Tag: Medication

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Peptide-Based mRNA Vaccine Offers New Hope for Neuroblastoma Treatment

In a world’s first, researchers from RCSI University of Medicine and Health Sciences in Dublin, Ireland, have developed an mRNA vaccine for neuroblastoma that has shown promising results in early laboratory testing.

Led by Olga Piskareva, senior lecturer in the RCSI Department of Anatomy and Regenerative Medicine, the study demonstrates the therapeutic potential of the vaccine for treating neuroblastoma and paves the way for further studies.

“We are at the beginning of the mRNA vaccine development journey, but we have successfully completed the first milestone, and we are very proud of it,” Piskareva told Inside Precision Medicine.

Neuroblastoma is an aggressive pediatric solid tumor that accounts for 15% of cancer-related deaths in children. Despite recent advances in treatment options, around 80% of patients with clinically aggressive disease do not show sustained responses, highlighting the need for novel treatments.

Piskareva has worked in neuroblastoma research since 2011 and felt the time was right to develop a vaccine. Her proposal was strongly endorsed in funding calls and supported by the Conor Foley Neuroblastoma Cancer Research Foundation. This support was particularly important to Piskareva as the charity was founded by a family who lost their son after a 14-year battle with neuroblastoma.

Unlike many mRNA vaccines that use lipid nanoparticles to deliver their payload, Piskareva and team instead used self-assembling peptide nanoparticles.

The self-assembling peptide, known as RALA, is composed of a repeating amino acid sequence of arginine (R), alanine (A), leucine (L), and alanine (A) that come together to form stable nanoparticles that protect mRNA encoding glypican 2 (RALA/mGPC2), a potent tumor-associated antigen in neuroblastoma. After entering a cell, the RALA nanoparticles react with the intracellular environment and change their structure, which allows them to deliver the GPC2 mRNA.

Piskareva and co-authors explain in Molecular Therapy Oncology that the RALA technology offers several advantages over more commonly used lipid nanoparticle delivery including high mRNA encapsulation efficiency, straightforward purification, no immune response to RALA itself, no restriction on the size or number of mRNA cargos to be delivered, stability at room temperature, and lower costs.

After initial experiments showing the viability of the vaccine in vitro, the researchers tested its efficacy in mouse models.

They showed that RALA/mGPC2 vaccination generated an antigen-specific cellular immune response against GPC2, with significant increases in interferon-γ and interleukin-2 expression by splenocytes and tumor necrosis factor-α expression by CD4+ and CD8+ T cells.

Investigating tumor control, the team demonstrated that immunization delayed tumor development by 10–11 days and reduced tumor volume by 70% compared with unvaccinated controls in a subcutaneous murine model of neuroblastoma, with the potential further to reduce tumor progression via prolonged administration.

Piskareva noted that as biological ageing in mice does not follow the same pattern as it does in humans, it is fair to assume that a 10–11 day delay in mice would equate to two years in preadolescent humans and one year in adulthood.

“However, the most important clinical message from this number is that there is significant potential to further delay tumor growth by trying a different vaccination schedule or dose, or by co-treating with immune-stimulating drugs,” she remarked.

The vaccine also has the potential to be highly personalized. “We can profile a given patient with neuroblastoma, select its shared and unique targets, design and synthesize mRNA, coat it with peptides, and have a personalized vaccine ready for use,” said Piskareva. “We can also create a pool of the most common targets and have the mRNA vaccine on demand.”

“By developing mRNA for multiple targets, we can increase the vaccine’s ability to help the host’s immune system kill cancer cells. The mRNA vaccine technology is like LEGO bricks. By combining different bricks, we can tailor the vaccine to the individual’s needs with high precision,” she added.

Piskareva and team are now planning further studies to investigate optimal vaccination doses and frequency, and characterize the immune response on a wider scale and in greater detail.

“The move to clinical trials will depend largely on the quality and quantity of data collected in pre-clinical studies. We will closely monitor developments in clinical trials for adult mRNA vaccines, learn from their experience and adopt the best approaches to avoid unnecessary delays,” Piskareva concluded.

