Dr. Palavicini presenting his research poster Dr. Palavicini recently attended the annual American Aging Association (AGE) meeting in Provo, Utah. At this meeting, Dr. Palavicini presented a research poster titled "Beyond Longer Life: Does Mitoglitazone's Sex-Dependent Lifespan Extension Translate Into Improved Healthspan?" Dr. Palavicini also volunteered as a poster judge. Dr. Palavicini serving as a poster judge Dr. Palavicini attended the AGE meeting with this family and finished off the meeting by taking in Utah's beautiful landscapes! Dr. Palavicini, with his wife, Cinthia, and daughter, Mia, enjoying the scenery in Utah To learn more about the American Aging Association and its annual meetings, click here!

Charlie getting settled into her new cubicle! We are excited to welcome Charlie Sconiers into our lab! Charlie is a recent graduate of Howard University and will be in the Palavicini lab for two years as a post-baccalaureate trainee. Charlie's primary project focuses on chronic jet lag and how environmental stressors may contribute to Alzheimer's disease. After this post-baccalaureate program, Charlie hopes to earn a PhD to pursue a research career in academia.

Max presenting his research poster Max recently represented the Palavicini lab at the Systems Aging Gordon Research Conference (GRC) in Newry, Maine. The GRC Max attended focused on the "Complexities of Aging Across Species, Evolution, Reproduction, Human Longevity and Frailty". At this conference, Max presented his research in the Palavicini lab with a poster titled "Intermittent Inhibition of Ceramide Synthesis Improves Metabolic Health and Reduces Early Mortality in Mice Fed a Western Diet". To read more about the 2026 Systems Aging GRC, click here!

Pratush at his workstation in the Palavicini lab We are excited to welcome Pratush Saravanan into our lab! Pratush is a first-year MD/PhD student through the South Texas Medical Scientist Training Program (STX-MSTP) at UTSA. As an MD/PhD student, Pratush is completing a rotation in the Palavicini lab over the summer. In the lab, Pratush's research will focus on the core biological processes in Alzheimer’s disease and on characterizing the relationship between glial cells and the hallmarks of Alzheimer's disease and related dementias. Welcome to the lab, Pratush!

Jude examining brain regions and what glial cells they contain We are excited to welcome Jude Aden into our lab! Jude is an undergraduate student at UTSA who is interning with us through the Summer Physiology Undergraduate Researcher (SPUR) program. Jude will be researching how PLCG2 gene variants are linked to Alzheimer’s disease, related dementias, and longevity. His project will specifically focus on PLCγ2 to better understand how these cellular pathways contribute to neurodegeneration. Jude is a pre-med student and hopes to pursue a career as an allergist-immunologist.

Max at his workstation in the Palavicini lab We are excited to welcome Maximus Peto to the Palavicini lab! Max is an affiliate of the lab who will focus on testing whether ceramide‑lowering drugs and mitoglitazones can improve overall health, brain function, and healthy aging in older mice. Max will research how these treatments affect metabolism and the body's ability to produce energy, to identify ways to help people stay healthier as they age. Welcome to the lab, Max!

