It’s not enough to just publish a great scientific paper.
Somebody else has to think it’s great too and include the work in the references at the end of their paper, the citations. The more citations a paper gets, presumably the more important and influential it is. That’s how science works — you know, the whole standing-on-the-shoulders-of-giants thing.
So it always comes as a chest swelling affirmation for Dukies when we read all those Duke names on the annual list of Most Cited Scientists, compiled by the folks at Clarivate.
This year is another great haul for our thought-leaders. Duke has 30 scientists among the nearly 7,000 authors on the global list, meaning their work is among the top 1 percent of citations by scientific field and year, according to Clarivate’s Web of Science citation index.
As befits Duke’s culture of mixing and matching the sciences in bold new ways, most of the highly cited are from “cross-field” work.
Duke’s Most Cited Are:
Biology and Biochemistry
Charles A. Gersbach
Robert J. Lefkowitz
Clinical Medicine
Scott Antonia
Christopher Bull Granger
Pamela S. Douglas
Adrian F. Hernandez
Manesh R. Patel
Eric D. Peterson
Cross-Field
Chris Beyrer
Stefano Curtarolo
Renate Houts
Tony Jun Huang
Ru-Rong Ji
Jie Liu
Jason Locasale
Edward A. Miao
David B. Mitzi
Christopher B. Newgard
John F. Rawls
Drew T. Shindell
Pratiksha I. Thakore
Mark R. Wiesner
Microbiology
Barton F. Haynes
Neuroscience and Behavior
Quinn T. Ostrom
Pharmacology and Toxicology
Evan D. Kharasch
Plant and Animal Science
Xinnian Dong
Sheng Yang He
Psychiatry and Psychology
Avshalom Caspi
William E. Copeland
E. Jane Costello
Terrie E. Moffitt
Social Sciences
Michael J. Pencina
John W. Williams
Congratulations, one and all! You’ve done us proud again.
“After COVID-19,” senior Cynthia Dong (T’23) remarks, “so much of what was wrong with the medical system became visible.”
Duke undergraduate Cynthia Dong, Class of 2023
This realization sparked an interest in how health policy could be used to shape health outcomes. Dong, who is pursuing a self-designed Program II major in Health Disparities: Causes and Policy Solutions, is a Margolis Scholar in Health Policy and Management. Her main research focus is telehealth and inequitable access to healthcare. Her team looks at patient experiences with telehealth, and where user experience can be improved. In fact, she’s now doing her thesis as an offshoot of this work, researching how telehealth can be used to increase access to healthcare for postpartum depression.
Presenting research on telehealth
In addition to her health policy work, however, Dong also works as a research assistant in the neurobiology lab of Dr. Anne West, and her particular focus is on the transcription mechanism of the protein BDNF, or brain-derived neurotrophic factor.
While lab research can be clearly visualized by most people (think pipettes, rows of benches littered with bottles and plastic tubes, blue rubber gloves everywhere), health policy research is perhaps a little more abstract. When asked what the process of research through Margolis is like, Dong says that “it’s not team-based or individual – it’s a lot of both.” This looks like individual research on specific topics, talking to different stakeholder groups and people with certain expertise, and then convening for weekly team meetings.
With other Margolis Scholars
For Dong, research has been invaluable in teaching her to apply knowledge to something tangible. Doing that, you’re often “forced to understand that not everything is in my control.” But on the flip side, research can also be frustrating for her because so much of it is uncertain. “Will your paper get published? Is what you’re doing relevant to the research community? Will people invest in you?”
In that vein, research has humbled her a lot. “What it means to try to solve a societal problem is that it’s not always easy, you have to break it down into chunks, and even those chunks can be hard to solve.”
After graduation, Dong plans on taking a couple of gap years to be with family and scribe before ultimately pursuing an MD-MPH. Because research can be such a long, arduous process, she says that “It took me a long time to realize that the work we do matters.” In the future, though, she anticipates that her research through Margolis will directly inform her MPH studies, and that “with the skills I’ve learned, I can help create good policy that can address the issues at hand.”
What brings seniors Deney Li and Amber Fu together? Aside from a penchant for photoshoots (keep scrolling) and neurobiology, both of them are student research assistants at the lab of Dr. Andrew West, which is researching the mechanisms underlying Parkinson’s in order to develop therapeutics to block disease progression. Ahead lie insights on their lab work, their lab camaraderie, and even some wisdom on life.
