Power of 3

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Finding out why cancer cells become drug resistant should help patients recover

Back when she was in Boston, Raffaella Sordella was a part of an incredible discovery. Some patients with non-small cell lung cancer had mutations that made their tumors sensitive to drugs such as Tarceva and Iressa.

When the patients took the medicine twice a day, “the tumor was shrinking,” recalled Sordella. “Within a couple of weeks, the patient could resume a normal life, more or less.”

To top it off, the drug didn’t have all the side effects of conventional chemotherapy.

“This was a turning point in my career,” explained Sordella, who is originally from Turin, Italy, and was conducting her research at Massachusetts General Hospital.

The promising therapy for these patients, however, wasn’t as effective as researchers, clinicians and patients had hoped. Within a year, the tumors in even these patients had developed a resistance to the drugs.

Undeterred, Sordella decided she would search for reasons for the change. Now an associate professor at Cold Spring Harbor, Sordella is pursuing several possible explanations which she hopes one day will extend the effectiveness of drugs.

Lung cancer is the leading cause of cancer deaths in the world. It was responsible for 160,340 deaths in the United States in 2012, according to the American Cancer Society. More than 226,000 cases were diagnosed last year.

Tarceva and Iressa were sometimes effective initially on the tumors that harbor specific mutations because they blocked the epidermal growth factor receptors (or EGFR). Without signals from the EGFR sites, the tumors either stopped growing or began shrinking.

As Sordella and others have observed, however, these drugs became less effective over time. One possible explanation was that the cancers were changing, developing a secondary mutation that altered the way the tumor grew or developed. That likely accounted for about half of the cases. In the rest, scientists now know that resistance can develop through other mechanisms, such as the expression of other genes.

“If we understand the mechanism, we can slow down the process,” she explained. Scientists may not find a cure in the short term, but they may be able to extend the period when the tumors are sensitive to the drug out from one year.

Sordella discovered that the interleukin-6 protein, which was produced during inflammation, was responsible for decreasing the sensitivity of the tumor to the drugs.

Resistance was increased “by factors secreted during inflammation,” Sordella observed.

By turning off or blocking interleukin-6, researchers may be able to create a combination of drugs that blocks the growth and spread of tumors.

This, Sordella offered, would be considerably easier than trying to anticipate and stop the next cancerous mutation.

When she first started exploring the ways tumors might develop drug resistance, the most obvious, and medically most challenging possibility was that the tumor was heterogeneous, which means that it had a mix of cells with different genetic codes that kept it several steps ahead of the available drugs.

Sordella feels a scientific urgency to continue with her research, in the hopes of helping those suffering with cancer.

“What we are doing is not just for us,” she said. “It can make a difference to patients.”

Sordella and her husband Manuel Barriola, a theoretical physicist who works as a consultant, live on campus at Cold Spring Harbor. They have two daughters, Victoria, who is in second grade and Alicia, who is in kindergarten.

Sordella and her husband, who is from Spain, miss their connection to Europe. She explained that the Italian culture she grew up with is considerably different from that for third-generation Italian Americans.

“When I was in Boston, there was this old guy that learned I was Italian,” she recalled. “He spoke to me in what he thought was Italian.” Sordella suspected that he was speaking a dialect from Sicily and wasn’t able to understand a single word.

Sordella enjoys going to Manhattan to people watch. She said she doesn’t think about her research when she’s in the city, even though she knows cancer is so prevalent that any medical breakthrough could make a difference for everyone.

 

African violets

Continued from page B16

Any number of small insect pests, including aphids and spider mites as well as mealybugs, can attack African violets. I find that the yellow sticky traps are very helpful in dealing with insect pests in the house in general. If that doesn’t work, you may have to resort to using a pesticide. Make sure that the one you select can be used on houseplants and that you follow directions carefully.

Prevention is the best route to take. Check any new acquisitions carefully before bringing them into the house. You may also want to quarantine them for a few weeks so that if there is a problem it won’t affect your entire houseplant collection.

For more information, the African Violet Society of America can be reached at www.avsa.org.

 

Ellen Barcel is a freelance writer and master gardener. To reach Cornell Cooperative Extension and its Master Gardener Program, call 727-7850.

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Using remote sensing, Rogers and other scientists look for evidence of water on Mars

By Daniel Dunaief

After searching in 40 other places — albeit from millions of miles away — Deanne Rogers and her scientific colleagues from the U.S. and U.K. found what they were seeking. Using images beamed back to Earth, they found minerals on rocks that typically form in the presence of water.

The discovery, in the McLaughlin Crater on Mars, where deposits are probably 3.8 billion years old or older, is consistent with an expanding body of knowledge about the Red Planet.

“I almost expected we should see something like this,” explained Rogers, an assistant professor of geoscience at Stony Brook. “A lot of recent observations point to groundwater in the subsurface. There was a hint of water deep in the subsurface.”

Without channels going into or out of the basin, scientists suggested that the water likely came from under the ground.