The post Peptide-Based mRNA Vaccine Offers New Hope for Neuroblastoma Treatment appeared first on Inside Precision Medicine.

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Catheter-Based OCT Imaging Shows Promise for Noninvasive Endometrial Cancer Diagnosis

A research team at Washington University in St. Louis has developed a catheter-based optical imaging method that could be used as an “optical biopsy” for detecting endometrial cancer and its precancerous lesions. The approach, described in the journal npj Imaging, uses three-dimensional optical coherence tomography (OCT) imaging combined with a machine learning algorithm which examines and analyzes the entire endometrial cavity to identify tissue changes associated with endometrial intraepithelial neoplasia (EIN) and endometrial cancer.

“Current endometrial biopsy practice has an estimated false-negative rate of about 10% (approximately 90% sensitivity), largely due to sampling limitations and interpretive variability,” said senior investigator Quing Zhu, PhD, a professor of engineering at Washington University. “With our three-dimensional OCT imaging system combined with machine learning, we can image the entire endometrial cavity in two to three seconds and may have a potential to achieve higher sensitivity than random biopsy sampling.”

Endometrial cancer is the most common gynecologic malignancy in the United States, with estimated 69,000 cases projected to be diagnosed in 2025. As with most cancers, early detection has a significant impact on treatment outcomes with five-year survival rates between 80% and 90% when it is diagnosed at stage I.

Existing diagnostic tools have limitations that can impact early and accurate diagnosis. For instance, transvaginal ultrasound is ineffective for early EC, while endometrial biopsy has a 10% false-negative rate due to sampling and interpretive variability.” Although hysteroscopy allows direct visualization of the uterine cavity, it does not provide information about subsurface tissue architecture.

In an interview with Inside Precision Medicine, Zhu said the most widely used diagnostic approaches can miss cancers or depend heavily on operator skill. She noted that the low resolution of transvaginal ultrasound limits detection of early disease, while operative hysteroscopy requires cervical dilation and carries procedural risks. Endometrial biopsy, she added, can miss cancers that occupy less than half of the endometrial cavity surface.

The new approach developed by Zhu and team uses OCT, a light-based imaging technology that creates high-resolution cross-sectional images of tissue. This imaging method uses low-coherence interferometry to measure the echo time delay and intensity of backscattered light, producing real-time images of tissue microstructure with micrometer-scale resolution with tissues penetration depths of approximately one to two millimeters.

To create a method to comprehensively image the endometrium the WashU team developed a custom 3.1-millimeter catheter. Zhu said that the catheter rotates within the endometrial cavity at roughly 600 revolutions per minute while being pulled back automatically at a constant speed. Depending on uterine size, a 3- to 5-centimeter segment of the cavity can be imaged in approximately two to three minutes. The resulting volumetric scans provide three-dimensional views of tissue structure and optical properties throughout the cavity. The team then applied computational analysis to identify functional, structural, and radiomic features based on OCT intensity and scattering images.

To test this OCT/machine learning approach, the researchers evaluated the technology on 57 freshly excised hysterectomy specimens representing a range of conditions, including normal endometrium, benign abnormalities, EIN, and endometrial cancer. OCT identified 34 specimens that contained either high-risk precancerous lesions or early-stage cancers.

The OCT images revealed differences among normal endometrium, benign endometrium, high-risk precancerous lesions, and cancers at different stages. This new method attained an exploratory sensitivity of 94% and specificity of 87%. A cross-validated logistic regression classifier produced sensitivity of 91% and specificity of 83%.

“These findings support catheter-based 3D OCT as a promising noninvasive optical biopsy approach to improve detection of endometrial cancer,” the researchers wrote in the abstract.

The work builds on earlier investigations of OCT in endometrial disease. Previous research had shown that OCT could distinguish endometrial pathologies, but in those studies the imaging was slow or limited to two-dimensional analysis. “This study is the first to combine catheter-based 3D OCT imaging with functional, structural and radiomic feature analysis to assess the endometrial cavity,” the researchers wrote.

