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No Boundaries: The Spirit and Science of Lynne Maquat
No Boundaries: The Spirit and Scienceof Lynne Maquat
by Emily Boynton and Christine Roth
“Beam me up, Scotty!” The famed Star Trek phrase sped through 17-year-old Lynne Maquat’s head while standing anxiously in front of her high school classmates in the spring of 1970. She was about to give a dreaded final presentation in a public speaking course, and prayed that she might be magically transported to the Starship Enterprise, or at least, that the right words would find their way from her brain to her lips.
Fast-forward to October 2017, and all eyes are on her again as she speaks before more than 200 doctors and scientists at one of the oldest and most prestigious medical lectures in the country.
There is no trace of the shy girl—the first in her family to attend college—as she flawlessly summarizes more than three decades of RNA biology research in 30 minutes, engaging the Harvey Society Lecture audience at Rockefeller University with her quick wit and humor. There is no fumbling for words as she effortlessly explains how solving the vast and complex mysteries of gene expression may one day help to cure nearly every disease on the planet.
Impeccably dressed—as is her trademark—in an elegant, custom-tailored ball gown, Maquat could be any graceful woman laughing and mingling over cognac at the post-lecture reception in New York City. But beneath her feminine, fashion-forward
exterior is a gritty and determined iconoclast. She is living proof that doing things the hard way—defying doubts, exceeding expectations, and pushing boundaries— is the right way, and the only way for her.
Poised on one of the newest and most promising frontiers of discovery, Lynne Maquat, PhD, is boldly going where few scientists have gone before.
“Lynne has always done things that seemed counter to doctrine, things so strange that you think they just couldn’t happen,” says her friend and colleague Gregory Petsko, PhD, professor of Neuroscience in the Brain and Mind Research Institute at Weill Cornell Medical College. “But she believes in what she’s doing and never gets discouraged. Her science is rigorous and deep, and you’re a damn fool if you don’t believe her.”
Years of meticulous focus led to Maquat’s discovery of nonsense-mediated mRNA decay (NMD), one of the most prominent
surveillance systems in the body to protect against mistakes in gene expression that lead to disease. Maquat and other scientists are now working to gain a deeper understanding of the sophisticated mechanisms related to NMD, knowledge that is contributing to the development of new drug therapies for genetic disorders such as Fragile X syndrome, cystic fibrosis, and hundreds of others.
“Before Lynne, we really didn’t know how NMD worked,” says Joan A. Steitz, PhD, the Sterling Professor of Molecular Biophysics and Biochemistry at Yale University and an investigator at the Howard Hughes Medical Institute. “It was clear that this process was important…but it was a huge, looming question in the field.”
Solving that looming question, and a litany of subsequent accomplishments as a researcher and mentor, place Maquat at a table with the most influential scientists in the world.
J. Lowell Orbison Endowed Chair and Professor in the Department of Biochemistry and Biophysics Lynne Maquat, PhD, in her URMC lab
A member of the National Academy of Medicine (2017) and National Academy of Sciences (2011), she is the recipient of Canada’s Gairdner International Award (2015), the RNA Society Lifetime Achievement Award in Science (2017), and the Vanderbilt Prize in Biomedical Science (2017).
In February, she received the 2018 Wiley Prize in Biomedical Sciences, one of the highest international honors recognizing the work of researchers who improve the understanding of biological systems and processes, champion novel approaches, and challenge accepted thinking.
Indeed Maquat’s success flows from her courage to go against the grain of conventional wisdom and her willpower to “get back in the ring” any time the strength and validity of her science was questioned.
Now at the pinnacle of her career, she admits it’s not always pleasant to revisit her early years when she wasn’t as sure-footed as she is now in the highly competitive, male-dominated arena. But she acknowledges the lessons other aspiring scientists—men and women—might learn from her journey.
“I have given a very large chunk of my life to science, but science also saved me,” she says, adding that the solitary pursuit of answers—sometimes huddled over a microscope in a darkened laboratory until the wee hours of the morning—helped carry her through difficult chapters in her life. “There were hard times when it would have been easy to quit, but I never retreated. My salvation was always my work, not as an escape, but as a portal to a better place.”
Her work, she explains, not only enabled her to support herself financially, but also to make amazing discoveries, train young scientists now running labs all over the globe, and work toward desperately needed therapeutics for complex diseases.