Much of the water on Mars is likely a result of volcanic activity, although comet impacts may have also carried some. The water likely percolated through soil that is much more porous on Mars than it is on Earth. It likely collected several kilometers below the surface. The water may have come back up in deep basins, such as the McLaughlin Crater.

Indeed, there could still be water in the Martian crust.

If manned missions went to Mars, experts have suggested that the astronauts might need to find water on the planet to drink while they’re there and to restock their supplies for the long journey back to Earth.

Rogers suggested that astronauts probably wouldn’t be able to drill deep enough to get any groundwater. Some scientists, however, have been working on how to free the water trapped in the minerals on the rocks. By heating the rocks, astronauts might be able to release water. They could also go to high latitudes, where there is water ice within centimeters of the surface.

So far, the McLaughlin crater “is the only place where we find evidence of these minerals” together in a basin setting, Rogers offered. Some are covered in dust, which obstructs the scientists’ view, while others may never have had water upwell in that region.

The presence of water, even long ago, might suggest that conditions on Mars could have supported life. Those extraterrestrial organisms could have lived in the subsurface, where they might be sheltered from the harsh environment on the surface.

Despite the pervasive dust, Mars presents a clearer picture in some areas of geological processes than the Earth. Plate tectonics — the slow movement of the enormous landmasses on which the continents rest — on our planet muddy the waters of interpreting how the planet may have changed over its history.

Mars, however, does not have any such movement of tectonic plates. Additionally, the meteorites that slammed into its surface have helped reveal what is and was beneath the surface.

“It’s a lot easier to study craters on Mars because they are well preserved,” explained Rogers. “On Earth, they are buried under vegetation or erased from Earth’s surface” by the movement of the plates and by erosion or weathering.

Rogers explained that she has divided her research into analyzing data sent from orbiters and studying the properties of similar rocks and minerals that other researchers at Stony Brook have created.

“We can look at the spectra of altered samples to compare it to Martian data,” she explained. “We can confirm it in the lab.”

She also does some remote sensing of the moon and asteroids.

Rogers lives in Selden with Tim Glotch, who is also an associate professor in the same department (see July 17, 2012 issue), and their two preschool-age children.

Glotch, Rogers and a few other Stony Brook faculty are working on a multidisciplinary proposal, which is due in April, that considers the possibility of human exploration of the moon and asteroids. Glotch is the lead investigator, while Rogers and others have responsibilities specific to their expertise.

Their research is benefiting from a resurgence of interest in Mars, in part because of the newest rover, Curiosity.

Rogers said she hopes to continue to participate in research on Mars because “there are so many things left unexplored at this point.”

 

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Finding a contrast agent that a surgeon could use to help delineate cancer cells from healthy ones

Jonathan Liu wants to see inside people’s brains. Specifically, he is working on a way he hopes will eventually give neurosurgeons a clearer look at the difference between malignant cells they want to remove in a specific type of tumor and healthy cells they’d rather not touch.

Taking out too many cells can damage the health of a patient, while not removing enough can give the tumor a chance to grow.

An assistant professor in biomedical engineering at Stony Brook University, Liu has tapped into his background in engineering to create microscopes that, in connection with a chemical called a contrast agent that lights up cancer cells, surgeons may one day use to see the edges of a tumor.

A doctor would “spray the contrast agent on at the final stages of surgery,” he explained. “It’s a way to check if there are any residual tumor cells.”

At this point, Liu and his graduate students, Danni Wang, Steven Leigh and Ye Chen, in conjunction with Stanford University, where Liu started this work as a postdoctoral student, have developed a system in animal models of medulloblastoma, a type of brain cancer, that makes the tumor glow.

In those animal models, medulloblastoma cells have a higher than normal amount of protein on their surface called Vascular Endothelial Growth Factor Receptor 1 (or VEGFR-1). Liu and his colleagues looked for a contrast agent that would stick to this protein and make it easy to find for surgeons.

“This is a specific contrast agent that we believe is labeling the tumor cells very accurately,” Liu said. “Normal cells would not overexpress this particular protein.”

The transition from these animal models of medulloblastoma to human forms will likely involve considerable study. Cancers can be highly variable and Liu explained that he wouldn’t expect all medulloblastomas to express VEGFR-1.

While the contrast agent and microscope could be years away from use in an operating room, the choice of a topical chemical, rather than a dye injected into a patient, may expedite the review process through the Food and Drug Administration.

Using a dye means the overall dosage could be lower, which would limit the introduction of the dye into the patient’s circulation.

Surgery has not yet reached the point where doctors can choose single cells to remove, Liu offered. Many brain tumor margins are diffuse and the cells can infiltrate and migrate through the brain, he explained. The goal, however, is to give the surgeon better guidelines.

A patient typically goes through chemotherapy to handle the remaining tumor. When surgeons remove more of the tumor, the postoperative therapies are generally also more effective, he asserted.

While the contrast agent the Stony Brook scientist used is innovative, the strengths of the design come from building the three-dimensional microscopes.

Liu designed a tabletop system for the recent results that were published in Translational Oncology. He is also creating a miniature handheld version that would be considerably more compact, in the form of a pen-like device.

