This mechanism is at the center of a new study by biologists at Washington University in St. Louis, published in Current Biology.

“Corollary discharge is found in every animal, in every system, and that’s because it solves a universal problem, which is: How do animals distinguish sensory inputs coming from the outside world versus sensory inputs caused by their own actions?” said Bruce Carlson, a professor of biology in WashU Arts & Sciences. “That’s a universal problem, and it’s something that our sensory systems can’t solve by themselves.”

This type of neuroscience research can help uncover mechanisms that afflict human sensory processing and prediction. Once scientists understand a brain circuit inside and out, they can better fix broken circuits.

To study the inner workings of corollary discharge, Carlson and his team turned to weakly electric fish. These animals generate brief electrical pulses called electric organ discharges to communicate and sense their surroundings. But this form of communication presents a problem. Every time a fish sends out a pulse, it also “hears” itself. Without some way to filter its own pulse out, the sensory system would be overwhelmed.

That’s the role of corollary discharge. When the fish’s brain sends the command to produce an electric pulse, it also sends a predictive signal to cancel out the expected self-generated input. Thus, the fish remains sensitive to outside signals.

But as with everything else in nature, nothing is fixed. These electrical pulses vary widely from species to species over evolutionary timelines, but also within individual fish. Hormones such as testosterone can fluctuate over the course of days, lengthening the pulse, and signals can grow longer as an animal ages. So the question becomes: How does the corollary discharge system keep up with these timing changes?

For the new study, researchers recorded electrical activity in several brain regions involved in producing electric signals, comparing fish with short and long electric discharges, including hormone-treated fish and different species.

Martin Jarzyna, a graduate student in the Carlson lab and first author on the new paper, recorded the electrical activity at every step of the corollary discharge pathway within multiple individual fish. “It’s a tortuous path from the motor area to the sensory area,” Jarzyna explained. “Never before has anybody recorded from each area within an individual animal. We never had the full picture of activity across the entire circuit.”

By measuring when neural activity occurred relative to the fish’s motor command, they identified the brain region where timing shifts first appeared: a small population of neurons called the mesencephalic command-associated nucleus (MCA). Unexpectedly, they found that all three kinds of change they studied — hormonal, developmental and evolutionary — converged on this same mechanism.

In other words, MCA works as a kind of central timing hub. Rather than recalibrating multiple neural pathways independently, the brain can coordinate changes through a single structure. This is particularly important because the MCA branches into three pathways: one devoted to communication behavior, one involved in sensing behavior and one that regulates the production of electric signals.

These findings suggest evolution repeatedly relied on MCA instead of developing entirely new mechanisms. “A common solution evolved that can maintain these accurate sensory predictions, such that new solutions don’t need to be reinvented,” Jarzyna said.

Although this study was conducted in electric fish, the potential impacts extend beyond aquatic communication. Corollary discharge is essential for sensory processing in many animals, including humans, yet the underlying circuitry remains poorly understood.

“We’ve known about corollary discharge for a long time, but we know very little about the mechanisms operating that pathway,” Carlson said.

He said this new work highlights the broader value of studying animals with unusual sensory abilities: “Studying animals that have unique behaviors can inform general questions in neuroscience. Whatever it is that’s unique about their behavior can make them suited to asking certain sorts of questions that you couldn’t ask in another system.”

Looking ahead, researchers in the Carlson lab plan to investigate what is changing at the cellular and molecular levels within MCA neurons. Future work will involve intracellular recordings from MCA neurons to figure out not just where these events are taking place in the brain, but what is actually happening during them.

Jarzyna noted that this research also could help future researchers better understand disorders in which sensory predictions go wrong, such as schizophrenia. “Our study, while not directly addressing these conditions, is helping us to better understand the normal mechanism by which these sensory predictions operate,” he said.

Jarzyna MW, Carlson BA. Developmental and evolutionary changes in sensorimotor integration to maintain coordination of corollary discharge and afferent input in electric fish, Current Biology, 2026. DOI: https://doi.org/10.1016/j.cub.2026.04.068

This work was supported by the National Science Foundation (IOS-2203122 to B.A.C.) and the National Institutes of Health (F31NS139904 to M.W.J.)

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Matthew A. Powell, MD, the Ira C. and Judith Gall Professor of Obstetrics and Gynecology at WashU Medicine and a gynecologic oncologist who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine, has been installed as president of the Society of Gynecologic Oncology after having served as president-elect for the past two years. 

A nationally recognized physician-scientist, Powell focuses his research program on improving care for uterine, ovarian and endometrial cancers. He leads clinical trials of new chemotherapy, targeted therapy and radiation approaches, and studies medications to treat disease so some patients can avoid surgery and preserve fertility.  