(Interview edited for clarity. Author notes in italics.)
What are you guys studying here at Duke? What brought you to the West lab?
DL: I am a biology and psychology double major, with a pharmacology concentration. I started working at a lab spring semester of freshman year that focused on microbial and environmental science, but that made me realize that microbiology wasn’t really for me. I’ve always known I wanted to try something in pharmaceutics and translational medicine, so I transitioned to a new lab in the middle of COVID, which was the West lab. The focus of the West lab is neurobiology and neuropharmacology, and looking back it feels like fate that my interests lined up so well!
Deney Li
AF: I am majoring in neuroscience with minors in philosophy and chemistry, on the pre-med track. I knew I wanted to get into research at Duke because I had done research in high school and liked it. I started at the same time as Deney – we individually cold-emailed at the same time too, in the fall! I was always interested in neuroscience but wasn’t pre-med at the time. A friend in club basketball said her lab was looking for people, and the lab was focused on neurobiology – which ended up being the West lab!
Amber Fu
What projects are you working on in lab?
DL: My work mainly involves immunoassays that test for Parkinson’s biomarkers. My postdoc is Yuan Yuan, and we’re looking at four drugs that are kinase inhibitors (kinases are enzymes that phosphorylate other proteins in the body, which turns them either on or off). We administer these drugs to mice and rats, and look at LRRK2, Rab10 and phosphorylated Rab10 protein levels in serum at different time points after administration.These protein levels are important and indicative because more progressive forms of Parkinson’s are related to higher levels of these proteins.
AF: For the past couple of years, I’ve been working under Zhiyong Liu (a postdoc in the lab). There are multiple factors affecting Parkinson’s, and different labs ones study different factors. The West lab largely studies genetic factors, but what we’re doing is unique for the lab. There’s been a lot of research on how nanoplastics can go past the blood-brain barrier, so we are studying how this relates to mechanisms involved in Parkinson’s disease. Nanoplastics can catalyze alpha-synuclein aggregation, which is a hallmark of the disease. Specifically, my project is trying to make our own polystyrene nanoplastics that are realistic to inject into animal models.
What I’m doing is totally different from Deney – I’m studying the mechanisms surrounding Parkinson’s, Deney is more about drug and treatments – but that’s what’s cool about this lab – there are so many different people, all studying different things but coming together to elucidate Parkinson’s.
Another important project
How much time do you spend in lab?
DL: I’m in lab Mondays, Wednesdays, and Fridays from 9 to 6. All my classes are on Tuesdays and Thursdays!
AF: I’m usually in lab Tuesdays and Thursdays from 12 to 4, Fridays from 9 to 11:45, and then whenever else I need to be.
Describe lab life in three words:
DL: Unexpected growth (can I just do two)?
AF: Rewarding, stimulating, eye-opening.
Lab life also entails goats and pumpkins
What’s one thing you like about lab work and one thing you hate?
DL: What I like about lab work is being able to trouble-shoot because it’s so satisfying. If I’m working on a big project, and a problem comes up, that forces me to be flexible and think on my toes. I have to utilize all the soft skills and thinking capabilities I’ve acquired in my 21 years of life and then apply them to what’s happening to the project. The adrenaline rush is fun! Something I don’t like is that there’s lots of uncertainty when it comes to lab work. It’s frustrating to not be able to solve all problems.
AF: I like how I’ve been able to learn so many technical skills, like cryosectioning. At first you think they’re repetitive, but they’re essential to doing experiments. A process may look easy, but there are technical things like how you hold your hand when you pipette that can make a difference in your results. Something I don’t like is how science can sometimes become people-centric and not focused on the quality of research. A lab is like a business – you have to be making money, getting your grants in – and while that’s life it’s also frustrating.
What do you want to do in the future post-Duke? How has research informed that?
DL: I want to do a Ph.D. in neuropharmacology. I’m really interested in research on neurodegeneration but also have been reading a lot about addiction. So I’ll either apply to graduate school this year or next year. My ultimate goal would be to get into the biotech startup sphere, but that’s more of a 30-years-down-the-road goal! Being in this lab has taught me a lot about the pros and cons of research, which I’m thankful for. Lab contradicts with my personality in some ways– I’m very spontaneous and flexible, but lab requires a schedule and regularity, and I like the fact that I’ve grown because of that.