As either a tabletop version or a handheld type, the microscope is “highly customized,” he related. “There’s nothing there that you can buy and get off the shelf.”

At Stanford, Liu built a similar microscope for the gastrointestinal tract. At Stony Brook, he has a new grant to develop a microscope to help with the early detection of oral cancers.

Receiving approval from regulators to use the newest microscope designs in the brain will require careful steps to ensure the instrument remains sterilized.

“You have to be very stringent,” Liu assured. He may surround the microscope in a plastic sheath, as medical researchers have done with similar devices.

Liu lives in Port Jefferson with his wife, Evie, a violin teacher who works at the Stony Brook School and gives lessons from home. They are both of Chinese descent and grew up in Hawaii.

Liu is an amateur surfer and enjoys going to the South Shore when a storm along the coast kicks up larger waves.

If he weren’t a scientist, Liu said he might consider a career as a doctor. He appreciates a physician’s opportunity to have a positive impact on their patients’ lives.

Still, he recognizes that his translational research may one day help those same patients.

 

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With far-reaching technological development, the group works to contribute to new BNL programs

He takes over a team that has had a hand in everything from the creation of video games to the silicon drift detector (which is used in X-ray spectrometry and electron microscopy).

As the recently appointed head of the instrumentation group at Brookhaven National Laboratory, Graham Smith, who has led the Gas and Liquid Detector Group for 15 years, now takes over as the leader of 40 professionals, most of them scientists, engineers and technicians. Smith helps coordinate the development and refinement of technology designed to answer questions ranging from understanding why neutrinos have mass to determining the structure of complex protein molecules.

A part of the Nuclear and Particle Physics directorate, the instrumentation division also works with the other four units at BNL, which include Basic Energy Sciences, Photon Sciences, Global and Regional Solutions and Environmental and Life Sciences.

The division applies some of its work with gas-filled neutron detectors to national security. His group is developing instruments that can “identify contraband material being brought into the country,” which could include uranium or plutonium, he said. Those materials emit neutrons, which are hard to stop, even for a lead-lined shipping container.

“There are only certain materials in nature that are sensitive to neutrons,” he explained. “Hydrogen and Helium-3 are good at stopping thermal neutrons.”

The instrumentation division at BNL has collaborated with professionals in nonproliferation and national security to build neutron detectors that are many pinhole cameras in a single instrument, which can be placed at ports around the country to look for radioactive objects that generate neutrons.

The instrumentation division is also playing an important part in the Long Baseline Neutrino Experiment (or LBNE). The centerpiece of the LBNE will be a liquid argon detector and electronics that BNL’s expertise is making possible, Smith said.

BNL’s Milind Diwan (Power of Three, Jan. 10) has been working closely with the instrumentation group, as well as with the physics, chemistry, accelerator, nuclear engineering and magnet units at BNL.

“The instrumentation division is crucial because they are going to be responsible for the wire chambers and the electronics that must operate at very low temperatures and with a lifetime of several decades without any maintenance,” he explained. “The technological development is far-reaching and extraordinary.”

Diwan is confident the group is up to the task, suggesting that the Instrumentation Division is “considered the best in the world in developing such advanced technologies.”

Smith and his colleagues have also been involved in developing a medical imaging instrument called RatCAP (for Rat Conscious Animal Positron Emission Tomography).

It’s the same principle as a PET scan for humans. The innovation, however, is that it allows an animal to wear the monitor while engaging in its normal activities. Typically, animal PET scans have required anesthesia, to keep an animal still as scientists survey the brain or other areas of the body. The instrumentation group designed and integrated a detector system for annihilation gamma-rays that is compact, lightweight and low power, which benefits from microelectronics.

“When the animal is anesthetized,” suggested Smith, “the brain activity is compromised. The idea is to investigate brain activity without putting the rat under any drug-induced sleep.”

Smith lives in Port Jefferson with his wife, Anne, a teaching assistant at Setauket Elementary School. Their older son, Edward, works in Manhattan in information technology, while their younger son, Michael, is a building manager in Seattle.

The couple enjoy the similarities between the village of Port Jefferson and their home villages in the United Kingdom. They enjoy walking through town, grabbing a cup of coffee, observing the harbor and trekking back.

In addition to the potential professional collaboration with Stony Brook scientists, Smith also appreciates the chance to play squash at the university campus. He met his wife on a squash court when they were at the University of Leicester.

In leading the instrumentation group, Smith said he hopes to continue to create a positive atmosphere that he likens to an extended family.

As for following in the footsteps of William Higinbotham, who invented the video game “Tennis for Two” at BNL in 1958, Smith suggested: “My goal is to provide the motivation for our outstanding staff to continue making significant high technology contributions to new BNL programs, for a better understanding of nature and for an overall benefit to society.”

 

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Computer model predicted that sodium would become transparent under pressure, and it does

Finding new materials has been a field where industrious and determined workers mixed elements, hoping to come up with the right combination to form a structure that might meet their needs.

While their choices of ingredients weren’t random, their results often proved disappointing, as the process produced considerably more failures than breakthroughs.