With more than 3,000 members, the Society of Gynecologic Oncology brings together gynecologic oncologists, physician assistants, nurse practitioners, patient advocates and other experts dedicated to advancing innovative, high-quality, equitable and comprehensive gynecologic cancer care.  

Read more on the Siteman Cancer Center website. 

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Celeste M. Karch, a national leader in the study of the genetic and cellular basis of Alzheimer’s disease and other neurodegenerative disorders, has been installed as the inaugural Barbara Burton and Reuben M. Morriss III Professor in the Department of Psychiatry at Washington University School of Medicine in St. Louis.

Karch’s research integrates human stem cell models and genomics to decode the biological underpinnings of Alzheimer’s disease.

“Celeste Karch is helping redefine how scientists understand Alzheimer’s disease and related neurodegenerative conditions,” said Chancellor Andrew D. Martin. “Her work is revealing new possibilities for earlier detection, prevention and treatment. We are deeply grateful to the Morriss family, whose generosity makes it possible to recognize not only scientific discovery but also the collaborative, forward-looking approach that drives progress in making transformative contributions to science that can benefit patients.”

David H. Perlmutter, MD, executive vice chancellor for medical affairs, the Spencer T. and Ann W. Olin Distinguished Professor and the George and Carol Bauer Dean of WashU Medicine, installed Karch.

“Celeste Karch is reshaping how the field thinks about the genetic and cellular drivers of neurodegeneration,” Perlmutter said. “She is way ahead of the field in recognizing the importance of human cellular models of Alzheimer’s disease and other neurodegenerative diseases. These models have accelerated scientists’ understanding of disease pathogenesis and the testing of new therapies. This professorship is a fitting recognition of her remarkable accomplishments and will help ensure her continued impact in the field.”

Karch’s lab takes an integrative approach to Alzheimer’s disease and dementia, bringing together genetics and “disease-in-a-dish” stem cell models to identify the cellular mechanisms that drive neurodegeneration. Her team has developed methods to analyze a person’s genetic code and determine which variants are dangerous, which are harmless, and which may even be protective — work that has helped patients and families understand their disease risk and eligibility for clinical trials.

Among her major breakthroughs, Karch discovered that when the brain’s cellular recycling centers, called lysosomes, stop working correctly, the malfunction serves as an early warning sign of disease — a finding that points toward a preventive treatment strategy for a variety of neurodegenerative diseases. She also revealed how certain genes control the brain’s immune cells and can be harnessed to improve their ability to clear Alzheimer’s-related damage. And, using stem cells grown from patient skin samples, her team has demonstrated that specific genetic mutations cause immune cells to malfunction in ways that likely accelerate the progression of dementia.

Among Karch’s most significant contributions is creating one of the world’s largest collections of stem cells for dementia research. This “biorepository” contains more than 1,000 cell lines from diverse individuals, allowing scientists globally to study the human brain in ways that were previously impossible.

Karch’s scientific contributions have won her recognition as a leader in the field of neurodegeneration. Her research has been supported by the National Institutes of Health (NIH), the Alzheimer’s Association and other major funders. She is scientific director of the Dominantly Inherited Alzheimer Network (DIAN) and an active member of the Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) at WashU Medicine. Karch has also received numerous honors, including the Rainwater Charitable Foundation’s Rainwater Prize for Innovative Early Career Scientist, and she was named an investigator for the Chan Zuckerberg Initiative, a philanthropic organization founded in 2015 by Priscilla Chan and Mark Zuckerberg to help cure, prevent or manage all diseases by the end of the century.

To ensure that medical breakthroughs benefit everyone, Karch helped launch the African iPSC Initiative in 2025. This global program, established at the Biomedical Science Research Training Centre at Yobe State University in Nigeria — in partnership with Sussex Neuroscience in the U.K. and the Knight ADRC — studies how African ancestry influences dementia. Alongside her global impact, Karch remains a dedicated mentor, spending much of her time training the next generation of neuroscientists and advocating for diversity within the scientific community.

“Celeste Karch brings her extraordinary scientific vision and gift for multidisciplinary problem-solving to everything she does,” said Eric J. Lenze, MD, the Wallace and Lucille K. Renard Professor of Psychiatry and head of the WashU Medicine Department of Psychiatry. “Her lab has produced multiple major discoveries, each addressing a different piece of the Alzheimer’s disease puzzle, while simultaneously building resources and networks that elevate the entire field. We are tremendously proud to recognize her with this professorship and grateful to the Morriss family for making it possible.”

