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CAR-astrocytes can clear amyloid plaques. 26 Mar 2026 New cellular immunotherapy approach for Alzheimer's disease shows promise in mice. Researchers at WashU Medicine in St. Louis have engineered a new cellular immunotherapy that requires just a single injection to prevent amyloid plaques from developing when given before plaques start to form in mice. Furthermore, a single treatment in mice that had already developed plaques cut the amount of amyloid plaques in half. Like CAR-T therapies used for cancer treatment, in which T cells are genetically modified to attack cancer cells, this new approach equips cells - in this case, astrocytes - with a CAR homing device to grab onto a target for destruction. These new CAR-astrocyte cells have features that transform them into super cleaners that remove damaging proteins from the brain that play a role in cognitive decline. "This study marks the first successful attempt at engineering astrocytes to specifically target and remove amyloid beta plaques in the brains of mice with Alzheimer's disease," said the study's senior author, Marco Colonna, the Robert Rock Belliveau, MD, Professor of Pathology at WashU Medicine. "Although more work needs to be done to optimize the approach and address potential side effects, these results open up an exciting new opportunity to develop CAR-astrocytes into an immunotherapy for neurodegenerative diseases and even brain tumors." Alzheimer's disease starts with a sticky protein called amyloid beta that builds up into plaques in the brain, setting off a chain of events that results in brain atrophy and cognitive decline. Microglia, immune cells that reside in the brain, are responsible for removing brain waste but can become dysfunctional when overwhelmed in the context of neurodegenerative disease. To reduce the cleaning burden on microglia, first author Yun Chen, then a graduate student in the labs of Colonna and David M. Holtzman, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology at WashU Medicine, transformed astrocytes, the most abundant cell type in the brain, into amyloid-cleaning machines. He custom-designed and delivered a gene to astrocytes that codes for the CAR via an AAV vector injected into mice. The CAR, now present on the surface of astrocytes, enabled the cells to capture and engulf amyloid beta proteins. With their newly acquired ability, the astrocytes concentrated their efforts on only cleaning amyloid beta plaques in mice prone to its buildup. Mice carrying genetic mutations that increase people's risk of developing Alzheimer's disease develop amyloid beta plaques that saturate the brain by six months of age. Chen injected two groups of mice with the virus carrying the CAR-expressing gene: young mice before they developed plaques and older mice with brains saturated with plaques. As the younger mice aged, the CAR-astrocytes prevented amyloid beta plaque development. At nearly six months of age, when untreated mice normally have brains saturated with harmful plaques, brains of treated mice were plaque-free. Meanwhile, older mice with plaque-saturated brains at the time of treatment saw a 50% reduction in the amount of amyloid beta plaques compared to mice receiving an injection of a virus lacking the CAR gene. The researchers have filed a patent, with help from the Office of Technology Management at WashU, related to the approach used to engineer CAR-astrocytes. "Consistent with the antibody drug treatments, this new CAR-astrocyte immunotherapy is more effective when given in the earlier stages of the disease," said Holtzman, who is a co-author on the paper. "But where it differs, and where it could make a difference in clinical care, is in the single injection that successfully reduced the amount of harmful brain proteins in mice." In future studies, the authors aim to continue improving their CAR-astrocyte immunotherapy by fine-tuning its design to better target harmful proteins, while ensuring no harmful effects on normal brain cell functions. Additionally, by adjusting the CAR homing device to recognize specific markers on brain tumors, they could potentially switch astrocytes' function from cleaning up debris to directly killing tumor cells. Such an approach could offer a promising new way to treat brain tumors and other central nervous system diseases.

Levy appointed executive vice chancellor for medical affairs, dean of WashU Medicine. Bruce D. Levy, MD, a highly regarded leader in academic medicine and an accomplished physician-scientist, has been named executive vice chancellor for medical affairs and dean of Washington University School of Medicine in St. Louis - one of the nation's top medical schools. He begins his new role July 1, announced Chancellor Andrew D. Martin. Levy succeeds David H. Perlmutter, MD, who is concluding his deanship after leading WashU Medicine with extraordinary distinction for more than 10 years. "Bruce Levy is a deeply respected leader in academic medicine whose career reflects a strong commitment to advancing discovery, improving patient care and training the next generation of physicians and scientists," Martin said. "His collaborative approach, innovative mindset and dedication to expanding access to research-driven care make him uniquely suited to build on WashU Medicine's extraordinary momentum at this important moment. "I'd also like to once again share my deep gratitude for David Perlmutter. His leadership over the past decade has left an enduring mark on WashU Medicine and on the field of academic medicine more broadly. His experience, wisdom and commitment to advancing translational science will continue to benefit our community and the patients we serve for generations to come." Levy, who grew up in St. Louis and specializes in pulmonary and critical care medicine, is returning after more than 35 years at Harvard Medical School and Brigham and Women's Hospital, one of Harvard's leading teaching hospitals. He has served in senior leadership positions at both institutions and currently is the inaugural executive vice chair of medicine at Mass General Brigham - which includes Brigham and Women's Hospital - and the Hersey Professor of the Theory and Practice of Physic at Harvard Medical School. At Brigham and Women's Hospital, he was co-director of the medical residency program for 13 years, then chief of the Division of Pulmonary and Critical Care Medicine for 10 years, before becoming chair of the Department of Medicine and, most recently, executive vice chair of medicine for Mass General Brigham, where he has played a key role in integrating the departments of medicine at Massachusetts General Hospital and Brigham and Women's Hospital, along with their 1,000 faculty members and 900 trainees. He brings extensive leadership experience in academic medicine to his new role at a time of uncertainty surrounding federal research funding and health-care reimbursements, as well as growing demands on academic health systems to advance discovery while expanding access to care. At Brigham and