About eight years ago, however, Artem Oganov tried to change that. He didn’t want to build a better workbench or come up with a way to test more materials in a lab. He wanted to come up with a more efficient approach. Armed with a computer and working in an office at Stony Brook University, Oganov hoped to improve the process.

Predicting the crystal structure of an element or molecule in its lowest possible energy state presented an enormous challenge.

“Mathematically, when you formulate this problem, it looks intractable,” explained Oganov.

“The number of possible structures can be boiled down to ten to the power of 20 or 10 to the power of 50. Technically, you can’t sample all those structures,” he continued.

In 2003, Swiss scientists developed a computational method called metadynamics. It provided the first hope that the problem of crystal structure prediction might not be totally hopeless. Still, the process had significant limitations, Oganov said.

Oganov and several graduate students over the years, including Colin Glass, Andriy Lyakhov, Qiang Zhu, Guangrui Qian and Salah Eddine Boulfelfel, attempted to create a computer program that would narrow down those possibilities.

When their first several efforts were unsuccessful, “we were ready to give up.”

By combining several innovative approaches, including uniting global optimization (looking for the most likely solution in the big picture) with local optimization (narrowing the choices down among more subtle differences), they came up with a program that worked.

“The whole trick is to invent an algorithm which can work efficiently and reliably for a nearly infinite size,” he offered. “The problem was so big that we were dreaming without really hoping to get it.”

Oganov’s work has become “the gold standard,” suggested Stony Brook Geosciences Chairman Richard Reeder. “Discovering structures before was kind of random trial and error. There’s no systematic way to do it.”

Using the computer model, Oganov and his team predicted that sodium would become transparent under pressure. They found a collaborator who would conduct the test and, as they predicted, the metal became transparent.

The Oganov lab also became involved in an important discovery about carbon. Under high temperatures and pressure, carbon becomes diamonds. Under the same pressure, but at room temperature, carbon becomes superhard, without turning into diamonds.

Scientists had made guesses about the structure of this superhard carbon, but had trouble narrowing down the list in part because of the low resolution of experimental data. Using his computer model, Oganov predicted its structure. With some experimental support, Oganov’s prediction of a so-called M Carbon proved accurate.

Because other forms of carbon have had applications in technology, Oganov suggested this form might become instrumental in future manufacturing breakthroughs.

Oganov’s discoveries “won’t be seen to be applicable immediately,” Reeder explained, but could impact a wide range of fields, from planetary sciences to drug design.

In his presentations about his work, Oganov includes numerous historical references.

Indeed, if he hadn’t become a scientist, the Russian-born Oganov would have become a historian.

“History,” he explained, “gives very valuable lessons of wisdom: what were the good decisions and the bad decisions people made. How does progress work? History gives you good perspective on that.”

It’s important, he suggested, for people to have historical role models. Some of his include Linus Pauling, whom he described as being the “greatest chemist of the 20th century,” as well as Lev Landau. A physicist, Landau could “throw more ideas on one page than in a whole book written by other people.”

Laudau worked on his couch, scribbling notes that became the basis for papers and books, including one that physicists are still using, Oganov said.

A resident of East Setauket, Oganov would like to become a role model to future generations.

Oganov’s chairman believes he already stands out in his field, not only for his accomplishments but also for his intelligence.

“He’s well on his way. His code is the best out there,” Reeder said. “He has the motivation and the drive to do it.”

 

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Usually kept in check by the body, C. albicans can cause damage for those who are immunosuppressed

This is the second in a two-part series that began last week on two scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems.

Like the cracks in the sidewalk that we don’t notice most of the time, Candida albicans is everywhere. Mostly, though, it’s on and around us. While this fungus is harmless much of the time, it has a dark side.

After prolonged catheterization (tubes entering the body) or in people with weakened immune systems, Candida can enter the bloodstream, where it can cause significant damage.

“It’s considered to be the fourth most commonly acquired hospital infection,” explained James Konopka, a professor in molecular genetics and microbiology at Stony Brook Medical School. It often targets the kidney. Even with current state-of-the-art antifungal drugs, Candida can become life threatening.

In most people, Candida often can’t get past the skin or the lining of the gastrointestinal tract. That, however, changes when, for example, patients have surgical procedures.

“A tube going into a patient can provide a site for a biofilm and can get it across the skin,” Konopka explained.

This can also be compounded, he explained, by the use of antibacterial drugs, which eliminate the bacteria and give the fungus more room to grow.

Patients with weakened immune systems, through AIDS, cancer treatments or immunosuppressive therapies, can also be the target of fungal infections.

Konopka is looking from the outside of Candida in, trying to alter the cell wall, or plasma membrane. Everything in the membrane is not randomly moving around, he explained. There are specialized sensors that can be instrumental in its life cycle.

He’s been studying genes that are responsible for 30 proteins in the membrane. He has deleted the genes for most of these proteins and plans to pick the best candidates for more study and drug development.

“If we disrupt the function of those proteins, that leads to a global defect in how the membrane is organized,” he said.

