Article Topic: Brain Tumor

Zipfel Elected President of the Society of Neurological Surgeons

Head of Taylor Family Department of Neurosurgery is a national leader in the treatment and research of brain tumors and cerebrovascular disorders

Gregory J. Zipfel, MD, the Ralph G. Dacey Distinguished Professor of Neurosurgery and head of the Taylor Family Department of Neurosurgery at WashU Medicine and a research member of Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine, has been elected president of the Society of Neurological Surgeons.



Zipfel has led the Taylor Family Department since 2019 and is the neurosurgeon-in-chief at Barnes-Jewish Hospital. He also treats patients at The Brain Tumor Center at Siteman, where he specializes in complex tumors of the skull base, including meningioma, schwannoma, acoustic neuroma, craniofacial tumors and chordoma/chondrosarcoma.

Zipfel also specializes in the treatment and research of cerebrovascular conditions such as stroke — work that has led to the development of new treatments to reduce brain injury after brain aneurysms rupture. Additionally, he studies vascular contributions to dementia.

The Society of Neurological Surgeons is the oldest neurosurgical society in the world and was founded to advance the quality of care for neurosurgical patients through education and research. WashU Medicine’s connections to the society go back to Ernest Sachs, MD, a faculty member who was the first professor of neurosurgery in the U.S. and a founding member of the organization in 1920. All five chairs of the WashU Medicine Taylor Family Department of Neurosurgery — including Zipfel’s predecessor and mentor Ralph G. Dacey Jr., MD, who also treated patients at Siteman — have served as president of the society. Zipfel serves as president until the society’s 2027 annual meeting in May.

As a mentor himself, Zipfel is strongly committed to neurosurgery education and is the principal investigator of the National Institutes of Health-funded National Neurosurgeon Research Career Development Program. He also serves in leadership roles with the Neurosurgery Research and Education Foundation and the Emerging Investigator Mentoring Program of the American Academy of Neurological Surgery.

Nasal drops fight brain tumors noninvasively

Nano-sized medicine boosts anti-cancer immune response, eradicates tumors in mice

Researchers at Washington University School of Medicine in St. Louis, along with collaborators at Northwestern University, have developed a noninvasive approach to treat one of the most aggressive and deadly brain cancers. Their technology uses precisely engineered structures assembled from nano-size materials to deliver potent tumor-fighting medicine to the brain through nasal drops. The novel delivery method is less invasive than similar treatments in development and was shown in mice to effectively treat glioblastoma by boosting the brain’s immune response.

The findings were published this month in PNAS.

Glioblastoma tumors form from brain cells called astrocytes and are the most common kind of brain cancer, affecting roughly three in 100,000 people in the U.S. Glioblastoma generally progresses very quickly and is almost always fatal. There are no curative treatments for the disease, in part because delivering medicines to the brain remains extremely challenging.

“We wanted to change this reality and develop a noninvasive treatment that activates the immune response to attack glioblastoma,” said Alexander H. Stegh, PhD, a professor and vice chair of research in the WashU Medicine Taylor Family Department of Neurosurgery and co-corresponding author of the study. Stegh also is research director of The Brain Tumor Center at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine. “With this research, we’ve shown that precisely engineered nanostructures, called spherical nucleic acids, can safely and effectively activate powerful immune pathways within the brain. This redefines how cancer immunotherapy can be achieved in otherwise difficult-to-access tumors.”

Cold Tumors Warmed with STING

Glioblastoma tumors are known as “cold tumors” because they do not induce the body’s natural immune response as do so-called “hot tumors” that are easier to treat with immunotherapies. Researchers have developed ways to spark an immune reaction against tumors by stimulating a pathway within cells called STING, which stands for stimulator of interferon genes. STING is triggered when a cell detects foreign DNA and activates the immune system to respond to the threat.

Past studies have shown that drugs activating STING in glioblastoma tumors can prime the body’s immune system to better fight the cancer. However, these agents break down quickly in the body and must be delivered directly into the tumor to work. Because repeated dosing is required for sustained benefit, relying on direct intratumoral administration requires highly invasive procedures.

“We really wanted to minimize patients having to go through that when they are already ill, and I thought that we could use the spherical nucleic acid platforms to deliver these drugs in a noninvasive way,” said Akanksha Mahajan, PhD, a postdoctoral research associate in Stegh’s lab and the first author on the study.

