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Authors Posts by Daniel Dunaief

Daniel Dunaief

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Annie Laurie W. Shroyer and Thomas Bilfinger

By Daniel Dunaief

Convenience can come at a cost, even in medicine. When it comes to a heart procedure called cardiac artery bypass surgery, that cost could make a difference in the outcome for the patient.

Annie Laurie W. Shroyer, vice chair for research and professor in the Department of Surgery at Stony Brook University School of Medicine, and Thomas Bilfinger, a professor of surgery in the Division of Cardiothoracic Surgery at SBU, found that the mortality and major morbidity rates were lower for patients of surgeons performing procedures at a single center compared to those performing procedures at more than one center. 

Among physicians who operated at two or more hospitals, these surgeons performed better at their home hospital than at a secondary center.

They’ve published their findings in the Annals of Thoracic Surgery. The Society of Thoracic Surgeons identified the article as the Continuing Medical Education article for the month. The article will provide a much more in-depth learning experience to a subgroup of the journal’s subscribers who seek Continuing Medical Education credits. This, Shroyer explained, will make it more likely that cardiac surgeons will read it thoroughly and discuss it.

“We believe that, based on the results, particularly complex coronary artery bypass grafting (CABG) procedures may have a better outcome at bigger institutions,” Bilfinger explained in an email. Mortality for these procedures overall in the United States is low and the analysis is about differences of a few tenths of a percent, which becomes statistically significant due to the low number.

The central issue, Bilfinger said, is whether “the mother ship does better or worse than the satellite. Decision making about centralizing versus a de-centralized approach seems to be less driven by outcomes and rather by business decisions in many circumstances. The study adds some subjective data to this discussion.”

Using a measure called observed-to-expected mortality ratios based on the health of the patient and risks of the procedure, the ratio for multicenter surgeons was higher for the satellite facilities compared to their home facilities. The ratios were 1.17 for surgeons operating at satellite facilities versus 1.01 for multicenter surgeons performing the procedure at their home hospital.

The volume of surgeries is a complicated issue, Bilfinger cautioned. “There are very well-performing smaller volume places throughout the country,” he explained in an email. “It involves dedication to the procedures from admission to discharge.”

Assuming the surgeon is just as effective in different hospitals, which is “open to discussion,” any observed difference could be attributable to the system, Bilfinger explained. Measuring the effectiveness of the participants in the process, including nurses, anesthesiologists and orderlies, is a question for ongoing research, he continued.

Joseph Carey, a cardiovascular and thoracic surgeon in Torrance, California, conducted a study based on information from California about a decade ago. In an email, Carey suggested that “you pay a price in quality working in unfamiliar conditions and I believe hospital managers do not want their surgeons traveling about.” He added that this paper “is an important reminder” of this.

Carey added that hospital systems and the makeup of the “heart team” may also be important to the outcome of a surgery.

Future research, which Shroyer plans to conduct, will evaluate other factors, such as patient risk, processes and structures of care, that impact cardiac surgical outcomes.

Other researchers could extend this study, which compares the quality of care for surgeons who work at single sites and multisites, to other areas of medical care, enabling hospital networks, insurance companies and patients to make informed risk-based decisions prior to approving difficult procedures.

The challenge, however, with similar studies for other conditions, is in finding national information. “This is the best documented group of procedures there is in the country,” Bilfinger said. For a procedure like back surgery, it might be difficult to come up with a comparable study, although Bilfinger said he “suspects strongly that this is a very similar relationship.”

Shroyer and Bilfinger will extend their work to another cardiothoracic operation. They have submitted a proposal to the Society of Thoracic Surgeons to start a parallel project to look at the difference in risk-adjusted outcomes for mitral valve procedures that compare single-center versus multicenter surgeons. The diversity of procedures may need to be considered in comparing single and multicenter surgeons.

Bilfinger said he recognizes that some doctors and hospital networks may find these conclusions disconcerting. It may give them pause in the internal discussion about value added by new satellites in any system, he explained. “This is worth a public debate. This is one of these aspects of modern health care that the consumer is not aware of.” The average consumer may not put too much emphasis on this, although the sophisticated consumer on Long Island may change or make decisions based on this type of information, he said.

Shroyer and Bilfinger, who have worked on the same floor at the Health Sciences Center since Shroyer arrived from Colorado in 2007, decided to collaborate on this project after a discussion during lunch. The duo were eating at SBU’s Simons Center Café when they were discussing the differences in outcomes for single and multicenter surgical procedures. They submitted a request to access the National Adult Cardiac Surgery Database in 2014 to the Society of Thoracic Surgeons.

For patients who are going to have a cardiac surgical procedure, Shroyer recommends that people choose their surgeon and surgery center “wisely.” She recommends researching the surgeons and their corresponding center’s bypass specific outcomes. She highlights two publicly available resources, which are Adult Cardiac Surgery Database Public Reporting|STS Public Reporting Online and Doctor Ratings — Consumer Reports.

Shroyer cautions that these ratings are somewhat outdated, so she suggests patients ask their surgeons directly about their more recent outcomes. She would also recommend contacting patients.