Karch completed her undergraduate education at Kalamazoo College in Michigan before earning her PhD from the University of Florida. She conducted postdoctoral research at WashU Medicine before joining the faculty in 2013.

About Barbara Burton and Reuben M. Morriss III

A graduate of Saint Louis Country Day School and Princeton University, Reuben Morriss III earned a law degree from WashU in 1964. He joined Boatmen’s Bank, beginning a long career as a leader of the St. Louis financial sector. He eventually became chairman and president of Boatmen’s Trust Co., a position he held until his retirement in 1995. He was a board chair of Mary Institute and Saint Louis Country Day School in Ladue, Mo., and of William Woods University in Fulton, Mo. He also served on the boards of St. Luke’s Hospital in Chesterfield, Mo., and the St. Louis Bi-State American Red Cross.

Barbara Burton Morriss was a graduate of John Burroughs School in Ladue and Briarcliff College in Westchester County, N.Y. She was a board member of the Alzheimer’s Association and the Central Institute for the Deaf, and she donated time and resources to many other local charitable and cultural institutions.

The couple maintained strong ties to WashU. A member of the Alumni Board of Governors, Mr. Morriss was actively engaged with WashU Law as a member of the school’s national council, campaign cabinet and alumni association board. Throughout their lifetimes, the Morrisses generously supported the School of Law, the Alvin J. Siteman Cancer Center and the Charles F. and Joanne Knight Alzheimer Disease Research Center.

The couple was married for 48 years and had two children, Burton Douglass Morriss and Barbara Dulany Morriss, and five grandchildren. Reuben Morriss III died in 2006, and Barbara Burton Morriss died in 2018.

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By their nature, cancer cells have different nutritional needs than healthy cells. 

“Cancer cells have a distinct metabolism,” said Patti, the Michael and Tana Powell Professor of Chemistry at Washington University in St. Louis and a professor of genetics and medicine at WashU Medicine. 

Understanding those differences could open new possibilities for tracking and ultimately defeating the disease. That’s why Patti and others at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, are turning their attention to a relatively new frontier of research: Cancer metabolomics, the comprehensive study of the small molecules that cancer cells either consume or produce as they attempt to grow and multiply. 

Earlier this year, Patti and co-author Joe Rowles, a postdoctoral researcher in the Department of Chemistry in Arts & Sciences and molecular oncology trainee in Siteman Cancer Center’s Cancer Biology Pathway Program, explored the latest research and most pressing questions in cancer metabolism in Nature Reviews Cancer.

Patti is an internationally recognized leader in mass spectrometry, a technology that makes it possible to identify and quantify specific molecules in a sample. With more than 20 mass spectrometers in his ultra-clean lab, Patti has the power to track even the tiniest of changes in the levels of cancer metabolites — small molecules involved in cellular metabolism. The challenge is determining which of those molecules can be targeted in the fight against cancer.

“The fact that cancer cells run distinct metabolic programs gives us two big opportunities,” Patti said. Metabolites could be used as markers to identify tumors, he explained. More importantly, a deeper understanding of cancer metabolism might lead to new drugs or dietary strategies that slow tumor growth while sparing healthy cells.

Tracking the metabolic needs of cancer cells is no simple task. For one thing, cancerous cells can act very differently depending on the context. “A cancer cell in a lab dish might use completely different nutrients than the same cell that’s growing in a mouse or a human,” Patti said. “One of the defining attributes of cancer cells is that they are very flexible.”

The complexity of tumors also poses a challenge. “A lung tumor, for example, might have dozens of cell types, and they aren’t all malignant,” Patti said. “Some of them, like immune cells, can actually be helpful.” It’s hard to zero in on the metabolites associated with the cancer cells and not with the other parts of the tumor, he explained, and it’s challenging to find a healthy comparison sample for experiments. “There’s no such thing as a healthy tumor.” 

Patti, PhD, and his team are collaborating with WashU Medicine researchers  — including David Mutch, MD, a professor of obstetrics and gynecology, and Yin Cao, ScD, an associate professor of surgery and of medicine — to address these challenges. All three are research members at Siteman Cancer Center.

In ongoing experiments, they’re using isotopically labeled glucose to track the dynamics of tumor metabolism in patients. “WashU is a great place to do this kind of work, because the medical school has been a pioneer in developing innovative clinical tests using isotopes,” Patti said. 

In many cases, it’s a cancer cell’s appetite that really sets it apart from healthy cells. “They generally consume many of the same things that healthy cells consume,” Patti said. “They just do it much faster.”

