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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 Engel, 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 Engel. “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 Engel.

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 Engel] 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.”

Your adventure awaits! Photo from Sue Avery

By Karen Smith

There are days when we need a break from the general craziness of life, and we just want to get outdoors to walk in a peaceful place. Three Village residents are fortunate to have a number of options for this peaceful pursuit and one of the very loveliest is the Three Village Garden Club Arboretum, accessible through the parking lot of the adjacent and separately owned Frank Melville Memorial Park, 101 Main St., Setauket.

This “hidden haven” contains 4.5 acres of wooded pathways that meander through an open meadow, past 30 varieties of specimen trees and shrubs, and offers views of the Conscience Bay headwaters. It’s a habitat for birds, butterflies, frogs, turtles and the rabbits, squirrels and deer that are found throughout our area. 

In early spring you can view the trees and shrubs starting to bud, and as the months pass there are flowers in bloom, then the fall colors and finally the stark beauty of winter. Each offers a different experience, but the feeling of tranquility always is there.

While the arboretum is open to the public, it is privately owned and maintained by the Three Village Garden Club, a 501(c)(3) nonprofit corporation. Our volunteer and hardworking arboretum administrators oversee the planting of new trees, shrubs and plants, regular mowing of the meadow, removal of invasive plants and management of bamboo. In addition, arborists are called in as needed to remove tree limbs, and when necessary, entire trees. When required, wood chips are added to pathways to ensure that trails remain dry. 

The thousands of dollars expended annually on this maintenance by the TVGC is deemed necessary to ensure the safety of all visitors and the beauty of the property. 

In addition, many hours of volunteer work are provided by members of Students Taking Action for Tomorrow’s Environment (S.T.A.T.E.), part of the Avalon organization, and at times, Scouts and of course, garden club member-volunteers.

The arboretum also is used for educational purposes, chief among which are the Arbor Day celebration held in spring and the Meet the Trees program in the fall. 

Second-grade students from all elementary schools in the Three Village School district are invited to visit and have these “hands-on” experiences to supplement their science curriculum. For the past 10 years it also has been the site of a Teddy Bear Picnic for preschoolers and their parents, offering a walk through the property to introduce them to the natural environment.

You’re cordially invited to visit! Come with a friend or family member. Leashed pets are permitted. Enjoy this beautiful haven whenever you’re in the mood for a peaceful place!

Karen Smith is a member of the Three Village Garden Club.

Aunt Edith’s Strawberry Shortcake

By Barbara Beltrami

When June finally busts out all over, local strawberries will be at their peak. Despite their slow start because of the rain, they will be their usual juicy ruby red selves ready to be picked or purchased at local farms or those out east. There will be plenty for dropping into baskets and just as many for popping into our mouths as we move between the rows. When fresh strawberries are so naturally delicious without any adornment except maybe a little sugar and cream, anything further seems like sacrilege.  

On the other hand, when they’re that good, any recipe that features them is always that much better because those little gems themselves are so good. So when you get home from your strawberry picking with your baskets of ruby treasures, consider an old-fashioned strawberry shortcake, a strawberry-arugula-radish salad with balsamic dressing or a strawberry sorbet.

Aunt Edith’s Strawberry Shortcake

 

Aunt Edith’s Strawberry Shortcake

YIELD: Makes 10 servings

INGREDIENTS:

1 quart fresh strawberries, washed and crushed

¼ cup sugar

2½ cups flour

1/3 cup sugar

1 tablespoon baking powder

¼ teaspoon salt

1/3 cup cold butter, cut into small pieces

1 cup milk

1 egg yolk, slightly beaten

2 tablespoons sugar

1 cup heavy whipping cream

1 tablespoon sugar

1 teaspoon vanilla extract

DIRECTIONS: 

Heat oven to 400 F. In a large bowl combine the berries with the quarter cup sugar and set aside. In a medium bowl combine the flour, one-third cup of sugar, baking powder and salt. Using a pastry blender or two knives, cut the butter into the flour mixture until it resembles coarse crumbs; stir in milk. Knead until dough forms, then, on a lightly floured surfaced, pat into a half-inch thickness.  