After conducting this study, Shroyer believes it would likely help patients if they searched for doctors who only perform bypass procedures at a single hospital. She also believes it is important for patients to consider surgeon-specific and center-specific risk-adjusted outcomes.

Ultimately, she said, the decision about a surgeon and a site for surgery is an important one that patients should make based on the likelihood of the best outcome.

“Patients should research their cardiac surgeon-hospital decision even more carefully than if they were buying a new home or a new car,” she explained in an email. “Their future health lies in their cardiac surgeon’s hands.”

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The morning routine for all four of us was slightly off kilter. My daughter, who usually doesn’t have the energy to complain about starting her day, suggested that she really needed a day off. Sorry, but that wasn’t going to happen. Besides, she doesn’t generally want a day at home because she feels as if she would fall behind in her classes and would rather keep pace.

I dropped her off at school as she groaned something to the effect of, “Bye, have a good day, I hate this.”

I returned to pick up my wife and take her to the train. She was also slightly behind schedule. My son came “elephanting” down the stairs. It’s an expression we use that is exactly as it sounds. He throws his feet so heavily and loudly on the steps that the house shakes until he reaches the first floor, turns hard to his right twice and collapses into his chair.

My wife and I raced out of the house two minutes behind our usual departure time. Two minutes? How was I supposed to make it to a train that is only early when we’re late? It’s Murphy’s law of trains. Whatever can go wrong with the commute does go wrong and, often, in conjunction with other problems.

We came to the final light seconds before the train was scheduled to pull in.

We reached the traffic light just as it turned red, in that small window when all the lights are red at the same time. Despite the line to my left waiting for a green light, I made a right on red and pulled into the intersection behind another car waiting to make the immediate left into the train station.

Unfortunately, the cars on the other side of the street hadn’t left an opening for the frantic commuters to reach the station. When their light changed, the traffic immediately started moving, blocking us from making the turn.

My wife considered getting out, racing across the street and trot-running through the parking lot. The cars speeding by near her door made that impossible.

A car behind me honked, moved to our right and slowly passed. A woman in her 60s flipped us the bird.

Do we still do that? Do we still raise our middle finger to strangers? I do it to my computer when it’s frozen and to my phone when it’s not allowing me to respond to an email or text, or when it adds an error to one of my emails because it retyped a name into something potentially problematic.

But this woman, with her tight lips, curled and dyed hair, and menacing eyes, slowly rolled past me, extending the curse finger just in front of her left shoulder. That raised digit was so stiff, long and rigid that it looked it could have just as easily have been a weapon as a gesture.

I was stunned to react immediately. Then a few responses ricocheted around my head as my wife raced out of the car: “Sorry? Right back at you, sweetheart.” … “You know what you can do with that finger.”

It’s possible her day had, or was expected to have, much bigger problems than mine. I am sorry I upset her so much that she needed to express her outrage.

Or maybe I gave her a chance to be angry at something other than herself, her family, her boss or the people who work for her. Could I have done her a favor, providing a target for her anger?

I don’t know her story, but I do know that my day suddenly seemed less problematic.

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A friend recently told me she’s pregnant with her first child. She sounded thrilled and anxious. She is, as I’ve known for years, incredibly organized and efficient. She has been a standout in her job for several years.

“What’s the concern?” I asked.

“Everything,” she giggled.

As my children take one standardized test after another, I thought perhaps I would share a test-format version of what to expect when you’re expecting. No. 2 pencils ready? OK, let’s begin:

Question 1: Before the baby is born, you should:

a. Panic buy everything, including a crib and six months worth of food and clothing. You never know if you’ll be trapped in your house without access to the outside world.

b. Sleep as much as you can because the days of sleeping at your leisure are over.

c. Read everything you can about parenting and the delivery, and then realize that every process, including childbirth, can go off script.

d. Don’t tell anyone because people will write about you.

Question 2: When people give you advice, you should:

a. Write everything down because friends, family and strangers always know better and will enlighten you with wisdom that far exceeds that which you’d get on a fortune cookie.

b. Nod politely, say, “That’s a great idea,” and wonder what to eat for dinner.

c. Pretend your phone is ringing.

d. Ask them how many Nobel prizes their children have won.

Question 3: Taking Lamaze classes can be helpful because:

a. It allows you to meet parents who are older than you.

b. It allows you to practice breathing together because sometimes parents forget to breathe.

c. It’s so relaxing that you can doze off without punishment.

d. It gives you a sense of control that you’re unlikely to have in the actual moment.

Question 4: People generally love other people’s children unless:

a. They are sitting on a plane near them.

b. They have to do something for them.

c. The children are crying constantly and they don’t know why.

d. The children have dropped or broken something.

Question 5: Parents can be so tired in the early stage that they forget:

a. To take pictures of everything.

b. To feed themselves.

c. To go to the bathroom when they need to.

d. To revel in a new baby smell that will change into something much more challenging to the nose within a year.

Question 6: When you have a baby, it’s a great idea to:

a. Change jobs.

b. Move to a new city.

c. Start attending a new and rigorous educational course.

d. All of the above, because you’ll never have a chance to juggle more challenges at the same time than when a baby is born.

