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Authors Posts by Daniel Dunaief

Daniel Dunaief

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They aren’t unicorns, tooth fairies or fantastic creatures from the C.S. Lewis “Narnia” series. And yet, for a Long Islander who spent considerable time standing knee deep in the waters around West Meadow Beach, listening to the aggressive screech of territorial red-winged blackbirds, the sight of a green ruby-throated hummingbird moving forward and backward in North Carolina brought its own kind of magic.

By the time I got out my cellphone and clicked open the camera app, the bird had disappeared.

While there are hummingbirds that periodically appear on Long Island, the sight of one in Charlotte so soon after our move here seemed like a charming welcome from the nonhuman quarters of Southeastern life.

Behind a Chili’s and Qdoba — yes, they are side by side in a strip mall here — we discovered a spectacular lake with a small walking path over the water near the shore. Looking down, we saw numerous fish hovering below and, to our delight, a collection of turtles, who all clearly have an appetite for the leftovers from the nearby restaurant.

We have also seen, and felt, considerably more bugs and mosquitoes, while we’ve heard cicadas, which, unlike the 17-year kind on Long Island, emerge here every year.

So, what about the two-legged creatures?

After the initial shock from the level of consideration other drivers displayed, it’s become clear that:

(a) The Northeast hasn’t cornered the market on aggressive and anxious drivers.

(b) You can take the New Yorker out of New York, but you can’t take New York out of the New Yorker.

Until I get North Carolina license plates, I have been driving the speed limit on smaller, local roads. Other cars have tailgated me so closely that I can practically read their lips as they talk on the phone or sing songs.

I watched a woman in a Mustang convertible, with rap music shouting profanities, weave in and out of traffic as her long hair waved in the breeze behind her. From a distance, the music and expletives were one and the same.

We have also seen an extensive collection of tattoos. A young FedEx driver climbed out of her truck and rang the bell to deliver a package. Her arms were so covered in colors and designs that it was difficult to discern a theme or pattern.

I walked into a supermarket behind a young couple pushing a baby stroller. The father had tattoos along the back of his muscular calves, while body ink adorned the well-defined shoulders and arms of his wife. I wondered if and when their young child might get her first tattoo.

When they find out we’re from the Northeast, people in North Carolina frequently become self-deprecating about their inability to handle cold weather. They laugh that flurries, or even a forecast for snow, shuts down the entire city of Charlotte. They assure us that no matter how much we shoveled elsewhere, we won’t have to lift and dump snow by the side of the road.

They ask how we’re handling the heat, which is often in the mid-90s, and the humidity, which is fairly high as well. While the three H’s — hazy, hot and humid — are my least favorite combination, I have certainly experienced many warm summers on Long Island, where shade or a trip into the ocean or a pool provide small comfort in the face of oppressive warmth.

With birds and insects of all sizes flying around, and drivers weaving in and out of traffic, North Carolina has displayed an abundance of high-energy activity.

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Stephanie Maiolino. Photo by Elizabeth Anne Ferrer

By Daniel Dunaief

This one’s a head scratcher, literally.

For years, people assumed early primates — small creatures that lived 55 million years ago — had nails. That, however, is not the complete story, as Stony Brook University Assistant Professor Stephanie Maiolino and a team of researchers discovered.

In addition to nails, which lay flat on our fingers and which make it easy to scratch an itch after a mosquito bite, earlier primates had something called grooming claws. These claws, which were on the toes next to their big toes, allowed them to remove external parasites like ticks and lice, which likely helped them survive against an onslaught of various critters eager to steal, or even infect, some of their blood.

Maiolino, who is in the Department of Anatomical Sciences at SBU, teamed up with lead author Douglas Boyer, an associate professor in the Department of Evolutionary Anthropology at Duke University; Johnathan Bloch, the Florida Museum of Natural History curator of vertebrate paleontology at University of Florida; Patricia Holroyd, a senior museum scientist at UC-Berkeley’s  Museum of Paleontology; and Paul Morse, from the Florida Museum of Natural History at the University of Florida at Gainesville to report their results recently in the Journal of Human Evolution.

“It was generally assumed that only a certain type of primate had grooming claws,” Maiolino said. “Finding these structures was quite surprising.”

Maiolino spent considerable time during her doctoral work, which she conducted at SBU prior to becoming an instructor at the university, analyzing the differences in the bones of species that have nails, claws and grooming claws. By understanding the anatomical features of the phalanges — or fingers and toes — leading up to the claws or nails, Maiolino was able to go back into the fossil record to explore the prevalence of these digit protrusions.

Oftentimes, she suggested, researchers collect a bone, or even a fragment of a bone, in which a nail or claw is almost never preserved in the fossil record. Maiolino used her analysis to extrapolate the parts that extend beyond the remaining fossils.