Researchers believe the technology could improve patient care by reducing dependence on repeated tissue biopsies. In the introduction, they wrote that “a real-time, noninvasive, high-resolution modality for subsurface imaging could improve diagnostic accuracy, reduce unnecessary biopsies, and support fertility-sparing management.” Such a tool could be particularly useful for women undergoing serial monitoring while receiving hormone-based treatment.

The investigators describe the method as an optical biopsy because it provides diagnostic information without requiring removal of tissue. “Unlike traditional tissue biopsy, it does not require painful physical tissue samples,” Zhu told Inside Precision Medicine.

The technology is still in an early stage of development. Zhu said future development will require a forward-viewing catheter to improve imaging of the uterine fundus and developing methods for faster data acquisition.

Zhu is now looking to secure funding and begin studies in patients to establish in vivo feasibility and to eventually move the technology into clinical trials.

The post Catheter-Based OCT Imaging Shows Promise for Noninvasive Endometrial Cancer Diagnosis appeared first on Inside Precision Medicine.

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Labcorp Launches Expanded Test for Severe Chemotherapy Side Effects

In step with the trend toward more selective use of chemotherapy, Labcorp has launched an expanded version of its DPYD Genotype test, which helps identify cancer patients at increased risk for severe side effects from fluoropyrimidine-based drugs. The test is now the only offering, from a national laboratory provider, that detects all Tier 1 and Tier 2 DPYD variant alleles recommended to be tested for by the Association for Molecular Pathology.

The DPYD gene encodes the enzyme DPD, which metabolizes more than 80% of 5-FU. Patients with reduced or absent DPD activity can experience serious, potentially life-threatening side effects, including diarrhea, neutropenia, and neurotoxicity when given fluoropyrimidines 5-FU or capecitabine.

Such pharmacogenomic (PGx) testing is used to help identify patients who are at greater risk for adverse drug reactions from certain treatments based on their genetic makeup. Once a chemotherapy regimen is recommended, PGx testing can help guide treatment decisions and reduce the risk of toxicity. DPYD testing is one of the most well-established examples of PGx. 

“Pharmacogenomic testing is typically incorporated early in the treatment process, once a chemotherapy plan has been established, to give clinicians information about a patient’s inherited ability to metabolize certain medications or respond to them,” Annette Taylor, PhD, MS, told Inside Precision Medicine. She is associate vice president, strategic director, pharmacogenomics, Labcorp.

Fluoropyrimidines are one of the most widely used chemotherapy agents for colorectal, pancreatic, gastrointestinal, breast, and head and neck cancers. However, up to 9% of cancer patients carry DPYD variants that can negatively affect their ability to break down such drugs. That variant contributes to an estimated 1,300 deaths in the U.S. each year. By identifying the full range of Tier 1 and Tier 2 DPYD variants, the new test helps reduce the risk that vulnerable patients will receive the treatment.

 “Advances in pharmacogenomics are reshaping cancer care,” said Marcia Eisenberg, PhD, chief scientific officer at Labcorp. “Our expanded DPYD test identifies patients at risk for severe toxicity before treatment begins, supporting safer, more personalized care.”

The U.S. Food and Drug Administration (FDA) recently updated its product labeling for 5-FU and capecitabine, which includes a Boxed Warning about the risk of severe adverse reactions or death in patients with complete DPD deficiency. The agency also advises testing for DPYD variants before treatment with 5-FU or capecitabine unless immediate treatment is necessary and recommends avoiding use of these drugs in patients with certain homozygous or compound heterozygous DPYD variants associated with complete DPD deficiency. 

In addition, recent updates to National Comprehensive Cancer Network (NCCN) guidelines for colon cancer and other relevant indications reference these Boxed Warnings and the recommendation for DPYD testing. Further, Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines recommend adjusting or avoiding treatment based on a patient’s DPYD metabolizer status as determined by DPYD testing.