Question 7: The families of the father and mother are likely to:

a. Always agree on everything you should do for the child.

b. Never agree on anything you should do for a child.

c. See evidence of their family’s genes in the child.

d. Put small differences aside and enjoy the moment when they share a new relative.

Question 8: Once you have a child, you will:

a. Be thrilled when young children come over to play with your child.

b. Be worried that the young children who come over are sniffling.

c. Want everyone to bathe in Purell sanitizer before coming near your child.

d. Not be like me and will relax when people sneeze across the room.

Question 9: You know you’ve had a great day with your child when:

a. You keep replaying something he or she said or did as you’re preparing to sleep.

b. You actually go to sleep instead of passing out with Oreo cookie crumbs in your mouth.

c. You and your spouse are laughing, quietly, for hours before you go to sleep.

d. You can’t wait to start the next day.

Question 10: Parenting is:

a. Awesome.

b. Terrifying.

c. Exhausting.

d. All of the above.

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Maurizio Del Poeta. File photo from SBU

By Daniel Dunaief

Sometimes, fixing one problem creates another.

People with multiple sclerosis have been taking a medication called fingolimod for a few years. The medicine calms immune systems that attack the myelin around nerve cells. Fingolimid decreases the lymphocyte number in the bloodstream by trapping them in the lymph nodes.

In a few cases, however, the drug can reduce the immune system enough that it allows opportunistic infections to develop. Cryptococcosis, which is a fungal infection often spread through the inhalation of bird droppings or from specific trees such as eucalyptus, is one of these infections, and it can be fatal if it’s not caught or treated properly, especially for people who have weakened immune systems.

Swiss pharmaceutical giant Novartis contacted Stony Brook University fungal expert Maurizio Del Poeta, a professor in the Department of Molecular Genetics & Microbiology, to understand how this drug opens the door to this opportunistic and problematic infection. He is also exploring other forms of this drug to determine if tweaking it can allow the benefits without opening the door to problematic infections.

Most of the human population has been exposed to this fungus. In a study in the Bronx, over 75 percent of children older than 2 years of age had developed an antibody against Cryptococcus neoformans, which means they have been exposed to it. It is unknown whether these people harbor the fungus or if they have just mounted an immune reaction. Exposure may be continuous, but infections may only occur if a person is immunocompromised.

Fingolimid “inhibits a type of immunity” that involves the movement of lymphocytes from organs into the bloodstream,” Del Poeta said. “Because of this, there are certain infections that can develop.”

Through a spokeswoman, Novartis explained that the company was “happy to have started a scientific collaboration” with Del Poeta to understand the role of a specific pathway in cryptococcus infections.

Cryptococcal meningitis is one of several infections that can develop. Others include herpes meningitis and disseminated varicella zoster. Before starting fingolimid, patients need to receive immunization for varicella zoster virus. At this point, doctors do not have a vaccine for cryptococcosis.

To study the way this drug and its derivatives work, Del Poeta recently received a $2.5 million grant over a five-year period from the National Institutes of Health.

Yusuf Hannun, the director of the Cancer Center at SBU, was confident Del Poeta would continue to be successful in his ongoing research.

Del Poeta “does very important and innovative work on fungal pathogenesis and he is a leader in the field,” Hannun wrote in an email. “His work will enhance our understanding of the molecular mechanisms.”

Fingolimid mimics a natural lipid. Years ago, Del Poeta showed that this sphingolipid, which is on the external surface of the membrane, is important to contain cryptococcosis in the lung. If its level decreases, the fungus can move from the lung to the brain.

While people with multiple sclerosis have developed signs of this infection, it is also prevalent in areas like sub-Saharan Africa, where people with AIDS battle cryptococcosis. About 40 percent of this HIV population develops this fungal infection, Del Poeta said. About 500,000 people die of cryptococcosis every year.

In certain areas of the United States, such as the Pacific Northwest, this fungus is also endemic. On Vancouver Island, about 19 people died from Cryptococcus gattii infections between 1999 and 2007. Most of those patients were immunocompromised.

When the fungus migrates from the lung to the brain, it is “very difficult, if not impossible in most cases, to eradicate,” Del Poeta explained in an email. If the diagnosis is made early enough before the infection spreads to the brain, the recovery rate is high, he suggested. In people whose immune systems are not compromised by drugs or disease, “death is rare.” 

Del Poeta plans to study the interaction between the drug and the fungal infection through a mouse model of the disease. The mouse model mimics the human disease and will provide insights on how to control the infection, particularly when the fungus reaches the brain.

Some of the derivatives Novartis has developed do not cause a fungal infection. Del Poeta is working with Novartis to study other forms of fingolimid that do not reactivate cryptococcosis. Del Poeta said Novartis is currently in Phase III clinical trials for another drug for multiple sclerosis. The new drug acts on a different receptor.

“We think the reason the fingolimid reactivates cryptococcosis is that it is blocking one receptor, which is important for the containment” of the fungus. The other drug doesn’t allow the disease-bearing agent to escape.

