Arts & Entertainment

Alan F. Poole

Four Harbors Audubon Society will present a summer lecture titled “Osprey 2019: The Revival of a Global Raptor” at Avalon Park and Preserve’s Barn on Shep Jones Lane in Stony Brook on Saturday, July 13 at 6:30 p.m. Guest speaker Alan F. Poole, who has been studying ospreys for over 35 years, will speak about the extraordinary resurgence in osprey numbers globally and bring participants up-to-date on the current state of one of our best-loved birds of prey. Free and open to all. Reservations are required by emailing fourharborsheron@gmail.com.

By Heidi Sutton

Who doesn’t love a good fairy tale, especially one like “Cinderella,” which is reputed to be one of the most adapted and re-interpreted children’s stories of all time?

To the delight of all the little princesses out there, Theatre Three in Port Jefferson kicks off its 2019-20 children’s theater season with an original musical retelling of the “rags to riches” tale through Aug. 9. With book, music and lyrics by Douglas J. Quattrock, this version of “Cinderella” combines Charles Perrault’s classic tale with Mark Twain’s “The Prince & the Pauper” to produce a lovely afternoon at the theater.

Perrault (Steven Uihlein) serves as narrator as well as “squire to the sire” and transports audiences to the kingdom of King Charming (Andrew Lenahan) who wishes to retire to Boca Raton and pass the crown to his son, Prince Charming (Matt Hoffman). However, the king feels that his son should get married first and invites all eligible maidens to a royal ball.

The squire delivers the invitations to the home of Cinderella (Meg Bush) who after 300 years is still being treated badly by her stepmother Lady Jaclyn (Nicole Bianco) and stepsisters Gwendolyn (Michelle LaBozzetta) and Madeline (Krystal Lawless). When Cinderella asks if she can go to the ball, her stepmother tells her she has to do all her chores first, including washing the cat, but we all know how that ends. 

Left behind while the step meanies go to the ball, the poor girl is visited by her fairy godmother, Angelica (Emily Gates) who cooks up a beautiful gown and sends her on her way.

Meanwhile, the prince concocts a plan to switch places with the squire in hopes of meeting a girl who will like him “for who he is, not what he is.” Things go horribly wrong at the ball, thanks to the ill-mannered stepsisters, and it ends before Cinderella can get there. When she finally arrives, Cinderella is greeted by a squire (the prince) who asks her to dance because “the band is paid till 1.” Will she take him up on his offer? Will they waltz the night away?

Directed by Jeffrey Sanzel, the eight-member cast does an excellent job in portraying this adorable story. One of the funniest scenes is when the prince and squire show up at Cinderella’s house with the glass slipper and the stepsisters and even stepmother try it on with the same result: “I think it’s on. All hail the queen! Ouch, take it off!”

Accompanied on piano by Douglas J. Quattrock, all of the sweet musical numbers are wonderfully choreographed by Nicole Bianco, with a special nod to “Please, Mother, Please!” and “A Girl Like Me (and a Boy Like You).” 

The costumes, designed by Teresa Matteson and Toni St. John, are flawless, from the royal garbs worn by the king and prince to the fancy gowns worn at the ball. The wings on the fairy godmother even light up — a nice touch. Lighting design by Steve Uihlein along with some special effects pull it all magically together.

If you’re looking for something to do with the kids for the summer, Theatre Three’s “Cinderella” fits the bill perfectly. Souvenir wands are sold before the show and during intermission. Meet the cast in the lobby after the show.

Theatre Three, 412 Main St. in Port Jefferson presents “Cinderella” through Aug. 9. Children’s theater continues with “Pinocchio” from Aug. 2 to 10; and “A Kooky Spooky Halloween” from Oct. 5 to 26. All seats are $10. For more information or to order, call 631-928-9100 or visit www.theatrethree.com. See more photos online at www.tbrnewsmedia.com.

Photos by Peter Lanscombe, Theatre Three Productions Inc.