Still, a closer look at metabolomics data could lead to new dietary strategies to prevent and control cancers. “I’m very enthusiastic about the idea that we can leverage diet to improve the lives of cancer patients,” Patti said. To reach that point, metabolomics studies will have to expand to thousands of people with different diets, genetic profiles and overall lifestyles. “We’ll need tons of data points to try to figure out how all of these different things are connected,” he said. 

In 2024, Patti and co-authors reported in Nature that fructose — a sugar found in high-fructose corn syrup — can indirectly fuel tumor growth in mouse models of melanoma, breast cancer and cervical cancer. Metabolomics studies found that the tumors were especially fond of a fructose product created in the liver.

The finding underscores the importance of close examination of the metabolic and nutritional pathways that allow cancer cells to flourish. “If you take cancer cells and put them in a dish and give them fructose, they won’t use it,” Patti said. “But if you have a tumor and you eat tons of fructose, it makes the tumor grow, in some cases, four or five times faster.”

Patti is especially alarmed by the growing rates of cancer among young people, a surge that has yet to be fully explained. “Cancers are still fairly rare in that age group, but they’re becoming increasingly common,” Patti said. “It’s happening so quickly that it can’t be caused by genetics alone. There must be a lifestyle factor, and it might come down to diet.”

Cancer metabolomics may seem like a niche area of research, but the insights could ultimately tip the fight against cancer to our advantage. “It is not a new idea to fight cancer with dietary modifications, but it’s too complicated to design interventions based on simple studies of cancer cells alone in isolation,” Patti said. “We are excited that metabolomics data from human patients can provide the knowledge needed to sort out the complexity.” 

Above all, Patti noted, cancer cells are greedy. And their greed could ultimately be their undoing. 

Rowles JL Patti GJ. Decoding cancer across scales with metabolomics. Nat Rev Cancer 26, 312–327 (2026). https://doi.org/10.1038/s41568-026-00908-0

This work was delivered as part of the PROSPECT team supported by the Cancer Grand Challenges partnership funded by Cancer Research UK (CGCATF-2023/100037 to G.J.P.), the National Cancer Institute (OT2CA297576 to G.J.P.), the French National Cancer Institute and the Bowelbabe Fund for Cancer Research UK.

Originally published on the Ampersand website

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Vij, a professor of medicine in the department’s Division of Oncology, was installed by Chancellor Andrew D. Martin and David H. Perlmutter, MD, executive vice chancellor for medical affairs, the Spencer T. and Ann W. Olin Distinguished Professor and the George and Carol Bauer Dean of WashU Medicine. The professorship was funded by St. Louisans Jeffrey and Prue Gershman, who are dedicated philanthropists and volunteers supporting local education, health and arts organizations.

“Jeffrey and Prue are deeply committed to improving the lives of the people of St. Louis, and it is a true honor that they have chosen WashU to be partners in that goal,” Martin said. “Through this professorship, their generosity will accelerate progress against blood cancers by supporting Dr. Vij’s work to bring new, more effective treatments to patients. His leadership has helped grow WashU Medicine’s reputation as a national force in stem cell transplantation and immunotherapy, and with the Gershmans’ support, that momentum will continue.”

Vij treats patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine. As the principal investigator of the Multiple Myeloma Tissue Banking initiative at Siteman, Vij leads a collaborative research team studying the genetic underpinnings and cellular microenvironment of multiple myeloma, a cancer of the plasma cells in bone marrow. He has led several clinical trials of investigative therapies for blood cancers, including immunotherapy agents and novel stem cell transplant strategies, that went on to become standard treatments. He has authored over 300 scientific publications in the arena of blood cancers.

“Dr. Vij has consistently pushed the field forward, pursuing multiple promising avenues to improve outcomes for patients with blood cancers, particularly multiple myeloma,” Perlmutter said. “His work spans discovery science, clinical trials and national collaboration — advancing new therapies while building the partnerships that move the field as a whole. His ability to translate scientific insight into real-world advances continues to shape the future of care in this field.”

Vij has served on the American Society of Clinical Oncology education and scientific committees and on the myeloma committees of the Clinical Trials Network and Alliance for Clinical Trials in Oncology. He currently serves as senior editor of the journal Clinical Lymphoma, Myeloma and Leukemia and is a past chair of the American Society of Hematology scientific committee on plasma cell dyscrasias, a type of cell disorder linked to blood cancers. Vij has received the Multiple Myeloma Research Foundation Innovator Award, the Center of Excellence Award and the Leukemia & Lymphoma Society Visionary of the Year Award.

A respected and effective educator, Vij has mentored 25 early-career researchers over his career and in 2007 received the Teacher of the Year Award from the Hematology and Oncology Fellowship Program at WashU Medicine.