One of the challenges in fungal research is that humans and fungi are more closely related, evolutionarily, than humans and bacteria. On the positive side, that means research into basic cellular mechanisms of fungi may provide information about human cells.

On the downside, however, it provides a tricky type of Venn diagram for medical treatment. Doctors and researchers have to find drugs that only affect fungi and that don’t harm human cells at the same time.

The existing therapies have limitations. As with bacteria, some fungal strains have developed resistance.

Even finding a specific therapy that targets and eliminates Candida could lead to another unintended consequence. Because Candida lives within most of us without causing problems, eliminating all of the fungus could create an opening for an infection from another type of bacteria or fungus.

“There’s been some suggestion that that possibility may be occurring in certain patients in long-term drug therapy,” Konopka acknowledged.

He’s not convinced that’s the case, but it has caused some researchers to think Candida might be filling a niche that keeps worse invaders out.

The ideal therapy may involve a short-term treatment that clears Candida from internal organs, but resets the relationship to where the fungus lives within humans without doing any damage.

At the University of Washington in Seattle, Konopka had been doing basic fungal research under the guidance of Leland Hartwell, who shared the Nobel Prize in 2001 for discovering protein molecules that control the division of cells. When Konopka moved to Stony Brook, he transitioned to studying Candida.

In 2008, he discovered that deleting the proteins in the plasma membranes caused the cell wall to grow backwards.

“There’s a layer of regulation that keeps the cell wall on the inside,” he explained.

Konopka lives in East Setauket with his life, Susan Watanabe, a scientist who is studying HIV, the virus that causes AIDS.

He said he wades out into the water at West Meadow Beach, where he catches bluefish and striped bass.

As for working with fungus, there is an upside: yeast. In the fall, he hosts an Oktoberfest party for his entire building, where he and his guests sample each other’s home-brewed beer. Last fall, the offerings included Strong Island Ale, Rye Smile and Midnight Spice. Konopka provided Hoppy Oktoberfest, a beer he describes as a “classic,” which has “the taste of fresh grown hops, but brings with it a fair amount of sweetness.”

 

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Long term goal is to find drugs that help immunocompromised individuals fight fungal diseases

One of them brews beer, while the other makes his own pizza. While it sounds like a great mealtime combination, what Maurizio Del Poeta and James Konopka do when they’re at work may one day help you or your friends and family.

The two are scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems. Del Poeta is studying Cryptococcus neoformans, a fungus that can kill if it reaches the brain, while Konopka is  working with Candida albicans, a fungus that normally lives with and on us but that can also do damage to internal organs, particularly the kidney.

Del Poeta, the pizza maker, has found a drug that targets a sphingolipid on the surface of Cryptococcus that clears the infection in the brains of mice. He recently applied to start testing that drug on humans. That process could take five years.

Konopka, the beer brewer, is targeting a 30-protein sequence in the cell wall of Candida. He is narrowing down the list of targets and hopes to start searching for effective drugs or therapies.

“These two men are superb,” said Jorge Benach, the chairman of the Department of Molecular Genetics and Microbiology. “They are sought after internationally and nationally” to address scientific audiences.

The Molecular Genetics and Microbiology department includes researchers who study viruses, bacteria and fungi. Benach said they are all aware of the potential medical benefit, even as they perform basic research to understand the way these pathogens work.

“It takes a while from what we do to the point where we can save lives,” he offered. “We are on that track. If you hit the ground running, you shorten that distance.”

The Times Beacon Record will profile the research of Konopka and Del Poeta in a two-part series. The Del Poeta feature will run today, while the Konopka story will run next week.

 

Maurizio Del Poeta loves stories. There’s the one about how he met his Italian wife when they were at Duke University. They were, he said with a laugh, two of the only three people originally from Italy at Duke.

He met her at a dinner party after he returned from a ski trip. The only complication: she was dating someone else.

“I was waiting for her to drop this guy,” he laughed. “He wasn’t good for her.”

Six months later, she became single and Del Poeta’s wait was over.

An avid reader, Del Poeta also has a story for a key insight into his research. While reading the late Michael Crichton’s anti-climate change novel “State of Fear,” an ironic choice given his findings, Del Poeta decided he had to test a fungus in a higher carbon dioxide environment, like that in the lung.

He was working with Cryptococcus neoformans, a fungus that is especially problematic in people who are immunocompromised — either through cancer treatments, drugs that suppress the immune system after organ transplants or in people with AIDS.

In the outside environment, a mutant type of this fungus grew normally, but “when you transfer it into the lung, it can’t grow anymore,” he explained.

When he studied it more closely, he found that a specific sphingolipid attached to the surface of the fungus in the mutant prevents it from growing in an environment that has 5 percent carbon dioxide (the concentration in the lung), compared with the approximately 0.4 percent in the atmosphere.

This sphingolipid and the genes and enzymes that lead to its production became a “fantastic target for developing drugs,” Del Poeta offered.

That discovery came in 2005. Del Poeta has spent the last seven years, including the last six months as a professor in the school of medicine at Stony Brook Medical School, looking for drugs that might target that sphingolipid.