“This is a hypothesis,” Del Poeta said. He is waiting to corroborate the cell culture data in animal models.

Del Poeta has been working with Novartis for over three years. The Stony Brook scientist used some preliminary studies on the way fingolimid analogs behave as part of the research grant application to the NIH that led to the current grant.

Del Poeta said he is excited about the possibility of contributing to this area.

“Not only will this work contribute to the field of MS, but it will also have a contribution to the field of cryptococcosis,” he said. “This will have important implications for MS patients [and] for the entire HIV population.” He said he believes patients may have some other defect. If he is able to discover what that is, he may be able to protect them from a cryptococcosis infection.

Ultimately, Del Poeta hopes this work leads to a broader understanding of fungal infections that could apply to other pathogens as well.

“Mycobacterium tuberculosis causes a granuloma very similar to the one caused by the cryptococcosis and we could potentially study whether the same molecular mechanisms involved in the control of the infection in the lung are similar between the two infections,” he explained in an email.

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Hello, my name is Dan and I’m a … journalist.

It’s been a few days since my last meeting and a lot has happened since then.

For starters, I’ve decided to hate myself. I’m coming to grips with the idea that, as a journalist, I am detested and detestable.

I ask questions. All the time. Just ask my wife and kids, although they’re too annoyed with my questions to entertain yours.

I have this insane urge to understand and appreciate the nuance of a word or phrase. I even have a dictionary. Didn’t we burn those long ago? Aren’t we supposed to look for the underlined red words in a document?

My editors and I also change my words. What you see doesn’t just leap from my fingers onto the page. How are you supposed to know what I’m thinking if I let my ideas develop before shouting them at you?

I don’t have a specific character limit. Oh, and I only use hashtags when I’m pushing the button on my phone. Sacrebleu! And I write foreign phrases like “sacrebleu” to express my surprise.

Additionally, I absolutely adore alliteration. I can’t help smiling when I think about the movie “Broadcast News.” I know, I know, we’re supposed to hate everything with the word “news” in it, but I grin when I hear Albert Brooks asking, “Pretty peppy party, isn’t it, pal?”

I frequently read. Sometimes, I’ll be in a room with a television and I’ll have a book or a, gasp, newspaper in my hands with the TV off. How am I supposed to relate to everyone when I’m not watching TV?

And deadlines? They’re so real for me that I sometimes don’t talk to my wife and kids just before they arrive. I used to work for Bloomberg News — the fastest twitch environment I’d ever experienced. An editor once followed me into the bathroom to find out how long I would be in there because I had a story to write. When I was on deadline at Bloomberg, particularly around earnings season, I would give my wife all of five seconds to share whatever she needed to communicate before I raced to the next story.

Oh, and I sometimes make mistakes. That’s horrific, especially when I have to explain how I could have erred. I used to have to write letters reviewing how I blundered; I called them the “I suck because …” letters. I periodically imagined weaseling my way out of trouble by claiming how tired I was from getting up at 4 a.m. when I learned of a story I’d missed in Europe.

That, however, would never fly, because a mistake has no defense; it requires a correction. I also use semi-colons and colons, which have nothing to do with my bathroom habits.

Sure, there are times when someone claimed I made a mistake when, in fact, the mistake was not agreeing with their opinion. That’s not a mistake — a difference of opinion.

But, hey, that’s another reason to hate me. I think about whether something is an opinion or a fact. An opinion lives in a realm where people need to repeat it to make sure everyone agrees. A fact can and should stand on its own.

It’s hard, when we’re all human, to ignore the pleas of people in power who want journalists and their stories to go away. One of my journalism professors said he tried to limit his friendships so they wouldn’t prevent him from doing his job.

That’s tough because I enjoy interacting, even with people who don’t share the same viewpoint. But, wait, I hate that because, ultimately, I’m loathsome and detestable.

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First Row from Left to Right: Kapeel Chougule, Computational Science Developer II; Mariana Neves Dos Santos Leite, Lab Aide (no longer at CSHL); Sharon Wei, Computational Science Analyst II; Andrew Olson, Computational Science Analyst II Second Row from Left to Right: Joshua Stein, Computational Science Manager III; Christos Noutsos, Postdoctoral Fellow (no longer at CSHL); Vivek Kumar, Computer Scientist; Doreen Ware, CSHL Adjunct Associate Professor & USDA/ARS Research Scientist; Yinping Jiao, Post Doc Computational; Sunita Kumari, Computational Science Analyst III; Marcela Tello-Ruiz, Computational Science Manager II; Young Koung Lee, Post Doc 11; Jerry Lu, Computational Science Developer III; Michael Regulski, Research Investigator Third Row from Left to Right: Christophe Liseron-Monfils, Post Doc Computational (no longer at CSHL); Bo Wang, Post Doc Computational; Liya Wang, Computational Science Manager III; Joseph Mulvaney, Computational Science Analyst III (no longer at CSHL); Lifang Zhang, Research Associate; James Thomason, Computational Science Developer III; Peter Van Buren, Systems Engineer III Not Pictured but in Ware Lab: Nicholas Gladman, Post Doc III; Fangle Hu, Research Technician II; Demitri Muna, Computational Science Analyst III; Pragati Muthukumar, Lab Intern, High School; Xiaofei Wang, Computational Science Analyst I; George Wang, Lab Intern, College; Christy Bedell, Senior Scientific Administrator. Photo by William Ware

By Daniel Dunaief

In a two-month span, members of Doreen Ware’s lab at Cold Spring Harbor Laboratory have published three articles that address fundamental properties of plants. 