Grounds and Sounds Cafe at the Unitarian Universalist Fellowship, 380 Nicolls Road, E. Setauket welcomes Toby Walker in concert on Friday, July 12 at 8 p.m. Hailed as an award-wining roots guitar virtuoso and songwriter, Walker blends the styles of blues, ragtime, country, bluegrass, old-time jazz and rock in his music. Tickets are $15 at the door or at www.groundsandsounds.org. For further info, call 631-751-0297.

Gluten is found mainly in wheat, rye and barley. Stock photo
Antibiotics may contribute to celiac disease

By David Dunaief, M.D.

Dr. David Dunaief

Gluten-free diets are a hot topic. When we hear someone mention a gluten-free diet, we may automatically think that this is a healthy diet. However, gluten-free is not necessarily synonymous with healthy. There are many beneficial products containing gluten.

Still, we keep hearing how more people feel better without gluten. Could this be a placebo effect? What is myth and what is reality in terms of gluten? In this article I will try to distill what we know about gluten and gluten-free diets, who may benefit and who may not.

But first, what is gluten? Gluten is a plant protein found mainly in wheat, rye and barley.

While more popular recently, going gluten-free is not a fad, since we know that patients who suffer from celiac disease, an autoimmune disease, benefit tremendously when gluten is removed (1). In fact, it is the main treatment.

But what about people who don’t have celiac disease? There seems to be a spectrum of physiological reaction to gluten, from intolerance to gluten (sensitivity) to gluten tolerance (insensitivity). Obviously, celiac disease is the extreme of intolerance, but even these patients may be asymptomatic. Then, there is nonceliac gluten sensitivity (NCGS), referring to those in the middle portion of the spectrum (2). The prevalence of NCGS is half that of celiac disease, according to the NHANES data from 2009-2010 (3). However, many disagree with this assessment, indicating that it is much more prevalent and that its incidence is likely to rise (4). The term was not even coined until 2011.

What is the difference between full-blown celiac disease and gluten sensitivity? They both may present with intestinal symptoms, such as bloating, gas, cramping and diarrhea, as well as extraintestinal (outside the gut) symptoms, including gait ataxia (gait disturbance), malaise, fatigue and attention deficit disorder (5). Surprisingly, they both may have the same results with serological (blood) tests, which may be positive or negative. The first line of testing includes anti-gliadin antibodies and tissue transglutaminase. These measure a reaction to gluten; however, they don’t have to be positive for there to be a reaction to gluten. HLA–DQ phenotype testing is the second line of testing and tends to be more specific for celiac disease.

What is unique to celiac disease is a histological change in the small intestine, with atrophy of the villi (small fingerlike projections) contributing to gut permeability, what might be called “leaky gut.” Biopsy of the small intestine is the most definitive way to diagnose celiac disease. Though the research has mainly focused on celiac disease, there is some evidence that shows NCGS has potential validity, especially in irritable bowel syndrome.

Before we look at the studies, what does it mean when a food says it’s “gluten-free”? Well, the FDA has weighed in by passing regulation that requires all gluten-free foods to have no more than 20 parts per million of gluten (6).

Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a nebulous disease diagnosed through exclusion, and the treatments are not obvious. That is why the results from a 34-patient, randomized controlled trial, the gold standard of studies, showing that a gluten-free diet significantly improved symptoms in IBS patients, is so important (7). Patients were given a muffin and bread on a daily basis.

Of course, one group was given gluten-free products and the other given products with gluten, though the texture and taste were identical. In six weeks, many of those who were gluten-free saw the pain associated with bloating and gas mostly resolve; significant improvement in stool composition, such that they were not suffering from diarrhea; and their fatigue diminished. In fact, in one week, those in the gluten group were in substantially more discomfort than those in the gluten-free group.

As part of a well-written March 4, 2013 editorial in Medscape by David Johnson, M.D., a professor of gastroenterology, questions whether this beneficial effect from the IBS trial was due to gluten withdrawal or to withdrawal of fermentable sugars because of the elimination of some grains themselves (8). In other words, gluten may be just one part of the picture. He believes that nonceliac gluten sensitivity is a valid concern.