“Today I can pretty much go anywhere in the world and have friends,” she says. “How wonderful is that? What’s most important to me now is staying devoted to my science, and giving back as much as I can.”
At age 65, the exceptionally youthful J. Lowell Orbison Distinguished Service Alumni Professor in the Department of Biochemistry and Biophysics, seems to be just warming up for the next stage of her career.
“She’s like the Energizer Bunny,” says Robert H. Singer, PhD, professor in the department of Anatomy and Structural Biology at Albert Einstein College of Medicine. “When other people bow out, she keeps going.”
While Maquat frequently treks to far-flung locales for speaking engagements, conferences, award ceremonies, and mentoring work, she calls Rochester home.
“Being a part of the larger University and city community and being able to interact with such highly accomplished people here, not only in science but in history, music, and art, is inspiring and so important to my perspective and vision,” she says. “When I have space in my brain to be perceptive, the best ideas come through.”
Making Strides
Whether crossing city streets, navigating hospital hallways, running her laboratory in Rochester or visiting others around the world, Lynne Maquat doesn’t “walk” anywhere—she strides.
Her slender 5’11” frame is in constant motion even while meeting in her always open-door office as she chews on a piece of gum, peers over her glasses at data, pecks away at her standing computer keyboard, or rolls her chair across the floor to grab a folder from a teetering pile on her desk. Her physical energy is surpassed only by her quick mind, which you can almost hear whirring like hummingbird wings as she dives from one topic to the next.
She runs a relatively small lab for a scientist who has produced a football-fieldsized list of 130 publications, 23 book chapters, and too-many-to-count editorials and presentations. She’s trained more than 50 post-doctoral fellows, undergraduate and graduate students who now work at institutions such as the National Cancer Institute, University of Texas Health Science Center, Pasteur Institute in Lille, France, A*STAR Institute of Medical Biology in Singapore, and the University of Geneva in Switzerland.
Maquat in the early ’80s
It’s an impressive resume for any scientist, let alone a woman who was told in grammar school that she wasn’t college material.
“If you had told me when I was younger that one day I would be giving the Harvey Society Lecture, first of all, I wouldn’t have known what it was, and second of all, I wouldn’t have believed you,” she says.
What’s a Scientist?
Growing up in the pastoral town of Easton, Conn., Maquat’s mother was a registered nurse and operating room supervisor, and her father an industrial mechanical engineer trained under the G.I. Bill. Her first inkling of an interest in science was apparent in her love of the outdoors, and her ability to recall the names of native birds, plants, and trees. In school however, she gravitated more toward the arts. She liked English and writing, became fluent in Spanish, and played piano and clarinet.
“I didn’t have the foggiest notion of what a scientist was,” she says.
Though she was a strong student on paper, her intellect was often overshadowed by her shyness around her peers and her teachers. “I would clam up when my fourth-grade teacher called on me, because I was afraid of her,” recalls Maquat.
Later, that same teacher told her mother that Maquat didn’t have what it takes to go to college, and should put it out of her mind. “I often tell that story to high school students as a reminder to never allow themselves to be defined or held back by anyone,” she says.
Indeed, Maquat’s grades spoke for themselves, and she enrolled at the University of Connecticut-Storrs in 1970. It was there, studying under biochemist Stuart Heywood, PhD, that she was drawn to the beauty and mystery of science.
She was fascinated by the subject matter of Heywood’s Cell Biology course, and his studies of protein synthesis in embryonic chick muscles. When the course ended after her sophomore year, she desperately wanted to work in Heywood’s lab, but wasn’t sure if it was allowed.
“Finally I asked him—I think while looking down at my shoes—‘Um, can I work in a lab?’ He replied, ‘A lab?’ and I eventually squeaked out, ‘Well…your lab?’ To my shock and surprise, he said, ‘Sure!’”
From there, any self-doubt began to take a back seat to her hunger for knowledge while working long hours in Heywood’s lab. She was in awe of what was already known about the steps of eukaryotic protein synthesis and the experiments that could uncover new effectors of mRNA translation.
Completing her research thesis in cell biology, Maquat graduated magna cum laude in Biology, packed a small suitcase and boarded a flight to start grad school in Biochemistry at the University of Wisconsin-Madison in 1974.
With no car and very few belongings, she was shocked and thrilled to learn the university would cover her tuition and pay her a $4,000 stipend.