AF: The future is so uncertain! I am currently pre-med, but want to take gap years, and I’m not quite sure what I want to do with them. Best case scenario is I go to London and study bioethics and the philosophy of medicine, which are two things I’m really interested in. They both influence how I think about science, medicine, and research in general. After medical school, though, I have been thinking a lot about doing palliative care. So if London doesn’t work out, I want to maybe work in hospice, and definitely wouldn’t be opposed to doing more research – but eventually, medical school.
What’s one thing about yourself right now that your younger, first-year self would be surprised to know?
DL: How well I take care of myself. I usually sleep eight hours a day, wake up to meditate in the mornings most days, listen to my podcasts… freshman-year-Deney survived on two hours of sleep and Redbull.
AF: Freshman year I had tons of expectations for myself and met them, and now I’m meeting my expectations less and less. Maybe that’s because I’m pushing myself in my expectations, or maybe because I’ve learned not to push myself that much in achieving them. I don’t necessarily sleep eight hours and meditate, but I am a little nicer to myself than I used to be, although I’m still working on it. Also, I didn’t face big failures before freshman year, but I’ve faced more now, and life is still okay. I’ve learned to believe that things work out.
“To me [this image] captures the wonder, the awe, the beauty of sound and the brain that tries to make sense of it,” said professor Nina Kraus, Northwestern University researcher and author of “Of Sound Mind: How Our Brain Constructs a Meaningful Sonic World.”
Stop. What do you hear?
We might not always think about the sounds around us, but our brains are always listening, said Northwestern University professor Nina Kraus.
Kraus, auditory researcher and author of “Of Sound Mind: How Our Brain Constructs a Meaningful Sonic World,” spoke via Zoom to a Duke audience in October. She has published more than four hundred papers on the auditory system in humans and other animals and how it’s affected by conditions like autism, aging, and concussion. She discussed some of her findings and how “the sound mind” affects us in our day-to-day lives.
One of the slides from Kraus’s presentation. We can think of sound as having many “ingredients.”
“I think of the sound mind as encompassing how we think, how we move, how we sense, and how we feel,” Kraus said. We live in a “visually dominated world,” but for hearing people, sound plays an important role in language, music, rhythm, and how we perceive the world.
One of the slides from Kraus’s presentation. The human auditory system involves not just the ears but also several regions of the brain. The “hearing brain” engages movement, cognition, and emotions along with interpreting direct sensory input from all senses.
Kraus discussed the auditory system and how much of what we think of as hearing takes place in the brain. We can think of sound as signals outside the head and electricity as signals inside the head (neural processing). When those two merge, learning occurs, and we can make sound-to-meaning connections.
Another slide from Kraus’s presentation. In an experiment, teaching rabbits to associate a sound with meaning (in this case, more carrots) changed patterns of neuron firing in the auditory cortex, even in individual neurons. “Same sound, same neuron, and yet the neuron responded differently… because now there’s a sound-to-meaning connection,” Kraus said.
Despite how sensitive our neurons and brains are to sound, things can get lost in translation. Kraus studies how conditions like concussions and hearing loss can adversely affect auditory processing. Even among healthy brains, we all hear and interpret sounds differently. People have unique “sonic fingerprints” that are relatively stable over time within an individual brain but differ between people. These patterns of sound recognition are apparent when scientists record brain responses to music or other sounds.
“One of the biological measures that we have been using in human and in animal models,” Kraus said, is FFR (frequency following response) to speech. FFR-to-speech can be used to analyze an individual’s auditory processing system. It also allows scientists to convert brain responses back into sound waves. “The sound wave and the brainwave resemble each other, which is just remarkable.”
One of Kraus’s slides. Technology called frequency following response (FFR) can be used to convert brain waves back into original sound (like a song).
This technology helps reveal just how attuned our brains are to sound. When we hear a song, our brain waves respond to everything from the beat to the melody. Those brain waves are so specific to that particular song or sound that when scientists convert the brain waves back into sound, the resulting music is still recognizable.
When scientists try this on people who have experienced a concussion, for instance, the recreated music can sound different or garbled. Experiments that compare healthy and unhealthy brains can help reveal what concussions do to the brain and our ability to interpret sound. But not everything that affects auditory processing is bad.