Antibiotics

The microbiome in the gut may play a pivotal role as to whether a person develops celiac disease. In an observational study using data from the Swedish Prescribed Drug Register, results indicate that those who were given antibiotics within the last year had a 40 percent greater chance of developing celiac disease and a 90 percent greater risk of developing inflammation in the gut (9). The researchers believe that this has to do with dysbiosis, a misbalance in the microbiota, or flora, of the gastrointestinal tract. It is interesting that celiac disease may be propagated by change in bacteria in the gut from the use of antibiotics.

Not everyone will benefit from a gluten-free diet. In fact, most of us will not. Ultimately, people who may benefit from this type of diet are those patients who have celiac disease and those who have symptomatic gluten sensitivity. Also, patients who have positive serological tests, including tissue transglutaminase or anti-gliadin antibodies, are good candidates for gluten-free diets.

There is a downside to a gluten-free diet: potential development of macronutrient and micronutrient deficiencies. Therefore, it would be wise to ask your doctor before starting gluten withdrawal. The research in patients with gluten sensitivity is relatively recent, and most gluten research has to do with celiac disease. Hopefully, we will see intriguing studies in the near future.

References:

(1) Am J Gastroenterol. 2013;108:656-676. (2) Gut 2013;62:43–52. (3) Scand J Gastroenterol. (4) Neurogastroenterol Motil. 2013 Nov;25(11):864-871. (5) medscape.com. (6) fda.gov. (7) Am J Gastroenterol. 2011; 106(3):508-514. (8) medscape.com. (9) BMC Gastroenterol. 2013:13(109).

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.

Photo courtesy of Leg. Spencer’s office

Legislator William Spencer made a special visit to Cold Spring Harbor’s Goose Hill Primary School on June 24 to present first-grade student, Sloane Yormack, with a proclamation recognizing her as the first-place winner for the 18th Legislative District in Suffolk County’s 2019 Be Pool Smart poster contest.

With drowning being the leading cause of unintentional injury-related deaths of children between the ages of 1 and 14 nationwide, and the third leading cause of injury-related deaths of children in New York, the Suffolk County Legislature conducts an annual Be Pool Smart public education campaign. 

Students are invited to participate in a poster contest to express their interpretation of what can be done to protect children and families against accidental pool drownings.

With nearly 200 posters submitted from the 18th Legislative District this year, Sloane’s artwork, depicting pool smart swimmers, was selected as the winning poster for the district. 

Pictured with Sloane, above, from left, principal of Goose Hill Primary School, Lynn Herschlein; PE teacher Rory Malone; first-grade teacher Michelle Riggles; dad David Yormack; mom Amy Yormack; and Leg. Spencer.

Stock photo

By Stephanie Quarles

Many organizations, universities, scientists and government officials have studied and spoken out on Long Island’s water issues, with regard to our oceans, estuaries, rivers and our aquifers.  

A recent conference in Riverhead on May 30, organized by the Environmental Advocates of New York (EANY), focused on the contamination of drinking water supplies in Suffolk County and aimed to educate and strengthen advocacy and partnerships on these issues. At the conference the following bills that were pending in the NYS Legislature and supported by EANY were highlighted. Since the conference, the Senate and Assembly have debated and passed all but one of these bills. They are described below (source: EANY). 

Stock photo

1,4-Dioxane Ban A.6295, S.4389 prohibits the distribution and sale of household cleaning products and personal cosmetic products containing 1,4-dioxane to protect our health and waterways that will take effect Dec. 21, 2021. The USEPA has classified it as likely to be “carcinogenic to humans, and it is listed by California Proposition 65 as known or suspected of causing cancer or birth defects. Studies show that it causes chronic kidney and lever effects and liver cancer.” Since it is not listed as an ingredient in health and beauty and home care products, “it is difficult for consumers to avoid.” Alternative manufacturing processes exist.  

The NY State Drinking Water Council recommends that for 1,4-dioxane, more than 1 part per billion requires treatment. Nassau and Suffolk water suppliers have reported the highest levels of 1,4-dioxane contamination in the nation. It is most prevalent in our Long Island waters with 82 of the 89 wells above the threshold.         