To overcome the problem, the Stegh team collaborated with co-corresponding author Chad A. Mirkin, PhD, director of the International Institute for Nanotechnology and the Rathmann Professor of Chemistry at Northwestern University, and his team. Mirkin invented spherical nucleic acids, a class of nanostructures that arrange DNA or RNA densely around a nanoparticle core, and he has shown that they have greater therapeutic potency compared to the standard delivery methods. The WashU Medicine and Northwestern researchers prepared a new class of spherical nucleic acids with gold cores studded with short snippets of DNA to trigger activation of the STING pathway in specific immune cells. To deliver these drugs to the brain, the team turned to the nose.

Intranasal therapy has been explored as a potential delivery method for medications targeting the brain, but no nanoscale therapies had yet been developed using this method to activate immune responses against brain cancers.

“This is the first time that it has been shown that we can increase immune cell activation in glioblastoma tumors when we deliver nanoscale therapeutics from the nose to the brain,” Mahajan said.

The team wanted to show that this approach could be used to deliver the medicine selectively to the brain, and that it would act on the appropriate cells once it got there.

For the first objective, they used a molecular tag on the spherical nucleic acid that was visible under near-infrared light. They found that the nanomedicine, when delivered as droplets into the nasal passages of mice with glioblastoma, traveled along the path of the main nerve that connects facial muscles to the brain. The immune response evoked in the brain by the medicine was concentrated in the specific immune cells, especially those in the tumor itself, and triggered some helpful responses in the lymph nodes. The medicine did not spread to other parts of the body where it might cause unwanted side effects.

Examinations of immune cells in and near the tumor showed that the therapy successfully activated the STING pathway and armed the immune system to fight the tumor.

When applied in combination with drugs designed to help activate T lymphocytes, another type of immune cell, the new therapy eradicated the tumors with just one or two doses and induced long-term immunity against their recurrence. Taken together, the results were much better than those of current STING-activating immune therapies.

Stegh cautioned that firing up the STING pathway isn’t capable of curing glioblastomas without reinforcement from other therapeutic approaches. Turning on the STING pathway by itself isn’t enough to fight glioblastoma, because the tumor has many ways to block or shut down the immune response that STING is meant to activate. His team is looking to add capabilities to their nanostructure that activate other immune responses. This could allow physicians to double or triple the therapeutic targets all in a single therapy.

“This is an approach that offers hope for safer, more effective treatments for glioblastoma and potentially other immune treatment-resistant cancers, and it marks a critical step toward clinical application,” said Stegh.

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Mahajan AS, Dussold C, Kim, S, Jarvis R, Hurley LA, Tommasini-Ghelfi S, Park J, Forsyth CM, Zhang B, Miska J, Heimberger AB, Mirkin CA, Stegh AH. cGAS-agonistic spherical nucleic acids reprogram the glioblastoma immune microenvironment and promote antitumor immunity. PNAS. Nov. 4, 2025. DOI: 10.1073/pnas.2409557122

This work was supported by the National Cancer Institute of the NIH (grant numbers P50CA221747 and R01CA275430), the NIH (grants R01CA120813, R01NS120547, and R01CA272639), the Melanoma Research Foundation, the Chicago Cancer Baseball Charities at the Lurie Cancer Center of Northwestern University and grants from Cellularity, Alnylam, and AbbVie. Imaging at Siteman Cancer Center Small Animal Cancer Imaging was supported by NIH instrumentation grants S10OD027042, S10OD025264, and National Cancer Institute Cancer Center grant P30CA091842. PET and MRI imaging was supported by Robert H. Lurie Comprehensive Cancer Center Grant P30CA060553.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Competing interests: Alexander Stegh is a shareholder of Exicure Inc., which develops SNA therapeutic platforms. Mirkin is a shareholder in Flashpoint, which develops SNA-based therapeutics. Stegh and Mirkin are co-inventors on patent US20150031745A1, which describes SNA nanoconjugates to cross the blood-brain barrier.

Study sheds light on how pediatric brain tumors grow

Blocking a chemical messenger in the brain that helps tumor cells multiply could offer new route to treatment

The most common type of brain tumor in children, pilocytic astrocytoma (PA), accounts for about 15% of all pediatric brain tumors. Although this type of tumor is usually not life-threatening, the unchecked growth of tumor cells can disrupt normal brain development and function. Current treatments focus mainly on removing the tumor cells, but recent studies have shown that non-cancerous cells, such as nerve cells, also play a role in brain tumor formation and growth, suggesting novel approaches to treating these cancers.

