Following the people and events that make up the research community at Duke

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Category: Medicine Page 1 of 24

Making Sure Drugs Work Where They’re Needed in the Brain

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Treating Parkinson’s and other neurological conditions has been challenging due to a lack of tools capable of navigating the complexity of neural circuits. New precision tools like DART.2 help make those therapeutic aspirations a reality, one tethered drug at a time.

The brain is one of our most complex organs, full of neurons that are constantly communicating with one another at places called synapses. Synapses both release molecules called ligands and express cell surface receptors that the ligands bind to, prompting the cells to undergo various processes within. The kinds of ligands and receptors that are important to disease are often released by and found on a variety of cell types. It is crucial, therefore that when we use a drug that targets a certain receptor, we also make sure that they only interact with receptors on the desired cell type.

To achieve this, in 2018 a team led by Duke professor Mike Tadross introduced “Drugs Acutely Restricted to Tethering” or “DART,” a drug delivery system that allows researchers to administer drugs to specific neuronal cell types. In June of this year, the Tadross lab unveiled DART.2. Pairing the cell-type specificity provided by DART.2 with the cellular receptor-specificity already provided by a given drug is essential to treating diseases like Parkinson’s without severe off-target effects, something researchers have been unable to do until tools like DART entered the scene.

Think of it like cutting the water supply to an apartment that has had a pipe burst. You don’t want to cut the water to the entire building, just the flooding apartment, because the other tenants still need water. This newest version of DART increases the ability of researchers to flip the right switches.

With increased cell type specificity optimized for drugs targeting two different receptor types, enabling broader dosing techniques and opening the door for discoveries of unknown roles of well-known receptors, researchers have made DART.2 into an “even more subtle, refined, yet transformative drug delivery system, a marked improvement from more rudimentary options that operate more like sledgehammers,” said Brenda Shields, one of the lead scientists on the DART.2 project.

The HaloTag protein (HTP) helps recruit drugs tethered to the HaloTag ligand (RXDART) to the desired cell types. Courtesy of Erin Fykes.

This is, in part, owing to the use of natural, or endogenous, receptor machinery in its design. Organisms are infected with a virus that prompts only certain cell types to express HaloTag, a protein that sits on the surface of the cells of choice. A HaloTag ligand, or small molecule that binds specifically to the HaloTag surface protein, is tethered to a drug of choice. This allows the tethered drug to be selectively recruited to the cells that have the HaloTag protein, bringing the drug into closer proximity to its intended cellular receptor, discouraging it from binding to unintended receptors, and reducing the amount of drug needed for efficacy.

DART.2 is not changing receptors that are already present, nor is it affecting the signaling cascades activated by engagement with the receptors. Cell-specificity of drug delivery was improved in DART.2 by decreasing the time and drug concentration needed to achieve intended effects – it is 100 times more precise than the previous system, with desired effects achieved in just 15 minutes.

Using the previous version of DART, researchers tried delivering a tethered version of the drug gabazine to GABA receptors (neural receptors associated with inhibitory neurotransmission) on a select group of neurons – gabazine blocks GABA from binding to GABA receptors and subsequently increases neural activity. Unfortunately, DART did not achieve high enough cell-specificity and gabazine bound to enough off-target receptors to trigger epileptic responses in mouse models. DART.2, however, is capable of delivering gabazine without these effects. The original version of DART was only optimized to work with drugs targeting excitatory (AMPA receptors) neurotransmission. The ability of the current version to work with inhibitory (GABA) and excitatory (AMPA) neurotransmission makes this system useful for “bi-directional” modifications, greatly increasing its utility.

Interestingly, while testing the effects of the drug gabazine on GABA receptors in ventral tegmental area dopamine neurons, they found that GABA receptors on these cells actually suppress locomotion, opposite to findings in other studies that more broadly focused on GABA receptors in multiple cell types. This highlights the need for tools like DART.2 that allow us to understand diverse receptor/ligand dynamics on a cell-by-cell basis to gain more nuanced approaches to understanding and treating disease.

To visualize dispersion and binding of tethered drugs to HaloTag proteins versus off-target receptors, Tadross’s team developed a way of seeing where the tethered drugs accumulated by introducing a small percentage of HaloTag ligands bound to a fluorescent reporter rather than a drug into the pool of tethered drugs. This visualization further confirmed a significant increase in cell-type specificity and a decrease in off-target effects of DART.2.