Shared By: Claire Kowalick Alzheimer’s is a highly heritable disease with about 60% of the risk coming from a person’s genes. The other 40% of the risk remains less well-studied and may, in part, come from environmental stressors. The University of Texas at San Antonio was recently awarded a highly competitive Alzheimer’s Association research grant to investigate the gene-environment interaction and how it may contribute to an increased risk for Alzheimer’s disease. The grant will begin in April and provides $200,000 to fund the study over the next three years. “We are trying to incorporate as many genetic variants and environmental stressors as we can to have a robust model that mimics late-onset Alzheimer’s disease, as opposed to other preclinical work that shows early onset, highly aggressive, non-physiological models,” said principal investigator Juan Pablo Palavicini, PhD, assistant professor in the Department of Cellular and Integrative Physiology in the Joe R. and Teresa Long School of Medicine. He is also a researcher with the Sam and Ann Barshop Institute for Longevity and Aging Studies. Circadian disruption as an environmental stressor Palavicini is teaming with Kevin B. Koronowski, PhD, assistant professor in the Department of Biochemistry and Structural Biology in the Long School of Medicine and researcher with the Barshop Institute, to primarily study the effects of circadian rhythm disruption as an environmental stressor and its effects on human phosphorylated-tau proteins. The aggregation of tau proteins and amyloid plaques are well-known hallmarks of Alzheimer’s disease and other dementias. “In modern society, it’s difficult to reduce environmental stressors like disrupted sleep schedules and diet. That is the whole point of our study. We don’t yet know all the potential consequences of this disruption,” Koronowski said. Creating chronic jet lag With Koronowski’s expertise in circadian rhythm, the team developed an earlier study funded by the William and Ella Owens Medical Foundation. A chronic jet lag condition was created in an animal model by shifting the light-dark schedule forward by eight hours twice per week. “It is as if you traveled from Texas to Europe, from Europe to Australia and then back to Texas,” Palavicini said. During that study, some mice started misbehaving and developing metabolic abnormalities, but the effects were not strong. For the upcoming study, the research team will incorporate changes to create more dramatic consequences of circadian rhythm disruption. “A key adjustment will be to start the process in middle-aged subjects instead of younger ones to account for age-related resiliency and recovery capacity,” Palavicini said. For the upcoming study, researchers will also provide a Western diet with higher fat and sugar content. Many clinical studies show that people who work rotating or night shifts tend to have lower-quality diets. In replicating actual human scenarios of circadian disruption, Koronowski said it makes sense to include dietary stress. “This type of food falls perfectly into the big picture of what we are doing,” he said. “This shows the additional stress of an unhealthy diet that many people eat, the typical Western-style diet.” The research team is also proposing a second aim of the study in which they will determine if a time-restricted feeding schedule rescues circadian disruption-induced metabolic abnormality. In their previous study, the team noticed the chronic jet lag caused eating at all times of the day and night. In the upcoming study, they will have an automated system that only allows for feeding 12 hours a day. Cause or effect? “We are especially testing whether restoring metabolic rhythms while light is disrupted can prevent the progression of Alzheimer’s disease. In the context of neurodegeneration, we still don’t know if circadian disruption is a cause or effect, so this study can help us determine that,” Koronowski said. Rather than only focusing on the genetic component, Koronowski said this study is a more holistic view of health and how loss of homeostasis in the body and misalignment of natural rhythms can contribute to disease. “Night is a critical time for our brains because these proteins that accumulate, like tau and amyloid beta, get flushed out as we are sleeping. The different stages of sleep, especially REM, are essential for memory consolidation. Disrupted sleep, even for one night, can alter the amount of tau and amyloid in the brain substantially,” Palavicini said. Findings from this study could help clarify how environmental stressors such as disrupted sleep and diet interact with genetic risk, offering new insight into how Alzheimer’s disease develops later in life. Other researchers on the team include Qing Zhang, MD, a research scientist in Koronowski’s lab, and Andrea Gonzalez, a student associate in Palavicini’s lab.

Lucas analyzing data (effects of mitoglitazone on body composition) in his cubicle We are excited to welcome Lucas Orme, a senior student at BASIS San Antonio–Shavano Campus, to the Palavicini Lab. From March through mid‑May, Lucas will complete his senior project with us, focusing on the effects of mitoglitazone, an insulin sensitizer, on healthspan while contributing approximately 20 hours per week. He will gain hands‑on experience working with mice and computational analyses and will be mentored closely by Vicki.

Third‑year PhD student Eduardo Gutierrez was selected to give a research talk at the UT Health San Antonio Cellular & Integrative Physiology Research Day, held April 2, 2026 on the Long Campus. His presentation, “PLCG2‑Dependent Microglial TLR4 Innate Immune Responses: In Vivo and In Vitro Studies in PLCG2‑Deficient Mice,” showcased collaborative work between the Hopp and the Palavicini labs.

At the recent San Antonio Walk to End Alzheimer’s Corporate Breakfast, hosted by HealthTexas, Juan Pablo Palavicini, PhD, was invited to give a brief overview of the lab’s Alzheimer’s Association‑funded projects and ongoing clinical research efforts. Surrounded by local corporate and community leaders, the event highlighted the strong regional commitment to advancing brain health, expanding clinical trial participation, and supporting innovative, locally driven Alzheimer’s research. Juan Pablo expressed his gratitude to Carlos Torres and the HealthTexas team for championing the 2026 Walk to End Alzheimer’s, and to Anna Schragin and the local Alzheimer’s Association chapter for organizing such a thoughtful, energizing gathering. Lab members are honored to contribute to this mission, and we invite our community partners, friends, and families to join or start a Walk team and support the cause as we work together toward a future without Alzheimer’s.