Doreen Ware. Photo by Gina Motisi, Cold Spring Harbor Laboratory

Printed in the journal Nature Genetics, researchers in her lab studied the genes involved in conferring disease resistance across a range of species of rice. Another study, featured in Nature Communications, found the genes and the molecular pathway that determines the number of fertile flowers in the cereal crop sorghum.

In Frontiers in Plant Science, her productive team identified the causal genes that enable sorghum to develop a waxy outer layer that allows it to resist drought by containing water vapor.

 

“I am pleased with the recent publications from the laboratory,” Ware, who is also a computational biologist for the U. S. Department of Agriculture, explained in an email. “This is a sign of productivity, as well as the impact [technological] advances and drop in sequencing [costs] that is supporting these science advancements.”

Her lab is interested in the link between the genes in a plant and the way it develops.

“I want to understand mechanistically how the outputs in a genome interact with one another to produce a product,” Ware said. This will allow the lab to inform breeding models. “We would like to use the biological mechanism to support predictive modeling.”

In the rice article, Ware, informatics manager Joshua Stein at Cold Spring Harbor Laboratory and University of Arizona plant scientist Rod Wing searched for the specific genetic sequences different species of rice around the world use to develop resistance to infections by fungi, bacteria and other pathogens.

They used wild varieties of rice that had not been domesticated and looked for signals in the DNA. These were selected by their collaborators based on phenotypes that may be of value to introduce into domesticated varieties.

Stein looked at rice in areas including Asia, Africa, South America and Australia. Through this analysis, he was able to focus on specific genetic sequences that helped these species survive local threats.

As a first step, Stein explained, they have identified all of the genes in these species, but do not yet know which are important for local adaption. This article could provide information on the region of the genome that had disease genes that have been successful over time against threats in the environment.

One potential route to reducing dependency on pesticides is to introduce natural resistance or tolerance. By providing multiple ways of defending itself, a plant can reduce the chance that a pathogen can overcome all of these defenses.

“This is a similar strategy that is used to address both viral diseases and cancer treatment,” Ware explained.

Boosting the defenses of some of these crops with genes that have worked in the past is one strategy toward sustainability, although the scientists would need to work on the specifics to see how they were deployed.

Stein explained that his role in this specific study was to annotate the genes by using computer programs to look at DNA sequences. Stein used a process called comparative genomics, in which he studied the genes of numerous species of rice and compared them to look for similarities and differences.

“Because these different species grow in different climates and geographical ranges, they will be locally adapted to those regions,” Stein said. “Those genes might be important to improve cultivated rice.”

As climates change and people and materials such as seed crops move around the world, rice may need to develop a resistance to a bacteria or fungi it hasn’t encountered much through its history. Indeed, even those species of rice that haven’t moved to new areas may face threats from new challenges, such as insects, fungi, bacteria and viruses, that have moved into the area.

By understanding successful adaptive strategies, researchers like Ware and Stein can look for ways to transfer these defenses to other rice varieties.

Stein likens the process to an arms race that pits pathogens against food crops. “There are real examples of where a resistance gene has been transferred from a wild species to a cultivated species using traditional approaches,” he said. This includes knocking out specific genes in wheat that provide powdery mildew resistance.

Ware’s lab also produced an article in which they explored the genetic pathway that tripled the grain number of sorghum. The grain is produced on the panicle, which has many branches. In a normal plant, more than half of the flowers are not fertile, producing fewer grains.

“We have recently published a paper on a variety of sorghum where nearly all of the flowers are fertile, increasing the grain number on each head,” said Ware.

The work was led by Yinping Jiao and Young Koung Lee, postdoctoral researchers in Ware’s lab. Jiao focused on the computational analysis while Lee explored the development.

The researchers reduced the level of a hormone, which generated more flowers and more seeds. Other researchers could take a similar approach to boost yield in other grain crops.

Employing a commonly used technique to introduce new variation to support trait development, Department of Agriculture plant biologist Zhanguo Xin created a new variant that resulted in a change in a protein. This plant had a lower level of the hormone jasmonic acid in the developing flower. The researchers believe a reduction in the activity of a transcription factor that controls gene regulation caused this.

“We are currently exploring if this is associated with a direct or indirect interaction with biosynthetic genes required to make the plant hormone,” Ware said.

Early in January, Ware’s lab also produced a study in which they used mutations in sorghum to reveal the genetic mechanism that enables the plant to produce a wax that helps with its drought resistance.

Ware suggested these studies are linked to an underlying goal. “In human health, genomics and mechanism support the development of management of disease and in some cases cures,” she explained. “In agriculture, it leads to improved germplasm development and sustained agriculture.”