“If you aren’t following in the footsteps of someone who’s been involved in academics at this level, you have no idea what grad school actually involves,” she says. “I couldn’t believe they were going to pay me to learn and conduct research…to do what I loved to do.”
She was thrown for a loop however, when she didn’t get a spot in the lab of her choice. Instead of studying RNA in human cells, she landed in a lab focused on RNA in E. coli. But the lab’s principal investigator, William Reznikoff, PhD, persuaded her to stick it out.
While not the same as human cells, bacteria have a redeeming quality—they grow very fast. Maquat learned to use bacteria for many purposes, a process that helped her develop a level of technical precision she would call upon again and again in her career.
Reznikoff’s lab also gave her an opportunity that most others at the time did not.
“I’m old enough to have entered graduate school at a time when there were very few female faculty,” she says. “And the men in many scientific circles made no secret of the fact that they thought women did not belong there. That was the reality of the day.”
Reznikoff—whose wife Cathy was a scientist and daughter Sarah is now a university mathematician—was an exception. He welcomed female grad students into his lab where they received equal respect and training as their male colleagues.
“The culture of Bill’s lab was definitely unusual for the times, and it was always one of encouragement, regardless of your gender,” says Maquat.
With Reznikoff’s guidance, Maquat earned her PhD in four-and-a-half years, and in 1979, chose to study RNA in human diseases as an NIH post-doctoral fellow in Wisconsin’s McArdle Laboratory for Cancer Research.
There, her advisor Jeffrey Ross, MD, now professor emeritus of Oncology at Wisconsin, was working on human hemoglobin gene expression. It was in Ross’ lab that Maquat began to focus on beta 0 thalassemia, a group of inherited disorders that reduce the body’s production of hemoglobin. Low levels of hemoglobin lead to a shortage of mature red blood cells and a lack of oxygen in the body, which can cause severe anemia, bone deformity, an enlarged spleen, slowed growth, heart problems, and other issues.
Like any young post-doc, Maquat had no idea where her investigations would lead.
“We just went where the research took us,” she says.
In 1980, the research took her to Jerusalem, Israel, to analyze bone marrow aspirates from four Kurdish-Jewish children with thalassemia major (Cooley’s Anemia). Looking out at the tarmac before her first flight overseas, she was completely unaware that this trip would shape the trajectory of her science and career.
In blue are HeLa cells stained with DAPI (a dye that detects DNA and designates the nucleus), and in green is the RNAbinding protein, Staufen 1. This image shows that most of Staufen 1 resides in the cytoplasm ofHeLa cells—outside the cell’s nucleus. Maquat’s lab seeks to gain adeeper understanding of the cytoplasmic steps of RNA regulation, mediated by Staufen 1, including the steps of mRNA translation and decay.
Making Sense of Nonsense
The central dogma of biology is that genetic instructions in DNA are transcribed into messenger RNAs (mRNAs) that deliver the instructions to ribosomes, which then translate that information into the proteins that carry out myriad functions throughout the body. The production of mRNA is a crucial component of gene expression.
In simplest terms, disease is gene expression gone awry, and Maquat has devoted her career to elucidating one of the most important and incredibly complex aspects of gene expression: quality control.
As in most areas of life, mistakes in cells happen all the time. Humans have 20,000 protein-coding genes but are able to produce many more than 20,000 proteins through alternative pre-mRNA splicing. A single gene can generate multiple proteins by encoding a pre-mRNA from which various exons (including protein-coding regions) can be mixed and matched (alternatively spliced).
This ability to diversify greatly increases the margin of error, but fortunately, the human body has built-in systems to eliminate potentially harmful slip-ups.
Maquat is credited with discovering one of the most prominent of these quality control systems: nonsense-mediated mRNA decay, or NMD.
With School of Medicine and Dentistry dean and URMC CEO Mark Taubman, MD, at the Harvey Society Lecture.
One common flaw in gene expression is the introduction of an early “stop” signal. Normally, this stop signal (termination codon) appears at the end of the genetic instructions in mRNA for protein synthesis to indicate that the instructions have been read start-to-finish and that all of the information has been translated into a full-length, functional protein.
Early stop signals, called “premature termination codons” or “nonsense codons,” prevent the genetic instructions in mRNA from being read completely. Consequently, protein synthesis is cut short, resulting in an incomplete or truncated protein that doesn’t function normally, and worse, could be toxic.
