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Daniel Dunaief

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File photo from Stony Brook University

An award-winning scientist, grandmother, aunt, mother and wife, Dr. Lina Obeid, died Nov. 29 at the age of 64 after a recurrence of lung cancer.

Lina Obeid spending time with her granddaughter Evelyn. Photo by Marya Hannun

Born in New York and raised in Lebanon, Obeid was a State University of New York distinguished professor of medicine and the dean of research at Renaissance School of Medicine at Stony Brook University, where she conducted research on cancer and aging. In 2015, she was named as one of The Village Times Herald’s People of the Year along with her husband Dr. Yusuf Hannun.

A Celebration of Life memorial service for Obeid will take place Dec. 7 at Flowerfield in St. James from 11 a.m. until 2:30 p.m. and will include remarks and a reception. Attendees are encouraged to wear bright colors.

SBU faculty appreciated Obeid’s scientific, administrative and mentoring contributions, as well as her engaging style.

Michael Bernstein, interim president of SBU, said Obeid was “very well liked and respected” and that her loss leaves a “big hole” at the university.

Obeid “oversaw our research programs, specifically the core facilities on which all our laboratory scientists depend, for sample analysis, for microscopy of cells” among other areas, Dr. Kenneth Kaushansky, dean of Renaissance School of Medicine wrote in an email.

He lauded Obeid’s personable approach, which he said, “rubbed off on many people,” creating a “renewed sense of optimism in our ability to impact all three missions: research, teaching and clinical care.”

Obeid and Hannun, who is the director of the Stony Brook Cancer Center, knew each other in high school, started dating in medical school and were married for 36 years. The couple recently shared a Lifetime Achievement Award at the 16th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases in October. The award represents the first time a woman received this honor.

Supriya Jayadev, who was a graduate student in Hannun’s lab at Duke University and is the executive director of Clallam Mosaic in Port Angeles, Washington, called Obeid a “role model” for women in science. “Not only was she a strong leader with the ability to compete in a male-dominated field, but she retained her femininity and grace.”

Daniel Raben, a professor of biological chemistry at Johns Hopkins Medicine, has known Obeid and Hannun for more than two decades.

“She had a huge impact on the sphingolipid field because of the contribution she made,” Raben said. “It’s a huge loss. She was a giant.”

Dr. Maurizio Del Poeta, a professor in the Department of Microbiology and Immunology at SBU, knew Obeid since 1995.

“I once asked her if she had any advice for my grants to get funded,” he recalled in an email. Obeid suggested she didn’t know how to get funded, but that his work wouldn’t get funded if he didn’t submit proposals.

She “never took ‘no’ for an answer. She would insist and insist and insist again until she [would] persuade you and get a ‘yes,’” he added.

Del Poeta said Obeid did a “marvelous” job enhancing research facilities, while she was a “caring physician” for veterans at the Northport VA Medical Center.

Obeid and Hannun were co-directors of a National Institutes of Health program in Cancer Biology and Therapeutics, which this year received a grant renewal for another five years.

Obeid’s daughter Marya Hannun recalled her mother as “warm, honest, and funny” without being cynical. Marya said her mother cared about everyone around her and was rooting for them to succeed.

“During my childhood, she taught me that nothing was impossible if you are determined and gutsy.”

— Mayra Hannun

“During my childhood, she taught me that nothing was impossible if you are determined and gutsy,” Marya Hannun wrote in an email.

She suggested her mother was passionate about food, which shaped how they lived and traveled. When the family visited Greece, Obeid swam out for sea urchins, cracked them on rocks and ate them on the beach. She was a passionate cook who learned from her mother, Rosette, who wrote a Palestinian cookbook.

The Hannun family laughs “about how we plan out holidays around food and spend
our meals talking about the next meals,” Marya wrote.

Obeid was part of one of the first class of women admitted into the International College High School. She earned her bachelor of arts at Rutgers University, but was also creative as a child and interested in fashion and design.

“Anyone who [saw] her wouldn’t be surprised,” Marya said.

Obeid is survived by her husband, her parents, Rosette and Sami, her nieces and nephews, her triplet children and her two grandchildren.

Obeid and Hannun’s daughter Reem is married to Dr. Khaled Moussawi and lives in Baltimore. Awni and his wife Kathy Hannun have two children, Evelyn and Yusuf, and live in New York City.

Binks Wattenberg, a professor in the Department of Biochemistry and Molecular Biology at Virginia Commonwealth University, believes that “people like [Obeid] only come along a few times in one’s lifetime.”

In an email, he recalled how she had a
“way of looking into your eyes and persuading you to do an experiment that she thought absolutely had to be done.” He appreciated her enthusiasm, which made Wattenberg feel as if he was doing “absolutely
essential work.”

Obeid regularly invited her researchers for meals at her house, where they felt as if they also joined the family, said Dr. Gerard Blobe, a professor of medicine at Duke University School of Medicine who earned his doctorate in Yusuf Hannun’s lab over 20 years ago.