While nails sit on the end of fingers, grooming claws stick up, which puts them in an ideal position for combing through hair, which would allow the primates to remove pests that could compromise their health or threaten their survival.

“From a functional standpoint, it’s often overlooked how important the need to remove these parasites [is],” she said. When people see lemurs whose ears are completely covered in ticks or they hear about dogs that have so many ticks on them that the dog is at risk of dying, they recognize that “having an adaptation to help you remove them is actually surprisingly a big deal.”

Like any other adaptation, however, the development of these grooming digits comes with a cost. Instead of having that digit available for locomotion or grasping branches, it becomes more useful in removing unwanted insects. “There are significant pressures shaping the feet of these primates,” said Maiolino.

To provide some perspective on the importance of grooming claws, Maiolino highlighted how the primates from the fossil record were not much bigger than a mouse. Having less blood because they are smaller than current primates, and dealing with ticks that are closer to their size, suggests that the health consequences of an infestation are much greater.

As primates became more social — interacting with other members of their species and taking turns grooming each other — the pressure to have these grooming claws may have reduced.

Nonetheless, Maiolino said, a few primates that spend hours each day picking ticks off each other in a process called allogrooming still have these claws. “Some of the animals that do have [the claws] groom each other considerably,” she said, which suggests that there is still work to do to understand the evolution of these features.

When Maiolino and her collaborators first started exploring the claws versus nails discussion, they knew that researchers believed anthropoids didn’t have them.

“Now we know that anthropoids did,” she said. “We’re getting more of a sense of the distribution” of these claws.

From here, Maiolino would like to continue to explore the evolutionary trajectory from claw-bearing nonprimates to nail-bearing primates. There are a “lot of questions about why early primates ended up evolving nails in the first place,” she said.

William Jungers, a distinguished professor emeritus at Stony Brook University who was Maiolino’s doctoral thesis adviser, described her as “an outstanding and innovative young scientist with a very bright future as an educator and comparative anatomist.” He said Maiolino uses “cutting edge imaging methods to advance our understanding of primate origins and paleobiology, especially the evolution of unique aspects of primate hands and feet.”

Jungers explained that claws and nails are the “key features linked to both locomotion and social behavior.”

Maiolino, who currently lives in Port Jefferson, said when she visits zoos, she’s always on the lookout for the way primates and other mammals use their nails or claws. She also studies photographs and videos.

When she first started graduate school, Maiolino was much more interested in skulls than in nails. Once she linked nails and claws, however, to questions about primate origins, she became much more interested in them.

Outside of the lab, Maiolino said she enjoys watching horror movies. One of her favorites is the second “Aliens” film in the Signourney Weaver centered franchise. She is also a fountain pen enthusiast.

Back in high school in New Jersey, Maiolino  was especially interested in studying evolution. Embryology and embryological development appealed to her, as she was amazed by how growth in the womb affected what organisms became.

As for her work, a Holy Grail question for her would be to better understand why primates developed nails in the first place. She’s trying to understand the interplay between body size, behavior and other variables that affected these structures.

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The president of the United States is taking full credit for the relief those crazy leftist environmental groups are feeling in response to the resignation of the latest misunderstood and much maligned member of his cabinet, Scott Pruitt.

You see, President Donald Trump knew that Pruitt would do his bidding, gutting unnecessary government regulations designed to protect the water, air and food that Americans and, indeed, others on the planet need on a daily basis.

He knew Pruitt would do everything he asked, and more. It’s like the old Stalin philosophy. You remember that ruthless Soviet Union dictator, right? He never wanted any of his tank commanders to be too powerful because he didn’t want their leader taking over.

So, he chose Pruitt knowing that he’d do what Trump wanted and then would become so enmeshed in the world he tried to help — lobbyists, coal interests, insecticide manufacturers — that he would eventually cause harm to himself and his political aspirations.

Trump is, rightfully, taking full credit for the resignation of a man he supported when it was expedient to do so and that he needed to cut loose when the combination of foibles and follies entered the public realm.

Sure, some nasty journalists may have quoted unnamed sources who shared questionable details about Pruitt’s spending habits, his requests for football tickets, his security detail and his desire to get his wife a job. Ultimately, it was Trump who made the call, putting the thorn in the side of the environmental groups and then pulling it out ever so quickly and gracefully.

Well, maybe it wasn’t all that quick. Pruitt lasted far longer in Washington than even members of the “Trump Party” — that’s the new name of the group formerly known as the Republican Party — might have wanted. But, hey, the more people who found Pruitt’s actions and decisions questionable, the greater the relief when he was finally removed from office.

OK, so technically the guy resigned, which means he walked out of the seat of power and into an enormous gas-guzzling sport utility vehicle. But, seriously, does anyone believe Pruitt thought he blew it on his own? No, no, people, wake up. News that the environmental groups all thought was good because they imagined that the EPA might return to its mandate of protecting the environment and the people, animals and trees living here came courtesy of His Truly: President Trump.