Similar to installing a sink with only half of the instructions, or baking a cake with half of a recipe, premature termination codons lead to undesired, and oftentimes dire, results in a cell.
Before Maquat officially arrived on the scientific scene in 1981 with her breakthrough manuscript, “Unstable beta-globin mRNA in mRNA-deficient beta 0 thalassemia,” published in Cell, scientists didn’t understand the molecular cause of this disease.
Heading her own research lab, Maquat then set out to define the mechanism that helps cells detect the difference between a premature stop signal and a normal stop signal, and extended her studies to other diseases. Her studies de-mystified NMD’s crucial role in gene expression, revealing how it works to identify and eliminate mRNAs containing premature termination codons and thereby prevents production of truncated proteins. Her paper also opened the floodgates for scientists to pursue an entirely new and auspicious field of research into how mRNAs are monitored and regulated, with Maquat leading the way.
“Before Lynne, nobody could come up with a logical explanation for how NMD worked,” says colleague Steitz, who follows Maquat’s work at Yale. “When everyone else abandoned ship, she stuck with it, and slowly made significant advances. It was hard, and at times the answers weren’t coming, but she really wanted a scientific explanation, so she kept at it. I admire her persistence, and her uncanny ability to keep thinking of the next experiment that would lead to answers.”
A Lucky Bout of Food Poisoning
Maquat’s novel understanding of NMD’s role in human cells had its genesis in her 1980 study of bone marrow aspirates from four children in Jerusalem suffering from thalassemia major, the most severe form of thalassemia. Still a young researcher in Jeffrey Ross’ University of Wisconsin lab, Maquat set out to learn why the children’s marrow contained no beta-globin protein.
However, the study almost ended before it even began.
After retrieving and spending days working up the bone marrow samples provided by Israeli hematologist Eliezer Rachmilewitz, MD, Maquat stopped for lunch with a colleague at Israel’s Weizmann Institute of Science in Rehovot on her way to the Ben Gurion airport.
“We ate at an outdoor café in the blazing heat, and my colleague suggested I try the pickles, which were delicious,” she recalls. “However, I realized later that they had probably been marinating in the hot sun for who knows how long.”
On the cab ride to the airport, Maquat’s stomach began to revolt and she fell ill with what was most likely food poisoning.
“I got to the airport, feeling horrible, just wanting desperately to get home, with my precious RNA and DNA samples sealed tightly in a Styrofoam container,” she says. “But after getting my boarding pass, security officers wanted to search the container, which would have been very bad. Everything in a tube looks dangerously foreign to non-scientists, and they would have contaminated my samples.”
Fortunately, just as she was about to be violently sick again, security was momentarily distracted by a scuffle at another checkpoint, and Maquat bolted to the bathroom, container in hand. “I honestly wasn’t trying to escape them, but I had a real emergency,” she says.
It worked nonetheless. She quietly left the bathroom and proceeded to the gate unnoticed.
“Having food poisoning probably saved me and my samples from being detained,” she says. “The airline was very kind, and let me sit by the bathroom on the flight back to the states. I must have looked a complete wreck. When my Columbia University colleague met me at JFK airport, his first words were, ‘What the hell happened to you?’”
From Little World to Big Impressions
Right before her trip to Jerusalem, Maquat’s 1980 publication in Proceedings of the National Academy of Sciences began turning heads in the scientific community, as it was the first to show that a human disease (beta + thalassemia) could be due to a pre-mRNA splicing defect.
But her landmark study arose from the series of carefully executed experiments she conducted on the bone marrow samples she retrieved from Jerusalem. Published in Cell in 1981, it was the first demonstration of a human disease (beta 0 thalassemia) caused by unstable mRNA.
Honors & Awards
2006 Elected to American Academy of Arts and Sciences
2011 Lifetime Achievement Award in Service, RNA Society
2011 Elected to National Academy of Sciences
2015 Canada Gairdner International Award (First winner from upstate New York)
2017 Vanderbilt Prize in Biomedical Science
2017 Lifetime Achievement Award in Science, RNA Society
2017 Elected to National Academy of Medicine
2017 FASEB Excellence in Science Award
2018 Wiley Prize in Biomedical Sciences
The ABC’s of NMD
The genetic information in DNA is transcribed into mRNA.
The mRNA makes its way from the nucleus to the cytoplasm where ribosomes, during the pioneer round of translation, inspect it for a premature termination codon (early stop signal). This signal will prevent the genetic information from being read completely, barring the formation of a full-length and functional protein.