In lieu of flowers, the family has asked for donations in Obeid’s name to the Stony Brook University Cancer Center. Potential donors can access the site at cancer.stonybrookmedicine.edu/giving.

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Daniel Dunaief

By Daniel Dunaief

What is it about “The Play That Goes Wrong” that is just so right for so many people, including me?

My wife and I recently went to this farcical show, where my wife informed me that she, the couple attending the performance with us, and just about everyone around us could tell how much I enjoyed the experience. 

In case you haven’t heard about it and can’t figure it out from the title, “The Play That Goes Wrong” is an absurd show where everything goes so wrong — the props, the actors, the staging, the lighting and the music. Indeed, it’s almost challenging to follow the simple murder mystery plot amid gales of laughter, much of it coming from me.

My family has numerous qualities that we have shared from one generation to the next. My late father laughed so hard at the pratfalls and theater-of-the-absurd dialogue of Danny Kaye movies like “The Court Jester” (1955) that I can still picture him gasping for air as he wiped away the tears slaloming down his face, where they joined the muddy sneaker stains, the dirty paw prints and the soda spills on a white carpet that chronicled our active lives.

The current play follows in the footsteps of Kaye, Benny Hill, the Three Stooges and a host of other characters who do anything for a laugh, stepping on rakes that slam into their heads or interacting in nonsensical ways with other actors as a part of a skit. The show makes the sketch comedy of many of today’s late night shows appear pedestrian by comparison. Granted, the plot follows a singular theme and, once completed, can and does create a full length and ridiculous drama.

Now, some people may find the pedestrian antics of the cast too absurd. I agree that the show isn’t for everyone and doesn’t provide life lessons, memorable songs, gritty entertainment or an insightful view of existence.

And yet, it does offer much needed self-parody and perspective on a country thoroughly divided by events in Washington, D.C. The people who run our country seem intent on making their supporters cheer, while their detractors roll their eyes, shake their heads and seek solace from people who share their beliefs.

Fine, but, the actors in a show written by Henry Lewis, Jonathan Sayer and Henry Shields of the Mischief Theatre Company, seem intent on roping as much of the audience as possible into their shenanigans. 

One of the actors, who plays Cecil Haversham, seems delighted by the presence of the audience. He plays to the crowd so often that he shares in their enthusiasm when he does something well or when the crowd appreciates an ongoing joke.

This intentionally imperfect play isn’t perfectly imperfect, either. Some moments fall flat. The second half of the show, which is shorter than the first, isn’t quite as engaging, entertaining and uproarious.

Knowing the general plot of the story before I attended, I tried to anticipate the wide range of possible intentional stumbles and humorous moments that actors struggling to maneuver through a story might endure. The range of mistakes and blunders exceeded my expectations among numerous welcome and delightful surprises.

A play that delves in the world of funny gaffes takes real work on the part of the writers and the actors. To anyone sick of the political headlines, the conspiracy theories, the name calling, the accusations and counter accusations, this play is a welcome comedic retreat. It’s no wonder it won Best New Comedy at the 2015 Laurence Olivier Awards in London and is now on Broadway.

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Mirna Kheir Gouda

By Daniel Dunaief

Mirna Kheir Gouda arrived in Commack from Cairo, Egypt, in 2012, when she was entering her junior year of high school. She dealt with many of the challenges of her junior year, including taking the Scholastic Aptitude Test, preparing for college and adjusting to life in the United States.

Her high school counselor at Commack High School, Christine Natali, suggested she apply to Stony Brook University. Once she gained admission, she commuted by train to classes, where she planned to major in biology on the road to becoming a doctor.

She did not know much about research and wanted to be involved in it to learn, especially because Stony Brook is so active in many fields.

“After some time conducting research, I came to be passionate about it and it was no longer just another piece of my resume, but rather, part of my career,” she explained in an email.

She reached out to Gábor Balázsi, a relatively new faculty member at the time, who suggested she consider joining a lab.

Balázsi uses synthetic gene circuits to develop a quantitative knowledge of biological processes such as cellular decision making and the survival and evolution of cell populations.

Balázsi knew Kheir Gouda from the 2015 international Genetically Engineered Machine team, which consisted of 14 members selected from 55 undergraduate students.

“Having this iGEM experience,” which included deciding on a project, raising funds, carrying out the project and preparing a report in nine months, was a “very promising indication” that Kheir Gouda would be an “excellent student,” Balázsi explained in an email.

Kheir Gouda chose Balázsi’s laboratory, where she worked with him and his former postdoctoral fellow Harold Bien, who offered her guidance, direction and encouragement.

As a part of the honors program, Kheir Gouda had to conduct an independent research project.

She wanted to “work on a project that involved adaptations and I always thought, ‘What happens when the environment changes? How do cells adapt?’”