Scientists have long known that a nerve cell signaling chemical called glutamate can increase growth of cancers throughout the body, but despite years of investigation, they haven’t figured out exactly how this happens, or how to stop it. Now, an interdisciplinary team of researchers at Washington University School of Medicine in St. Louis has uncovered how glutamate regulates pediatric brain tumor growth. Using tumor cells isolated from patient PA samples, they found that PA cells hijack the function of proteins on cells’ surface that normally respond to glutamate, called glutamate receptors. Instead of transmitting glutamate’s typical electrical signal, these receptors are reprogrammed to send signals to increase cell growth.

They also observed that drugs that block these glutamate receptors — including memantine, which is approved to treat dementia and Alzheimer’s disease — reduced human pediatric brain tumor growth in mice, a finding that points to a potential new treatment opportunity.

The results appear Sept. 1 in Neuron.

“With these kinds of pediatric brain tumors, we just don’t have that many tools in our toolbox for treating patients,” said senior author David Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology at WashU Medicine. Gutmann treats patients at Siteman Kids at St. Louis Children’s Hospital.

“The potential to repurpose drugs that are already in use for other neurological disorders means we may have another trick up our sleeves for treating patients.”

The research team, which included first author Corina Anastasaki, PhD, a research assistant professor of neurology at WashU Medicine, also showed for the first time that glutamate receptors abnormally couple with growth receptors in PAs to fuel the tumors. The findings offer a roadmap for future studies to explore if the same process is happening in different types of cancers.

New uses for familiar tools

Glutamate is what is known as a neurotransmitter, a molecule that nerve cells, including neurons in the brain, use to communicate with each other. On their path to understand how glutamate helps brain tumors grow, Gutmann, who is also the director of the Neurofibromatosis Center at WashU Medicine, and Anastasaki worked closely with collaborators across WashU Medicine — including in neurosurgery, pediatrics, genetics, neuropathology, biostatistics and more — to acquire and analyze samples of PAs that had been surgically removed. They found that these PA cells had unusually high levels of glutamate receptors.

By testing how glutamate affected these tumors, the researchers discovered that glutamate increased PA cell numbers by kicking off a chain reaction inside the tumor cells that urged cells to divide. These findings suggest that tumor cells exploit normal brain-cell interactions to spur their own growth.

“This novel mechanism for tumor growth combines two normal but unconnected brain processes — growth and electrical signaling — in an aberrant way,” Anastasaki said. “Now that we’ve figured out how these cells work and grow, the sky’s the limit for looking at other neurotransmitters and the different avenues of communication between neurons and cancer cells. Understanding that will tell us why tumors grow and behave the way they do. That may lead to us treating them very differently.”

Such new treatments might come from familiar sources. The researchers showed that inhibiting glutamate receptors of tumor cells in mice with PAs — either with medications or by genetically altering the cells — reduced tumor growth. This points to a potential opportunity to repurpose glutamate receptor-targeting drugs such as memantine for the treatment of PAs.

The next steps are to determine whether such medications are safe to use in children with brain tumors and in what amounts they would be effective, Gutmann noted, which will require clinical trials.

“This study provides compelling preclinical data to look at medications that are otherwise safe and approved to treat other neurological conditions,” Gutmann said. “That would enable new therapeutic approaches and could help minimize the damage to a child’s developing brain by reducing engagement between brain cells and tumor cells.”

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Anastasaki C, Mu R, Kernan CM, Li X, Barakat R, Koleske JP, Gao Y, Cobb OM, Lu X, Eberhart CG, Phillips JJ, Strahle JM, Dahiya S, Mennerick SJ, Rodriguez FJ, Gutmann D. Aberrant coupling of glutamate and tyrosine kinase receptors enables neuronal control of brain tumor growth. Neuron. September 1, 2025.