If a premature termination codon is detected, the mRNA is flagged and destroyed, averting the creation of a shortened, potentially disease-causing protein.
If there is no premature termination codon, the mRNA will be remodeled, allowing it to deliver the genetic information to the ribosomes, so that normal protein will be made.
Nonsense-mediated mRNA decay (NMD) is one of the most important “quality control” mechanisms within gene expression. It keeps the body from creating truncated proteins that lead to disease. NMD is a valuablesafeguard, but it may not always function properly, and sometimes causes more harm than good. Maquat and other scientists are seeking to gain a deeper understanding of NMD and its many related mechanisms, and are exploring ways NMD can be manipulated with therapeutics to prevent and treat genetic diseases.
Above, Maquat works with research assistant professor Tatsuaki Kurosaki, PhD. Though her lab is centered on NMD-related research, she also encourages lab members to pursue new areas of investigation.
Maquat’s 1981 discovery marked the beginning of years of investigation to understand the NMD mechanism, and more than 35 years later, insights are still emerging. mRNA surveillance was, and still is, such a notoriously difficult field, beset with such time-consuming, mind-bending questions, that many scientists simply gave up in frustration. But not Maquat.
“She doesn’t like run-of-the-mill projects that aren’t going to add much,” says Reyad Elbarbary, PharmD, PhD, who recently finished his post-doctoral fellowship in Maquat’s Rochester lab, and is now an assistant professor in the Center for Orthopaedic Research and Translational Science at Penn State University College of Medicine. “She gravitates toward the most difficult, ambitious projects that she thinks will contribute new and significant insights to existing knowledge.”
Maquat has not only identified the act of molecular gymnastics that is called NMD, but—much like analyzing a successful football play—she has identified the molecular “players,” and the routes and patterns they need to follow, for NMD to work properly.
Among her most noteworthy contributions is her discovery of the exon-junction complex (EJC), a splicing-dependent “mark” that tags an mRNA so the cell can define which termination codons are premature and should trigger NMD. She defined the 50-55-nucleotide rule, which determines which mRNAs containing premature termination codons are subject to degradation by NMD. She also discovered the “pioneer round of translation,” during which NMD occurs.
Despite what most of her peers now describe as “flawless” experiments, there were doubters along the way, including Maquat herself.
Einstein professor Robert H. Singer, PhD, first met a “ruminating” Maquat more than two decades ago in a café following one of her early presentations on NMD.
“She was nervous about how the presentation went and concerned about whether she’d be taken seriously,” Singer recounts. “She asked me, ‘Do you think people will believe it?’ I told her to keep on going, and fortunately, she did.”
When contradictory data emerged, Maquat pushed forward, evaluating and addressing opposing analyses with thoughtful answers in published reviews. Her science was so precise and her understanding so thorough, it was difficult to argue against her.
“Lynne’s grasp of detail is unparalleled,” says Singer. “The level of specificity that she reaches in her research is beyond what most scientists are capable of doing, or want to do. She drives ideas into the ground to their ultimate conclusion.”
Just as the creativity of many artists and musicians is fueled by past relationships, Maquat says her relentless research focus began in the aftermath of a failed marriage in her early 30s.
“At that time I lived in my own little world,” says Maquat, who conducted much of her early research as the only RNA-centric biologist at Roswell Park Cancer Institute in Buffalo from 1982 to 2000. “I could seek guidance and encouragement from faculty members when I needed it, but other than that I worked in relative isolation with my grad students and post-docs. I didn’t have people questioning me, or telling me ‘no,’ or that an idea I had was crazy. I just put my head down and focused on what I thought was right.”
Only at scientific meetings did she emerge from her bubble to share her findings with the world. It was at those meetings and through peer-reviewed publications that she slowly began to make her mark.
Anita Hopper, PhD, professor of Molecular Genetics at The Ohio State University, recalls a presentation Maquat gave at an RNA Society meeting in Banff, Canada, more than 15 years ago.
Maquat presented on the pioneer round of translation, the stage of gene expression where NMD occurs.
“The talk was so beautiful and the experiments so smart, that the room fell silent,” says Hopper. “You could hear a pin drop. She nailed it, and everyone knew she had done something special.”