She started her project by working with a mutant gene circuit that was not functioning at various levels, depending on the mutation. She wanted to know how cells adapt after beneficial but costly function loss.

An extension of this research, as she and Balázsi discussed, could involve a better understanding of the way bacterial infections become resistant to drugs, which threaten their survival.

“The idea for the research was hers,” Balázsi explained in an email. Under Bien’s mentorship skills, Kheir Gouda’s knowledge “developed quickly,” Balázsi said.

Balázsi said he and Kheir Gouda jointly designed every detail of this project.

Kheir Gouda set up experiments to test whether a yeast cell could overcome various mutations to an inducer, which regains the function of the genetic gene circuit.

Seven different mutations caused some type of loss of function of the inducible promoter of the gene circuit function. Some caused severe but not complete function loss, while others led to total function loss. Some were more able to “reactivate the circuit” rescuing its function, while others used an alternative pathway to acquire a resistance.

The presence of the resistance gene was necessary for cell survival, while the circuit induction was not necessary. At the end of the experiment, cells were resistant to the drug even in the absence of an inducer.

“This synthetic gene circuit in yeast cells can provide a model for the role of positive feedback regulation in drug resistance in yeast and other cell types,” Balázsi explained.

Kheir Gouda said she and Balázsi worked on the mathematical modeling toward the end of her research.

“What our work suggests is that slow growth can turn on quiescent genes if they are under positive feedback regulation within a gene network,” Balázsi wrote.

This mathematical model of limited cellular energy could also apply to cancer, which might slow its own growth to gain access to a mechanism that would aid its survival, Balázsi suggested. 

Recently, Kheir Gouda, who graduated from Stony Brook in 2018, published a paper about her findings in the journal Proceedings of the National Academy of Sciences, which is a prestigious and high-profile journal for any scientist.

“Because PNAS has a lot of interdisciplinary research, we thought it would be a good fit,” Kheir Gouda said. The work she did combines evolutionary biology with applied math and synthetic biology.

The next steps in this research could be verifying how evolution restores the function of other synthetic gene circuits or the function of natural network modules in various cell types, Balázsi suggested.

Kheir Gouda’s experience proved positive for her and for Balázsi, who now has eight undergraduates working in his lab. “The experience of mentoring a successful undergraduate might help make me a better mentor for other undergraduates and for other graduate students or postdoctoral researchers, because it helps set goals based on a prior example,” Balázsi said.

He praised Kheir Gouda’s work, appreciating how she learned new techniques and methods while also collaborating with a postdoctoral fellow in Switzerland, Michael Mahart, who is an author on the paper.

“It is unusual for an undergraduate to see a research project all the way through to completion, including a publication in PNAS,” marveled Balázsi in an email. He said he was excited to have mentored a student of Kheir Gouda’s character.

Kheir Gouda has continued on a research path. After she graduated from Stony Brook, she worked for a year on cancer research in David Tuveson’s lab at Cold Spring Harbor Laboratory. She then transitioned to working at the Massachusetts Institute of Technology for Assistant Professor of Chemical Engineering Kate Galloway. Kheir Gouda, who started working at MIT in October, plans to continue contributing to Galloway’s effort until she starts a doctoral program next fall.

Kheir Gouda said her parents have been supportive throughout her education.

“I want to take this opportunity to thank them for all the sacrifices they made for me,” Kheir Gouda said.

She is also grateful for Balázsi’s help.

He has “always been a very supportive mentor,” she explained. She would like to build on a career in which she “hopes to answer basic biology questions but also build on research and clinical tools.”

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Daniel Dunaief

By Daniel Dunaief

Last year at this time, I wrote a column celebrating words. I feel compelled to share another homage this year. This may start a new annual tradition. I hope you enjoy.

Words dart away, just out of reach, like a fish in the ocean, a butterfly in a meadow or a Frisbee lifted overhead by a sudden breeze.

Words emanate from nearby, startling us while we lay in bed, coaxing us to search the house, the closet, the garage for the source of elusive sounds.

Words give strength to our arguments, power to our convictions, and a method to share our hopes, desperation, dreams, fears, needs, wants and cravings.

Individually and collectively, words enable us to invite others to share experiences.

Words form the backbone of a democracy always challenged by new words, concepts, people and ideas.

When we hold an infant, listen to the sound from the air leaving the lungs of a whale surfacing nearby or gaze from the top of a volcano at the rising sun over the horizon, we hope the words we choose to describe what we see, feel and experience bring us back to these magic moments.

Words grow into unmanageable bundles as jargon triggers a metamorphosis that confounds and clutters their meaning, turning them into a sesquipedalian mess — that is the practice of using long-winded, obscure words.

Words tell tales, show emotions and reach out across time from generations long since past, urging us to pay attention and learn lessons from those who came before.

We select rhyming words that sing like chirping birds. 

Words make us laugh, offering a salve to suffering and transportation out of intransigence.