“There are other pharmacogenomic tests available beyond DPYD testing that can provide clinically actionable information for certain therapies and treatment settings. Common tests include UGT1A1 genotyping for irinotecan and TPMT/NUDT15 testing for thiopurines,” Taylor said.

Other tests offered by Labcorp include the UGT1A1 Irinotecan Toxicity test, which helps guide chemotherapy with irinotecan, commonly used for metastatic colon and rectal cancer.  Labcorp also offers the TPMT and NUDT15 Genotyping test, useful for optimizing therapy with thiopurine drugs (azathioprine, mercaptopurine, and thioguanine). 

The post Labcorp Launches Expanded Test for Severe Chemotherapy Side Effects appeared first on Inside Precision Medicine.

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Self-Renewing Blood Progenitors Could Expand the Reach of Cancer Cell Therapy

A team of researchers at the University of Southern California has developed a method to expand a key population of blood-forming progenitor cells in the laboratory while preserving their identity and function, overcoming a longstanding barrier in hematology and opening new possibilities for cancer immunotherapy.

The study, published in Cell, describes how investigators generated large numbers of granulocyte-monocyte progenitors (GMPs)—immune precursor cells that give rise to macrophages, monocytes, and neutrophils—using a culture system that enables these cells to self-renew in vitro. The work not only challenges conventional assumptions about hematopoietic progenitor biology but also provides a potentially scalable platform for engineering immune cells designed to attack cancer.

“This is the first time we can pick single progenitor cells and expand them in large quantities without differentiation,” said senior author Qi-Long Ying, PhD, professor of stem cell biology at USC. “They retain the original identity.”

The achievement addresses a problem that has frustrated researchers for decades. Although hematopoietic stem cells and their descendants have been extensively studied, scientists have struggled to maintain specific blood-forming progenitor populations in culture over long periods without the cells differentiating into mature immune cells.

Ying said the project grew out of his laboratory’s experience working with embryonic stem cells, which can be maintained indefinitely in culture. He reasoned that if embryonic stem cells could be expanded long term, similar approaches might eventually be developed for stem and progenitor cells found in bone marrow.

After years of experimentation, the researchers established culture conditions that selectively support GMPs, a progenitor population responsible for generating several innate immune cell types involved in recognizing and destroying abnormal cells.

Challenging a longstanding paradigm

According to co-author Daniel McKim, PhD, one of the most surprising findings was not simply the ability to expand GMPs but the demonstration that these progenitor cells could undergo extensive self-renewal in vitro.

“The prevailing theory has been that hematopoietic progenitors are short-lived intermediate cells that are incapable of self-renewal,” McKim said. “One of the distinctions between hematopoietic stem cells and progenitors is the belief that these cells are not able to self-renew. What we found is that under the right conditions, they can.”

The researchers emphasize that the self-renewal phenomenon occurs in culture. Once transplanted back into animals, the GMPs behave like normal progenitor cells, producing downstream immune populations before eventually becoming depleted.

Still, the ability to generate vast numbers of GMPs in vitro represents a significant technical advance. The investigators report expansion levels approaching eight orders of magnitude while maintaining the cells’ progenitor characteristics.

Building better cell therapies

Beyond the basic biology, the researchers see major implications for cancer immunotherapy.

Current cellular immunotherapies are dominated by CAR T-cell approaches, which have transformed treatment for several blood cancers but have shown more limited success against solid tumors. Investigators have long been interested in developing therapies based on macrophages and other innate immune cells because those cells naturally infiltrate tumors and can reshape the tumor microenvironment.

However, translating those concepts into viable therapies has proven difficult. Mature macrophages and monocytes are challenging to genetically engineer, difficult to manufacture at scale, and often fail to persist after infusion.

The newly expanded GMPs may provide a solution. Because the progenitor cells can be generated in large numbers and genetically modified before transplantation, they offer a renewable source of tumor-fighting immune cells.

“In our body these cells are very rare,” Ying said. “The mature cells cannot grow, and it is very challenging to genetically modify them. Now we have progenitor cells that can be expanded long-term in large quantities, and we can easily genetically modify them. That makes everything possible.”