Yes, of course, you can thank him for taking nuclear weapons out of the hands of the North Koreans, and you can express your appreciation for the incredibly kind way he pulled back from a zero-tolerance policy he established because of laws the Democrats won’t fix, but don’t forget to give credit where credit is due.

You see, if the president had never tapped Pruitt, who built his career attacking the henhouse that was the EPA from his home in Oklahoma, the greenie groups would never be able to celebrate his removal. No, it’s a total credit to Trump that the reality TV show that was the Pruitt era at the EPA has been canceled.

So, take your time, think of the right words and make sure to thank the man in charge of the world for choosing the right man at the right time and then letting that man walk off into a sunset enhanced by all the pollution-generated particulates he helped put there.

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Camila dos Santos speaks at the Pershing Square Research Alliance’s Fifth Annual Prize Dinner at the Park Avenue Armory on May 23 with Bill Ackman, co-founder of the Pershing Square Sohn Foundation and CEO of Pershing Square Capital Management, and Olivia Tournay Flatto, the President of the Pershing Square Foundation.

By Daniel Dunaief

They aren’t quite wonder twins, but some day the dedicated work of husband and wife scientists Christopher Vakoc and Camila dos Santos may help people batting against a range of cancers, from leukemia to breast cancer.

An assistant professor at Cold Spring Harbor Laboratory, dos Santos recently won the prestigious and highly coveted Pershing Square Sohn prize. Dos Santos, who studies breast cancer, will receive $200,000 in funds per year for the next three years. She won the same prize her husband, an associate professor at Cold Spring Harbor Laboratory, collected two years earlier for his work using the gene-editing technique CRISPR to study the molecular pathways involved in leukemia.

Dos Santos and Vakoc are the first family of prize winners in the Pershing Square Foundation’s five years of supporting research in the New York area.“The board was very much taken by how original her approach is and how thoughtful she is about it,” said Olivia Tournay Flatto, president of the foundation. “There was a lot of early stage data that would say that the observations she’s making are interesting to pursue, but that the National Institutes of Health would not fund. We felt this was something we wanted to be a part of.”

Dos Santos is studying so-called epigenetic changes that protect women from breast cancer if they become pregnant before they are 25. Women who have pregnancies before that cut-off age have a 30 to 40 percent decrease in breast cancer, even decades after their pregnancy.

Dos Santos has been digging into this process, looking at why some women who are pregnant before this age still develop breast cancer later in life.

The Cold Spring Harbor scientist is exploring how infections block the protective effects of pregnancy. She hasn’t defined the panel of infections that could influence cancer risk before or after pregnancy. The hypothesis in her work is that “the whole process that is fighting inflammation could change the breast cells,” which could “take away the advantage that pregnancy brings.”

If she proves her theory — that changes to inflammation could take away benefits of an early pregnancy — she could define changes to proteins and genes as biomarkers to predict the risk of breast cancer, even in the event of an early pregnancy. One of the challenges in the three-step application process for this prize was to explain to a group of experts how what she’s doing was different from what others are pursuing. Her approach is to look at cells before and during the process of turning into cancer cells. That strategy led to the current hypothesis, which was the basis for her application for this prize.

To study breast cancer, dos Santos recently developed a mouse model in her lab, to see how pregnancy changes pre-malignant lesions. When the mice they are studying have a gene that would turn into cancer, some of them don’t develop cancer if they’ve already been pregnant. Those mice that haven’t been pregnant develop cancer. She uses this mouse model to ask questions about how pregnancy changes a cell such that oncogenes cannot operate to change a cell into a cancer.

“We are not only investigating how prevention works, but we are also learning what signals break that prevention,” dos Santos said.

Dos Santos has used the mouse model experiments to test an unusual element to human breast cancer resistance. Women who reach their second trimester before 25, but don’t give birth to a child, have the same resistance, decades later, to breast cancer. Mice whose pregnancies last through the equivalent of the second trimester also experience similar epigenetic benefits.

She has tested mice who have a pseudo-pregnancy —who have higher pregnancy hormone levels without being pregnant — to see if a similar pregnancy environment would convey the same resistance. “Even in those cases, with no fetus, no embryo, no birth and no nursing, we see that the epigenetics changes,” dos Santos said. The scientist plans to use the funds from this award to perform high-tech experiments, such as single-cell, multiple mouse models and human tissue analysis that she wouldn’t have been able to tackle without the funding.

Dos Santos is grateful for the funding, which she said she wouldn’t have been able to secure through other means based on “the stage we are right now,” she said. The work is “risky” and “provocative,” but it’s also “outside of the box ideas and experiments and approaches.”