When we can’t understand something, we name it, giving a word to the unknown that allows us to refer to something in the cosmos, in our minds or buried under our fingernails. Ancient Romans used words to construct fantastic stories about the stars, the heavens and the gods, who exhibited a wide range of emotions that seemed remarkably human.

We remember the words from our favorite movies: “May the force be with you” (“Star Wars”) and “Louis, I think this is the beginning of a beautiful friendship” (“Casablanca”). And from our favorite presidents, such as John F. Kennedy’s “Ask not what your country can do for you, but what you can do for your country” (1961) or Franklin D. Roosevelt’s “The only thing we have to fear is fear itself” (1933).

We carry with us the words that mean the most from our own lives. We don’t need to check them at the airport when we are in group 9, stuff them in an overstuffed backpack when we go to school or keep them from getting waterlogged when the evapotranspiration cycle decides to dump rain, sleet, hail or snow upon us. We remember the person so critical to our existence that he or she “ruined us for all other” men or women.

The words that elevate, inspire and encourage us to do and be our best allow us to stand straighter and taller, enabling us to wear a cryptic smile that those who know us best perceive immediately.

Words give us hope, help us believe in ourselves and allow us to feel connected to someone halfway across the world.

We pause from uttering words during moments of silence, as we pay respect with the unspoken words in our minds.

We are surrounded by paper thin walls of meaningless, angry, spiteful, hateful words. We can combat those messages with words that reflect the best of us and our country. Words fill the toolbox with the parts to build the world as we choose.

As you ponder words that matter at this time of year, I’d like to wish you and your family a Happy Thanksgiving.

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Ellen Pikitch, left, with Christine Sanora, taken in 2015 while the two scientists were researching Shinnecock Bay. Photo by Peter Thompson

By Daniel Dunaief

It’s one thing to make a commitment to a good idea; it’s another to follow through. Ellen Pikitch, endowed professor of ocean conservation science in the School of Marine and Atmospheric Sciences at Stony Brook University, is making sure countries around the world know where and how they can honor their commitment to protect the ocean.

In 2015, the United Nations had agreed to designate at least 10 percent of the oceans as Marine Protected Areas, which would restrict fishing and foster conservation. The goal of the proposal is to reach that figure by next year. 

Three years ago, with the support of the Italian Ministry of Environment and private donations, Pikitch started the labor-intensive process of finding ocean regions that countries could protect. 

Ellen Pikitch, right, with Natasha Gownaris at the United Nations Ocean Conference in June of 2017. Photo Courtesy of IOCS

She published the results of her analysis in the journal Frontiers in Marine Science. Her research could help countries move from the current 7.8 percent of oceans protected to the 10 percent target, and beyond that figure in the ensuing years.

The United States has met its target, although most of its marine protected ares are far from human population centers, so the coverage is uneven, Pikitch explained. The rest of the world has some gaps in high priority areas.

“I’m hoping that the study will light a fire under the policymakers so that they do meet their commitment,” said Pikitch. “It’s quite feasible for them to meet the goal. We’ve given [policymakers] advice in this paper about how exactly it could be done.”

The maps in the paper show areas that are within the current jurisdiction that are priority areas and are unprotected.

“There is quite a bit of area that meets this description — more than 9 percent — so there is flexibility in how countries can use the results and reach or exceed” the 10 percent target by next year, Pikitch explained in an email.

To determine where nations can enhance their ocean protection, Pikitch, Assistant Professor Christina Santora at the Institute for Ocean Conservation Science at Stony Brook University and Stony Brook graduate Natasha Gownaris, who is now an assistant professor in environmental studies at Gettysburg College, pulled together information from 10 internationally recognized maps indicating the location of global marine priority areas.

“We are standing on the shoulders of giants, capitalizing or leveraging all the hard work that has gone into other maps,” said Gownaris. 

One of the most unexpected findings from the study for Pikitch is that 14 percent of the ocean was considered important by two to seven maps, but over 90 percent of those areas remained unprotected. A relatively small part of this area is on the high seas, while most is within exclusive economic zones, which nations can control.

To preserve this resource that continues to remove carbon dioxide from the atmosphere while serving a critical role in the world’s food chain, conservationists have focused on marine protected areas because they provide the “one thing we felt was going to be the most effective single step,” said Mark Newhouse, the executive vice president for newspapers at Advance Publications and president of the Ocean Sanctuary Alliance. “It could happen overnight. A country could say, ‘This area is off limits to fishing,’ and it is.”

Countries can protect areas within their exclusive economic zones “more quickly than figuring out a way to solve global warming,” Newhouse added.

Santora explained the urgency to take action. “The situation in the ocean is worsening and we can’t wait to have perfect information to act,” Santora wrote in an email. “What we can do is put strong, effectively managed MPAs in the right places, with a high level of protection, that are well managed and enforced.”

Members of the Ocean Sanctuary Alliance, which counts Pikitch as its scientific officer, recognize that the 7.8 percent figure includes areas where countries have announced their intention to protect a region, but that doesn’t necessarily include any enforcement or protection.