The team engineered both mouse and human GMPs with chimeric antigen receptors (CARs) and evaluated them in mouse models. Unlike mature macrophages, which often become trapped in organs such as the lungs and liver after infusion, the progenitor cells distributed broadly throughout the body and engrafted within the bone marrow.

Once established, the cells generated populations of macrophages and monocytes capable of infiltrating tumors.

McKim noted that this approach may overcome several limitations that have hindered macrophage-based immunotherapies. “One of the big issues has been that it’s hard to engineer these cells, and when you put them back into the body they don’t get where they need to go,” he said. “The progenitors solve both problems. They’re easy to engineer, and they expand after transplantation.”

Implications for solid tumors

The researchers believe progenitor-derived innate immune therapies may offer advantages in solid tumors, where CAR T-cell approaches have struggled.

Tumors often create highly suppressive microenvironments that limit T-cell activity. Macrophages and related innate immune cells, by contrast, naturally migrate into tumors and can help stimulate broader immune responses.

“Monocytes and macrophages love going into tumors,” McKim said. “They can kill tumor cells themselves, but they can also help generate a natural antitumor immune response by the host.” That capability could prove particularly important in cancers that evade treatment by losing specific target antigens, a common mechanism of resistance to CAR T-cell therapy.

Although the work remains preclinical, the investigators believe the platform could eventually support a wide range of immune-engineering applications beyond cancer.

 

The post Self-Renewing Blood Progenitors Could Expand the Reach of Cancer Cell Therapy appeared first on Inside Precision Medicine.

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Medical AI Model Privacy Risks

Research led by the Technical University of Munich shows that data from some individuals used to train medical artificial intelligence (AI) models could be at much higher risk of exposure due to cyberattack than others.

Writing in Nature, the researchers explain that underrepresented groups, such as people with a rare disease or a minority ethnicity, are at particularly high risk of having their data exposed.

A type of cyberattack called a “membership inference attack” can be used to uncover sensitive information about individuals or learn about the training data behind an AI system, without seeing the original database. In the wrong hands, this kind of information can be used for discrimination, blackmail, or even to assess who might be vulnerable to exploitative marketing.

“The extent to which this constitutes a privacy violation is nuanced and depends on factors such as the underlying training population and the deployment context of the model. Although inferring membership for a model trained on a general population may be benign, doing so for a model trained on a narrow, disease- or center-specific cohort acts as a direct proxy for sensitive medical information,” explained lead author Moritz Knolle, a doctoral researcher at the Technical University of Munich, and colleagues.

In this study, the team studied seven large, real‑world clinical datasets including medical images, electrocardiograms, and electronic health records. They trained around 200 versions of an AI model for each dataset, then quantified, for every single record and patient, how accurately an attack would be at guessing if a patient was part of the training set.

They showed that membership inference attacks can be almost perfectly successful for some individual patients, such as those with an unusual disease or presentation, even though the average attack performance across the whole training set looked close to random guessing.

As the AI model capacity increased, the number of highly vulnerable patients rose substantially. Underrepresented groups in the training group, for example, by disease, ethnicity, insurance, sex, or imaging protocol, were among the most vulnerable records to this kind of attack.

Current practice tends to check the privacy vulnerability of AI models by taking an average from the whole dataset. “Together, our findings show that aggregate privacy metrics can severely underestimate individual privacy risk,” warned Knolle and colleagues.

“Given this vulnerability, medical AI models and their deployment contexts should be assessed for the sensitive information that attackers could obtain by successfully inferring training dataset membership. To prevent privacy harm, we recommend that vulnerable models be protected by verifiable risk mitigation strategies and/or strict access controls.”

The post Medical AI Model Privacy Risks appeared first on Inside Precision Medicine.