“Dr. Vij is an expert in myeloma whose warmth and support give his patients confidence that they are in the best possible hands and getting the best treatment,” said Victoria J. Fraser, MD, the Adolphus Busch Professor of Medicine and head of the Department of Medicine. “He is widely recognized as a leader in the field for his research, his thoughtfulness as a physician and his creativity as a clinical investigator and mentor. The tremendous energy he brings to resources such as the Multiple Myeloma Tissue Banking initiative will benefit the field for years and decades to come.”

Vij completed his medical education at Maulana Azad Medical College in New Delhi, India, followed by postgraduate training at Halifax General Hospital and Royal Infirmary in the U.K. He completed an internal medicine residency at Rush University in Chicago and fellowships in medical oncology and hematology and in bone marrow transplantation at WashU Medicine. He joined the WashU Medicine faculty in 2000.

Jeffrey S. and Prue H. Gershman

Jeffrey S. and Prue H. Gershman, of Clayton, Mo., have supported numerous programs and organizations in and beyond St. Louis through philanthropy and through volunteer service for the arts, education, healthcare and community organizations.

Jeffrey is an attorney who has practiced business, real estate and tax law in the St. Louis area since 1981. He is active in the St. Louis business community as a director on the boards of Central Bank of St. Louis and Gershman Investment Corp. Prue has worked for 40 years as an educator and social worker at several institutions, most recently as the director of counseling and wellness at John Burroughs School in Ladue.

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Combining clinical expertise and experience with the vast and ever-increasing knowledge of artificial intelligence (AI) has the potential to transform healthcare by providing earlier diagnoses and predicting outcomes. However, today’s AI has inherent risks of error or overconfidence in a prediction.  

Sizhe Wang, a graduate student in the lab of Chenyang Lu, the Fullgraf Professor at WashU McKelvey Engineering, developed a framework that teaches clinical AI when to be confident and when to be cautious by providing more trustworthy estimates of certainty and uncertainty in its predictions. The model, called Clinical Uncertainty Risk Alignment (CURA), will be presented at the Association for Computational Linguistics annual meeting in July.

Read more on the McKelvey Engineering website.

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Now, researchers at Washington University School of Medicine in St. Louis, in collaboration with colleagues at the University of Washington in Seattle and Genentech, Inc., have developed an experimental artificial intelligence (AI) system that can speed the scan review process and help doctors spot subtle signs of eye disease sooner. The technology, called OCTCube-M, includes a family of three AI models that are designed to read and interpret 3D images of the eye’s retina as well as other types of eye scans.

In a new study, the researchers found that, compared with older models, the new AI system more accurately identified eight different retinal diseases, including age-related macular degeneration, a common disease that damages the retina and is the leading cause of blindness in people over 50. It also was more accurate in its predictions of how fast a severe form of this condition, called geographic atrophy, would progress.

The findings describing the technology in its research stage were published recently in Nature Biomedical Engineering.

“Today’s eye scans provide physicians an unprecedented, highly detailed view of the inside of the eye, revealing structures and subtle changes that would otherwise go undetected,” said the study’s co-corresponding author Aaron Lee, MD, the Arthur W. Stickle Distinguished Professor of Ophthalmology and Visual Sciences and head of the John F. Hardesty, MD Department of Ophthalmology & Visual Sciences at WashU Medicine. “But we still lack the tools to help physicians process the volume of generated images. Our AI system has the potential to empower physicians to make faster diagnoses, tailor treatment more precisely and design clinical trials that bring new therapies to patients faster.”

Additionally, the study showed that the model could infer health risks beyond the eye, predicting outcomes such as heart attack, stroke and kidney failure based solely on retinal imaging. The tiny blood vessels in the retina are anatomically and developmentally the same as those in the kidney, and the processes that lead to plaque buildup inside the walls of blood vessels that feed the heart and brain also leave signatures in the eye.

“The model has the potential to turn a simple eye exam into a powerful tool for helping to detect illness beyond the eye,” said Lee. “It opens the door to earlier detection, more precise monitoring and potentially better outcomes for patients who might otherwise go undiagnosed until their disease is far more advanced.”

A diagnosis needle in a haystack of data

At least 2.2 billion people worldwide have vision impairment, according to the World Health Organization. The imaging method known as optical coherence tomography has transformed the diagnosis and care of conditions that cause vision loss by generating, via a single and swift scan, hundreds of cross-sectional images that together form a detailed, 3D picture of the retina and the optic nerve. It can reveal early signs of different eye diseases such as glaucoma, macular degeneration and diabetic retinopathy, among other conditions.

AI, meanwhile, has become a powerful tool for processing large medical datasets, and Lee and colleagues have made notable contributions to the field. Several years ago, they published, in Nature, results describing a model that is better at diagnosing eye disease in two-dimensional retinal images compared to older models.