Using a 2½-inch cutter or the same-size upside-down glass, cut into 10 circles and place on ungreased cookie sheet. Brush egg yolks over tops, then sprinkle with two tablespoons sugar. Bake 10 to 15 minutes, until golden brown on top. Remove from oven and let cool 10 to 15 minutes. Meanwhile, whip cream with remaining tablespoon sugar and vanilla. Split shortcakes in half horizontally, place on plates, then spoon whipped cream and strawberries in any order you wish and replace tops. Serve immediately with hot or iced coffee or tea.

Strawberry-Arugula-Radish Salad with Balsamic Dressing

YIELD: Makes 8 servings

INGREDIENTS:

10 ounces fresh arugula, washed and dried

1 quart fresh strawberries, washed, hulled and sliced

8 radishes, washed, trimmed and very thinly sliced

½ cup olive oil

3 tablespoons balsamic vinegar

1 teaspoon raspberry vinegar

1 tablespoon orange juice

1 teaspoon Dijon mustard

1 teaspoon honey

1 whole garlic clove, peeled

Salt and freshly ground pepper, to taste

DIRECTIONS: 

Have all ingredients at room temperature. Place arugula, strawberries and radishes in a large bowl. Combine remaining ingredients in a small bowl and let sit for one hour. Remove and discard garlic. With a fork or small wire whisk, emulsify the oil, vinegars, juice, mustard, honey, salt and pepper. Pour over greens and toss thoroughly. Serve immediately as a first course or with meat, poultry or fish.

Strawberry Sorbet

Strawberry Sorbet

YIELD: Makes 1 quart

INGREDIENTS:

2 quarts strawberries, washed and hulled

1 cup sugar

1 ounce freshly squeezed lemon juice

½ ounce vodka

Pinch coarse salt

DIRECTIONS:

Place all ingredients in a food processor and puree until there are no lumps left.  Transfer to another container, cover and refrigerate 6 hours. Place in an ice cream maker and churn according to manufacturer’s directions until mixture resembles soft ice cream.  Transfer one more time to airtight container and freeze at least 4 hours. Serve with crisp cookies, biscotti or pound cake.

Alta

MEET ALTA!

This sweet girl is a 5-year-old Shiba Inu mix who recently arrived at Kent Animal Shelter from Thailand. Rescued from the meat trade industry, she had a rough start in life but that is all behind her now. Alta takes a little time to warm up to new people because she is a little shy, but her gentle nature will capture your heart if you give her a chance. Stop by and meet her today! Alta comes spayed, microchipped and up to date on all her vaccinations.

Kent Animal Shelter is located at 2259 River Road in Calverton. The adoption center is open from 10 a.m. to 4 p.m. every day. For more information on Alta and other adoptable pets at Kent, visit www.kentanimalshelter.com or call 631-727-5731. 

 

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.

Overuse may lead to serious side effects

By David Dunaief, M.D.

Dr. David Dunaief

Reflux (GERD) disease, sometimes referred to as heartburn, though this is more of a symptom, is one of the most commonly treated diseases. Continuing with that theme, proton pump inhibitors (PPIs), which have become household names, are one of the top-10 drug classes prescribed or taken in the United States. In fact, Centers for Disease Control and Prevention data shows that use has grown precipitously in the 10 years ending in 2010 for those ages 55 to 64, from 9 percent of the population to 16 percent (1). This is a 78 percent increase in the number of prescriptions for these drugs.

In 2010, there were 147 million prescriptions filled for PPIs (2). The class of drugs includes Prevacid (lansoprazole), Prilosec (omeprazole), Nexium (esomeprazole), Protonix (pantoprazole) and Aciphex (rabeprazole). This growth may not capture the fact that several of these medications are now available over the counter.

I remember when PPIs were touted as having one of the cleanest side effect profiles. This may still be true, if we are using them correctly for reflux disease. They are supposed to be used for the short term. This can range from 7 to 14 days for over-the-counter PPIs to 4 to 8 weeks for prescription PPIs.

Why did we not know that this class of drugs might be associated with chronic kidney disease, dementia, bone fractures and Clostridium difficile (a bacterial infection of the gastrointestinal tract) before they were approved? Well, if you look at the manufacturers’ package inserts for these drugs, the trials, such as for Protonix, were no longer than a year (3), yet we are putting patients on these medications for decades. And the longer people are on them, the more complications arise.