He has found several that have worked. The survival rate of animals treated with these targeted drugs is 90 percent, compared with a 100 percent mortality rate when untreated.

Del Poeta submitted a grant to the National Institutes of Health for one of the drugs in February. It received a high score, he said, but it was not funded. After he conducted the promising mouse experiments this year, he resubmitted that grant in the middle of December. He hopes to hear back in the next few months.

The drug not only prevents the spread of an infection in the animal models but it clears the fungus from the brain. Currently in humans, there are no drugs that effectively eradicate the fungus in the brain.

Del Poeta said it may take five years before the drug goes through clinical testing to reach the pharmaceutical shelves.

While the drug is not toxic in animals, it’s unclear what reactions humans might have to it.

Del Poeta got involved in fungal research when he was a medical doctor at Duke. He observed that the patients he had who were immunocompromised, mostly because of AIDS, were dying because of this fungal infection.

He needed “to do something.” He consulted with his mentor John Perfect, who is now the director of the Division of Infectious Diseases at Duke, who suggested he choose between seeing patients and conducting research.

While he misses seeing patients, he finds his research satisfying, especially because of its potential practical impact.

In his research, he combines basic science with the search for drugs.

He explores the mechanism by which the sphingolipid limits the growth of the fungus. He is also looking at ways to boost other parts of the immune system that are not often weakened, even in immunocompromised individuals. He would like to raise the activity level of macrophages, neutrophils and Natural Killer (NK) cells.

A temporary resident of Port Jefferson, Del Poeta and his wife Chiara Luberto, who is studying leukemia at the cancer center at Stony Brook, recently bought a house in Mount Sinai. The couple have two young sons, Matteo and Francesco.

Del Poeta combined his passion for cooking and sharing amusing anecdotes in a cookbook called “Pasta con Amici.”

When he moved to South Carolina (a stop he made before landing at Stony Brook), he missed pizza so much that he built a brick oven with his father. He plans to build another one here, perhaps in 2013.

“I love stories,” he explained. “Behind a story, there is everything. Each of us has a fantastic story.”

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Physical factors, such as exercise and even vibrating platforms may have profound health benefits

One way to shake up an immune system may be, in fact, to shake up the immune system.

Clinton Rubin, the chairman of the Department of Biomedical Engineering at Stony Brook, has been studying the effects of low intensity vibrations as substitutes for physical activity on bone growth in animal models. He’s found, for example, that older sheep standing on a platform that’s vibrating at a level that’s barely noticeable show bone growth.

His latest finding is that these same slightly moving platforms can also raise the level of immune cells, including T cell and B cell levels, in an obese mouse.

While it’s early to extend this to humans, the findings present the possibility that these small vibrations may help contain or even prevent significant health problems that often threaten or damage the lives of people who are significantly overweight.

“Obesity makes you susceptible to a number of disorders,” explained Rubin, who is also the director at the Center for Biotechnology. “We hope that some day, if we are able to extrapolate these findings in mice to people, that these low magnitude mechanical signals can help mitigate the health complications that arise in those that are obese.”

Rubin cautioned that these signals would not be a substitute for a healthy diet, exercise and active interaction with a physician’s advice.

Ever since he arrived at Stony Brook University in 1987, Rubin has been studying how physical factors influence the musculoskeletal system, to understand, for example, how exercise can generate a profound health benefit. He has also looked at how the removal of these physical factors, through bed rest, extended time in space, and spinal cord injuries, can affect these systems. These low intensity vibrations have served as surrogates for typical mechanical loading signals.

Recently, he has studied the effects of these small vibrations on mesenchymal stem cells (or MSC). These cells can become bone cells, cartilage or fat cells. Low intensity vibrations for as little as 10 minutes a day can bias these cells away from becoming fat cells.

Rubin suggests the process may involve a signaling pathway that mimics the way muscles move bones. Muscles are generally inefficient motors, shaking as they contract (as anyone who has challenged themselves to do a few extra push ups or do a few more reps with weights can attest). The vibrations from these plates may provide a substitute signal for the muscle vibrations.

Rubin is the chief scientific advisor for a company called Marodyne Medical, which hopes to translate his science into a medical device that can address such problems as bone wasting, muscle wasting, obesity and diabetes.

Rubin readily recognizes he has a potential conflict of interest because of his involvement with a company he hopes will one day sell a product that could offer a nonpharmaceutical alternative for people with various bone or muscle challenges.

“Do I look at this stuff with rose-colored glasses?” he asked. “As a scientist, I hope not. I try to insulate myself as much as possible from the subjects in evaluating the data.”

Rubin said the university helps him address these concerns by ensuring he provides full disclosure, in publications, grants and lectures and by informing any human subject who participates in his studies of his dual roles.

He does not interact with potential subjects in his studies and all his scientific methods are performed in a double blind fashion. That means he doesn’t know which animal received which treatment when he records results.

As for the immune system response, the benefit from these low intensity vibration is through another class of cells, called the hematopoietic stem cells (HSC).