With previous levels of cell specificity, local delivery of the tethered drugs via cannula insertion at the brain region of interest was necessary to ensure drugs made it to the right targets. With increased specificity and a new visualization method for seeing where DART.2 drugs bind, researchers were able to assess whether brain wide dosing would be possible, decreasing deleterious effects of pumping high concentrations of drug into a certain area. Excitingly, they found that broad administration of tethered drugs across large areas of the brain did not significantly increase binding at receptors on cells not expressing the HaloTag protein. Drug delivery in the brain is notoriously difficult, so having the flexibility to administer a drug from an easier delivery point without reducing binding at target sites translates to a greater chance of therapeutic success.  

For those unfamiliar with the process of drug and therapeutic development, the improvements presented in DART.2 represent a realistic look into the measure of scientific progress. Originally used to treat Parkinson’s mouse models, our conception of DART.2’s therapeutic relevance to other conditions is continually expanding. Shields shared that adaptions for conditions such as anxiety and depression may not be far off, just to name a few. DART.2 also makes it possible to use drugs like opioids in new ways. While helpful for pain management, the addictive potential of opioids sometimes renders them more harmful than helpful. Utilizing DART.2, opioids could be administered more specifically to cells that benefit from the drug, potentially reducing interactions with cell types involved in addiction development. Additionally, researchers are beginning to couple DART.2 with other tools on the market that can enhance its therapeutic promise and applicability (and vice versa). Each improvement of DART brings us closer to the reality of treating conditions we once deemed hopeless.

Post by Erin Fykes, Ph.D. student in cell and molecular biology

Determining Who’s White: How Vague Racial Categories Mask Health Vulnerabilities

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Good healthcare decisions depend on good data – whether you’re making federal health policy or treating a single patient.

But the data is often incomplete – particularly when it comes to defining a group that still makes up the majority of the U.S. population — a ‘non-Hispanic White’ person. That’s the primary reference category used in health data.

“Nobody questions who’s white, but they should,” said Jen’nan Read, a Duke sociologist and lead author of new research recently published in the journal Demography. “The white category contains diverse ethnic subgroups, but because we lump them all together, we miss important health vulnerabilities for millions of Americans.”

Read and co-author Fatima Fairfax, a Duke doctoral student in sociology, analyzed data from the 2000 to 2018 waves of the National Health Interview Survey to compare the health of white adults born in the U.S., Europe, the Middle East, and the Former Soviet Union.

Duke sociology professor Jen’nan Read and PhD student Fatima Fairfax

Separating groups collapsed into the white category, they found that foreign-born Whites have a smaller health advantage over U.S.-born whites than is commonly assumed, and immigrants from the Former Soviet Union are particularly disadvantaged. Those immigrants report worse health, including higher rates of high blood pressure, compared to U.S.-born whites as well as people from Europe and the Middle East.

These findings illustrate how global events, such as the wars in the Ukraine and Syria, have contributed to changes in the composition of white immigrants over time.

Understanding these changes – and the distinct experiences of white immigrant subgroups – is vital to understanding long-term patterns in health disparities within the broad white category, the authors argue.

“If we truly care about reducing health disparities in this country, we need to know where the disparities are. And they get hidden when people are lumped into broad categories,” Read said. “Ukrainian immigrants, for example, we see in the news what they’re leaving. Death, destruction, their kids may have gone years now without education. This has lifelong impacts on their wellbeing. The physical consequences from stress are enormous–we know stress increases all sorts of physical health problems. High blood pressure, cholesterol, the list goes on.”

And the science is clear. The more accurate the information healthcare providers have on their patients, the better the outcomes.

“We’re missing health patterns here,” Read said. “Our country is extremely diverse, and not talking about diversity doesn’t change that fact. Health inequality costs us a lot–it costs the healthcare system and society as a whole.” 

“Health is arguably the most important indicator of how a society is doing, and paying more attention to diversity within broad categories will allow us to do better.” 

Post by Eric Ferreri, Duke Marketing & Communications

How the body’s own defense system plays a role in Alzheimer’s disease

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Carol Colton, a distinguished professor in neurology and pathology and a member of the Duke Institute for Brain Sciences, is renowned for her groundbreaking research on the immune response’s role in the onset and progression of brain diseases, particularly Alzheimer’s disease (AD). She is a firm believer in using animals such as mice for scientific research, saying that progress in understanding and treating diseases like Alizheimer’s would not be possible without them. With a shorter life cycle than humans, mice can be studied throughout their whole life and across multiple generations. They are also biologically similar to humans and susceptible to many of the same health problems, such as Alzheimer’s. Her work has reshaped our understanding of the brain’s immune system, challenging the long-held notion that the brain is “immune privileged.” 