When she puts all the variants together, the risky outcome could be beneficial, leading to a better understanding of how to copy or, perhaps, understand nature to try to cure or prevent cancer.

Dos Santos said she learned about the award when she was on a train on the way to Jamaica, where she was catching a flight to Washington, D.C. She said she turned into a “texting machine,” sharing the good news with everyone, including her husband Vakoc, who called her as soon as he saw the news. “He was super happy,” she recalled.

She said Vakoc was particularly helpful in discussing the work and in watching their sons Lucas and Marcus who are 8 and 5, respectively. She also received some unexpected help from him before an extensive seven- to eight-minute finalist screening process.

She asked him about the interview, and he remembered that there were five people in the audience and that he didn’t get that many questions. When she appeared for her interview, she saw about 25 people in the audience and received numerous questions. In a way, she said, his memory of his experience may have helped her, because she didn’t have time to worry about the size of the audience or the number of questions.

Dos Santos said their sons are proud of their parents for winning awards for their work on cancer.

When her sons are upset with dos Santos, they sometimes warn, reflecting their parents’ threat to take away TV, that they’re going to “take your epigenetics away.”

Dos Santos said the couple maintains a healthy work-life balance. She is grateful for her husband’s support, as well as for the environment and expertise at Cold Spring Harbor Laboratory.

“Here at the lab, we not only have the technology to move this forward, but we also have a pretty outstanding body of scientists that are very collaborative,” she said.

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By Daniel Dunaief

Replacing batteries in a flashlight or an alarm clock requires simple effort and generally doesn’t carry any risk for the device. The same, however, can’t be said for battery-operated systems that go in human bodies and save lives, such as the implantable cardiac defibrillator, or ICD.

Earlier versions of these life-saving devices that restore a normal heart rhythm were large and clunky and required a change of battery every 12 to 18 months, which meant additional surgeries to get to the device.

Esther Takeuchi with Michaëlle Jean, the secretary general of the Organisation Internationale de la Francophonie, and moderator Fernando Tiberini at the award ceremony in Paris on June 7. Photo courtesy of European Patent Office

That’s where Esther Takeuchi, who is now Stony Brook University’s William and Jane Knapp Endowed Chair in Energy and the Environment and the chief scientist of the Energy Sciences Directorate at Brookhaven National Laboratory, has made her mark. In the 1980s, working at a company called Greatbatch, Takeuchi designed a battery that was much smaller and that lasted as long as five years. The battery she designed was a million times higher power than a pacemaker battery.

For her breakthrough work on this battery, Takeuchi has received numerous awards. Recently, the European Patent Office honored her with the 2018 innovation prize at a ceremony in Paris. Numerous high-level scientists and public officials attended the award presentation, including former French Minister of the Economy Thierry Breton, who is currently the CEO of Atos, and the Secretary General of the International Organisation of Francophony Michaëlle Jean. 

Takeuchi was the only American to win this innovation award this year.

Takeuchi’s work is “the epitome of innovation, as demonstrated in this breakthrough translational research for which she was recognized,” Dr. Samuel L. Stanley Jr., the president of Stony Brook and board chair of Brookhaven Science Associates, which manages Brookhaven National Laboratory. “Her star keeps getting brighter, and I’m proud that she is part of the Stony Brook University family.”

As a winner of this award, Takeuchi joins the ranks of other celebrated scientists, including Shuji Nakamura, who won the European Inventor Award in 2007 and went on to win the Nobel Prize in physics, and Stefan Hell from Germany, whose European Inventor Award predated a Nobel Prize in chemistry. 

Among the over 170 innovators who have won the award, some have worked on gluten substitutes from corn, some have developed drugs against multi-drug-resistant tuberculosis, and some have developed soft close furniture hinges.

“The previous recipients have had substantial impact on the world and how we live,” Takeuchi explained in an email. “It is incredible to be considered among that group.” Nominated for the award by a patent examiner from the European Patent Office, she described the award as an “honor” for the global recognition.

The inventor award is a symbolic prize in which the recipients receive attention for their work, explained Rainer Osterwalder, the director of media relations at the European Patent Office.

Takeuchi was one of four women to receive the award this year — the largest such class of women innovators.

“It was very meaningful to see so many accomplished women be recognized for their contributions,” she explained. “I was delighted to meet them and make some additional contacts with female innovators as well.”

About half the researchers in her lab, which currently includes three postdoctoral researchers and usually has about 12 to 16 graduate students, are women. Takeuchi has said that she likes being a role model for women and that she hopes they can see how it is possible to succeed as a scientist.

Implantable cardiac defibrillators are so common in the United States that an estimated 10,000 people receive them each month.

Indeed, while she was at the reception for an awards ceremony attended by over 600 people, Takeuchi said she met someone who had an ICD.

“It is very rewarding to know that they are alive due to technology and my contributions to the technology,” she explained.