Update: Passed by NYS Senate and NYS Assembly, waiting for governor’s signature to become law.

PFAS-Free Firefighting Foam A.445, S.439 bans the use, manufacture, sale and distribution of firefighting foam containing perfluroalkyl and polyfluoroalkyl substances known as PFAS chemicals two years after the effective date. These bills are to eliminate a major source of drinking water contamination and encourage alternatives. PFAS is associated with cancer, hormone disruption, liver and kidney damage, developmental and reproductive harm and immune system toxicity. There is no safe level of exposure.

Hampton Bays Fire Department was designated as a Superfund site (contamination site) due to groundwater contamination by PFAS.

Update: Passed by NYS Senate and NYS Assembly, waiting for governor’s signature to become law.

“Polluter Pays” A.5377-C, S.3337-C allows public water suppliers and wholesale water suppliers to sue a polluter for damages within three years of water testing that reveals elevated levels of dangerous contaminants in the water supply. This bill makes it easier to hold polluters accountable and helps prevent the costs of remediation from falling on New York taxpayers.

Update: Passed by NYS Senate and NYS Assembly, waiting for governor’s signature to become law.

Restricting Nitrogen Fertilizer A.4568, S.2130 adds to the Environmental Conservation Law to require that only low-level fertilizer with no more than 12 percent nitrogen by weight is sold in Suffolk and Nassau counties. Limits on nitrogen in fertilizers will reduce the nitrogen that runs off during rain. EANY recommends that the bill be extended to cover all of NY state and not be delayed to Dec 31, 2021.

Update: Currently in the Environmental Committee in the Assembly. 

Although the focus of the seminar was on drinking water contaminates, other topics of concern for our water quality were brought up as well; the drop in the aquifer, nitrogen levels and the sewage discharge, lead pipe run off, salt intrusions and septic systems were also noted as major issues affecting water quality. The importance of appropriate standards for detecting contamination was stressed.

Tyrand Fuller of the Suffolk County Water Authority described the water quality mapping and database project known as WaterTraq. It tracks potential threats in the water supply and provides supply information to the public and regulators. It has an interactive map providing the status of LI groundwater for health officials, industry professionals and the public and provides both untreated (raw) water test results and treated water that is sent to the public. http://liaquifercommission.com/watertraq.html.

Another way to find out information about the water quality in your community is at the Suffolk County Water Authority’s Water Quality Report website: http://s1091480.instanturl.net/2019waterreport/water-quality-by-distribution-area-2019-scwa_index.html.

Our fellow Suffolk County residents must be more aware of how fragile and difficult it is to safeguard the quality of our drinking waters. We must continue to educate ourselves and speak loudly for support of legislation dealing with our water crisis. For a list of conference speakers as well as additional resources from expert sites on our drinking water, visit http://www.lwv-suffolkcounty.org/TakeAction.html.

Stephanie Quarles is a director of the League of Women Voters of Suffolk County, a nonprofit, nonpartisan organization that encourages the informed and active participation of citizens in government and influences public policy through education and advocacy. For more information, visit www.lwv-suffolkcounty.org or call 631-862-6860.

Honorees Katharine Griffiths, Andy Polan, Leah Dunaief, Anna Kerekes

The Ward Melville Heritage Organization hosted its annual Jewels & Jeans Gala at Flowerfield in St. James on June 19. This year’s event honored Katharine Griffiths, Executive Director, Avalon Park & Preserve; Leah Dunaief, Editor and Publisher of Times Beacon Record News Media; Anna Kerekes, WMHO Trustee; and Andy Polan, President, Three Village Chamber of Commerce “for their outstanding achievements to the community.” The evening featured music by Tom Manuel and The Jazz Loft All Stars, cocktails, dinner and a live and silent auction. 

Photos by Ron Smith, Clix|couture

By Elof Axel Carlson

Elof Axel Carlson

When I first read a biography of Darwin as a teenager, I was attracted to his reputation of having “an enlarged curiosity.” It also described my own personality.  