Carol Colton, PhD, professor of neurology and pathology at Duke

Central to Colton’s research is the role of “microglia,” the brain’s resident macrophages. Once thought to be passive observers in brain immunity, microglia are now recognized as active defenders, crucial in maintaining brain health. Colton’s early studies revealed that these cells not only eliminate harmful substances but also adapt to chronic conditions like Alzheimer’s. In this disease, microglia’s prolonged immune activity disrupts the brain’s metabolic balance, necessitating adaptations in neurons, astrocytes, and microglia themselves. She likens this adaptation to the brain coexisting with a parasite – functional but at a metabolic cost.  

Her research underscores how microglia can initially protect against Alzheimer’s by combating amyloid plaques and phospho-tau proteins but eventually contribute to the disease’s progression as metabolic disruptions intensify.

Colton’s approach integrates physiology and pathology, exploring how changes in normal physiological processes influence disease pathology. Her lab employs a variety of advanced techniques, from cellular microscopy to gene and protein analysis, to map the intricate relationships between brain metabolism and disease. This multidisciplinary approach enables a deeper understanding of how the brain’s unique environment shapes disease progression.

A cornerstone of Colton’s recent work is her discovery of “Radical S-Adenosyl domain 1 (RSAD1),” a mitochondrial protein found at the bottom of the ocean critical to understanding Alzheimer’s. RSAD1 is overexpressed in Alzheimer’s neurons, altering methionine metabolism and mitochondrial function. These disruptions contribute to the disease’s characteristic metabolic imbalance. By developing RSAD1-negative and RSAD1-overexpressing mouse models, her lab provides crucial tools to study the protein’s impact on neuronal and mitochondrial metabolism in the presence of amyloid plaques and phospho-tau.

RSAD1 also appears to be linked to methionine depletion in the brain, which may further exacerbate Alzheimer’s pathology. These findings pave the way for novel therapeutic targets aimed at restoring metabolic equilibrium in the brain.

Colton’s scientific journey is deeply influenced by her family’s academic legacy, particularly her mother, who earned a chemistry degree during an era when women faced significant barriers in science. Inspired by her mother’s determination, Colton is a passionate advocate for women scientists, often emphasizing the importance of diversity and mentorship in STEM fields.

Colton’s work highlights the slow, insidious nature of Alzheimer’s disease, driven by metabolic and immune system changes over decades. By asking fundamental questions, such as whether Alzheimer’s results from the loss of key metabolites or whether microglia contribute to this depletion, her research aims to uncover the mechanisms that underlie the disease and identify strategies for intervention.

In the fight against Alzheimer’s, Colton’s discoveries, particularly those surrounding RSAD1 and microglial activity, are setting the stage for innovative treatments. Her dedication to unraveling the complexities of brain metabolism and immune response solidifies her place as a leader in neurology and pathology, with an enduring impact on the field of Alzheimer’s research.

Post by Lydia Le, NCSSM class of 2026

Meet a Duke Expert on Pain: the Sixth Sense

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Duke associate professor of anesthesiology Andrea Nackley is a kind, passionate scientist, although her most notable quality is determination. 

As a first generation college student, a mother of two teenagers, and a triathlon athlete, she is nothing but dedicated. She challenges herself not only in a professional environment, but strives for personal and physical growth in her free time as well. 

Andrea Nackley, PhD, Duke School of Medicine

I had the pleasure of interviewing Nackley in her office and labs, where we discussed her life as a scientist, mom, and leader. When asked how she manages her many responsibilities, she responded with a single word: “acceptance.” Nackley accepts her busy schedule and strives to prioritize daily to make the most of every moment. 

As a young adult, she initially pursued the pre-med psychology path, with support from her hard-working family. She remembers a pivotal moment in her journey, in a biopsychology class where she studied brain circuits and the brain-behavior connection. She found this class absolutely riveting, and knew that this is where her passion lied. 

She describes pain, her research’s current focus, as a sixth sense of sorts, not quite like touch but something different and intriguing. Her approach to studying chronic pain is collaborative and aims to make her findings applicable to medical pursuits regarding pain management. She has even worked closely with a clinical trial centered in Duke, an experience that directly exemplifies this bench-to-bedside approach. 