Because the model was trained on 2D tomography images, the researchers sought to determine if adding 3D tomography images could further improve disease diagnosis and prognosis. Because disease often extends in all three dimensions around the fovea, a small pit in the center of the retina responsible for the sharp, detailed vision required to read text and recognize faces, they hypothesized that training models on 3D images would provide more complete and accurate views of the tissue. To that end, more than 26,000 3D optical coherence tomography images comprising 1.62 million individual retinal slices — cross-sectional images of the retina — were used to train OCTCube-M.

When compared to the model trained on 2D images, OCTCube-M more accurately identified six of the eight retinal diseases by about four to six percentage points. That translates to the tool finding 43 to 60 additional cases out of every 1,000 individuals with eye disease. This was true across scans taken from individuals at multiple clinical sites, imaging modalities and diverse patient populations.

The eight diseases identified by the model include serious conditions that primarily affect the back of the eye, including the retina and optic nerve. Together they are the leading causes of vision loss and are linked to other conditions such as diabetes, hypertension and cardiovascular disease.

The researchers, including Cecilia S. Lee, MD, the Jane Hardesty Poole Distinguished Professor in ophthalmology and visual sciences at WashU Medicine; Sheng Wang, PhD, an assistant professor in the Paul G. Allen School of Computer Science & Engineering at the University of Washington; and Miao Zhang, PhD, a senior AI scientist at San Francisco-based biotech company Genentech, then adapted the 3D model by adding data from two other eye imaging techniques — infrared retinal imaging and fundus autofluorescence imaging.

By combining optical coherence tomography with one or both of the other imaging types, the AI models can construct a more complete view of the eye and a deeper understanding of what’s happening inside, Aaron Lee explained. Indeed, the model trained on all three imaging types excelled at predicting the growth rate of the severe form of macular degeneration, geographic atrophy, significantly outperforming the current state-of-the art model that trains only on fundus autofluorescence images of the retina by an average of nearly 50%.

Geographic atrophy affects about 5 million people worldwide, and there are few effective treatment options. By providing information on the growth rate of the condition, Lee and colleagues’ tool could effectively detect and classify the stage of the illness, information that researchers could use to design better clinical trials of potential therapies for the disease.

“By better predicting how fast disease will worsen, we can run smaller, more efficient studies,” Lee said. “That could lower costs, shorten the time it takes to test new therapies, reduce the number of people exposed to treatments that don’t work and help effective drugs reach patients sooner.”

Next, the WashU Medicine researchers will train OCTCube-M with larger datasets encompassing more patients, more diseases and even more types of imaging data to continue improving upon it.

Zixuan Liu Z, Xu H, Woicik A, Shapiro LG, Blazes M, Wu Y, Steffen V, Cukras CA, Lee CS, Zhang M, Lee AY, Wang S. A 3D multi-modal foundation model for optical coherence tomography. Nature Biomedical Engineering. April 24, 2026. DOI: 10.1038/s41551-026-01662-2.

This work received no specific funding. The authors disclose current grant funding not directly associated with this manuscript from the National Institutes of Health (NIH), grant numbers R01AG060942, OT2OD32644 and U19AG066567; from Gates Venture and Alzheimer’s Drug Discovery Foundation; from Carl Zeiss Meditec; and from Lowy Medical Research Institute. This content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. 

Zhang M and Steffen V are employees of Genentech, Inc. and hold stock in F. Hoffmann-La Roche Ltd. Cukras CA is an employee of F. Hoffmann-La Roche Ltd. and holds stock in the company.

About WashU Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 3,100 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 78% since 2016. Together with institutional investment, WashU Medicine commits over $1.6 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently among the top five in the country, with more than 2,550 faculty physicians practicing at 200 locations. WashU Medicine physicians exclusively staff Barnes-Jewish and St. Louis Children’s hospitals — the academic hospitals of BJC HealthCare — and Siteman Cancer Center, a partnership between BJC HealthCare and WashU Medicine and the only National Cancer Institute-designated comprehensive cancer center in Missouri and southern Illinois. WashU Medicine physicians also treat patients at BJC’s community hospitals in our region. With a storied history in MD/PhD training, WashU Medicine recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

Originally published on the WashU Medicine website

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“Disaggregases have a lot of promise, but previous methods for producing and identifying them were extremely slow and tedious,” Jackrel said. “Our new method is a significant step forward.”