Musical training is famously good for the brain, and experiments done by Kraus and other scientists support that conclusion. “The musician signature—something that develops over time—” has specific patterns, and it can enhance certain components of auditory processing over time. Making music might also improve language skills. “The music and language signatures really overlap,” Kraus said, “which is why making music is so good for strengthening our sound mind.” Kids who can synchronize to a beat, for example, tend to have better language skills according to some of the experiments Kraus has been involved with.
Musicians are also, on average, better at processing sound in noisy environments. Musicians respond well in quiet and noisy environments. Non-musicians, on the other hand, respond well in quiet environments, but that response “really breaks down” in noisy ones.
Interestingly, “Making music has a lifelong impact. Making music in early life can strengthen the sound mind when one is seventy or eighty years old.”
A slide from Kraus’s presentation. Musicians tend to be better at processing sounds in noisy environments.
Exercise, too, can improve auditory processing. “Elite division 1 athletes have especially quiet brains” with less neural noise. That’s a good thing; it lets incoming information “stand out more.”
In experiments, healthy athletes also have a more consistent response over time across multiple trials, especially women.
These benefits aren’t limited to elite athletes, though. According to Kraus, “Being fit and flexible is one of the best things you can do for your brain,” Kraus said.
Kraus and her team have a regularly updated website about their work. For those who want to learn more about their research, they have a short video about their research approach and an online lecture Kraus gave with the Kennedy Center.
Nina Kraus with a piano. “Science is a deeply human endeavor,” she said, “and I think we often forget that. It’s made by people.” Photo courtesy of Kraus and colleague Jenna Cunningham, Ph.D.
It’s May! Time for our 2022 Duke graduates to endure Pomp and Circumstance on repeat, shed a tear, and then take wing. Always bittersweet for those of us who work with students.
This year, the Duke Research Blog celebrates the graduation of three outstanding student-bloggers. This class produced some real gems and we will be greatly diminished by their commencement.
Most memorably, Anna took us along when she spent the summer of 2019 at an archaeology dig in Italy.
Her other topics were a liberal arts education in themselves: she wrote about invisible malaria, climate change, dance, drinking water standards, snow leopards, muscular dystrophy, cybercrime, autism and some fascinating classmates. This year, as she readied for her career, she wrote a three-part series about blockchain and bitcoins.
After graduating with a psychology major, an econ minor and an innovation and entrepreneurship certificate, Anna will be moving to Atlanta to work as an associate consultant at Bain and Company. She plans to continue learning about the web3 space in her “free time” and hopes to find an outlet to continue writing about cryptocurrency as well.
Cydney Livingston, the pride of Anson County, NC, joined us as a sophomore and proceeded to shoot out the lights with 31 career posts.
Cydney Livingston
Cydney’s biggest hit, by far, was her first-person account of trying to continue with college after the pandemic shut down Spring Term, 2020. “Wednesdays, My New Favorite Day,” appealed to Duke alumni, family and friends everywhere who were wondering what the heck was going on in Durham. Short answer: It was weird.
She was integral to our (mostly virtual) coverage of the COVID crisis, and helped the campus keep up with some of the larger questions the emerging virus presented, including social inequity and vaccine hesitancy. She also profiled some grad students, sharing a look inside their worlds from a student’s perspective. And in between, Cydney saw paleontologist Richard Leakey in one of his last public appearances and wrote about space junk, cervixes, lead poisoning, dog smarts, visual perception and North Carolina’s pungent pork industry.
Cydney is graduating with a BS in Biology and an AB II in History and is moving to Boston in the fall to begin work as an analyst with ClearView Healthcare Partners. But she is leaving open the possibility of a return to academia in history of science, technology and medicine, or science and technology studies. “I’m excited to spend a few years working and reflecting on my time at Duke and what lies ahead in my life journey.”
As Alec Morlote emphasizes, he’s a Biology major because “I’m really interested in it. I’d definitely be a Biology major whether I was pre-med or not.”
Morlote, a Trinity junior from northern New Jersey, works in the lab of Dr. Pelin Volkan studying the neurobiology of fruit flies. Why fruit flies, of all things? Well, Morlote initially signed up for a research fellowship program during the summer following his freshman year.
Of course, in March of that year, COVID-19 happened, so Morlote ended up postponing his work to this past summer. He got paired with the Volkan lab because he didn’t want to work in an area of research that was very familiar to him.
“I wanted to use research as an opportunity to learn something completely new,” he said. The neurobiology of fruit flies hit the nail on the head.