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I looked around the packed

Pennsylvania Convention Center in Philadelphia this past weekend. Let’s face it, I and — more importantly — my genes, fell short.

It’s not necessarily a character flaw, but it’s not exactly the kind of advantage I’d want to give my children.

There I was, cheering on my vertically challenged daughter in a game where height matters. Despite her stature, she has developed a royal passion for volleyball. The perpetual smile that crosses her face when she steps across the lines makes it all worthwhile, despite the effort, the expense, the endless attempts to get the stink out of her knee pads — and the driving through horrific traffic.

She couldn’t be happier than when she’s throwing her small body around the floor, trying to get to some giant’s smash that seemed only a moment earlier out of her reach.

When you have children, you want them to find their way, to develop outlets that they find rewarding and to contribute to something bigger than they are.

Sports, I know, don’t cure disease. And yet, somehow, it’s become part of the American way, with people flying, driving and caravanning from all over the country to play in competitive tournaments where, if they succeed, they can get enough points to make it to nationals.

So, there we were, listening to whistle after whistle at this volleyball attention-deficit-disorder factory when it occurred to me how my genes did my daughter no great favors. Many of the fathers towered over me. If I lived in a land where food were placed near the ceiling, I and my offspring would starve.

My mother played volleyball when she was younger. She was tallish for her generation. I played volleyball as well, although not nearly at the competitive level that has taken my daughter to places around the area, including Penn State.

While my daughter is involved in numerous activities inside and outside school, it is volleyball that tops the list. When we go on vacation anywhere, the first thing she looks for is a place to play volleyball.

As I watched her warm up for the third match of the day, I chatted with some of the parents from Virginia, Texas and Arizona that we met this past weekend. After some pleasantries about the event, the conversation inevitably turned toward the identity of our daughters.

I could see the satisfaction they felt at pointing out their children from across the convention center floor. “My daughter is the one ducking her head down to walk under the exit sign over there.” “My daughter? She’s just a hair over 6 feet tall, but she’s still growing. How about you?”

I’d smile sheepishly. “My daughter is in the middle of her teammates over there.”

“Where?” they’d ask politely.

“She’s No. 9.”

They’d squint into the group. Just then, my daughter would laugh her way to the outside of a circle of girls that looked like a group of gnats, diving in and out of the center of a circle of joy.

Then again, as I watched her throw herself across the floor, I thought about the match between her personality and the role she plays in this sport. Sure, it’d be easier for her to stand out if she were taller. But, given her need to defy expectations, she’d probably want to be a jockey if she were 6 feet tall.

As the weekend came to a close, I asked her if she wished she could play volleyball every day. “Of course,” she said.

“Can you imagine having a job one day that made you feel that way?” I asked.

“Yeah,” she smiled, trying to imagine a job that fits her interests as well as volleyball.

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Sherif Abdelaziz. Photo by Juliana Thomas, SBU

By Daniel Dunaief

When the temperature drops dramatically, people put on extra layers of clothing or rush inside. At the other extreme, when the mercury climbs toward the top of thermometers, they turn on sprinklers, head to the beach or find cold drinks.

That, however, is not the case for the clay that is often underneath buildings, cliffs or the sides of hills on which people build picturesque homes. Clay shrinks after heating-cooking cycles in summer and also after freezing-thawing cycles in winter. “We want to understand why and how this behavior happens,” said Sherif Abdelaziz, an assistant professor in the Department of Civil Engineering at Stony Brook University.

Sherif Abdelaziz. Photo by Juliana Thomas, SBU

Abdalaziz recently received a prestigious Young Investigator Program award from the U.S. Army Research Office, which will provide $356,000 in funding over three years to study these properties. While the work will explore the basic science behind these clay materials, his findings could have a broad range of applications, from providing potential early-warning systems for future landslides or mudslides to monitoring coastal bluffs to keeping track of the soil around high-temperature nuclear waste buried in the ground.

Miriam Rafailovich, a distinguished professor in the Department of Materials Science at SBU who is beginning a collaboration with Abdelaziz, suggested that Abdelaziz’s work is relevant in multiple areas. “It applies to shoring infrastructure,” she wrote in an email. “The collapse of roadbeds under heavy traffic is a very common problem.”

Additionally, the clay around nuclear waste is subjected to very high temperatures during the period the waste is active. These temperatures recover to initial temperature with time, which will mainly subject the clay to a heating-cooling cycle that is part of this study, Abdelaziz explained. He is pleased to have the opportunity to explore these kinds of questions.

The Young Investigator Program award is “one of the most prestigious honors bestowed by the Army on outstanding scientists beginning their independent careers,” explained Julia Barzyk, a program manager in earth materials and processes at the U.S. Army Research Office, in an email. Abdelaziz’s research “is expected to contribute to improved approaches to mobility and siting and maintenance of infrastructure, especially in cold regions such as the Arctic.”

The field in which Abdelaziz works is called the thermomechanical behavior of soil. The challenge in this area, he said, is that the scientists are often divided into two groups. Some researchers focus on the heating effect on soil, while others explore cooling. In the real world, however, soil is exposed to both types of conditions, which could affect its ability to support structures above or around it.