The study was published in the journal Molecular Cell. The lead author is Jeremy Ryan, PhD ’23, a former graduate student in Jackrel’s lab who is now a scientist at Bayer. Other co-authors include postdoctoral researcher Anuradhika Puri; staff scientist Macy Sprunger, PhD ’23; graduate students Karlie Miller, Madalyn Bochantine, and April Lopez; and several former undergraduate students. 

Jackrel and her team focused on Hsp104, a disaggregase enzyme naturally found in yeast. The enzyme is known as a disaggregase because it can break apart aggregates of proteins. Yeast uses the enzyme for protection from heat and other stresses, but it also has the power to dissolve proteins, including TDP-43, a misfolded protein that clumps in the nervous systems of people with ALS, and α-synuclein, which accumulates in Parkinson’s patients. “Not only does Hsp104 break down the misfolded proteins, but it can also help them to refold, which can restore healthy cell functions,” Jackrel said. 

Using an engineering strategy, the team produced a “library” where they introduced many different mutations into a region of Hsp104, and then introduced this library into yeast. In this way, each yeast cell makes a different version of Hsp104. Some varieties are more potent than others, but previous methods for identifying versions of Hsp104 with optimal features were tedious and impractical. 

“You can grow yeast colonies on a plate and pick them up with a toothpick,” Jackrel said. Researchers can then use DNA sequencing to identify promising versions of Hsp104, but it’s a painstaking process that only allows them to analyze at most a few hundred versions at a time.

As described in the new paper, Jackrel and her team have found a way to rapidly produce, identify and sort the versions of Hsp104 that can break down misfolded TDP-43 or α-synuclein. “We start with the wild-type Hsp104 gene, and then we introduce mutations to create tens of millions of variations,” Jackrel said. “We’re building a vast library of possibilities.” The team then used deep sequencing, a highly sensitive process that sequences many fragments of DNA all at the same time, to identify mutations. “We can essentially look at the entire population at once and see which versions of Hsp104 work well in some situations and not in others,” she said. 

Not every version of Hsp104 in the new library will be any more effective than previously known varieties, but the new system allows researchers to analyze many more versions of Hsp104 at once, making it much easier to create and search for new and improved disaggregases, Jackrel said. The new versions that emerged from this process have several characteristics that make them more promising than earlier versions of Hsp104. 

TDP-43 is already a top target for scientists and pharmaceutical companies. In addition to playing a fundamental role in ALS, it’s also associated with dementia, including some forms of Alzheimer’s disease. So far, efforts to develop drugs that clear the protein or slow disease progression have been unsuccessful.

It will likely take years of further experiments and fine-tuning before Hsp104 could be considered a potential therapy for ALS, Jackrel said. 

“We know that buildups of misfolded TDP-43 and α-synuclein are important in the development of neurodegenerative disease, so anything that can reverse that buildup could be helpful,” Jackrel said. “Hsp104 could be a part of the answer, so this is a major accomplishment for our team.”

Related video: Can we prevent Alzheimer’s disease?

Ryan J, Miller K, Puri A et al. High-throughput screening approach identifies substrate-selective Hsp104 variants that counter amyloid seeding with diminished off-target effects. Molecular Cell, 2026; 86, 2012-2030.e11. DOI: 10.1016/j.molcel.2026.04.015

Studies were supported by NIH grant F31GM140622 and a Center for Science and Engineering of Living Systems (CSELS) Fellowship (to J.J.R.); a WUSTL uSTAR Award (to A.B.); a WUSTL HHMI BioSURF Award (to C.L.); a Beckman Scholar Award (to C.C.); and NIH grant R35GM153303, a TargetALS Springboard Award, a Frick Foundation for ALS Award, and an ALS Association Award (to M.E.J.).

Originally published on the Ampersand website

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An irregular heartbeat, or arrhythmia, leads to inefficient pumping of blood by the heart, which then prevents blood and oxygen from getting to the body’s other organs. When blood and oxygen flow poorly to the brain, the risk of stroke and cognitive decline increases. 

A team of researchers based at Washington University in St. Louis used cardiac optogenetics to noninvasively study arrhythmia and its impact on the brain. Using highly sensitive imaging in a mouse model, they found that arrhythmia in a mouse heart alters oxygen concentration in the brain during and after arrhythmia.

Results of the research are published in Science Advances June 3.  

Chao Zhou, a professor of biomedical engineering at WashU McKelvey Engineering; Abby Matt, a graduate student in Zhou’s lab; and Marcello Magri Amaral, a former visiting researcher from Universidade Brasil, led a team using optogenetics — the combination of genetic engineering and light to control neurons or cardiac cells. They produced a stimulation in genetically modified mice. By shining a red light on the skin over the mouse heart, they could safely change the pacing of the heartbeat up to 175% of resting heart rate to create arrhythmia on demand. Afterward, the heart rate returned to its initial resting rate.