The Power and Promise of RNA
In 2000, Maquat came to the University of Rochester as professor of Biochemistry and Biophysics at the School of Medicine and Dentistry. In 2007, she founded the Center for RNA Biology: From Genome to Therapeutics. Taking note of her research skills and long-term productivity, the NIH transitioned one of Maquat’s two existing R01’s to a MERIT Award, which secures funding for her research and training through 2023.
As she continues to peel back the layers of understanding with respect to RNA biology, her work clarifies that while NMD evolved to shield humans from innate mistakes, it has the power to cause harm, too.
Inherited and acquired mutations can also introduce premature termination codons. In fact, one-third of all genetic disorders are caused by mutations that result in a premature termination codon. Many individuals with beta 0 thalassemia have a nonsense mutation that introduces a premature termination codon in the gene encoding the beta-globin protein. The premature termination codon springs the NMD machinery into action and the mRNA transcript for beta-globin protein is destroyed. No beta-globin protein is produced and patients can’t make hemoglobin.
Some individuals with cystic fibrosis are similar. A nonsense mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene leads to a premature termination codon and NMD follows. The CFTR protein, which is responsible for regulating the flow of salt and fluids in and out of cells, is defective or isn’t made. The result is the buildup of thick mucus and persistent lung infections that characterize cystic fibrosis.
Research assistant professor Maximillian Popp, PhD, pictured here with graduate student Bronwyn Lucas, says one of the best parts of working in Maquat’s lab is “being able to work independently and find our own niche.”
The Global Impact of Lynne Maquat
In both of these cases, if you could override or stop NMD—for example, by efficiently suppressing the nonsense codon— normal, healthy proteins would be made and individuals wouldn’t be sick.
Thanks to 35 years of research by Maquat and others, scientists are beginning to put the mechanistic findings related to NMD to use to design treatments. Maquat and her team are focusing on the many diseases that are dominantly inherited because NMD fails to occur, despite the presence of a premature termination codon.
“RNA presents an alternative universe of drug targets and gives us an opening to correct diseases that you can’t reach with conventional drugs,” says Charles Thornton, MD (Flw ’90, ’92), the Saunders Family Distinguished Professor in Neuromuscular Research, who is partnering with several groups to develop RNA-based therapies for myotonic dystrophy and ALS. “Much that’s being done in this area builds on Lynne’s work, and I count myself fortunate to be in the same institution, to benefit from her wisdom, and indirectly, from the supportive, collegial environment she helps to create.”
Therapies in development include small molecules inhibiting the core NMD machinery, and so-called “read-through” therapeutics that aim to turn early “stop” signals into “go” signals so that genetic instructions are read all the way through and full-length proteins are made. These treatments fit squarely into the domain of precision medicine, as they are based on the molecular underpinnings that lead to disease in the first place.
In the last several years, Maquat has discovered that NMD is a more dynamic pathway than originally thought. It also helps cells adjust to changes in their environment and more rapidly respond to certain stimuli. For example, Maquat and Maximilian Popp, PhD, a research assistant professor in her lab, found that exposing breast cancer cells to a molecule that inhibits NMD prior to treatment with doxorubicin—a drug used to treat leukemia, breast, bone and other cancers—hastens cell death. They speculate that blocking NMD primes cells for programmed death by boosting the activity of genes that respond to the cellular stress caused by chemotherapy.
The study, published in Nature Communications in 2015, is one of several that describe a role for NMD beyond quality control, raising the possibility that drugs targeting NMD could prove useful in other situations. As new information regarding NMD continues to emerge, Maquat believes it could lead to additional technological and clinical advances not yet imagined.
Preparing the ‘Next Wave’
As Maquat’s years of dedication to her research catapult her into the scientific spotlight, she remains intently focused on training and encouraging the next wave of scientists to even greater heights.
In her lectures and award acceptance speeches, she’s quick to acknowledge that her success wouldn’t be possible without the graduate students and post-docs who have shared her lab over almost four decades.
“They’re my lifeline and I’m theirs,” she says. “I expect a very high level of commitment from them, but they also get that from me.”
Being her trainee isn’t easy, but is an experience you won’t regret, say past lab members.
“When I first joined the lab we sat down in her office and she said, ‘I know that being demanding, and asking for all you can give me, is what brings results,’” recalls Dobrila Nesic, PhD, who studied in Maquat’s lab in the early ’90s. “She also told me, ‘I’ll put you on the right track and when you leave my lab you will have all the tools you need to succeed.’ And that’s true.”