“Intentions don’t protect the environment,” Newhouse said.

Ambassadors from several nations have reached out to OSA to discuss the findings. 

These diplomats are “exactly the people we want paying attention” to the research Pikitch and her team put together, Newhouse said.

Pikitch also plans to reach out proactively.

According to Pikitch’s recent analysis, the largest gaps in policy coverage occurred in the Caribbean Sea, Madagascar and the southern tip of Africa, the Mediterranean Sea and the Coral Triangle area, although they found additional widespread opportunities as well.

Pikitch calculated that an additional 9.34 percent of areas within exclusive economic zones would join the global marine protected area network if all the unprotected area identified as important by two or more initiatives joined the MPA network. 

“When effectively managed, when strong protections are put in place, they work,” Pikitch said.

Indeed, one such example is in Cabo Pulmo, Mexico, where establishing a marine protected area resulted in an 11-fold increase in the biomass of top predators within a decade. Many MPAs become sites for ecotourism, which can bring in hefty sums as people are eager to see the endemic beauty in their travels.

Pikitch hopes this kind of study spreads the word about the benefit of protecting the ocean and that policymakers and private citizens recognize that protecting sensitive regions also benefits fisheries, refuting the notion that environmentally driven policy conflicts with the goal of economic growth.

The groups involved in this study are already discussing the new goal for the ocean. Several diplomats and scientists would like to see the bar raised to 30 percent by 2030, although the United Nations hasn’t committed to this new target yet.

“Studies show that 10 percent is insufficient — it is a starting point,” Santora wrote. “I do think that targets beyond 2020 will increase.”

Pikitch said the ocean has always been one of her passions. Her goal is to “leave the world in better shape than I found it” for her children and six grandchildren.

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By Daniel Dunaief

Daniel Dunaief

I have been working out at a gym, where my routine consists mostly of pushing my body as long as I can on a treadmill, bike or elliptical machine until my sweat has soaked through my T-shirt. I play mind games while I’m running, telling myself that I can take a break once I get to 3 miles, or maybe 4 or closer to 5.

Each time I hit a milestone, I think about how much better I’ll feel if I can go just a bit farther, even as I’m taking an inventory of all the barking body parts, which typically includes my knees and back.

What helps get me over the hump lately, though, is the music I listen to as I work out.

I started with a collection of ’80s songs, hoping, perhaps, that the combination of familiar tunes from my youth would make my body remember the energy that defined this younger period.

As I was running, the songs reminded me of the times I danced with friends at Ward Melville High School, played Uno in a friend’s living room or decorated a Christmas tree with another friend who patiently showed a group of us how to thread popcorn and cranberries through a line.

As I was running, a montage of these images played through my head, making me feel as if my legs were turning back the clock. Fortunately, no one at my gym looks closely at me or my facial expressions, so I could indulge in musical — and life — nostalgia without interruption or without questions from people wondering what I was thinking as I reacted to people who have long since gone their separate ways.

For a few days, I switched to my favorite singer, Billy Joel. Hearing the words from “Only The Good Die Young,” “Piano Man,” and “Movin’ Out,” brought me back to the study breaks I took in high school when I stared out the window between my house and the neighbor’s colorful Santa sleigh down the street, hoping that the snow forecast for that evening was sufficient to close school the next day.

I’m planning to see Billy Joel in concert before too long, so I switched to another genre, playing the soundtrack from the original 1975 version of the musical, “A Chorus Line.” While others rarely cite it as one of their favorite musicals, I know it was the song “Nothing,” in which Diana Morales receives nonstop criticism from her teacher Mr. Karp, that brought to life the magic of Broadway for me. 

I always measured every other performance, including of musicals like “West Side Story” that I supported by playing clarinet in the pit orchestra, against the desperate hopes of each of the cast members in a chorus line to “make it” into the show.

Eventually, I needed a pulsating beat, so I shifted to exercise music, which, of course, included songs from “Rocky the Musical,” as well as other inspirational films. Each time the beat got faster, I found another pocket of energy that helped me conquer the next mile, using the beat as a metronome for my legs.

Music, in all its forms, serves many functions, allowing us to connect with the artist, to travel on an acoustic journey, to remember friends, and to exercise feelings and emotions even as we exercise the rest of our bodies.

I coached many sports when my children were younger. If I could do it over again, I would have added contemporary music to mundane practices to spice up the experience in real time and to inspire me on the nostalgia treadmill.

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By Daniel Dunaief

It’s a big leap from an encouraging start to a human, especially when it comes to deadly diseases like amyotrophic lateral sclerosis, or Lou Gehrig’s disease. Cold Spring Harbor Laboratory Associate Professor Molly Hammell knows that all too well.

Hammell has been studying a linkage between a mutated form of a protein called TDP-43 and ALS for eight years. About a year and a half ago, she worked with 178 human samples from the New York Genome Center’s ALS Consortium and found a connection between a subset of people with the disease and the presence of abnormal aggregate forms of the protein.