Typical symptoms of reflux are heartburn and/or regurgitation. Atypical symptoms include coughing and throat clearing. But these atypical symptoms may not be as common as you might think. In fact, in one study, coughing and throat clearing taken together only resulted in a very small portion of patients having reflux disease (4). Having one of these two symptoms showed a slightly higher risk of reflux, but very modest.

Let’s look at some of the research.

Though PPIs may increase the risk of a number of complications, keep in mind that none of the data are from randomized controlled trials (RCTs), which are the gold standard of studies, but mostly observational studies that suggest an association, but not a link. Long-term RCTs to determine side effects are prohibitively expensive.

PPI and kidney disease

Recent research has tied proton pump inhibitors to a host of alarming health problems. Stock photo

In two separate studies, results showed that there was an increase in chronic kidney disease with prolonged PPI use (5). All of the patients started the study with normal kidney function based on glomerular filtration rate (GFR). In the Atherosclerosis Risk in Communities (ARIC) study, there was a 50 percent increased risk of chronic kidney disease, while the Geisinger Health System cohort study found there was a modest 17 percent increased risk. The first study had a 13-year duration, and the second had about a six-year duration. Both demonstrated a modest, but statistically significant, increased risk of chronic kidney disease.

 But as you can see, the medications were used on a chronic basis for years. In an accompanying editorial to these published studies, the author suggests that there is overuse of the medications or that they are used beyond the resolution of symptoms and suggests starting with diet and lifestyle modifications as well as a milder drug class, H2 blockers (6).

PPI and bone fractures

In a meta-analysis (a group of 18 observational studies), results showed that PPIs can increase the risk of hip fractures, spine fractures and any-site fractures (8). Interestingly, when it came to bone fractures, it did not make a difference whether patients were taking PPIs for more or less than a year. How much less than a year was not delineated. They found increased fracture risks of 58, 26 and 33 percent for spine, hip and any site, respectively. It is not clear what may potentially increase the risk; however, it has been proposed that it may have to do with calcium absorption through the gut. 

PPIs reduce the amount of acid, which may be needed to absorb insoluble calcium salts. In another study, seven days of PPIs were shown to lower the absorption of calcium carbonate supplements when taken without food (9).

PPI and dementia

Stock photo

A German study looked at health records from a large public insurer and found there was a 44 percent increased risk of dementia in the elderly who were using PPIs, compared to those who were not (7). These patients were at least age 75. The authors surmise that PPIs may cross the coveted blood-brain barrier and have effects by potentially increasing beta-amyloid levels, markers for dementia. With occasional use, meaning once every 18 months for a few weeks to a few months, there was a much lower increased risk of 16 percent. 

The researchers also suggested that PPIs may be significantly overprescribed in the elderly. Unfortunately, there were confounding factors that may have conflated the risk, such as multiple drug use, having diabetes, or patient also having depression or a stroke history. Researchers also did not take into account family history of dementia, high blood pressure or excessive alcohol use, all of which have effects on dementia occurrence.

Need for magnesium

PPIs may have lower absorption effects on several electrolytes including magnesium, calcium and B12. In one observational study, PPIs combined with diuretics caused a 73 percent increased risk of hospitalization due to low magnesium (10). Diuretics are water pills that are commonly used in disorders such as high blood pressure, heart failure and swelling.

Another study confirmed these results. In this second study, which was a meta-analysis (a group of nine studies), PPIs increased the risk of low magnesium in patients by 43 percent, and when researchers looked only at higher quality studies, the risk increased to 63 percent (11). The authors note that a significant reduction in magnesium could lead to cardiovascular events.

The bottom line is even though some PPIs are over-the-counter and some are prescription medications, it is best if you confer with your doctor before starting them. You may not need PPIs, but rather a milder medication referred to as H2 blockers (Zantac, Pepcid). Even better, start with lifestyle modifications including diet, not eating later at night, raising the head of the bed, losing weight and stopping smoking, if needed, and then consider medications (12). If you do need medications, know that PPIs don’t give immediate relief and should only be taken for a short duration: 7 to 14 days, according to the FDA (13), without a doctor’s consult, and 4 to 8 weeks with one. Most of the problems occur with long-term use.