Takeuchi said that many people contributed to the battery project for the ICD over the years who were employed at Greatbach. These collaborators were involved in engineering, manufacturing, quality and customer interactions, with each aspect contributing to the final product.

The battery innovation stacks alternating layers of anodes and cathodes and uses lithium silver vanadium oxide. The silver is used for high current, while the vanadium provides long life and high voltage.

Takeuchi, who earned her bachelor’s degree from the University of Pennsylvania and her doctorate from Ohio State University, has received over 150 patents. The daughter of Latvian emigrants, she received the presidential level National Medal of Technology and Innovation from Barack Obama and has been inducted into the National Inventors Hall of Fame.

Takeuchi continues to push the envelope in her energy research. “We are now involved in thinking about larger scale batteries for cars and ultimately for the grid,” she wrote in an email. “Further, we have demonstrated methods that allow battery components to be regenerated to extend their use. This could potentially minimize batteries going into land fills in the future.”

Takeuchi is one of a growing field of scientists who are using the high-tech capabilities of the National Synchrotron Light Source II at BNL, which allows her to see inside batteries as they are working.

“We recently published a paper where we were able to detect the onset of parasitic reactions,” she suggested, which is “an important question for battery lifetime.”

In the big picture, the scientist said she is balancing between power and energy content in her battery research.

“Usually, when cells need to deliver high power, the energy content goes down,” she said. “The goal is to have high energy and high power simultaneously.”

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Want to know why biscuits in North Carolina are so much better than they are in the rest of the world?

I did, which was why I interrupted a woman who was loading her groceries at a Harris Teeter supermarket and chatting with the cashier.

One word: love.

“Well, it’s love and a lot of butter,” she said. “You can’t be afraid of the butter.”

She suggested that biscuits were invented in North Carolina and that everyone’s grandmother has a recipe for them. They all taste somewhat different, but they’re all so much better than everywhere else.

That was just one of the many stories we’ve overheard ever since we picked up our two high-school-aged kids, threw our unwitting and desperately frustrated cats into their carriers, and relocated to the Tar Heel State.

Putting the cats in the carriers is always challenging, but it was as if they recognized that the trip would
be especially difficult for them. The older one, who is cautious and only likes members of our family, stuck his paws out as we tried to lower him into the case.

It reminded me of all the times our children used to arch their backs as we tried to put them in the car seat. Reasoning with the cats didn’t work, but eventually we won the battle.

We arrived here during a heat wave in the Northeast. As it turns out, our first few days have been a few degrees cooler than what we left behind. Our son observed on the way to the airport that we used to make this drive when we were leaving home, but we were now taking the drive toward a plane that would take us to our new home.

Our interactions with people here have been remarkable. For starters, it really is challenging to find someone who is originally from Charlotte. We have met people from Connecticut, Pennsylvania, New York and New Jersey.

The Northeasterners have universally described how much they enjoy living here. Some of their own complaints are the lack of bagels and authentic Chinese food.

People, wherever they are from when they’re here, have been noticeably courteous, even before they read our Yankees shirts, our Brooklyn Cyclones hats and the names of Northeastern schools on our attire. I was pulling out of a store with an enormous rental car. The drivers from two lanes in front of me stopped to let me go.

The North Carolinians are also more than ready to share their stories. Randal, the driver who delivered our cars, gave us advice about where to go for mechanical and auto-body needs. He also shared a few harrowing
anecdotes from his days driving a truck and responding to various emergency calls.

On my trip to the grocery store, where I met the woman who was so proud of her biscuits, I also noticed how people violate the typical New York peripheral vision rule. You know how when you’re in the city and you’re walking down the street, you’re supposed to notice people without staring at them or looking them directly in the eye? The opposite was true among the people I saw in the supermarket. They not only look you in the eye, but they greet you with a “hello” and “how are you doing?”

While I will never be able to test the North Carolina biscuit theory because of my lactose intolerance, I would have to say that, so far, our first impressions of our new state have been remarkably positive.

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First of all, we’re going to need a big cake. No, I know you think most cakes are big and that most people’s eyes are bigger than their stomachs, but this one is going to have to be huge.

You see, we’re about to celebrate an important birthday. Next week, it’s the 242nd birthday of the country, so we’ll need a place to put all the candles.

So, what do we get for the country that has everything?

Well, for starters, it depends on what you imagine represents the country. Is it the Statue of Liberty? The bald eagle? A baseball game? Mount Rushmore? The Grand Canyon?

Seriously, this is one huge country and we haven’t even discussed the last two states to join the union.

Alaska is a gem, with vistas stretching as far as the eye can see, as shimmering spawning salmon make streams and rivers glow orange, while bears nibble here and there as cars and buses pass them along the sides of the highways.

Hawaii reminded everyone this year that it’s a volcanic archipelago. It’s a magnificent and lush combination of majestic mountains, bamboo forests and striking cliffs.

