights into human phylogeny,” he wrote in an email, calling her an “exceptionally gifted research scientist” and described her as having an “extremely keen intellect.”

One of Mongle’s overarching research questions is, “How did we become human?” Reconstructing the phylogenetic tree is an important part of that exploration.

While it isn’t central to her thesis work, Mongle appreciated the opportunity to explore the transition to bipedalism, which is one of the “major turning points” in the development of humans.

Mongle explained that several possibilities exist on why human ancestors might have stood upright and walked on two feet.

“One of the prevailing theories is that upright walking may have evolved because climate change led to a loss of forests,” she wrote in an email. “As a consequence of walking upright, we now have free hands to carry tools.

Bipedalism evolved from a type of locomotion that was already efficient, so the question of its evolution remains open and is “hotly debated,” Mongle explained.

The next steps, literally and figuratively, are to study other bones in the feet. “We only looked at one particular part of the foot,” she said. “We would like to expand these approaches to using other bones in the forefoot,” seeking patterns and changes that would also contribute to a bipedal lifestyle.

Mongle, who started her doctoral research in 2012, hopes to graduate from the program next May, at which point she will be looking for postdoctoral research opportunities.

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I didn’t see a horrifying and preventable accident this morning. I didn’t see a little girl, let’s call her Erica, on her way to her first week of school.

Erica, who, in our story, is 10 years old, wants to be a veterinarian, and has pictures of animals all over her room. She begged her parents so long for a kitten that they relented. They saw how well she took care of the kitten, putting drops in her eyes when she needed them, making sure she got the correct shots and even holding her kitten in the office when they had to draw blood to test for feline leukemia, which, fortunately, her kitten didn’t have.

Two years after she got her kitten, Erica continued to ask for additional animals, adding a fish, a rabbit and a hamster to her collection. Each morning, Erica wakes up and checks on all the animals in her little zoo, well, that’s what her father calls it, to see how they’re doing.

Her mother is convinced that the animals respond to her voice, moving closer to the edge of the cage or to the door when they hear her coming. When mother leaves to pick up Erica from school, the animals become restless.

I didn’t see Erica walking with her best friend Jenna. Like Erica, Jenna has a dream. She wants to pitch for the United States in softball in the Olympics. Jenna is much taller than her best friend and has an incredible arm. Jenna hopes the Olympics decides to have softball when she’s old enough and strong enough to play. Jenna thinks bringing a gold medal to her father, who is in the Marines and has traveled the world protecting other people, would be the greatest accomplishment she could ever achieve.

I didn’t see a man, whom I’ll call Bob and who lives only four blocks from Erica and Jenna, put on his carefully pressed light-blue shirt with the matching tie that morning. I didn’t witness him kissing his wife Alicia, the way he does every morning before he rushes off to his important job. I didn’t see him climb into his sleek SUV and back quickly out of his driveway on the dead-end block he and Alicia chose more than a dozen years earlier.

I didn’t see Bob get the first indication from his iPhone 7 that he had several messages. I didn’t witness Bob rolling his eyes at the first few messages. I didn’t see him drive quickly toward the crosswalk where Erica and Jenna were walking. The girls had slowed down in the crosswalk because Jenna pointed out a deer she could see across the street in a backyard. Jenna knew Erica kept an animal diary and she was always on the lookout for anything her friend could include in her cherished book.

I didn’t see Bob — his attention diverted by a phone he had to extend to see clearly — roll too quickly into the crosswalk, sending both girls flying. I didn’t see the ambulances racing to the scene, the parents with heavy hearts getting the unimaginable phone calls, and the doctors doing everything they could to fix Jenna’s battered right arm — her pitching arm.

I didn’t see it because it didn’t happen. What I did see, however, was a man in an SUV, driving way too quickly through a crosswalk, staring at his phone instead of looking out for Erica, Jenna and everyone else’s children on his way to work.

It’s an old message that we should repeat every year: “School is open, drive carefully.”

This Column is reprinted from September 14, 2017 issue.