Alec Morlote
The Volkan Lab is a cell biology and neurobiology lab that studies how social behavior, specifically courting, is affected by stimuli, using fruit flies as a model organism. Morlote’s specific project has to do with olfactory stimuli – the things flies smell. In flies, as he explained, one gene is responsible for courtship behavior in male flies. If you take out the olfactory receptor of the fly, however, that gene won’t be active.
Morlote is interested in seeing how the olfactory receptor is critical to the expression of this gene.
To do this, he has been working on imaging the antennae of flies – work he describes as “cool, but tedious.” It’s incredibly detailed work to pick apart the antenna off of such a tiny creature. Once isolated, neurotransmitters in the antenna that have been tagged with green fluorescent protein (GFP) light up, thus showing the expression pattern of all cells expressing the neurotransmitter.
Humans clearly don’t have as simplistic a courtship behavior as fruit flies, but the simplicity of the fruit fly makes it an incredibly valuable organism for studying neurobiology. All discoveries in humans initially started with some sort of watered-down version of the human anatomy, whether mice or in this case, fruit flies. Discoveries into the neurobiology and neuroplasticity of fruit flies just might yield significant discoveries into the neurobiology and neuroplasticity of the human brain.
When asked about his favorite and least favorite parts about his research, Morlote laughed.
“I don’t like doing work for three months and getting no results at all,” he remarked in reference to the initial work he started on this summer – but alas, such is the nature of scientific research. But he adds that the best part of research is getting results, any at all. And even no results can mean something.
Morlote’s poster from his summer research
Research was a way for Morlote to narrow his post-graduation plans. He knows now that he wants to pursue an MD, or possibly an MD/PhD. But initially, research was a way for him to see whether this was the path for him at all. When asked why he chose to be pre-med, Morlote said that “it just seemed like the most practical way to apply a love for science.” Biology is the science that he loves the most, and so being pre-med seemed like a no-brainer.
It’s also a family business. Both of Morlote’s parents are doctors, so medicine “is not unfamiliar territory to me.” Being Latin American, both his parents have worked extensively with Latin communities in New Jersey, which is work he hopes to emulate in the future.
Whether or not benchwork stays a part of his life, Morlote knows that he wants his career to involve research somehow. The way he sees it, “you’re doing the bare minimum if you’re just a doctor but you’re not trying to better medicine in some way.”
Contributing to research just might become his way.
In an era of seemingly endless panaceas for age-based mental decline, navigating through the clutter can be a considerable challenge.
However, a team of Duke researchers, led by cognitive neuroscientist Edna Andrews, PhD, think they may have found a robust and long-term solution to countering this decline and preventing pathologies in an aging brain. Their approach does not require an invasive procedure or some pharmacological intervention, just a good ear, some sheet music, and maybe an instrument or two.
Dr. Edna Andrews, pictured in 2017. (Photo by Megan Mendenhall/Duke Photography)
In early 2021, Andrews and her team published one of the first studies to look at musicianship’s impact in building cognitive brain reserve. Cognitive brain reserve, simply put, is a way to qualify the resilience of the brain in the face of various pathologies. High levels of cognitive reserve can help stave off dementia, Parkinson’s disease or multiple sclerosis for years on end. These levels are quantified through structural measurements of gray matter and white matter in the brain. The white matter may be thought of as the insulated wiring that helps different areas of the brain communicate.
In this particular study, Andrews’ team focused on measurements of white matter integrity through an advanced MRI technique known as diffusion tensor imaging, to see what shape it is in.
Previous neuroimaging studies have revealed that normal aging leads to a decrease in white matter integrity across the brain. Over the past fifteen years, however, researchers have found that complex sensory-motor activities may be able to slow down and even reverse the loss of white matter integrity. The two most robust examples of complex sensory-motor activities are multilingualism and musicianship.
Andrews has long been fascinated by the brain and languages. In 2014, she published one of the seminal texts in the field of cognitive neurolinguistics where she laid the groundwork for a new neuroscience model of language. Around the same time, she published the first and to-date only longitudinal fMRI study of second language acquisition. Her findings, built upon decades of research in cognitive neuroscience and linguistics, served as the foundation for her popular FOCUS course: Neuroscience/Human Language.