So, what would this great country of ours want for its birthday?

Well, maybe it would want us, even for a day, to all get along. We are all Americans, we have all heard the
stories about the forefathers who fought for this country, who defied the British, and who wanted what was best for them and, all these years later, us.

Maybe it would want us to tidy up. After all, who doesn’t want to look good on their birthday, right? We could clean up our yards, clean up our neighbor’s yard, remove trash from the area around the school, a place so many enthusiastic children recently abandoned for the start of the summer.

Maybe we should take a moment to think about how we are helping ourselves, or others, reach the American Dream. We all want life to be better, but maybe we can encourage others to strive for, and reach, a dream that anyone from anywhere could reach greatness. We are not like Europeans of past centuries, who limited
opportunities for success by class, gender or ancestry.

The home of the free and the land of the brave is all about allowing anyone from any walk of life to reach their potential and, more importantly, to decide their potential.

America is about celebrating youth. We are a young country, filled with hope for the future, unbridled
optimism and joy.

Regardless of what politicians in Washington say, we are also a country that likes to laugh, even at ourselves. We have a great sense of humor. Need a laugh? Watch “Bridesmaids” or “Groundhog Day” — or if in the mood for something older, “Animal House.”

We pull apart and then we come together. We speak with different accents, depending on where we come from or what part of the world our ancestors originally inhabited.

When we come together, we are unstoppable, finding our best selves from the roles we play in companies, on teams, or in close-knit families that stand ready, willing and able to support each other through any challenge.

Sure, we can hang the flag, eat a hot dog, have a barbecue and sing a few American songs to celebrate our country. But, hey, maybe we can also look for the best in each other and in ourselves as we again give hope to the notion that a rising tide of optimism, of cooperation, of compassion lifts all boats.

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Hervé Tiriac during a recent visit to the University of Nebraska Cancer Center. Photo by Dannielle Engel

By Daniel Dunaief

What if doctors could copy human cancers, test drugs on the copies to find the most effective treatment, and then decide on a therapy based on that work?

Hervé Tiriac, a research investigator at Cold Spring Harbor Laboratory, moved an important step closer to that possibility with pancreatic cancer recently.

Tiriac, who works in the Cancer Center Director Dave Tuveson’s lab, used so-called organoids from 66 patients with pancreatic ductal adenocarcinoma tumors. These organoids reacted to chemotherapy in the same way that patients had. 

“This is a huge step forward,” Tiriac said, because of the potential to use organoids to identify the best treatments for patients.

Hervé Tiriac. Photo by Dannielle Engel

Tuveson’s lab has been developing an expertise in growing these organoids from a biopsy of human tumors. The hope throughout the process has been that these models would become an effective tool in understanding the fourth most common type of cancer death in men and women. The survival rate five years after diagnosis is 8 percent, according to the American Cancer Society.

The study, which was published in the journal Cancer Discovery, “shows real promise that the organoids can be used to identify therapies that are active for pancreatic cancer patients,” Tuveson explained in an email. “This may be a meaningful advance for our field and likely will have effects on other cancer types.”

Kerri Kaplan, the president and CEO of the Lustgarten Foundation, which has provided $150 million in financial support to research including in Tuveson’s lab, is pleased with the progress in the field.

“There’s so much momentum,” Kaplan said. “The work is translational and it’s going to make a difference in patients’ lives. We couldn’t ask for a better return on investment.”

Tiriac cautions that, while the work he and his collaborators performed on these organoids provides an important and encouraging sign, the work was not a clinical trial. Instead, the researchers retrospectively analyzed the drug screening data from the organoids and compared them to patient outcomes.

“We were able to show there were parallels,” he said. “That was satisfying and good for the field” as organoids recapitulated outcomes from chemotherapy.

Additionally, Tiriac’s research showed a molecular signature that represents a sensitivity to chemotherapy. A combination of RNA sequences showed patterns that reflected the sensitivity for the two dominant chemotherapeutic treatments. “It was part of the intended goal to try to identify a biomarker,” which would show treatment sensitivity, he said.

While these are promising results and encourage further study, researchers remain cautious about their use in the short term because several technical hurdles remain.

For starters, the cells in the organoids take time to grow. At best right now, researchers can grow them in two to four weeks. Drug testing would take another few weeks.

That is too slow to identify the best first-line treatment for patients with advanced pancreatic cancer, Tiriac explained. “We have to try to see if the organoids could identify these biomarkers that could be used on a much shorter time frame,” he added.

Tuveson’s lab is working on parallel studies to accelerate the growth and miniature the assays. These efforts may reduce the time frame to allow patients to make informed clinical decisions about their specific type of cancer.