“It’s really rewarding to see evidence in clinical samples from the processes that we predicted from cell culture and animal models,” she explained in an email.

Molly Hammell. Photo from CSHL

About 30 percent of the people with ALS Hammell examined had pathology of this protein in the upper motor neurons of the upper cortex. In this area, the mutated form of TDP allowed more so-called jumping genes to transcribe themselves. A normal TDP protein silences these jumping genes, keeping order amid potential gene chaos. The change in the protein, however, can reduce the ability of the protein to serve this important molecular biology maintenance function.

By using complementary studies of cell culture, the associate professor tried to determine whether knocking out or reducing the concentration of normal TDP caused an increase in these retrotransposons.

When she knocked out the TDP, she found a de-silencing of these jumping genes “was rapid,” she said. “We could see that in the samples we collected.”

Before she got the larger sample, Hammell worked with a smaller pilot data set of 20 patients. She found that three of the patients had this abnormal protein and an active set of these jumping genes.

“It’s hard to make an argument for something you’d only seen in three patients,” she said. “Getting that second, independent much larger cohort convinced us this is real and it’s repeatable, no matter whose patient cohort we’re looking at.”

Several diseases show similar TDP pathology, including Alzheimer’s and fronto-temporal dementia. She started with ALS because she believed “if we’re ever going to see” the link between the mutated protein and a disorder, she would “see it here” because a larger fraction of patients with ALS have TDP-43 pathology than any other disease.

The findings with ALS are a compelling start and offer a potential explanation for the role of the defective protein in these other conditions.

“We think it’s possible in a subset of patients with other neurodegenerative diseases that there might be overlapping” causes, Hammell said “We’re trying to get more data to branch out and better understand overlapping alterations.”

With these other diseases, she and her colleagues would like to explore whether TDP pathology is a necessary precondition in conjunction with some other molecular biological problems or whether these conditions can proceed without the disrupted protein.

The reaction among researchers working on ALS to Hammell’s finding has been encouraging.

Hemali Phatnani, the director of the Center for Genomics of Neurodegenerative Disease at the New York Genome Center, suggested Hammell’s work “opens up really interesting lines of investigation” into a potential disease mechanism for ALS. The research suggests a “testable hypothesis.”

Phatnani, who has been in her role for about five years, said she and Hammell speak frequently and that they serve as sounding boards for each other, adding that Hammell is “definitely a well-regarded member of the community.” 

Hammell has also been working through the Neurodegeneration Challenge Network in the Chan Zuckerberg Initiative, or CZI. This work brings together scientists who study Alzheimer’s, Parkinson’s, ALS and Huntington’s diseases. The group works to develop new approaches to the treatment and prevention of these diseases. These scientists, which includes researchers from Harvard University, Stanford University, Vanderbilt and Mount Sinai, among others, have webinars once a month and attend a conference each year.

Hammell was one of 17 researchers awarded the Ben Barres Early Career Acceleration Award from the CZI in 2018, which helped fund the research. She thinks the scientists from the CZI are excited about the general possibility that there’s overlapping disease mechanisms, which her work or research from other scientists in the effort might reveal. The CZI is “trying to get researchers working on different diseases to share their results to see if that’s the case,” she explained in an email.

She recognizes that numerous molecular and cellular changes also occur during the course of a disease.“There are always skeptics,” Hammell concedes. In her experiments, she sees what has happened in patient samples, but not what caused it to happen. She also has evidence that the retrotransposon silencing happens because of TDP-43 pathology.

“What we still need to confirm is whether or not the retrotransposons are themsleves contributing to killing the neurons,” she said.

If Hammell confirms a mechanistic link, other studies may lead to a treatment akin to the approach researchers have taken with viruses that alter the genetic code.

Future therapies for a subset of patients could include antiviral treatments that select specific genes.

Over time, she said her lab has cautiously added more resources to this work. As she has gotten increasingly encouraging results, she has hired more scientists who dedicate their work to this effort, which now includes two postdoctoral fellows, two graduate students and three staff scientists.

Some scientists in her lab still explore technology development and are devoted to fixing the experimental methods and data analysis strategies she uses to look for transposon activity.

Hammell is inspired by the recent results and recalled how she found what she expected in human samples about 18 months ago. She said she was “giddy” and she ran into someone else’s lab to “make sure I hadn’t done it incorrectly. It’s really exciting to see that your research might have an impact.”

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By Daniel Dunaief

Daniel Dunaief

You know the face dogs make when they’re taking care of their business? I’m not talking about number one. I’m talking about the big whopper: number two. For many dogs, I imagine that is the equivalent of the human concentration face, as we ponder everything from what we should have for dinner, to the best route home in a traffic jam, to the best use of our time on a Friday night when we’re exhausted but know we could contribute to our area through community service.