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Scaling Stem-Cell Manufacturing for Therapies

Human pluripotent stem cells (hPSCs) have long been viewed as one of regenerative medicine’s most promising raw materials. Now, as more than 100 clinical trials evaluate hPSC-derived therapies for diseases ranging from Parkinson’s disease to heart failure and type 1 diabetes, attention is turning toward a crucial challenge: how to manufacture these cells reliably and economically at industrial scale.

According to Kevin Cyrys and Robert Zweigerdt, PhD, both of Hannover Medical School in Germany, the field has entered a new phase. Rather than simply demonstrating that stem cells can be grown in bioreactors, researchers are increasingly focused on creating robust production platforms that can deliver consistent quality across facilities and patient populations.

“Human pluripotent stem cells can serve as an unlimited, renewable ‘raw material’ for essentially any therapeutic cell product,” the authors wrote, highlighting the technology’s potential to overcome limitations associated with donor-derived tissues and organs.

The manufacturing challenge is substantial. While some therapies, such as treatments for age-related macular degeneration, require only tens of thousands of cells per dose, others may demand billions of cells for a single patient treatment. Conventional laboratory-scale methods are unlikely to meet such requirements efficiently.

To address this gap, developers are increasingly adopting three-dimensional suspension cultures in bioreactors. Compared with traditional two-dimensional cell culture systems, bioreactors provide tighter control over temperature, oxygen levels, pH, and carbon dioxide while supporting automated, closed-system manufacturing compatible with good manufacturing practice (GMP) standards.

The field has already demonstrated notable progress across multiple therapeutic areas. Researchers have developed scalable processes for producing cardiomyocytes, pancreatic islet cells, hepatocyte-like cells, neural tissues, and immune effectors derived from hPSCs. Some cardiac manufacturing platforms have reported production of billions of cardiomyocytes in liter-scale bioreactors, while immune-cell manufacturing programs have successfully expanded induced pluripotent stem cell-derived natural killer cells in 1–10 L systems while maintaining product quality.

Yet scaling production involves more than increasing cell yields. “Industrial-scale success depends on more than headline totals,” Cyrys and Zweigerdt note, citing the importance of volumetric productivity, production time, reproducibility, and integration of expansion, differentiation, and downstream processing into a coherent GMP-ready workflow.

Looking ahead, Cyrys and Zweigerdt argue that the next generation of stem-cell manufacturing will be defined by data-driven process control. They predict that AI-enabled systems will help move the industry from retrospective quality analysis toward real-time decision support, ultimately improving comparability between batches and strengthening product definitions across manufacturing networks.

Despite ongoing challenges involving cost, quality control, and regulatory compliance, the authors conclude that stem-cell bioprocessing has already crossed an important threshold. Scalable culture systems are no longer the primary obstacle. Instead, the focus has shifted toward engineering reliable industrial processes capable of transforming complex stem-cell biology into reproducible therapeutic products.

The post Scaling Stem-Cell Manufacturing for Therapies appeared first on GEN – Genetic Engineering and Biotechnology News.

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STAT+: A dispatch on AI from BIOtech’s big summer bash

You’re reading the web edition of STAT’s AI Prognosis newsletter, our subscriber-exclusive guide to artificial intelligence in health care and medicine. Sign up to get it delivered in your inbox every Wednesday. 

I’m writing to you from a hotel room in San Diego, four hours before this newsletter is scheduled to send.

I’m also still reeling from this absolutely crazy story my colleague Lizzy Lawrence wrote. Imagine STAT executive editor Rick Berke reading of the top of the story out loud to a group of STAT reporters over dinner at a waterfront restaurant, and my jaw dropping as I realize what’s going on.

Continue to STAT+ to read the full story…

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Spotlight on RNA Therapeutics

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Image of Drew Weissman, MD, PhD

Drew Weissman, MD, PhD

Professor in Vaccine Research
Penn Medicine

Panelist

Image of Drew Weissman, MD, PhD

Drew Weissman, MD, PhD

Drew Weissman, MD, PhD, is a world-renowned physician and Roberts Family Professor in Vaccine Research at Penn Medicine. He is best known for his contributions to RNA biology and the development of COVID-19 RNA vaccines. Weissman and Katalin Karikó, PhD, were jointly awarded the 2023 Nobel Prize in Medicine for their discoveries that enabled the modified mRNA technology used in Pfizer-BioNTech and Moderna’s vaccines to prevent COVID-19. More than 15 years ago, Weissman and Karikó found a way to modify mRNA and developed a delivery technique to package the mRNA in lipid nanoparticles. The COVID-19 RNA vaccine received FDA approval in August 2021.