Although Maquat may be considered a tough mentor, she leads by example and is intimately involved in the day-to-day happenings in the lab. Her office is situated within the lab so trainees can walk in any time to design experiments, discuss data, talk over possible explanations for unexpected results, work on a manuscript for publication, or share anything else on their minds. “My goal is to never leave a lab member without an answer to a problem for more than a day,” she says. “If it’s outside my expertise, I’ll find the person who would know the answer, so that problems are solved without delay, and work moves forward.”
Though her lab is centered on NMD-related research, she welcomes new areas of investigation as long as ideas are scientifically sound and testing methods are available.
“Lynne is open-minded and lets us pursue projects that we think are interesting, even if she’s not familiar with the area,” says Popp, who is studying how Staufen 1, a protein involved in regulating RNA, influences translation and the innate immune response in macrophages. “With her guidance we’re able to work independently and find our own niche.”
Nesic, a recently appointed lecturer at the Clinic for Dental Medicine at the University of Geneva, Switzerland, aptly describes the sentiment of many former lab members.
“I was lucky and unlucky to have her as my PhD mentor,” she says. “Lucky because that was my most successful scientific period, and unlucky because with time and different experiences I came to realize that she was not the norm, but an amazingly rare exception. It was a privilege to work with her, to experience her way of mentoring, to feel that incredible energy and drive to learn, discover, grow and develop as a scientist and as a person.”
In 2003, Maquat founded the University of Rochester’s Graduate Women in Science program to address the “leaky pipeline” in science: the disappointing fact that fewer women than men who earn PhDs in science actually use the degree in their careers.
Each month, the program hosts high-profile speakers who are using advanced degrees in traditional and non-traditional ways. Twice a year, members can apply for travel awards to attend a conference or seminar that will advance their careers.
In 2013, Maquat received the UR Presidential Diversity Award for her work. In 2014 she also received the Rochester Athena Award, presented annually by the Women’s Council of the Rochester Business Alliance. It recognizes women who excel in their professions, give back to their communities, and inspire other women to lead.
In the lab, Maquat expects “a very high level of commitment from my trainees, but they also get that from me.”
Most of Maquat’s travels involve some form of mentoring, as well. As an example, every two years she attends a conference hosted by the International Center for Genetic Engineering and Biotechnology in Trieste, Italy. There, she teaches a course on RNA biology to graduate students from countries lacking strong histories in science, including countries in Africa, South America, and the Middle East. The sessions fill to the brim with students gravitating toward Maquat’s ability to make the content approachable and meaningful.
Since 2015, Maquat is also fast becoming an idol to high school and college students across Canada, where she visits often to inspire them toward science careers. This past October she spoke to about 300 high-schoolers in Saskatchewan, where she opens each talk by telling them how life is very likely not going to happen the way you think it will.
“Did I think when I was a shy girl in high school that one day I’d be talking about scientific research with high schoolers in Saskatchewan?” she says. “Not on your life.”
Going to the Dogs
On her way to and from the Harvey Society Lecture at Rockefeller University, Maquat happily stops to greet every dog crossing her path on the New York City sidewalks—a practice that helps her make four-legged and two-legged friends in whatever city, state or country she’s in that day.
Last year, these places included Singapore, Crete, Prague, Bordeaux, Edinburgh and Oxford. Next up: Belgium, Italy, Germany, and Japan.
“There’s rarely a culture that doesn’t welcome me with open arms when I want to say ‘hi’ to their dogs,” she says.
Back in Rochester, long walks with her black Labrador Lia and trips to the gym and yoga studio are her recipe for good sleep, mental focus, and surviving the long winters.
Not surpringly, when she does take time off, Maquat prefers “adventure” vacations over lounging on a beach. Hiking the Himalayas, exploring ancient ruins, or captaining an 18-foot Hobie Cat are more her cup of tea.
Enjoying a peaceful moment with her husband Mark and Labrador Lia.
The Joy is in the Challenge
“There is no easy path to most things worthwhile,” Maquat says. “I never mind interesting work, although at times it can be very difficult to figure things out. To me, science is an area where the time and energy that we invest can return in amazing ways provided we are smart about what we do. Science is like putting together a very large puzzle without being able to see all the pieces at once. And, if it’s not challenging, then where’s the innovation?”
To support research in the Maquat Lab, contact Dianne_Moll@rochester.edu or (585) 273-5506.