My dog must know that I’m watching him closely because every time he finds exactly the right spot to release the contents of his bowels, he turns his back to me. Before he enters his squatting position, he looks back over his shoulder to make sure no one or everyone is watching him. He’s easily distracted in the moment of separation from his solid waste.

I respect his wishes and give him his moment of privacy once he starts the process. Now, of course, much as we might watch them as they relieve themselves, I know that they watch us closely, wondering why we’re so meticulous, or not, as the case may be, about scooping up everything they’ve dropped.

My dog still seems to think that he’s doing sufficient cleanup duties by kicking a few blades of grass in the general direction of his creation. He starts tugging on the leash immediately after that, sending a nonverbal signal from his neck to my hand, as if to say, “I got this one, let’s move to that flower bed where Marshmallow left me a secret scented note.”

As I bent down recently to clean up his mess, he saw one of his favorite couples. That’s not exactly a fair characterization, as almost any combination of two people would immediately rank among his favorites if one or both of them came over to him and rubbed his stomach while he turned over on his back and dangled his paws in the air, as if he were at a canine nail salon. The challenge for me, as he was pulling, tugging and twisting on the leash, was to do the impossible: Chat with his human friends, keep him from knocking one or both of them over with his enthusiasm and politely scoop up his poop.

I waited for a moment to retrieve my retriever’s droppings, hoping that he’d calm down enough to allow me to bend my knees and lift the boulders from the ground. No such luck, as he seemed to be playing twist-the-leash-around-the-human-legs game.

One of the many sensory problems with my dog’s poop is that the longer it remains in place, the more it seems to spread out and sink into the ground. Knowing this, I was eager to bag it and to move on during our walk.

Just as the couple finally disengaged from my dog and his leash, another dog and his owner appeared, causing my dog’s tail to wag so violently that it looked like those whirling propellers on an old airplane. While my dog darted and retreated from his much bigger and more mellow friend, I got farther away from his droppings. In the back of my mind, I wondered whether I could, just this once, leave his biodegradable droppings where they landed.

When the other dog and his owner took off, my dog and I returned to the expanding pile. I’m convinced that my dog watched the entire pickup routine with rapt fascination, knowing he’d succeeded in extending the process into something considerably more challenging for the human scrunching his nose at the other end of the leash.

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Ken Dill. Photo from SBU

By Daniel Dunaief

Over the course of decades, aging skin tends to wrinkle, revealing laugh or frown lines built up through a lifetime of laughter, tears and everything in between. Similarly, when people age, the proteins in their bodies don’t fold up as neatly. Free radicals cause these misfolded proteins, which are then susceptible to further damage.

The cumulative effect of these misfolded proteins, which is a part of natural cell aging, can contribute to cell death and, ultimately, the death of an individual.

Researchers have typically focused on the way one or two proteins unfold as damage increases from oxygen that has an uneven number of electrons.

Ken Dill. Photo from SBU

Ken Dill, a distinguished professor and director of the Laufer Center for Physical and Quantitative Biology at Stony Brook University, and colleagues including Adam de Graff, a former postdoctoral researcher in Dill’s lab who is currently a senior scientist at Methuselah Health based in Cambridge, England, and Mantu Santra, a postdoctoral researcher in Dill’s lab, recently published research that explored the global effects of unfolding on the proteome. Their model represents average proteins, not individual proteins, detail by detail.

Researchers use the roundworm as a model of human aging because of the similarity of the main processes. The worm model presents opportunities to explore the cumulative effect on proteins because of its shorter life span. Worms in normal conditions typically live about 20 days. Worms, however, that are subjected to higher temperatures or that live in the presence of free radicals can survive for only a few hours.

The shorter life span correlates with the imbalance between the rate at which cells create new proteins and the collapse of misfolded proteins damaged by free radicals, the scientists explained in a paper published online recently in the journal Proceedings of the National Academy of Sciences.

While numerous processes occur during aging, including changes in DNA, lipids and energy processes, Dill explained that organisms, from worms, to flies, to mice to humans experience increasing oxidative damage over the course of their lives.

“The evidence made us think about proteome collapse as a dominant process,” Dill said.

De Graff explained that the paper uses the premise that “certain conformations of a protein are much more susceptible to oxidative damage than others. If you’re folded, you’re pretty safe.”

In the past, researchers have considered linking the way protein misfolding leads to cell death to a potential approach to cancer. If, for example, scientists could subject specific cancer cells to oxidative damage and to develop an accumulation of misfolded proteins, they could selectively kill those cells.

A few years ago, researchers explored the possibility of developing a therapeutic strategy that tapped into the mechanism of cell death. To survive with an accumulation of mutated proteins, cancer cells have increased the levels of chaperone concentrations because they need to handle numerous mutated, incorrectly folded proteins. 

A drug called 17-AAG aimed to reduce the chaperones. It worked for some cancers but not others and had side effects. New efforts are continuing in this area, Dill said.