A scene from the Translational Pain Research Laboratory, which Nackley leads

After earning her PhD at the University of Georgia, she moved to UNC Chapel Hill to complete a postdoctoral fellowship. In 2016 she moved to Duke, where she now leads an open-floor Translational Pain Research Laboratory and promotes an extraordinarily collaborative lab environment.

She has received grants for her work in vulvodynia, vestibulodynia, and peripheral ADRB3. When asked what her favorite aspect of working at Duke is, she endearingly responded with, “all the people here are just so… nice.” 

Nackley is close-knit with the individuals in her lab, a group ranging from high school students to postdocs, but especially with her lab manager, Marguerita Klein. 

Outside of work, she enjoys open-water swimming, training for an Olympic-length triathlon, baking, and cooking. She said baking allows her creative side to emerge, an often uncultivated aspect of any scientist’s left-dominant brain. 

Meeting Nackley and touring the innovative lab she cultivates was a wonderful experience, and I’m sure the future output from her work and leadership will be invaluable.

Post by Abigail Keaton, NCSSM Class of 2026

Advancing Immunotherapy for Glioblastoma

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Vidyalakshmi Chandramohan, associate professor in neurosurgery and pathology, and member of the Duke Cancer Institute. Credit: Duke Department of Neurosurgery

Duke professor Vidyalakshmi Chandramohan is a pioneering neuro-oncologist whose work is redefining the future of glioblastoma (GBM) treatment. As a researcher in the Department of Neurosurgery at Duke, she is driven by a profound commitment to improving patient outcomes and providing new hope for those battling one of the most aggressive forms of brain cancer.

Her journey into science began with an interest in immunology and oncology, which led her to earn a Ph.D. and conduct postdoctoral research focused on the complex relationship between cancer and immune responses. Her fascination with GBM stemmed from the urgent need to develop innovative treatments for a disease with limited therapeutic options. Today, her groundbreaking research offers new avenues for fighting GBM and improving patient survival.

PET scan showing glioblastoma brain cancer. Credit: Wikimedia Commons.

Chandramohan’s work is centered on immunotherapy, particularly the development of D2C7-IT, a dual-specific immunotoxin currently in Phase I clinical trials for recurrent GBM patients. This precision medicine approach targets tumors with remarkable specificity, minimizing damage to healthy tissue. Her ongoing research aims to enhance the efficacy of D2C7-IT and expand its potential as a viable alternative to traditional treatments.

For Chandramohan, translating her research into tangible solutions is essential. “Developing a therapy is one thing, but making sure it works in the real world is another,” she says. She is exploring ways to combine D2C7-IT with other therapies to improve treatment outcomes and minimize side effects, pushing the boundaries of what is possible in GBM care.

A critical aspect of her research involves identifying biomarkers that predict patient responses to treatment, enabling personalized therapies. “Personalized medicine is the future,” she believes. “Tailoring treatment to each patient’s unique response will improve survival rates and outcomes.”

Collaboration is at the heart of Chandramohan’s work. She fosters an interdisciplinary environment where scientists, clinicians, and engineers work together toward a shared goal. “No one person can do it all,” she emphasizes. “It takes a community of experts to make breakthroughs happen.”

Despite the challenges of translating research into clinical practice, Chandramohan remains unwavering in her determination. “When our work leads to better treatment options, it reminds us why we do this every day,” she says. Her dedication to improving patient care fuels her optimism for the future of GBM treatment.

Looking ahead, Chandramohan is hopeful that the integration of immunotherapy, precision medicine, and innovative technologies will revolutionize the field of neuro-oncology. “We’re just scratching the surface,” she says, confident in the potential to improve outcomes for GBM patients.

Through her relentless pursuit of excellence, Chandramohan is not only advancing the science of glioblastoma treatment but also inspiring the next generation of researchers to push the boundaries of what is possible in the fight against cancer.

Blog post by Adarsh Magesh, NCSSM Class of 2025


Advancing Care and Research in Traumatic Brain Injury

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Meet a trailblazer in the realm of neurocritical care and emergency medicine: Dr. Katharine Rose Colton, MD. Balancing roles as a clinician, researcher, and educator, Colton serves as an Assistant Professor of Neurology and Neurosurgery at Duke University. Her dedication to understanding and treating traumatic brain injury (TBI) exemplifies her commitment to improving the lives of patients facing severe neurological challenges.