This work was partially funded by grants from the National Institute of Neurological Disorders and Stroke (R35NS07211-01), National Cancer Institute (1-R50-CA233164-01), National Institutes of Health (P50MH122379 and R01MH123748), Taylor Family Institute for Innovative Psychiatric Research, and the Pediatric Brain Tumor Foundation. Corrine Gardner and the Pediatric Neurosurgery Tissue Bank coordinated the acquisition of fresh operative specimens. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

AI-driven blood test could aid earlier detection of brain cancer

WashU Medicine physician-researchers at The Brain Tumor Center at Siteman Cancer Center have co-developed an innovative approach that uses artificial intelligence (AI) to detect brain cancer, potentially leading to earlier diagnoses. Siteman is based at Barnes-Jewish Hospital and WashU Medicine.

The process incorporates a noninvasive blood test and machine learning that analyzes the blood sample for evidence of brain cancer – specifically, circulating DNA patterns associated with brain tumors. It then identifies repeating genomic patterns that indicate the presence of brain cancer. Such tests have already shown success in the earlier detection of lung cancer.

“We now have a method that detects brain cancer based on its unique characteristics, including DNA fragmentation and immune responses,” said WashU Medicine neurosurgeon Dimitrios Mathios, MD, who developed the test with Victor E. Velculescu, MD, PhD, co-director of the Cancer Genetics and Epigenetics Program at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

“The signals we detect come from both the tumor itself and the immune system’s reaction to it,” said Mathios, an assistant professor of neurosurgery and director of the Lab for Molecular Neuro-oncology at WashU Medicine and a Siteman research member.

Mathios and Velculescu published their work April 29 in Cancer Discovery.

Detecting brain cancer before symptoms appear is challenging, often leading to diagnoses at more advanced stages when tumors are larger and located in high-risk areas. This complicates treatment, making it both riskier and less effective. The blood-brain barrier, which protects the brain, also prevents biomarkers — signs of cancer — from entering the bloodstream, further complicating early detection.

Using their new approach, the researchers successfully detected brain cancer in approximately 75% of cases from a cohort of 505 patients in the U.S. and South Korea, according to their paper, and validated their results in a separate group of 95 patients in Poland. In contrast, traditional blood-based liquid biopsy methods have detected brain cancer in fewer than 10% of cases.

A key factor in this success is the detection of immune system changes associated with brain cancer. Brain cancer often leads to immune suppression and alters the immune cell profile in the blood. These immune changes occur throughout the body, bypassing the blood-brain barrier and making them detectable, Mathios said.

In a simulation, the researchers modeled the potential benefits of using their method to screen the 10 million patients who visit emergency rooms or primary care clinics annually due to headaches. Normally, these patients are only referred for brain imaging if a physician suspects a problem. However, the simulation showed that incorporating blood-based liquid biopsy results could help identify nearly 1,700 additional cancer cases in the U.S.

The next step for the team is to conduct a larger prospective trial to confirm these findings in a broader population at higher risk for brain cancer.

The Brain Tumor Center at Siteman announces associate directors

Huang is promoted, and Chheda joins the leadership team of the multidisciplinary practice

The Brain Tumor Center at Siteman Cancer Center, a multidisciplinary practice of physicians and scientists, has named two board-certified WashU Medicine faculty members as associate directors.

They are:

“We are proud to announce Dr. Huang’s new leadership role, which reflects his deep commitment to advancing clinical and translational care for brain tumor patients,” said WashU Medicine neurosurgeon Albert H. Kim, MD, PhD, director of The Brain Tumor Center and the August A. Busch Jr. Professor of Neurological Surgery, a professor of genetics, neurology and developmental biology, and the senior vice-chair of the Department of Neurosurgery. “We are equally excited to welcome Dr. Chheda as a key leader of our center. His strategic insights and deep understanding of the field will be instrumental in shaping the future of The Brain Tumor Center.”

Huang previously served as clinical director of The Brain Tumor Center. He has led investigations into the use of novel drugs in glioblastoma and meningioma and the late effects of treatment following radiation therapy for brain tumors.

Chheda researches new ways to eradicate cancer cells that are resistant to conventional therapies and new methods to activate the body’s immune system to recognize and clear tumors. His laboratory is also pursuing the relationship between the aging brain and brain tumors.

The Brain Tumor Center at Siteman is a multidisciplinary practice of WashU Medicine physicians and scientists whose mission is to provide leading-edge, patient-centric care for brain tumor patients while also developing transformative basic, translational and clinical research to develop new therapies and improve patient outcomes.

Other leaders of The Brain Tumor Center are:

To make an appointment at The Brain Tumor Center at Siteman, call 314-747-7222 or 800-600-3606, or complete this form.