Other researchers, including De Graff, are looking at ways to improve protein folding and, potentially, provide therapeutic benefits for people as they age.

At Methuselah Health De Graff and his colleagues are leveraging the fact that certain conformations are more susceptible to damage and thus the creation of altered “proteoforms.” Identifying these proteoforms could be key to the early detection of disease and the development of preventative treatments, De Graff explained.

Methuselah Health is not interested in treating the downstream symptoms of disease but, rather, its upstream causes.

Going forward, Dill hopes other experimental scientists continue to generate data that enables a closer look at the link between oxidative damage, protein misfolding and cell death.

Some people in the aging field look at individual proteins, he explained. In neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, which are associated and correlated with protein misfolding, scientists are taking numerous approaches. So far, however, researchers haven’t found a successful approach to tackle aging or diseases by altering misfolded proteins.

Dill hopes people will come to appreciate a role for modeling in understanding such varied cellwide processes such as aging. “How do we convey to people who are used to thinking about detailed biochemistry why modeling matters at all?” he asked. “We have our work cut out for us to communicate what we think matters and a way forward in terms of drug discovery.”

Theoretically, some proteins that are at a high enough concentration might be more important in the aging and cell death process than others, Dill said. “If you could reduce their concentration, you might pull the cell back from the tipping point for other proteins,” he said, but researchers know too little about if or how they should do this. He credits De Graff and Santra with doing considerable work to bring this study together.

A resident of Port Jefferson with his wife, Jolanda Schreurs, Dill is pleased that their house has solar panels. 

The couple’s son Tyler is married and has purchased a house in San Diego. Despite professing a lack of interest in biology at an early age, Tyler is working as a staff development engineer for Illumina, a company that makes DNA sequencing machines.

The couple’s younger son Ryan is earning his doctorate as a physical chemist at the University of Colorado in Boulder. He works with lasers, solar energy and quantum entanglements.

As for the most recent research, Dill suggested that it is “premised on the importance of oxidative damage, including by free radicals, which is now well established,” he explained in an email. “It then seeks to explain their effects on how proteins fold and misfold.”

De Graff added that the model in the PNAS paper attempts to “understand the consequences of slowed protein synthesis and turnover” that occurs during aging.

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By Daniel Dunaief

Daniel Dunaief

I wonder how the creators of the show “Seinfeld,” Larry David and Jerry Seinfeld, would portray today’s world? The answer resides in their approaches to other ideas and conflicts that became the focal point for shows that continue in reruns almost every day.

In one show, Elaine, played by Julia Louis-Dreyfus, is dating furniture mover Carl (David James Elliott). When Elaine finds out that Carl is a pro- lifer, they decide to end their relationship.

In Washington, D.C., and indeed throughout the country, that seems tame compared with the passions people feel when they share their views about the president and about the upcoming election of 2020.

I could imagine an entire modern “Seinfeld” episode dedicated to the efforts people take to avoid discussing politics. Changing the subject, walking out of the room and pretending they can’t hear each other seems like a way these characters might keep the political genie locked in the bottle, allowing them to enjoy the company of anyone and everyone, even if those people disagree with their views on national politics.

We play out that scenario regularly wherever we go, whether we’re looking to date someone or just chat with someone in a line at the deli, on vacation or at the Department of Motor Vehicles.

We are so concerned that we might offend the other person or that he or she might offend us.

When did we become so incapable of speaking with each other? Are we determined to live in echo chambers, where we only listen and speak with the people whose ideas, thoughts and words match our own?

Come on, that’s not how democracy is supposed to work. We can and should be capable of hearing from other Americans whose ideas differ from our own. In addition to the land, the flag, the monuments, the Constitution, the history and so many other facets of American life that we share, we owe it to ourselves and to future generations to be able to listen to each other and to remain open to ideas and opportunities.

Are we afraid that someone who seems rational and reasonable might convince us to change our mind? Are our ideas so fragile and our confidence so weak that we can’t have an informed discussion about our views and our ideas?

Surely, we are better than some homogenized party line. We are a land of rugged individualists, who can and should find a way to advance our local, state and national best interests to give everyone an equal opportunity.

It’s not up to the leaders to tell us what to think, who to be and how to live. We have the chance to make those decisions for ourselves. At their best, those leaders are working to give us a shot at pursuing the American Dream which, last time I checked, doesn’t belong exclusively to one political party or another.

By not talking with each other, we increase the tension that separates the parties and the people who support them. Rather than waiting for a bipartisan detente in Washington, we can and should gather ideas about each other.

If they were still making the show today, the characters from “Seinfeld” might have helped us laugh about how entrenched we have become in dealing with our differences. We, however, aren’t living in a TV show and we owe it to ourselves to gather real information, to listen to other people and to bridge the divide that’s causing the fabric to fray of a country we all call home. 

We can learn and grow from making decisions for ourselves, instead of following the same script with every conversation.

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