References:

(1) cdc.gov. (2) PLoS Med. 2014;11(9):e1001736. (3) protonix.com. (4) J Clin Gastroenterol. Online Jul 18, 2015. (5) JAMA Intern Med. 2016;176(2). (6) JAMA Intern Med. 2016;176(2):172-174. (7) JAMA Neurol. online Feb 15, 2016. (8) Osteoporos Int. online Oct 13, 2015. (9) Am J Med. 118:778-781. (10) PLoS Med. 2014;11(9):e1001736. (11) Ren Fail. 2015;37(7):1237-1241. (12) Am J Gastroenterol 2015; 110:393–400. (13) fda.gov.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician. 

By Kyrnan Harvey

Successful perennial plantings present landscaping solutions that endure for a few years at a minimum: right plant, right place. Yarrows, peonies, echinaceas, catmint, sages and grasses of all kinds are dependable year-in, year-out, with no worries that the deer will compromise the peak of their performance with unpredictable browsing.

But what about annuals? What possibilities are there for long seasons of color that deliver a strong return on our efforts, and that the deer will dependably leave alone? Here’s a few that my wife and I have successfully grown in our East Setauket garden, which happens to be Grand Central Station for deer. These plants supply many weeks of color and character and carry the garden from July through October, and they too can be counted on as year-in, year-out solutions. These here all require plenty of sun, so if you haven’t got enough, maybe it’s time to call an arborist and remove some Norway maples, Ailanthus (tree of heaven) or black locust.

Snapdragons flower in early summer. They are charming in a vase and there are some great colors out there. They self-seed for us and occasionally overwinter. We like the taller ones; the deer don’t.

Nor do they touch cosmos or zinnias. The former are charming daisies, the embodiment of simplicity in the garden; the latter have the colors that remind me of vintage psychedelic rock posters. Buy them at the garden center or start seeds in April. We prefer the tall zinnia seed strain, Giant. Dead-head spent flowers, especially the zinnias.

We love lantana. Readily available, we have certain varieties in certain colors that we look out for. The Bandana series is upright and not trailing. They are actually perennial, woody shrubs, native in the tropics and thus not hardy. Vibrantly colored, heat and drought tolerant, aromatic, they attract hummingbirds and butterflies. 

We started years ago supplementing clients’ sunny beds with them, and we’d cut them back to about a foot in early November; dig them up and squeeze them into as small an azalea pot (broader than deep) as possible; water them in just once; leave them a day or two outside; and leave them alone to be dormant in a cold (but not freezing) garage or basement. We try to place them where there is a window, just a tiny bit of light, let them get good and dry, and water only every three or four weeks. We move them outside in May, they start growing, and by late May they are planted out again. They get larger from year to year, but we still pot them up, not without questioning our sanity, and are rewarded with lantanas a yard high and wide — a splendid filler after spring and early summer perennials are finished.

One might expect zaftig dahlias to be irresistible to deer, but astonishingly they are unmolested. My wife has become the in-house dahlia enthusiast at Bosky Garden Design, adding each year to her collection of favorites. And there are indeed so many gorgeous varieties. The best cut flowers, you can grow them just for that, or they are easily incorporated in mixed planting schemes, color combination possibilities are endless. We overwinter them, again in a cold basement, bare of soil, wrapped first in newspaper and placed in those 5-cent plastic bags with peat moss.

We love the shock of red of scarlet sage, if used wisely (i.e., segregated), but salvias of all kinds are avoided by deer. Salvia greggii is sold as an annual, but some varieties will be perennial given favorable conditions. This is a plant to look for; there is a wide range of colors, some hardier than others.

Cleome will self-seed prolifically, not until late May. Sparkler is a great seed strain that is tall and that repels deer for sure.

Last, and certainly not least, we have Verbena bonariensis, a short-lived perennial, technically, that succumbs to temperatures below 10 degrees but that self-seeds more abundantly than even cleome. For us it is a tall matrix plant that intermingles everywhere in the garden. Loved by butterflies, loathed by deer, it epitomizes and unifies the naturalistic planting style.

Kyrnan Harvey is a horticulturist and garden designer residing in East Setauket. For more information, visit www.boskygarden.com.

All photos by Kyrnan Harvey

SWEET GETUP

Ellen Segal of Port Jefferson spotted this candy dress in the storefront window of Carl’s Candies on a recent visit to Northport’s Main Street and just had to stop and snap a photo. The outfit, with a top made of gummy bears, a belt of gumballs and lollipops, a skirt made of candy button sheets and twizzler shoes, is as sweet as sugar.

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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