“If these bone marrow are influenced by mechanical signals, why not HSCs?” Rubin reasoned.

Rubin and his wife, Jennifer Sigler, live in Port Jefferson with their 16-year-old son Jasper. Sigler works as an architect for the building department in their village. Jasper, meanwhile, has kept his own musculoskeletal system active by playing right defensive back for the Port Jefferson Royals, who have won back-to-back New York state class C soccer championships.

Rubin, who has been at Stony Brook since 1987, said he struggles on the Port Jefferson golf courses, but that hasn’t kept him from the links.

Rubin appreciates the support and talent of his colleagues at Stony Brook, including Assistant Professor Meilin Ete Chang and senior doctoral students Danielle Green and Ben Adler.

His work, he said, suggests that even supporting weight can send the right signals to their bodies.

“When people ask me what they should do if they can’t run or walk, I tell them stand up,” he offered.

 

Cast call

Cast is sought by Star Playhouse, Suffolk Y JCC, 74 Hauppauge Road, Commack for their upcoming play, “Dirty Rotten Scoundrels.” All roles are open; ages 17 and up. Prepare to sing 32 bars of contemporary theater music. Bring sheet music in the proper key and be prepared for dance audition. Call 462-9800, ext. 136, or go to starplayhouse.com for further information.

Free Irish language classes

The Gerry Tobin Irish Language School will be offering free Irish language classes beginning on Wednesday, Feb. 6, at the Ancient Order of Hibernians Hall, 27 Locust Ave., Babylon. Classes include “Mommy, Daddy and Me,” for young children and their parents. Classes for new and advanced students are also available. Call 521-1227 or go to www.scoilgaeilge.org for further information.

Seamanship course

The U.S. Coast Guard Auxiliary Flotilla 2204 will be offering a boating and seamanship course beginning on Thursday, Feb. 7, at 7 pm. Classes will be held at the Smithtown Library, 1 North Country Road, Smithtown, and runs for seven sessions.

Upon completion of the course a certificate will be awarded, satisfying the Suffolk County boaters requirements and the New York PWC operators certificate; this also covers the young boaters requirements for those under 18 years of age. Additionally, boat owners may be eligible for an insurance discount.

The course is free; there is a nominal charge for course materials. Family participation is encouraged. Call 732-3562 for further information and to register.

Pysanky Easter egg workshop

The third annual traditional Ukrainian Easter Egg (Pysanky) decorating workshop will be held on Sundays, March 10 and 17, at the Resurrection Byzantine Catholic Church, Edgewater and Mayflower avenues, Smithtown. All levels of experience are welcome. Cost of the class is $20; each participant must bring a candle in holder, pencils and roll of paper towels. Registration is required by Feb. 8. Call 246-5669.

 

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Long Baseline Neutrino Experiment seeks to understand why matter triumphed over antimatter

If two armies of twins fought against each other with identical protective gear and equally fatal weapons, the result would likely be fatal for every one of them. At least, that’s how particle physicists see it when they look at the early universe.

The twins in the primordial battle are matter and antimatter. Matter includes positively charged protons and negatively charged electrons (which are also called baryons). The antimatter equivalent are negatively charged protons and positively charged electrons.

Somehow, when these two armies mixed in something akin to a soup, matter wiped out its antimatter counterpart.

But why, physicists wonder, did matter win? Could the battle, which physicists believe lasted mere microseconds, have ended the other way, or could the two sides have left nothing behind?

Physicists, including Milind Diwan of Brookhaven National Laboratory, believe neutrinos may provide the answer. Almost as plentiful in the universe as particles of light, neutrinos are so small that a trillion of them pass through our bodies each second. Not only are they harmless, they barely interact with anything else, because, while they do have mass, they are spectacularly small.

The sun, stars and even the Earth produce them and, thanks to particle accelerators, humans can, too. Diwan is part of a collaboration of 350 scientists, mostly from American universities, who are teaming up in a program called the Long Baseline Neutrino Experiment (LBNE) to use these nearly massless particles to try to understand the early triumph of matter over antimatter.

In the LBNE, the scientists hope to shoot neutrinos and antineutrinos 800 miles through the Earth — the experiment wouldn’t require any tunnels — from the Fermilab accelerator outside of Chicago to a research facility in a former gold mine, now called the Sanford Underground Research Facility in Lead, South Dakota.

The effort suffered a funding setback this past summer, when the Department of Energy praised the goals but asked the scientists to return with a plan that was affordable. The LBNE researchers broke the project up in phases. After the LBNE team made the suggested revisions, they received approval in early December from the DOE.

Diwan and his colleagues anticipate that the LBNE will provide evidence of how matter and antimatter behave differently as neutrinos make the long journey underground to a receptor in what was once the Homestake Mine, which was, up until it closed in 2002, the largest and deepest gold mine in North America.

Neutrinos have three different types, changing readily from muon to tau to electron. It is over these distances that these oscillations, as the changes are called, may help unlock the key to the asymmetry between matter and antimatter.