Ute Moll. Photo courtesy of Stony Brook University

By Daniel Dunaief

In the battle against cancer, human bodies have built-in defenses. Cancers, however, can hijack those systems, turning them against us, not only allowing them to avoid these protective systems, but converting them into participants in a process that can often become fatal.

Such is the case for the p53 gene. One of the most closely studied genes among researchers and clinicians, this gene eliminates cells with damaged DNA, which could turn into cancer. Mutations in this genetic watchdog, however, can turn this genetic hero into a villainous cancer collaborator. Indeed, changes in the genetic code for p53 can allow it to produce a protein that protects cancer from degradation.

Ute Moll. Photo courtesy of SBU

Ute Moll, professor and the vice chair for research in the Department of Pathology at the Stony Brook University School of Medicine, has made important strides in studying the effect of mutations in this gene over the last five years, demonstrating how the altered gene and the protein it creates are an important ally for cancer.

Moll published her most recent finding in this arena in the journal Cancer Cell. The Stony Brook scientist, working with an international team of researchers that included collaborators from her satellite lab at the University of Göttingen, advanced the work on previous results.

This research, which is done on mice that develop tumors through a process that more closely resembles human cancer growth, is a “very good mimic in the molecular and clinical features of human colon cancer,” Moll said.

The main research was done on a faithful mouse model of human colorectal cancer that produces mutant p53, Moll explained. She then confirmed key findings in human colon cancer cells and in survival analysis of patients.

This model allowed Moll to “study tumors in their natural environment in the intact organism with its tumor surrounding connective tissue and immune system,” Ken Shroyer, the chairman of the Department of Pathology at SBU School of Medicine, explained in an email.

The tumors that develop in these mice are driven by mutant p53 and are dependent on it for their continued growth. “These tumors overexpress mutant p53 at high levels,” which makes them a “formidable drug target for their removal,” Moll said.

By deleting the mutant p53 gene, she was able to slow and even stop the progression of the cancer. “We can show that when we remove mutant p53 either genetically or pharmacologically, we are cutting down invasiveness.” Mice with deleted mutants had fewer and smaller tumors and showed over a 50 percent reduction in invasive tumor numbers, she explained.

Finding ways to mitigate the effect of mutant p53 is important for a wide range of cancers. The mutated version Moll studied is the single most common p53 mutation in human cancer, which has a mutation that switches an amino acid for an incorrect one. This amino acid change destroys the normal function of the p53 gene.

The mutation she studies represents about 4.5 percent of all cancers. That amounts to 66,000 cancer patients in the United States each year.

More broadly, mutations in p53 in general, including those Moll didn’t study, are involved in half of all human cancers, Shroyer explained, which makes it the “single most common cancer mutation.”

Yusuf Hannun, director of the Stony Brook University Cancer Center, suggested that the work Moll did could have important clinical implications.“The deciphering of this mechanism clearly indicates new cancer therapy possibilities,” Hannun wrote in an email. The models she worked with are “quite promising.”

In addition to finding ways to stop the progression of cancer in mice with this damaged gene, Moll and her colleagues also used an Hsp90 inhibitor, which blocks a protein that protects the mutant protein from being degraded.

Inhibiting this protein has other positive effects, as the inhibitor eliminates other co-mutant proteins that could also drive tumors. “We are hitting multiple birds with one stone,” Moll said.

Hsp90 inhibitors are a “complicated story” in part because they have strong side effects in the liver and the retina. Researchers are working on the next generation of inhibitors.

A class of anti-cholesterol drugs called statins, which Moll called “one of the blockbuster drugs of medicine,” also has mutant p53 degrading effects, which work against some mutants, but not in others. The benefits are inconsistent and involve confounding variables, which makes interpreting their usefulness difficult, she added.

Moll said her recent article in Cancer Cell has triggered a number of email exchanges with a range of people, including with a patient whose cancer involved a different type of mutation. She has also had discussions with researchers on several other possible collaborations and has started one after she published her recent work.

The scientist is hopeful that her studies will continue to contribute to an understanding of the development and potential treatment of cancer.

Degrading mutant p53 has shown positive results for mice, which indicates “in principle” that such an approach could work down the road in humans, she suggested.

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