I never got museum fatigue going through New York’s museums. They were free during the 1940s and my brother and I would enjoy many trips with our mother during the summer to visit them. 

It was fun to study paintings to see how artists differed in the way they drew facial features. It was fun to go through the fossils of dinosaurs and see how much their skeletons resembled those of birds. 

I could imagine being an unseen witness to the huge teeth and claws of meat-eating dinosaurs. I loved looking at gems in the mineral display gallery. I learned about New York City history by looking at the dioramas on the first floor of the American Museum of Natural History.

Curiosity is natural to children and they delight in discovering new facts. That curiosity is often stifled by parents who tire of an overload of questions. When a child becomes curious and discovers items parents do not want their children to know about, they often are told that “curiosity may kill a cat.”  

I often satisfied my curiosity at home reading in the Encyclopaedia Britannica, which my father bought on installment just before I was born. He argued that I could sleep in an open suitcase on the kitchen table and buying the encyclopedia was more important than the type of bedding an infant slept in. I bless him for that foresight.  

Random reading on rainy days in the encyclopedia filled me with facts about the universe. I read about the art of bonsai or miniaturized trees in Japanese gardens. I read about Egyptian mummies and learned under the topic Bubastis, that there was a city devoted to cats and their burial in ancient Egypt. The isolated facts over the years became a treasure trove of information. 

Curiosity is essential for science. It motivates adolescents and young adults to find careers in science and fields of scholarship. In antiquity, scholars like Aristotle or Pliny (both uncle and nephew) sought to amass all known knowledge and their works are a major source of what we know about Greek and Roman civilizations.  

William Bateson, who coined the term “genetics” in 1906 for my field, said, “Treasure your exceptions” because from them new fields may arise. How true that was for me when I found an unusual fly in an exercise in one of H. J. Muller’s classes as a graduate student. That unusual fly turned out to be a rare instance of two pieces of a gene being united in a new way. It led to my doctoral dissertation study.  

Today many scholarly tasks are done by computers. Wikipedia is now an essential starting tool to explore a topic and obtain several scholarly references to extend a search for knowledge. While the tools for scholars may change, the curiosity fueling scholarship cuts across all disciplines.

 Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

Maureen O’Leary wraps fossils during an expedition in Mali. Photo by Eric Roberts

By Daniel Dunaief

Mali is filled with challenges, from its scorching hot 125 degree temperatures, to its sudden rainstorms, to its dangers from militant and terrorist-sponsored groups.

The current environment in the landlocked country in West Africa makes it extraordinarily difficult to explore the past in a region that includes parts of the Sahara Desert, but that, at one point millions of years ago, was part of a waterway called the Trans-Saharan Seaway.

Maureen O’Leary, professor of anatomical sciences at the Renaissance School of Medicine at Stony Brook University, led three expeditions to Mali, in 1999, 2003 and 2008, collecting a wide array of fossils and geological samples from areas that transitioned from an inland seaway that was about 50 meters deep on average to its current condition as a desiccated desert.

Maureen O’Leary and Eric Roberts with Mali guards. Photo from Maureen O’Leary

On her third trip, O’Leary quickly left because she decided the trip was too dangerous for her and the scientific team. Rather than rue the lack of ongoing access to the region, however, O’Leary pulled together an international team of researchers from Australia, the United States and Mali to look more closely and categorize the information the research teams had already collected from the region.

“We made the most of a bad situation,” O’Leary said. “It is a silver lining, to some degree.”

Indeed, O’Leary and her collaborators put together a paper for the June 28 issue of the Bulletin of the American Museum of Natural History that is over 170 pages and contains numerous images of fossils, as well as recreations of a compelling region during a period from 100 million to 50 million years ago. This time period coincided with one of the five great prehistoric extinction events, during the Cretaceous-Paleogene boundary.

O’Leary characterized some of the more exciting fossil finds from the region, which include the first reconstruction of ancient elephant relatives and large predators such as sharks, crocodiles and sea snakes.