TBI is a significant public health issue, often resulting from falls, motor vehicle accidents, or sports injuries. It can range from mild concussions to severe brain trauma, leaving patients in comas or with long-term disabilities. While treatments for TBI have evolved, many gaps remain in understanding how to optimize recovery and outcomes. Colton’s work bridges this divide, combining cutting-edge research with compassionate patient care.

Colton’s journey into medicine wasn’t linear. A Canadian native, she initially pursued an eclectic range of interests, including ethnobotany and anthropology, during her undergraduate studies. She pivoted to medicine, taking the MCAT on a whim and earning her M.D. from Duke University School of Medicine.

Her first exposure to TBI occurred during a research year at the University of Maryland’s Shock Trauma Center. A project initially focused on trauma surgery shifted to neurocritical care, igniting her passion for studying brain injuries. “I loved it,” she recalls. “It was a completely different way of looking at medicine.”

Colton’s clinical path led her to a residency in Emergency Medicine at Northwestern University and a fellowship in Neurocritical Care. While she enjoyed the fast-paced decision-making of emergency medicine, she found herself drawn to the intricate details of critical care. “I struggled with letting patients go and handing them off to others,” she says. “I wanted to stay involved and see the whole story unfold.”

Now focused primarily on neurocritical care, Colton dedicates a third of her time to research, primarily on clinical trials targeting severe TBI. She has worked on large-scale, multi-site studies investigating drug therapies and monitoring systems to optimize treatment for comatose patients.

Her approach to research is pragmatic: “I’m a clinician first. I want to know how the things we do today will benefit the patient tomorrow.” For instance, her current trials explore the potential of older, cost-effective drugs previously overlooked by pharmaceutical companies to improve outcomes in TBI patients. These trials adopt adaptive designs, allowing for real-time adjustments based on early results to maximize impact.

Colton is also a strong advocate for personalizing TBI treatment. “TBI is an incredibly heterogeneous condition,” she explains. “We can’t treat a 20-year-old in a car accident the same as a 70-year-old who fell. They have completely different recovery pathways.” Her work aims to identify biomarkers and refine classifications of TBI to develop more targeted interventions.

One of the most memorable cases from Colton’s career underscores her dedication to patient care. A young woman struck by a car in Chicago arrived at the ICU in a deep coma, with little hope of recovery. Months later, to Colton’s astonishment, the patient returned to work and resumed her life. “You just don’t know,” she reflects. “That case taught me the importance of patience and persistence in medicine.”

Colton’s role extends beyond the ICU, often involving interactions with patients’ families during some of their most vulnerable moments. “Families often show incredible grace, even in tragedy,” she says. “It’s humbling to see their resilience and willingness to contribute to research, even when it might not help their loved one directly.”

Despite the challenges of long, emotionally taxing weeks in the ICU, Colton finds fulfillment in both the technical and human aspects of her work. “There’s something beautiful about the physiology — adjusting treatments and seeing how the body responds,” she explains. Yet, she never loses sight of the bigger picture: the patient. “Numbers on a screen don’t matter if we’re not improving their lives.”

Outside of work, Colton enjoys paddleboarding, camping, and spending time with her two young children. Her background in ethnobotany and love for snowboarding reflect her multifaceted personality, blending curiosity, determination, and a deep appreciation for life.

Dr. Katharine Colton is shaping the future of TBI care through her dedication to research, her patients, and the families she serves. Her journey is a testament to the impact of resilience, curiosity, and compassion in medicine.

Written by Amy Lei, NCSSM class of 2025

Charting New Territory in Genomics: Inside Dr. ZZ’s Lab

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“The beauty of research is freedom,” says assistant professor of pharmacology and cancer biology Zhao Zhang, when asked what drove him to research transposons and circular DNA at Duke.

Zhao Zhang, an assistant professor of pharmacology and cancer biology at the Duke University School of Medicine.

Though he is now a prominent researcher, Zhang reveals that he didn’t develop an interest in the research field until his senior year of college. It was when he was running his first PCR, a technique used to amplify small segments of DNA, nervously but excitedly waiting for the results, that he became “hooked” on research. He then pursued a master’s degree in China that further cemented his passion for biology.

He continued his education abroad and soon earned his Ph.D. from the University of Massachusetts Medical School. He then decided to forgo the traditional post-doctoral training period and instead established his research group at the Carnegie Institution for Science, where he stayed for nearly five years earning accolades like the NIH Director’s Early Independence Award and the Larry Sandler Award from the Genetics Society of America.