In their experiments, they used several frequencies, ranging from a below-resting heart rate of 6 Hz to 14 Hz, which is well above resting rate, while recording the electrocardiogram signal during rest, light pacing and recovery periods. The largest changes in the brain took place at 6 Hz and 14 Hz. Across the range of frequencies, changes in blood and oxygen concentration were in proportion with the discrepancy between the resting heart rate and the pacing frequency.

“With this model, we showed that we reduced the cardiac output, which is the volume of blood per second coming out from the heart, and then from this, we extended it to study a very highly perfused organ, the brain,” Matt said.

The team worked with the group of Adam Bauer, an associate professor of radiology at WashU Medicine Mallinckrodt Institute of Radiology, and of biomedical engineering at McKelvey Engineering.

“We can decrease the concentration of oxygenated hemoglobin and increase the amount of deoxygenated hemoglobin in the brain,” Matt said. “So, starting from a heart scale, we’re able to override rhythm. And we can use that to study highly perfused organs and how these are disrupted on a very short timescale.”

Optogenetics began at Stanford University in 2005 focusing primarily on neuroscience. Zhou first published his work in cardiac optogenetics in Science Advances in 2015 while at Lehigh University, where he used the method to change the heartbeat in the fruit fly. His team later made additional fruit fly models that are responsive to different colors of light.

Traditional methods of heart pacing are invasive and technically complex, requiring direct implantation of LED sources on the heart surface or high power, which risks burning the skin.

“Our advantage with using light is that it’s noninvasive and doesn’t require a wire or an electrical lead to do pacing,” Matt said. “Instead, the effect is only confined to where our light-sensitive proteins are expressed, so cardiac optogenetics is more targeted and gives us more control.”

Future work may combine optical intrinsic signal imaging with other methods that measure blood flow and oxygen saturation to give a wider perspective of how arrhythmia-induced blood flow changes affect the brain and other organs. While the team showed the method is effective in mice, they say it could be extended to other cardiac optogenetic models that may have greater potential for translational medicine.

Amaral MM, Matt A, Schloss KH, Wang F, Gracheva E, Wang Y, Liang H, Bice A, Ding J, Kovacs A, Weinheimer C, Diwan A, Cui J, Rentschler S, Nerbonne J, Zemlin C, Bauer AQ, Zhou C. Non-invasive optogenetic induction of cardiac arrhythmias alters systemic hemodynamics in mice. Science Advances, June 3, 2026. DOI: 10.1126/sciadv.aeb1092

Support for this research is provided by Washington University in St. Louis; the National Institutes of Health (R01-EB025209, R21-EB032684, R01-HL156265, R01NS10287005, R01NS12632601, and RF1AG07950301); the National Science Foundation Graduate Research Fellowship Program (GRFP); and American Heart Association (25PRE1365124).

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Three physician-scientists at WashU Medicine — Steven L. Brody, MD, the Dorothy R. and Hubert C. Moog Professor of Pulmonary Medicine in the John T. Milliken Department of Medicine; Jin-Moo Lee, MD, PhD, the Andrew B. & Gretchen P. Jones Professor and head of the Department of Neurology; and Timothy M. Miller, MD, PhD, the David Clayson Professor of Neurology — have been elected to the Association of American Physicians, an honorary society of leading physician-scientists advancing innovative, impactful biomedical research. The society elected 72 new members in 2026.

Brody investigates how the cells lining the airways malfunction in chronic lung diseases, including asthma, bronchitis, COPD and chronic infections, as well as how airway stem cells are influenced to differentiate into various cell types. In a multidisciplinary effort, Brody and his team are using targeted peptides to deliver therapeutics to the airway and track immune cells in chronic lung disease.

Lee is an internationally recognized leader in stroke and cerebrovascular research with a focus on the cellular and molecular mechanisms of brain injury and recovery. He has shown that sensory deprivation improves recovery after stroke in mice, with translational implications for enhancing brain adaptability in people who have had strokes.

Miller’s research focuses on the mechanisms that drive protein abnormalities in neurodegenerative diseases such as ALS and dementia. He is a pioneer in the development of therapies based on antisense oligonucleotides (ASOs), a targeted approach to disease treatment that interferes with the production of harmful proteins. He led the international clinical trials that resulted in FDA approval of tofersen, the first ASO drug for a rare form of ALS.

Brody, Lee and Miller were formally inducted April 18 at the annual joint meeting of the AAP, the American Society for Clinical Investigation and the American Physician Scientists Association in Chicago.

Read more on the WashU Medicine news website.

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