As for the RNA signatures, Tiriac believes this is a first step in searching for a biomarker. They could be used in clinical trials as is, but ideally would be refined to the minimal core gene signatures to provide a quick and robust assay. It is faster to screen for a few genes than for hundreds of them. He is studying some of these genes in the lab.

Researchers in Tuveson’s lab will also continue to explore biochemistry and metabolism of the organoids, hoping to gain a better insight into the mechanisms involved in pancreatic cancer.

Going forward, Tiriac suggested that his main goal is to take the gene signatures he published and refine them to the point where they are usable in clinical trials. “I would like to see if we can use the same approach to identify biomarkers for clinical trial agents or targets that may have a greater chance of impact on the patients,” he said.

The research investigator has been working at Tuveson’s lab in Cold Spring Harbor since the summer of 2012.

Tuveson applauded Tiriac’s commitment to the work. Without Tiriac’s dedication, “there would be no Organoid Profiling project,” Tuveson said. “He deserves full credit for this accomplishment.”

Tiriac lives in Huntington Station with his wife Dannielle Engle, who is a postdoctoral researcher in the same lab. He “really enjoyed his time on Long Island,” and suggested that “Cold Spring Harbor has been a fantastic place to work. It’s probably the best institution I’ve worked at so far.”

He appreciates the chance to share the excitement of his work with Engle. “You share a professional passion with your loved one that is beyond the relationship. We’re able to communicate on a scientific level that is very stimulating intellectually.”

Born in Romania, Tiriac moved to France when his family fled communism. He eventually wound up studying in California, where he met Engle.

Tuveson is appreciative of the contributions the tandem has made to his lab and to pancreatic cancer research. 

“Although I could not have imagined their meritorious accomplishments when I interviewed them, [Tiriac and Engle] are rising stars in the cancer research field,” he said. “They will go far in their next chapter, and humanity will benefit.”

Kaplan suggested that this kind of research has enormous potential. “I feel like it’s a new time,” she said. “I feel very different coming into work than I did five years ago.”

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0 1861

My family has become archeologists in our own home. After 12 years of collecting artwork from the kids’ classes in school, saving report cards and filing away binders from earlier grades, we are sifting through all that material, jettisoning or recycling what we don’t need.

Some of the finds are so remarkable that they stop us in our sorting tracks. My high school daughter isn’t much of a morning person. She often prefers short sounds or gestures in the car on the way to school, rather than actual conversations that might require her to form words.

As we were going through a pile of material, we found a note from her nursery school teacher. She described a charming little girl who often takes a while to get going each morning. That description is so apt today that we realized how much of people’s patterns and personalities form early in life.

Then, sorting further, we found papers from her spectacular first-grade teacher. A young woman with a soft voice and a determined style, her teacher brought out the best in our daughter, even early in the morning.

Our daughter kept a diary in that class, in which she shared stories about the family’s weekend activities. Clearly, her brother was jealous of that writing, as we also found a diary from him in which he thanks her for creating a similar book for him to record his experiences. He shared his thoughts from the weekend, and the rest of the family readily wrote back to him.

His sister also kept handwritten notes from her first-grade teacher. The letters are all clear and distinct, and offer a positive and supportive tone. Her teacher wrote to her, without talking down to her. What a wonderful role model. This teacher, through form and content, offered a ray of sunshine to our daughter even then, which was probably why we kept the papers.

These notes today take on a different meaning for us, as the teacher succumbed to cancer at a young age just a few years after our daughter had the privilege of being in her class. Our daughter was recently in a high school English class in which her first-grade teacher’s husband served as a part-time instructor. She shared some of these notes with him. He was delighted to take them home to his daughter, who was a toddler when
her mother died. His daughter has particularly appreciated seeing her mother’s handwriting and feeling an indirect connection to the encouraging words she offered.

We have also sorted through dozens — OK, hundreds — of pictures that have transported us to earlier memories. We have a photo of our 1-year old son standing on the warning track at the old Yankee Stadium, bunched up in a winter coat on a December day.

We also found numerous pictures of our son on baseball fields of his own, surrounded by younger versions of teammates who have stuck with him through the years, as well as of friends who have gone their separate ways — or have pursued other sports.

Amid all the trophies from sports teams, we discovered certificates indicating that one or both of our children had been successful lunch helpers.

We have unearthed old VHS tapes of movies we watched numerous times as a family, including a few Disney classics and a surprisingly amusing Barbie version of “The Princess and the Pauper.”

In addition to sending us down memory lane, sorting through all the accumulated clutter has made the house seem so much larger, giving us room to add modern memories and memorabilia to our collection.

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0 2011
From left, Evan Sohn, co-founder of the Sohn Conference Foundation; Benjamin Martin, associate professor at Stony Brook University; and Bill Ackman, co-founder of the Pershing Square Foundation and CEO of Pershing Square Capital Management at an awards dinner. Photo by Melanie Einzig/PSSCRA

By Daniel Dunaief

Up and coming scientists are often stuck in the same position as promising professionals in other fields. To get the funding for research they’d like to do, they need to show results, but to get results, they need funding. Joseph Heller, author of “Catch 22,” would certainly relate.