At Carnegie, Zhang conducted research on how Drosophila, or fruit flies, can lay eggs while suppressing transposons. Jumping genes, or transposons, comprise around half of our genome and get their name from jumping from one genomic location to another. They can cause genomic instability and oncogenesis, or the formation of cancer.

One day by “pure serendipity,” the focus of their research was completely transformed when they learned that these transposons can form circular DNA. While trying to figure out why this occurred, Zhang discovered that there wasn’t much that researchers knew about circular DNA. He says it was like stumbling onto a “golden mountain” of unexplored research topics and decided to switch his research focus from germline biology to cancer biology.

This switch coincided with Zhang’s move to Duke, where he asks people to call him ZZ. Currently, his lab studies both transposons and circular DNA. One major goal of Zhang’s lab is to understand transposon-mediated immunity and use this to create cancer vaccines.

Dr. Zhang in his lab at Duke University

Another major focus of the ZZ lab is circular DNA, which can reintegrate into the genome. According to Zhang, circular DNA may also amplify cancer genes since “30% of cancer patients have circular DNA but for really aggressive cancers like glioblastoma (a brain cancer), 60% of patients have circular DNA.” His lab aims to use their research on circular DNA to develop drugs for cancer therapy.

His lab is currently waiting on results that have the potential to be instrumental in bringing new therapies for the treatment of cancer, including more aggressive types and those with lower rates of survival.

However, there is a possibility that the results will be unfavorable and he and his team will have to go back and tweak the system and re-optimize conditions before testing again. 

 “With science, you always learn something,” ZZ says. “Maybe it’s not what you wanted, but it is always a foundation to build the next stage of learning.”

Guest post by Sindhu Paladugu, North Carolina School of Science and Math, Class of 2025

The Hearth of Aging Research and Discovery

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How do you motivate faculty, external colleagues, and curious undergraduates alike to brave the frigid cold to attend an 8:30am symposium?  

Short answer: biscotti and coffee. 

Of course, the breakfast delicacies are only a supplement to the strong, irresistible offerings of the annual Aging Center Research and Education Showcase, held Dec. 6 at the Trent Semans Center. As a first-semester undergraduate, I can attest to the captivating, inspiring nature of the speakers’ presentations; the research projects were interdisciplinary, comprehensive, and thought-provoking. What’s even more impressive is the intellectually stimulating questions prompted by the seasoned researchers in the audience. What an honor it was to listen to and learn from the legendary Dr. Harvey Cohen, Duke’s very own father of geriatrics, as he offered his advice to various presenters! 

Excited attendees at the exposition of the Aging Center Research and Education Showcase!

If I were to continue heaping praise on the symposium and narrate every detail of the 4-hour-long event, you would be bored to death. Instead, allow me to focus on the most impressive research undertakings (in my humble perspective): the PRISM Comparative Effectiveness Trial co-led by Dr. Cathleen Colon-Emeric, division chief of geriatrics, and the AI-driven clinical guidance project led by Dr. Juliessa Pavon.  

The PRISM trial presentation from Colon-Emeric was the second talk listed in the symposium agenda, the first after the welcoming remarks from Dr. Heather Whitson, director of the aging center. And its headline placement was justified from the get-go: data on the prevalence of fall-related injuries is astonishing and concerning. For instance, did you know that two deaths occur from falls every hour in America? How about the fact that fractures are a more potent cause of death than breast or prostate cancers? 

Having established the basis for her research, Colon-Emeric soon transitioned to her focus on post-acute care and the avenue by which she is investigating injury prevention mechanisms. Given that 90% of fracture patients take fall risk-increasing medications, with many taking up to three such medications simultaneously, Colon-Emeric and her co-investigators sought to design a randomized cluster crossover trial measuring injurious fall rates under three conditions. By assigning 3,780 patients in the study to deprescribing dangerous medications, treating osteoporosis, and both deprescription and treatment groups, the researchers hope to discern which model performs the best in preventing fall injuries. 

After a few more invigorating lectures, the audience welcomed Dr. Juliessa Pavon for her remarks on her research on leveraging AI to personalize medication deprescribing for older adults. While Pavon’s project similarly aims to confront the issue of polypharmacy in seniors, especially the use of multiple central nervous system (CNS) acting drugs, she focuses on the process of deprescribing and how to improve decision-making. Noting that the current deprescribing tools such as STOPP and START are limited by their “one size fits all” nature, Pavon proposed that AI, the driving force behind individualized treatment rules (ITRs), could be used as a better alternative.  