In more recent years, she has shifted her research focus to understanding the impact of musicianship on cognitive brain reserve. Invigorated by her lived experience as a professional musician and composer, she wanted to see whether lifelong musicianship could increase white matter integrity as one ages. She and her team hypothesized that musicianship would increase white matter integrity in certain fiber tracts related to the act of music-making
To accomplish this goal, she and her team scanned the brains of eight different musicians ranging in age from 20 years to 67 years old. These musicians dedicated an average of three hours per day to practice and had gained years’ worth of performance experience. After participants were placed into the MRI machine, the researchers used diffusion tensor imaging to calculate fractional antisotropy (FA) values for certain white matter fiber tracts. A higher FA value meant higher integrity and, consequently, higher cognitive brain reserve. Andrews and her team chose to observe FA values in two fiber tracts, the superior longitudinal fasciculus (SLF) and the uncinate fasciculus (UF), based on their relevance to musicianship in previous studies.
Relative location of subcortical white matter fiber tracts (lateral view). Image from Wikipedia.
Previous studies of the two fiber tracts in non-musicians found that their integrity decreased with age. In other words, the older the participants, the lower their white matter integrity in these regions. After analyzing the anisotropy values via linear regression, they observed a clear positive correlation between age and fractional anisotropy in both fiber tracts. These trends were visible in both tracts of both the left and right hemispheres of the brain. Such an observation substantiated their hypothesis, suggesting that highly proficient musicianship can increase cognitive brain reserve as one ages.
These findings expand the existing literature of lifestyle changes that can improve brain health beyond diet and exercise. Though more demanding, neurological changes resulting from the acquisition and maintenance of language and music capabilities have the potential to endure longer into the life cycle.
Andrews is one of the strongest advocates of lifelong learning, not solely for the satisfaction it brings about, but also for the tangible impact it can have on cognitive brain reserve. Picking up a new language or a new instrument should not be pursuits confined to the young child.
It appears, then, that the kindest way to treat the brain is to throw something new at it. A little bit of practice couldn’t hurt either.
Peak achievement in the sciences isn’t measured by stopwatches or goals scored, it goes by citations – the number of times other scientists have referenced your findings in their own academic papers. A high number of citations is an indication that a particular work was influential in moving the field forward.
Nobel laureate Bob Lefkowitz made the list in two categories this year.
And the peak of this peak is the annual “Highly Cited Researchers” list produced each year by the folks at Clarivate, who run the Institute for Scientific Information. The names on this list are drawn from publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index – the most-cited of the cited.
Duke has 38 names on the highly cited list this year — including Bob Lefkowitz twice because he’s just that good — and two colleagues at the Duke NUS Medical School in Singapore. In all, the 2021 list includes 6,602 researchers from more than 70 countries.
The ISI says that US scientists are a little less than 40 percent of the highly cited list this year – and dropping. Chinese researchers are gaining, having nearly doubled their presence on the roster in the last four years.
“The headline story is one of sizeable gains for Mainland China and a decline for the United States, particularly when you look at the trends over the last four years,” said a statement from David Pendlebury, Senior Citation Analyst at the Institute for Scientific Information. “(This reflects) a transformational rebalancing of scientific and scholarly contributions at the top level through the globalization of the research enterprise.”
Without further ado, let’s see who our champions are!
Hey everyone! My name is Vibhav Nandagiri, I use he/him/his pronouns, and I’m currently a first-year student at Duke. Amidst the sea of continuous transition brought upon by college, one area of my identity that has stayed fairly constant is my geography. I’ve lived in North Carolina for sixteen of my eighteen years, and my current home lies just twenty minutes from campus in sunny, suburban Cary, NC.
The two missing years are accounted for through my adventures in my parents’ hometown–Hyderabad, India–as a toddler. Spending some of my earliest years surrounded by a large and loving family impacted my life profoundly, forever cementing a strong connection to my emotional, cultural, and linguistic roots.
The latter had a secondary impact on me, one I wouldn’t discover until my parents enrolled me in preschool after returning to the States. With hubris, I marched into my first day of class, ready to seize the day, until I soon discovered an uncomfortable fact: I couldn’t speak English. I am told through some unfortunate stories that I struggled considerably during my first month in a new, Anglicized environment; however, I soon learned the quirks of this language, and two-year-old me, perhaps realizing that he had some catching up to do, fully immersed himself in the English language.