A New York-based philanthropy called the Pershing Square Sohn Cancer Research Alliance is seeking to fill that gap, providing seven New York scientists with $600,000 each over the course of three years.

In the fifth annual competition, Benjamin Martin, an associate professor in the Department of Biochemistry & Cell Biology at Stony Brook University, won an award for his study of zebrafish models of metastatic cancer. Martin is the first Stony Brook researcher to win the prize.

Working with Assistant Professor David Matus, whose lab is across the hall and whose research team conducts weekly group meetings with Martin’s lab, Martin is able to see in real time the way grafted human tumor cells spread through blood vessels to other organs in the transparent zebrafish.

“It’s been very challenging to understand what process cancer cells are using to metastasize and leave the blood vessels,” said Olivia Tournay Flatto, the president of the Pershing Square Foundation. “With this technology, he can see what’s happening. It’s a really powerful tool.”

The work Martin presented was “really appealing to the whole board, and everybody felt this kind of project” had the potential to bring data and insights about a process researchers hope one day to slow down or stop, said Flatto.

This year, about 60 early-stage investigators applied for an award given specifically to researchers in the New York City area. When he learned that he won, Martin said, “There was some dancing going on in the living room.” He suggested that the award is a “validation” of his research work.

The process of a cancer cell leaving a blood vessel is “basically a black box” in terms of the mechanism, Martin said. It’s one of the least understood aspects of metastasis, he added.

Indeed, a developmental biologist by training, Martin is hoping to discover basics about this cancer-spreading process, such as an understanding of how long it takes for cancer cells to leave blood vessels. The process can take hours, although it’s unclear whether what he’s seen is typical or abnormal.

Martin would like to identify how the cancer cells adhere to the blood vessel walls and how and why they leave once they’ve reached their target.

Metastatic cancer is likely using the same mechanism the immune system uses to travel to the sites of infection, although researchers still need to confirm several aspects of this model.

Moving in involves interactions with white blood cells, including macrophages. With white blood cells, an area of infection or inflammation becomes activated, which triggers a reaction of adhesion molecules called selectins.

By watching a similar transport process in cancer, Martin and Matus can “see things people haven’t seen before” and can explore way to inhibit the process, Martin suggested.

He is hoping to find ways to stop this process, forcing cancer cells to remain in the blood vessels. While he doesn’t know the outcome of a cancer cell’s prolonged stay in the vessel, he predicts it might end up dying after a while. This approach could be combined with other therapies to force the cancer cells to die, while preventing them from spreading.

Through this grant, Martin will also study how drugs or mutations in selectins generate a loss of function in these proteins, which affects the ability of cancers to leave the blood vessel.

Martin plans to use the funds he will receive to hire more postdoctoral researchers and graduate students. He will also purchase additional imaging equipment to enhance the ability to gather information.

Martin appreciates that this kind of research, while promising, doesn’t often receive funding through traditional federal agencies. This type of work is often done on a mouse, which is, like humans, a mammal. The enormous advantage to the zebrafish, however, is that it allows researchers to observe the movement of these cancer cells, which they couldn’t do in the hair-covered rodent, which has opaque tissues.

“There’s a risk that these experiments may not work out as we planned,” Martin said. He is hopeful that the experiments will succeed, but even if they don’t, the researchers will “learn a great deal just from seeing behaviors that have not been observed before.”

Indeed, this is exactly the kind of project the Pershing Square Sohn Cancer Research Alliance seeks to fund. They want scientists to “put forward the riskiest projects,” Flatto said. “We are ready to take a chance” on them.

One of the benefits of securing the funding is that the alliance offers researchers a chance to connect with venture capitalists and commercial efforts. These projects could take 20 years or more to go from the initial concept to a product doctors or scientists could use with human patients.

“We are not necessarily focused on them starting a company,” Flatto said. “We think some of those projects will be able to be translated into something for the patient,” which could be through a diagnosis, prevention or treatment. “This platform is helpful for young investigators to be well positioned to find the right partners,” he added.

Aaron Neiman, the chairman of the Department of Biochemistry & Cell Biology at SBU, suggested that this award was beneficial to his department and the university.

“It definitely helps with the visibility of the department,” Neiman said. The approach Matus and Martin are taking is a “paradigm shift” because it involves tackling cells that aren’t dividing, while many other cancer fighting research focuses on halting cancer cells that are dividing.

Neiman praised the work Martin and Matus are doing, suggesting that “they can see things that they couldn’t see before, and that’s going to create new questions and new ideas,” and that their work creates the opportunity to “find something no one knew about before.”

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