Beyond the complexity of models and algorithms used for this machine learning product and the behemoth dataset (containing information from 278,000 individuals) involved, I found Pavon’s explanation for the benefits of ITRs to be the most engrossing. Contrary to popular belief, ITRs don’t improve treatment outcomes for all patients, as portrayed in the depiction below. However, the strength of ITRs arises from their ability to achieve better outcomes for many patients beyond the baseline level, which is more desirable on a population level than applying the average treatment regimen. This realization was key for me to understand the rest of Pavon’s presentation.  

Graphic showing the effect of applying individualized treatment rules (ITRs) on a patient population

Of course, I must address the other fascinating talks and poster presentations before I conclude. Dr. Cara McDermott’s seminar on improving medication and safety for rural residents featured another exciting research project; the selected data on the costs and difficulties surrounding dementia care was enlightening and underscores the grave realities confronting the support networks of dementia patients. Additionally, Dr. Maria Marquine’s address on research education in the Aging Center featured much celebratory applause as the audience congratulated undergraduate, graduate, and postgraduate scholars affiliated with the Aging Center’s various initiatives. Marquine’s passion and dedication to cultivating the next generation of aging and geriatric physician-leaders are evidenced by her involvement in all levels of the Aging Center’s education model, which warrants acclamation from the population at large. Lastly, I must mention the innovative research project spearheaded by Dr. Darina Petrovsky, assistant professor of nursing, examining the effect of music-based intervention for dementia patients. Her work, combined with her unique educational background of music studies and nursing, illustrates the multidisciplinary nature of medicine and how all skillsets could be applied to improving human health. Pre-med students: take this to heart! 

While the weather outside was frightful, the fire of research and discovery inside the Trent Great Hall was surely delightful. As we celebrate another year of remarkable research progress at Duke Medicine and the Aging Center, let us congratulate our in-house experts on their work and together look forward to their exciting work in the coming year! 

By Stone Yan, class of 2028

The Dukies Cited Most Highly

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The Web of Science ranking of the world’s most highly-cited scientists was released this morning, telling us who makes up the top 1 percent of the world’s scientists. These are the authors of influential papers that other scientists point to when making their arguments.

EDITOR’S NOTE! — Web of Science shared last year’s data! We apologize. List below is now corrected, changes to copy in bold. We’re so sorry.

Twenty-three of the citation laureates are Duke scholars or had a Duke affiliation when the landmark works were created over the last decade.

A couple of these Duke people disappeared from this year’s list, but we’re still proud of them.

Two names on the list belong to Duke’s international powerhouse of developmental psychology, the Genes, Environment, Health and Behavior Lab, led by Terrie Moffitt and Avshalom Caspi.

Dan Scolnic of Physics returns as our lone entry in Space Science, which just makes Duke sound cooler all around, don’t you think?

This is a big deal for the named faculty and an impressive line on their CVs. But the selection process weeds out “hyper-authorship, excessive self-citation and anomalous citation patterns,” so don’t even think about gaming it.

Fifty-nine nations are represented by the 6,636 individual researchers on this year’s list. About half of the citation champions are in specific fields and half in ‘cross-field’ — where interdisciplinary Duke typically dominates. The U.S. is still the most-cited nation with 36 percent of the world’s share, but shrinking slightly. Mainland China continues to rise, claiming second place with 20 percent of the cohort, up 2.5 percent from just last year. Then, in order, the UK, Germany and Australia round out the top five.

Tiny Singapore, home of the Duke NUS Graduate Medical School, is the tenth-most-cited with 1.6 percent of the global share.

In fact, five Duke NUS faculty made this year’s list: Antonio Bertoletti, Derek Hausenloy and Jenny Guek-Hong Low for cross-field; Carolyn S. P. Lam for clinical medicine, and the world famous “Bat Man,” Lin-Fa Wang, for microbiology.

Okay, you scrolled this far, let’s go!

Biology and Biochemistry

Charles A. Gersbach

Clinical Medicine

Christopher Bull Granger

Adrian F. Hernandez

Gary Lyman

Cross-Field

Priyamvada Acharya

Chris Beyrer

Stefano Curtarolo

Vance G. Fowler Jr.

Po-Chun Hsu (adjunct, now U. Chicago)

Ru-Rong Ji

William E. Kraus

David B. Mitzi

Christopher B. Newgard

Pratiksha I. Thakore (now with Genentech)

Xiaofei Wang

Mark R. Wiesner

Environment and Ecology

Robert B. Jackson (adjunct, now Stanford U.)