“If you measure their properties in this far-away detector, there will be differences,” Diwan predicts. “I suspect those differences will be quite large and … can be directly linked to the way the universe evolved in its first few microseconds” when antimatter was annihilated.

“We have been struggling to understand this miraculous event,” Diwan explained. “This is one of the key problems in all of science.”

While scientists plan to send the neutrinos on a long journey through the Earth, the researchers themselves are expecting their own long trek.

Based on the current plan, the LBNE will start producing data in 2022. By then, would-be scientists who are planning to graduate from high school this year may contribute to the research.

While that might seem like a slow build for a long range project, there are competitive time pressures.

“Japanese physicists want to perform a similar experiment with a shorter distance and Europeans want to perform a bigger experiment with almost the same experimental features,” Diwan explained. “At this point, there is agreement that in terms of planning, we are ahead of them.”

A resident of Port Jefferson Station, Diwan and his wife Sucheta, an engineer at Hauppauge-based Parker Hannifin, have a 14-year old daughter, Renuka, and a 10-year old son, Yashodhan.

His wife’s job is “much more important than mine,” he offers. Her company makes fuel gauges for jumbo jets.

As for his work, Diwan has been in the physics department at BNL since 1994. He is eager to see the LBNE project through.

“I feel very fortunate that I am working on a question that is important,” he offered. “It is extraordinary that we have the tools to actually perform this experiment.”

 

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With ‘veto power,’ chandelier cells are theorized to keep order in the nervous system

Someone whose opinion he trusted told him he was going in the wrong direction. Every indication for years suggested success was as elusive four years after failing as it had been during his first unsuccessful attempt.

“It didn’t look very good,” confided Z. Josh Huang, a scientist at Cold Spring Harbor Laboratories. In those first years, he wondered if he should do something else.

Sticking with it, however, paid off, especially in the last few years. Huang and his team have made important discoveries about a type of neuronal cell in the cerebral cortex called chandelier cells.

Huang has not only been able to label these cells and watch them in action, but he has also figured out where and when they develop, before they move to their position inside the cerebral cortex (the part of the brain that is responsible for processing sensory information, for thinking and reasoning and for directing movement).

These chandelier cells are likely to be the most powerful cells in the cerebral cortex. They are only found in the cerebral cortex and humans appear to have more of them than other mammals, including monkeys and mice.

They got their name from the way their branches jut out from the main body of the cell. Their axon arbor looks like a chandelier light. Researchers believe they serve an important role in keeping order in the nervous system, quieting other nerve cells from vying for attention all at once.

Francis Crick, who won the Nobel Prize in 1962 for discovering the double-helical nature of DNA with James Watson, first suggested four decades ago that these cells had “veto” power, according to Huang.

“When the chandelier cell ‘speaks,’ it is like the president. All these other cells will be quiet, regardless of their urge to speak,” Huang explained.

While that metaphor hasn’t been proven precisely yet, Huang said the evidence is mounting to support Crick’s original contention. Huang’s research is testing this specific assertion.

Some medical challenges, including schizophrenia and epilepsy, have been linked to problems with chandelier cells.

“A variety of molecular markers were altered or reduced in the pre-frontal cortex in schizophrenia patients,” Huang explained. “That has been a very reliable finding from many labs.”

The possible explanation is that if these cells are compromised, the excitatory neurons will not function coherently. Some treatments are looking at ways to boost the output of the chandelier cells by enhancing the so-called GABA receptor.

GABA, named for the neurotransmitter gamma amino-butyric acid, is the only inhibitory neurotransmitter in the brain. GABAergic inhibitory cells, including chandelier cells, organize neuronal populations into groups that guide behavior.

Some of Huang’s early work, which proved so challenging, involved following the pathway of these chandelier cells, which develop outside the cortex and move to their central locations during development. When he started looking for ways to track these cells, scientists were using dyes, which weren’t reliable.

Huang built a better animal model system to track these cells. Now, he can see them every time they are active.

“You can activate them or silence them and see the consequence,” he explained. “It’s extremely powerful.”

In the latest finding, Huang discovered that these important cells start out in a region of the embryonic brain he called the ventral germinal zone. This part of the brain didn’t have a name because it wasn’t clear what types of cells it produced.

Chandelier cells are “born” after another region that is responsible for producing different neurological inhibitor cells disappears.

Huang’s work was published last month in the journal Science. Earlier this year, he also served as co-author on three papers in Nature, another prestigious scientific journal.

“This has been an amazing year,” he concedes. “It took us four years to fail, to build this experimental system” to make these findings.

Huang, who has been at Cold Spring Harbor for a dozen years, lives in Woodbury with his wife May Lim, a radiation oncologist in Queens, and his two daughters, Vivien, 12, and Julienne, 8.

In graduate school, he added the first name “Josh” because it has some phonetic resemblance to his Chinese first name.

In terms of his research, Huang said he received supportive advice from colleagues and advisors along the way, much of which he took to heart during the years that weren’t quite as productive as this one.

“What I came away with is to do something that is very fundamentally important and to stay the course,” he offered.