Women's Hospital, Levy was lauded for strengthening the hospital's clinical, research and education missions, even in the face of outside challenges. "Academic medicine is at a pivotal moment, and I believe institutions like WashU Medicine have an extraordinary opportunity and responsibility to shape the future of academic life sciences and health care," Levy said. "I'm inspired by WashU Medicine's remarkable strengths across its missions of clinical care, discovery, education and community engagement, and by the collaborative culture that enables bold ideas to move from the laboratory to the clinic and into the community. I look forward to working with faculty, staff, students and trainees to build on this solid foundation and advance innovations and care that improve health for people in St. Louis and around the world." WashU Medicine - a global leader in biomedical research and discovery - ranks No. 2 in funding from the National Institutes of Health (NIH) and invests $1.2 billion annually in research. The medical school brings together more than 3,000 physicians and scientists working to solve some of health care's most complex challenges. Through a longstanding affiliation with BJC HealthCare, WashU Medicine physicians care for patients at the nationally ranked Barnes-Jewish Hospital, St. Louis Children's Hospital and Siteman Cancer Center, where care is informed and infused by the latest research discoveries. Levy has strong personal connections to WashU. He grew up in a neighborhood bordering the university, and both his parents earned degrees from WashU: his mother an undergraduate degree in zoology and his father a medical degree. Both later joined the WashU Medicine community. His father was a hematologist and oncologist at what was then Jewish Hospital, and his mother was an electron microscopist in the Department of Cell Biology and Physiology. The younger Levy's first experiences conducting research, while in high school, were in the labs of WashU Medicine researchers Robert Mecham, PhD, a cell biologist, and the late Robert Senior, MD, a pulmonologist. "It was clear then, as it remains today, that WashU Medicine is a special place with exceptional strengths for inspiring and nurturing early careers in science and medicine," Levy said. "I believe my early experiences at WashU were formative in my ultimate decision to train as a physician-scientist." Levy earned his medical degree in 1988 from the University of Pennsylvania Perelman School of Medicine and attained board certification in internal medicine, critical care medicine and pulmonary disease. He has treated patients at Brigham and Women's Hospital since 1988, when he arrived for a residency in internal medicine. He was chief medical resident and stayed for clinical fellowships in pulmonary and critical care medicine and for research fellowships in medicine and biochemistry. He joined the Harvard faculty in 1993 and became an associate physician at Brigham and Women's that same year, rising through the ranks at both institutions. Among Levy's many accomplishments are improving access to care in outpatient subspecialty clinics, enabling more patients to receive care for complex medical conditions. He was instrumental in creating the Lung Clinical Center and the Lung Research Center, which he helped to lead for 10 years. These collaborative centers bring together physicians and investigators across several disciplines to provide the highest quality of care for patients and to investigate the underlying causes of lung conditions. He also has provided mentorship and support to early-career clinicians and scientists, increased grant application competitiveness and nurtured entrepreneurship and commercialization opportunities for faculty. The Mass General Brigham Department of Medicine is an internationally renowned research powerhouse, with more than $700 million in research expenditures annually. Under Levy's leadership, the department also has diversified its funding portfolio, including through innovative partnerships with industry. Beyond his accomplishments in research and academic leadership, Levy has demonstrated a longstanding commitment to caring for underserved communities. For 25 years, he served as the volunteer medical director and a provider of care at the New England Shelter for Homeless Veterans, and he currently serves on the board of Free Medical Group of Eastern Massachusetts, a nonprofit with the mission to provide health care to uninsured and underinsured patients. Levy cares for patients at Brigham and Women's Hospital and Massachusetts General Hospital, and he has helped to establish the Severe Asthma Clinical Center and the COVID Recovery Center at Mass General Brigham. His research focuses on how the body naturally turns off inflammation in healthy lungs after infection or injury. He and his team study specialized proresolving mediators produced by the body to stem inflammation and promote healing, with the goal of identifying new biological pathways and mechanisms that could lead to improved treatments that promote the resolution of inflammation. By understanding how these natural processes break down in inflammatory diseases of the lung such as asthma, pneumonia, acute respiratory distress syndrome and long COVID, Levy aims to develop therapies that help restore healthy immune responses in the lungs. He has been continuously funded by the NIH since 1993 and is widely published, having authored more than 300 peer-reviewed journal articles. He has more than 10 patents awarded or pending and is co-founder of Nocion Therapeutics, a biotech startup evaluating an investigational drug for its effectiveness in reducing chronic cough in phase 2 clinical trials in the U.S., Canada and Europe. "I am honored to lead WashU Medicine at this important time, and to build on Dean Perlmutter's remarkable achievements during the past 10-plus years," Levy said. "I look forward to working with the Executive Faculty, faculty, trainees, students and staff as we chart our future course together, in collaboration with Chancellor Martin, university leaders and BJC HealthCare."

American Society for Clinical Investigation honors early-career physician-scientists. March 17, 2026 WashU Medicine faculty members Siyan "Stewart" Cao, MD, PhD, an assistant professor in gastroenterology, and Mary M. Mullen, MD, an assistant professor in gynecologic oncology, have received the Young Physician-Scientist Award from the American Society for Clinical Investigation (ASCI). The honor recognizes 50 physician-scientists nationwide who are early in their careers and have achieved accolades in their research. The annual award supports their involvement with three scientific associations - the ASCI, the Association of American Physicians and the American Physician Scientists Association - by offering leadership development workshops, panel discussions with ASCI members, virtual poster sessions and other career-enhancing activities. The physician-scientists will be recognized in April at the associations' joint annual meeting in Chicago.