Microbiology

Barton F. Haynes

Neuroscience and Behavior

Quinn T. Ostrom

Plant and Animal Science

Sheng-Yang He

Psychiatry and Psychology

Avshalom Caspi

William E. Copeland

Terrie E. Moffitt

Space Science

Dan Scolnic

Climate of Care: Addressing the Health Impacts of Climate Change

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In an increasingly polarizing world, the discussion surrounding human rights remains at the forefront of all that we do as a society. People are becoming more aware, as, these days, violations are displayed right before our eyes. With a click of a button or a swipe of the thumb, people are able to see travesties occurring throughout all parts of the world. Developments in technology help us remain knowledgeable about such issues, but what about the offenses that we don’t see—the silent killers that we chalk up to poor fate, to chance? What about the violations in which we ourselves play a major role? These are urgent questions that researchers at the Duke School of Medicine are working to answer, with a specific focus on the deadly impacts of climate change.

In times of crisis, the most disadvantaged communities bear the greatest burden. The researchers recognize that climate change is no different and have strategized ways to reverse these effects. They presented their research in a recent talk, titled Climate Change and Human Health: Creating a Strategic Plan for Duke’s School of Medicine. Associate Professor and lung disease expert Dr. Robert Tighe led the conversation.

A photo of Dr. Robert Tighe. Courtesy of Duke’s Department of Medicine Website.

While presenting his research, Tighe identified a major shift in sea surface temperature trends, noting that the trend has deviated greatly from the statistical norm. Although the reasons behind this shift are not fully understood, it is believed to have serious implications, as excess heat poses risks to human health. According to the Centers for Disease Control, increasing temperatures and carbon dioxide have the potential to impact water quality, air pollution, allergens, and severe weather conditions. These conditions, in turn, bring forth respiratory allergies, cholera, malnutrition, and cardiovascular disease, to name a few. Tighe’s research goes beyond the general effects of these issues; it delves into how they disproportionately impact the most vulnerable members of society: children, the elderly, low-income communities, and communities of color.

A chart containing information about the most vulnerable parts of population to the effects of climate change. Courtesy of Biological Science.

On a local scale, Tighe highlights that many in these vulnerable positions often lack access to the healthcare necessary to mitigate these impacts. For instance, low-income citizens are often unable to afford the costs associated with repairing the physical damage climate change inflicts on their homes, leaving them exposed to pollutants and the effects of environmental toxins. The elderly also find themselves in similarly precarious scenarios, as many of these situations require evacuation—something not always feasible for those in fragile health. Consequently, they too are left exposed to pollutants and dietary challenges exacerbated by climate change.

On a global scale, these issues heavily impact countries in vulnerable positions. The United States, China, India, the European Union, and Russia are among the largest contributors to carbon emissions. However, the consequences of this burden fall disproportionately on countries like Bangladesh, Haiti, Mozambique, small island nations, and others. Due to their geographic locations, climate change brings far more than just hotter days—it brings devastating hurricanes, tsunamis, cyclones, and widespread malnutrition. The limited financial resources in these nations make rebuilding and mitigating these impacts extraordinarily challenging, especially as many climate effects are recurring. This disparity is particularly frustrating, as these countries contribute only a fraction of the world’s carbon emissions.

A map of the global climate risks. Courtesy of the New York Times.

This is precisely what Tighe’s work aims to address. He is working to connect the science on climate change effects, researched by those in the School of Medicine, with that of the Nicholas School of the Environment. Referring to this as an interdisciplinary issue, Tighe believes that the place to begin is within the community. He emphasizes the importance of starting with the people of Durham: What do they need? How can we best help them? How does this affect our own backyard? He stresses the importance of outreach, educating the community on how climate has long-term impacts on their health. Tighe also underscores the need to view this as an opportunity to combine diverse strengths to address the crisis from every angle.

In the face of a climate crisis that goes beyond borders and affects the most vulnerable among us, Tighe’s and his fellow researchers’ work is a call to action. By fostering collaboration between scientific fields and engaging directly with local communities, he develops an approach that is both comprehensive and compassionate.  His work reminds us that addressing climate change isn’t just a scientific or political issue—it’s a deeply human one, demanding a united effort for the wellbeing of all under the sun.

Post by Gabrielle Douglas, Class of 2027
Post by Gabrielle Douglas, Class of 2027

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