The size of some of these creatures far exceeds their modern relatives. For example, O’Leary’s scientific colleagues estimate that a freshwater catfish was about 160 centimeters in length, which is four times the total size of a modern catfish. The larger catfish dovetails with similar observations the researchers had made about sea snakes in 2016 and 2017. They started to knit this trend into a preliminary hypothesis in which a phenomenon known as island gigantism may have played a role in selecting for these unusually large creatures.

“Species become bigger in these environments,” O’Leary said, suggesting that other scientists have made similar observations. “It’s not clear what causes that kind of selection.”

Above, some of the species that lived in and around the TransSaharan Seaway, including an extinct species of crocodile. Illustrated by Lucille Betti-Nash/ Department of Anatomical Sciences, Stony Brook University.

 

In addition to studying vertebrate and invertebrate fossils, scientists including Eric Roberts at James Cook University in Australia looked at the geology of the region. Roberts helped name and describe many of the formations in the area. This provides context for the lives of creatures who survived in an environment distinctly different from the modern milieu of the Sahara Desert.

Roberts, who is a part of the Sedimentary Geology & Paleontology Research Group that has nicknamed themselves Gravelmonkeys, explained that his initial efforts in Mali came from the fieldwork over a course of weeks when he explored the rock sequences and took copious notes on them.

He suggested that the region still represents a geoscience frontier, in part because it is so difficult to get to, takes serious logistics to do fieldwork and is hard to maintain research.“Over many years, I have worked with collaborators on the project to analyze the samples in many different ways and especially to compare our notes and analytical results with descriptions of rocks and geological formations in other parts of the Sahara and further afield in Africa to understand how they are different and how they correlate,” he said.

O’Leary suggested that the paper provides some context for climate and sea level changes that can and have occurred. During the period she studied, the Earth was considerably warmer, with over 40 percent of today’s exposed land covered by water. Sea levels were about 300 meters higher than current levels, although the Earth wasn’t home to billions of humans yet or to many of the modern day species that share the planet’s resources.

Robert Voss, the editor-in-chief of the series at the American Museum of Natural History, praised the work for its breadth. “This was an unusually large and multidisciplinary author team, as appropriate for the broad scope of the report,” he explained .

“Seldom is such a large geographic area so poorly known paleontologically, so there was a unique opportunity here to break new ground and establish a broad framework for future work,” he added.

Voss described O’Leary as a “force of nature” who “responds constructively to peer reviews.” Roberts, too, appreciated the effort O’Leary put into this work.

O’Leary “drove the entire process and product,” which was only possible with someone of her “vision to wrangle so much science from so many different scientists into one place,” he offered in an email.

Roberts is very pleased with the finished product and added that it is “something that I will be proud of for the rest of my career. This took a lot of effort over the years and it great to see the end product.”

O’Leary said that much of the literature for the science in Mali was in French, which had kept it a bit below the radar for scientific discourse, which tends to be in English.

Indeed, O’Leary was able to facilitate conversations among the many people involved in this project because French was the common denominator language. She studied French at the Holton-Arms School in Bethesda, Maryland. “When I was sitting in my high school French class, I didn’t think it would come in so handy to be fluent in French” in her career, O’Leary said. “It was helpful as a female leader in this situation to be able to speak for [myself], whether speaking to other Americans or collaborating or working with guards.”

O’Leary plans to look at different projects in the United States, including in Puerto Rico, and in Saudi Arabia next. “We now have this synthetic story for Mali [and will be] building out from this to other areas. I anticipate a large time to ramp up to study areas like deposits in Nevada.”

Gábor Balázsi. Photo from SBU

By Daniel Dunaief

Take two identical twins with the same builds, skill sets and determination. One of them may become a multimillionaire, a household name and the face of a franchise, while the other may toil away at the sport for a few years until deciding to pursue other interests.

What causes the paths of these two potential megastars to diverge?

Gábor Balázsi, an associate professor in biomedical engineering at Stony Brook University, asked a similar question about a cellular circuit in the hopes of learning more about cancer. He wanted to know what is it about the heterogeneity of a cancer cell that makes one susceptible to treatment from chemotherapeutic drugs and the other resistant to them. Heterogeneity comes from molecular differences where the original causes may be subtle, such as two molecules colliding or a cell being closer to the tumor’s surface, while the consequences can create significant differences, even among cells with the same genes.