Nowadays, I read quite a bit. Fiction and journalism, academic and satire, I firmly believe that all styles of literature play a role in educating people on the ebbs and flows of our world. In recent years, I’ve developed a thematic fascination with the future. The genre of far-future science fiction, with its rich exploration of hypothetical advanced societies, has led me to ask pressing questions about the future of the human species. How will society organize itself politically? What are the ethical implications of future medical advancements? Will we achieve a healthy symbiosis with technology? As a Duke Research Blogger, I hope to find answers to these questions while getting a front-row, multidisciplinary seat to what the future has to offer. It’s an invigorating opportunity to grow as a writer and communicator, to have my curiosity piqued on a weekly basis, to understand the futuristic visions of innovators at the top of their field.
Prior to Duke, I had the opportunity to conduct research at the Appalachian State University Pediatric Exercise and Physiology Lab, where I co-authored a published paper about adolescent fat metabolism. Not only was I introduced to the academic research process, but I also learned the importance of communicating my findings clearly through writing and presentations. I intend to bring these valuable lessons and perspectives to the Duke Research Blog.
Beyond exercise science, I am intrigued by a diverse range of research areas, from Public Health to Climate Change to Business to Neuroscience, the latter of which I hope to explore further through the Cognitive Neuroscience and Law FOCUS. I was drawn to the program for the opportunity to build strong relationships with professors and investigators; I intend to approach my work at the Duke Research Blog with a similar keenness to listen and connect with researchers and readers alike. When I’m not reading or typing away furiously at my computer, you can find me hitting on the tennis courts, singing Choral or Indian Classical music, or convincing my friends that my music taste is better than theirs.
The discovery of a signaling pathway in the brain that could make mice into ‘superlearners’ understandably touched off a lot of excitement a few years back.
But new work led by Duke neurologist and neuroscientist Nicole Calakos MD PhD suggests there’s more to the story of the superlearner chemical pathway than anybody realized.
A genetically-enhanced ‘smart mouse’ doing some important work. (Boston University)
In a study led by postdoctoral researchers Ashley Helseth and Ricardo Hernandez-Martinez, the Calakos lab developed a new tool to visualize activity of this Integrated Stress Response (ISR) signaling pathway because it contributes to synaptic plasticity – the brain’s ability to rewire circuits – as well as to learning and memory.
What they didn’t expect to see is that a population of cells called cholinergic interneurons, which comprise only 1 or 2 percent of the whole basal ganglia structure, seem to have the ISR pathway working all the time. The basal ganglia, which is the focus of much of Calakos’ work, plays a role in Parkinson’s and Huntington’s diseases, Tourette’s syndrome, obsessive compulsive disorder and more.
Nicole Calakos, the Lincoln Financial Group distinguished professor of Neurobiology and Neurology. (Alex Boerner)
“This totally changes how you think about the pathway,” Calakos said. “Everybody thought this pathway used an on-demand response type of mechanism, but what if some cells needed it for their everyday activities?”
To answer this, they blocked the ISR in just those rare interneurons in mice and it actually reproduced the enhanced performance on learned tasks that the earlier studies had shown when the pathway was blocked universally throughout the brain. This finding focuses attention on this select subset of brain cells, the cholinergic interneurons that release the chemical signal acetylcholine, as being responsible for at least some of the ‘superlearner’ behavior.
Since the integrated stress response pathway and its potential to enhance learning and memory was identified, drugs for dementia and traumatic brain injury are being designed to manipulate it and help the brain recover. But there may be more to the story than anyone realized, Calakos said.
“Our results show that the ISR plays a major role in acetylcholine-releasing cells, and our current best dementia drugs boost acetylcholine,” she said.
With their new tool, SPOTlight, the team were able to highlight the presence of cholinergic interneurons (red) which are only 1 to 2 percent of the cell population in the ganglia. (Helseth et al)
Acetylcholine, the chemical that these rare cholinergic interneurons use to signal in the brain, is well known for its powerful effects on influencing brain states for attention and learning. This finding suggests that at least some of the ‘superlearner’ properties of inhibiting the ISR occur by influencing brain state, rather than acting directly in the cells that are being rewired during learning.
In addition to the full research article, Science published on April 23 an article summary by Helseth and Calakos and a perspective piece by a pair of University of Minnesota neuroscientists highlighting the finding’s importance.
More work is required to sort out what ISR is and is not doing, but it’s possible that these new findings can help to develop “more precise, more nuanced Alzheimer’s drugs,” Calakos said.