In general, Abdelaziz has focused on clay. So far, scientists have looked at a piece or chunk of clay to see how it behaves. They haven’t done enough exploration at the microscale level, he said. “Our scientific approach crosses between the scales,” he said. In conducting experiments at SBU and at Brookhaven National Laboratory, he starts at the microscale and looks at the larger macroscale.

At the National Synchrotron Light Source II at BNL, Abdelaziz and his partners at BNL, including Eric Dooryhee, the beamline director for the X-ray Powder Diffraction beamline, change the temperature of the clay and look at the microstructure.

The challenge in the experiments they conducted last year was that they could change the temperature, but they couldn’t mimic the pressure conditions in the ground. Recently, they conducted the first experiments on a sample environment that involved a change in temperature and pressure and they got “good results so far,” Abdelaziz said in an email. He is looking for more beam time in the summer to finish the development of the sample environment. He is also seeking funding for a project to develop an early-warning system for coastal bluff stability.

“We are pretty good at predicting the weather,” Abdelaziz said. “What we don’t know is how this storm will impact our slopes.” The goal of the work he’s exploring now is to use what he learns from these experiments to predict potential changes in the soil. The purpose of this work is to better engineer mitigation techniques to avoid evacuations.

Abdelaziz’s work has focused on one clay type. He has, however, built a numerical model using experimental data. Once that model is validated, it will be able to predict the behavior of other clay, and he can include the heterogeneity of earth surface material in his numerical studies.

Rafailovich appreciates Abdelaziz’s dedication to his research. “He is very passionate about his work,” she wrote in an email. “He really hopes that he can change the world, one small road at a time.”

A native of Cairo, Egypt, Abdelaziz lives in Smithtown with his wife Heba Elnoby and their children Mohamed, 10, and Malak, 7. The father of two suggested that he “owes every single piece of success” in his career to the support he received from his wife.

The idea to study coastal bluff stability came to Abdelaziz when he was grilling on the beach a few years ago. He saw a sign that indicated that a bluff was unstable and that there was excessive movement. He related that to what he was studying. Abdelaziz is pleased with the funding and with the opportunity to contribute basic knowledge about clay to civil and military efforts. The financial support from the Army suggests that his “work is meaningful to the nation in general,” he said.

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We’ve reached a period of outrageous outrageousness. Or maybe extremes of extremism.

I read recently about an advertisement by a beer company that seems overtly racist.

Now, I’m not going to name the company because that might accomplish what it could have been attempting in the first place, which is to get its brand name in front of people.

This company has caused quite a stir by linking the color of beer to its quality, which in turn is linked to race in the ad.

What’s happening in the country? Have we reached the stage where all news is good news?

We live in a world of such polarization, so many shrill messages and such a rapid news cycle that you almost have to be outrageous and ridiculous to get attention and to remain in the public’s eye for more than just a moment.

It’s not an unprecedented phenomenon. Borrowing from the fictional world, poor Roxie Hart from the show “Chicago” is “the name on everyone’s lips,” as the song goes. But then, once the gripping trial ends, the newest crime of passion captivates the city’s attention, relegating Roxie to a less prominent place in the
dramas of the Windy City.

In our real world, which sometimes seems to require a reality check, people doubt everything. Why, just the other year, the current president questioned the national origin of the previous one.

Doubt and cynicism are all by-products of a shrill time where people shout alternative facts from
the rooftops.

And to bring matters up to speed, current politicians are questioning the motives of the Parkland
shooting survivors. Some suggest that left-leaning people who want to take away everyone’s guns are manipulating America’s youth. These students are not too young to die, but are somehow considered too young to have formed such an energized national movement.

Are people becoming more extreme with their time, with their emotions and with their donations? Yes, without a doubt. As the ancient Greek physician Hippocrates suggested, “desperate times call for desperate measures.” He was describing the response to life-threatening diseases and not to people who feel their lives are threatened leaving their homes.

As Long Island native Billy Joel sang in 1989, “we didn’t start the fire.” While that’s true, and people have lived through periods of considerable instability and uncertainty, we are living in a time defined by extremes.

At some point, We the People have to decide what we can accept and what we can’t. That beer advertisement seems to be a cheap ploy put together by a cynical advertising executive, who has now pulled the ad after it may have served its purpose.

Maybe this executive got his or her wish and more. Not only are people talking about it, but the company may also not have to pay as much for the ad, because now they’re not running it anymore.

How do we combat such unacceptable messages and decide when a company has crossed the red line? One possible solution is to follow the example of the United States government. When other countries create intolerable situations for their citizens or our citizens or the world, we start by hitting these nations in their wallets and refuse to buy their products.

Maybe a decline in sales at a company would send the kind of message that defeats the notion that all press is good press. Other cynical executives might get the message if the stock price or sales fell after such an advertisement polluted the company’s image. With our consumer decisions, we can send messages that it’s not OK to be offensive and outrageous just to sell another product or a toxic idea.