In research published this week in the journal Nature Communications, Balázsi used two mammalian cell lines that were identical except that each carried a different synthetic gene circuit that made one more heterogeneous than the other. He subjected the two cell lines, which would otherwise perform the same function, to various levels of the same drug to determine what might cause one to be treatable and the other to become resistant. 

Through these mammalian cells, Balázsi created two circuits, one of which kept the differences between the cells low, while the other caused larger differences. Once inserted in the cell, these gene circuits created uniform and variable populations that could serve as models for low and high heterogeneity in cancer.

Working with Kevin Farquhar, who recently graduated from Balázsi’s lab, and former Stony Brook postdoc Daniel Charlebois, who is currently at the Department of Physics at the University of Alberta, Balázsi tried to test how uniform versus heterogeneous cell populations respond to treatment with different drug levels. 

Using the two synthetic gene circuits in separate but identical cell lines, the Stony Brook scientists, with financial support from the National Institutes of Health and the Laufer Center for Physical and Quantitative Biology at SBU, could re-create high and low stochasticity, or noise, in drug resistance in two cell lines that were otherwise identical.

While the work is in its preliminary stages and is a long way from the complicated collection of genes responsible for various types of cancer, this kind of analysis can test the importance of specific processes for drug resistance.

“Only in the last decade or so have we come to realize how much heterogeneity (genetic and nongenetic differences) can exist within a tumor in a single patient,” Patricia Thompson-Carino, a professor in the Department of Pathology at the Renaissance School of Medicine at SBU, explained in an email. “Thinking of cancer in a single patient as several different diseases is a bit daunting, though currently, this heterogeneity and its direct effects on how the cancer behaves remains poorly understood.”

Indeed, Thompson-Carino added that she believes Balázsi’s work will “shed light on cancer cell responses to therapy. With the rise in cancer therapies designed to specific targets and the resistance that emerges in patients on these therapies, I think [Balázsi’s] work is of extremely high value” which may help with the puzzle of how nongenetic or epigenetic heterogeneity affects responses to treatment, she continued.

In the future, researchers and clinicians may look to develop new ways of biomarker analysis that considers the variability, rather than just the average level of a biomarker.

Balázsi suggested that looking only at the variability of cells is analogous to observing an iron block sinking in water. Someone might conclude that all solids sink in liquids. Similarly, scientists might decide that cellular variability always promotes drug resistance from observations when this happens. To gain a fuller understanding of the effect of variability, however, researchers need to equalize the averages. They then need to explore what happens at various levels of drug treatment.

Current therapies do not target heterogeneity. If such future treatments existed, doctors and scientists could combine ways of treating heterogeneity with attacking cancer, which might work in the short term or prevent cancer from recurring.

Balázsi suggests his paper is a part of his attempt to address three different areas. First, he’d like to figure out how to categorize patients better, including the variability of biomarkers. Second, he believes this kind of analysis will assist in creating future combinations of treatments. By understanding how the variability of cancer cells contributes to its reaction to therapies, he might help create a cocktail of treatments, akin to the effort that helped with the treatment of HIV in the lab.

Third, he’d like to obtain cancer samples and allow them to evolve in a lab, where he can check to see how they respond to treatment levels and administration scheduling. This effort could allow him to determine the optimal drug combination and dosing for a patient.

For the work that led to the current Nature Communications paper, Balázsi explored how mammalian cells respond to various concentrations of a drug. Over 80 percent of the genes in these cells are also present in human cells, so the mechanisms he discovered and conclusions he draws should apply to human cancer cells as well.

He concluded that cells with more heterogeneity, where the cells deviate more from the average, resist drugs better when the drug level is high. These same cells, show greater sensitivity when the drug is low.

Balázsi recognizes that the work he’s exploring is a “complex problem” and that it requires considerable additional research to understand and appreciate how a therapy might kill one cancer cell, while the same treatment in the same environment doesn’t have the same effect on a genetically identical cell.

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