Shared By: Claire Kowalick New research shows that changes in brain fats, or lipids, play a major role in Alzheimer’s development and progression. More than a century ago, Alois Alzheimer noted unusual changes in brain fats, which he described as “lipoid granules,” along with the buildup of amyloid-beta (amyloid) plaques and tau protein tangles. These observations led to the identification of Alzheimer’s disease and related dementias. Since then, most Alzheimer’s research has focused on amyloid and tau, while brain lipid abnormalities have received far less attention. New research from The University of Texas at San Antonio, in collaboration with the University of California at Irvine, shows that changes in brain fats, or lipids, play a major role in Alzheimer’s development and progression. Lipid imbalances can influence how amyloid proteins build up, and certain genes that regulate lipid metabolism are linked to Alzheimer’s risk. “The brain is a unique organ,” said Juan Pablo Palavicini, PhD, assistant professor in the Department of Cellular and Integrative Physiology and co-lead of the study. “Unlike most other organs, which are rich in protein, more than half of the brain’s dry weight is made up of different kinds of lipids, including cholesterol, phospholipids, and sphingolipids. In Alzheimer’s disease, we see massive disruption of these lipids, yet most studies focus only on genes and proteins.” The study, published October 15 in Nature Communications, reveals how microglia, the brain’s immune cells, control some of these lipid changes. Depending on how they are manipulated, microglia can either help maintain balance or worsen the disease. The research was co-led by Palavicini and Xianlin Han, PhD, professor in the Department of Medicine, who are both investigators with the Sam and Ann Barshop Institute for Longevity and Aging Studies. Testing microglia’s role Using a mouse model of Alzheimer’s, the scientists tested two approaches to remove microglia. In one, they treated mice with a drug that nearly eliminated all microglia and in the other, they used genetically modified mice that lacked microglia. These strategies allowed researchers to separate effects caused by microglia from those caused by other brain cells. “We wanted to understand which cells are driving these lipid changes,” Palavicini said. “Some lipids go up, some go down, but which cell types are responsible? By removing microglia, we could see which changes depend on them and which do not.” The research team compared results from the mouse studies with post-mortem brain samples from people with and without Alzheimer’s. They found that amyloid buildup dramatically altered brain lipid patterns. Two groups of lipids stood out: lysophospholipids (LPC and LPE), which are linked to inflammation and oxidative stress, and bis(monoacylglycero)phosphate (BMP), a lipid that helps regulate the cell’s “recycling centers,” called lysosomes. The research team found that a form of BMP containing arachidonic acid (AA-BMP) accumulated near amyloid plaques, and that long-term removal of microglia prevented AA-BMP buildup, showing that microglia drive these changes. “BMP is still not well understood, especially in the brain,” Palavicini said. “It forms substructures in lysosomes that attract proteins to break down damaged lipids. Without microglia, AA-BMP levels drop, which can interfere with the brain’s cleanup processes.” Progranulin’s key effects The protein progranulin, made by both microglia and neurons, emerged in the study as a key lipid regulator. Progranulin levels rise in Alzheimer’s conditions and closely align with AA-BMP accumulation. Removing microglia lowered both progranulin and AA-BMP near plaques, suggesting that microglial progranulin helps regulate lipid balance. “In the Alzheimer’s brain, rather than lowering BMP, it may be important to maintain or support its levels,” Palavicini said. “Progranulin helps maintain this lipid and protect neurons. Therapies that boost progranulin could potentially restore balance and support brain health.” Influence from other brain cells Not all lipids are controlled by microglia. LPC and LPE levels were mostly influenced by astrocytes and neurons. LPC buildup was tied to astrocyte activation and enzyme activity, while LPE increases were linked to oxidative stress and weakened antioxidant defenses. “Even though we hypothesized microglia were driving the accumulation of these inflammatory lipids, it was actually other cell types, including astrocytes,” Palavicini said. “This distinction helps us understand which cells to target for therapies and shows how complex lipid regulation is in Alzheimer’s disease.” Microglia protect myelin and neurons The study revealed that microglia also help maintain myelin, a protective coating around neurons. Genetic removal of microglia under amyloid stress reduced myelin-related lipids. “The microglia are helping neurons, and if you remove them, neurons seem to experience more oxidative stress,” Palavicini said. “This is why some lipid levels increase when microglia are gone. In most cases, removal of microglia was damaging, which was somewhat unexpected but reveals how critical they are for brain lipid metabolism.” More complete picture of Alzheimer’s This research shows that Alzheimer’s is not just about amyloid plaques and tau tangles. It also involves disrupted lipid balance, with microglia, astrocytes and neurons each playing different roles. Microglia maintain protective lipids like BMP and support myelin, while astrocytes and neurons drive other changes, including lysophospholipid accumulation and oxidative stress. “Understanding which cells regulate which lipids opens the door to more precise therapies,” Palavicini said. “By targeting lipid balance along with amyloid and tau, we can develop better strategies to protect neurons and potentially slow or prevent Alzheimer’s disease.” https://news.uthscsa.edu/targeting-brain-immune-cells-could-restore-alzheimers-related-lipid-imbalance/

On September 1, 2025, Dr. Juan Pablo Palavicini joined the Department of Cellular and Integrative Physiology (CIP) in the Long School of Medicine at UT Health San Antonio as a faculty member. His laboratory focuses on the cellular and molecular mechanisms that link aging, lipid metabolism and neurodegenerative diseases, complementing CIP’s strengths in neurophysiology, glial biology and age-related neurological pathologies. Dr. Palavicini looks forward to collaborating with CIP colleagues to advance mechanistic discoveries and train the next generation of physician-scientists and basic scientists. Members of the Cellular and Integrative Physiology (CIP) family at the Back to School Social celebration.