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From left, Jason Sheltzer, Nicole Sayles (who is a former lab technician and a co-author of an earlier MELK paper) and SBU undergraduates Chris Giuliano and Ann Lin. Photo by Constance Brukin

By Daniel Dunaief

If eating macaroni and cheese made Joe sick, he might conclude he was allergic to dairy. But he could just as easily have been allergic to the gluten in the macaroni, rendering the dairy-free diet unnecessary.

Scientists try to connect two events, linking the presence of a protein, the appearance of a mutation or the change in the metabolic activity of a cell with a disease. That research often leads to targeted efforts to block or prevent that protein. Sometimes, however, that protein may not play as prominent a role as originally suspected. That is what happened with a gene called MELK, which is present in many types of cancer cells. Researchers concluded that the high level of MELK contributed to cancer.

Jason Sheltzer, a fellow at Cold Spring Harbor Laboratory, and Ann Lin and Christopher Giuliano, undergraduates at Stony Brook University who work in Sheltzer’s lab, proved that wasn’t the case. By rendering MELK nonfunctional, Sheltzer and his team expected to block cancer. When they knocked out MELK, however, they didn’t change anything about the cancer, despite the damage to the gene. But, Sheltzer wondered, might there be some link between MELK and cancer that he was missing? After all, scientists had found a drug called OTS167 that was believed to block MELK function.

To test this drug’s importance for MELK and cancer, Sheltzer used this drug on cancer cells that didn’t have a functioning MELK gene or protein. Even without MELK, the drug “killed cancer cells,” regardless of the disappearance of a gene that researchers believed was important for cancer’s survival, he said.

“We showed for the first time that [the drug] was killing cells that didn’t express MELK,” Sheltzer said. The drug had to have another, unknown target.

Sheltzer suggested that this is the first time someone had used CRISPR, a gene-editing technique, to take a “deep dive” into what a drug is targeting. This drug, he said, has a different mechanism of action from the one most people believed.

Sheltzer, whose work was published in early February in eLife, expanded the research from a petri dish, where researchers grow and study cells, to mouse models, which are often more similar to the kinds of conditions in human cancers. In those experiments, he found no difference between the tumors that grew with a MELK gene and those that didn’t have the MELK protein, continuing to confirm the original conclusion. “The tumors that formed in cells that had MELK and the tumors that formed in cells that didn’t have MELK were the same size,” he said.

Originally, Sheltzer believed the MELK protein might be involved in chemotherapy resistance. His lab found, however, that no matter what they did to MELK in these cells, the cancer appeared indifferent. Other researchers suggested that Sheltzer’s work would be instructive in a broader way for scientists.

Sheltzer’s research on MELK “will motivate a new set of standards for target discovery and validation in the field going forward,” Christopher Vakoc, an associate professor at CSHL, explained in an email. Sheltzer “brings a rigorous approach to cancer research and an impressive courage to challenge prevailing paradigms.” Sheltzer’s work highlights the challenge of understanding the mechanism of action of new medicines, Vakoc added.

Sheltzer plans to explore several other genes in which a high concentration of a specific protein coded by that gene correlates with a poor prognosis.

Using CRISPR, Sheltzer believes his lab can get precise information about drug targets and their effect on cancer. He’s also tracing a number of other types of cancer drugs that he thinks might have compelling properties and will use CRISPR to study the action of these drugs. “We want to know not just that a drug kills cancer cells: We want to know how and why,” he said.

By figuring out what a drug targets, he might be able to identify the patients who are most likely to respond to a particular drug. So far, the finding that a drug doesn’t work by interfering with a specific gene, in this case MELK, has been easier than finding the gene that is the effective target, he explained.

One of Sheltzer’s goals is to search for a cancer cell that is resistant to the drug, so that he can compare the genes of the vulnerable one with those of the cell that’s harder to treat. Detecting the difference in the resistant cell can enable him to localize the region critical for a drug’s success.

Sheltzer said finding that MELK was not involved in a cancer’s effectiveness was initially “depressing” because researchers believed they had found a cancer target. “We hope that by publishing these techniques and walking through the experiments in the paper that other labs can learn from this and can use some of the approaches we used to improve their drug discovery pipelines,” he said.

Sheltzer is pleased that Lin and Giuliano made such important contributions to this paper. CRISPR has made it possible for these undergraduates to “make these really important discoveries,” he said. Lin, who has worked in Sheltzer’s lab for two and a half years, was pleased. “It is very exciting to share my knowledge of MELK in regards to its role in cancer biology,” she wrote in an email. “Authoring a paper requires a great deal of work and I am super thrilled” to see it published.

Sheltzer, who lives with his partner Joan Smith, who is a software engineer at Google, said he was interested in science during his formative years growing up in Wayne, Pennsylvania, which is just outside of Philadelphia, and appreciates the position he has at Cold Spring Harbor Laboratory. Soon after earning his doctorate at MIT, Sheltzer set up his own lab, rather than conducting research for several years as a postdoctoral researcher. “I was really fortunate to be given that opportunity,” he said.

As for his work with MELK, Sheltzer hopes he’s saved other labs from pursuing clinical dead ends.

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