Weissman is one of the academic leaders of the NSF AIRFoundry, an effort to leverage AI to improve, accelerate, and scale the design, manufacture, and delivery of RNA, which officially opened in April 2026. Weissman’s lab is currently working on a pan-coronavirus vaccine, a universal flu vaccine, and a vaccine to prevent herpes. They are working with Penn colleagues to develop cancer therapeutics with mRNA technology. And they are developing a SARS-CoV-2 mRNA vaccine with Chulalongkorn University in Thailand to help residents of Thailand and other Asian countries access lifesaving vaccines.

Before joining Penn in 1997, Weissman was a fellow at the National Institutes of Health studying HIV in the lab of Anthony Fauci, MD. Weissman received his bachelor’s degree and master’s degree from Brandeis University. He earned his MD and PhD from Boston University and completed his residency at Beth Israel Hospital.



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Zachary Ives, PhD

Professor of Computer and Information Science
University of Pennsylvania

Panelist

Image of Zachary Ives, PhD

Zachary Ives, PhD

Zachary Ives, PhD, is the department chair and Adani President’s Distinguished Professor of Computer and Information Science at the University of Pennsylvania. Zack’s research interests include data integration and sharing, data provenance and trustworthiness, and machine learning systems. He is a recipient of the National Science Foundation (NSF) CAREER award, and an alumnus of the DARPA Computer Science Study Panel and Information Science and Technology advisory panel. He has also been awarded the Christian R. and Mary F. Lindback Foundation Award for Distinguished Teaching and an IEEE Technical Committee on Data Engineering Education Award, and he is a fellow of the ACM.

 

Zack is one of the academic leaders of the U.S. NSF Artificial Intelligence-driven RNA BioFoundry (NSF AIRFoundry), an $18-million effort to leverage AI to improve, accelerate, and scale the design, manufacture, and delivery of RNA. The center officially opened in April 2026.

Zack studied computer science at Sonoma State University and holds a PhD in computer science from the University of Washington. He joined the faculty of Penn in 2003. He is a co-author of the textbook Principles of Data Integration. He has been an associate editor for the Proceedings of the VLDB Endowment and The VLDB Journal.



Image of Silvi Rouskin, PhD

Silvi Rouskin, PhD

Asst. Professor of Microbiologyy
Harvard Medical School

Panelist

Image of Silvi Rouskin, PhD

Silvi Rouskin, PhD

Born in Bulgaria, Silvi Rouskin, PhD, is an assistant professor of microbiology at Harvard Medical School. She is the winner of the 2021 Vilcek Prize for Creative Promise in Biomedical Science. Following a six-year spell at the Whitehead Institute, where she was the Andria and Paul Heafy Whitehead Fellow, Silvi joined the faculty of Harvard Medical School in 2021.

Silvi’s Harvard lab studies alternative RNA structures and the myriad roles they have in both viral and human biology. In particular, the lab studies how RNA folding informs alternative splicing and how misfolding can lead to disease. The lab developed DMS-MaPseq (dimethyl sulfate mutational profiling with sequencing) and DREEM (Detection-of-RNA-folding-Ensembles-using-Expectation-Maximization) algorithm to distinguish multiple RNA conformations formed by the same underlying sequence in vivo at single nucleotide resolution.

Silvi immigrated to the United States as a teenager to pursue a career in science. She holds a degree in physics from Florida Institute of Technology and a PhD in biochemistry and molecular biology from the University of California, San Francisco. Her interest in RNA began while working as a staff research associate in the lab of Joseph DeRisi, PhD, at UCSF, where she began developing techniques for the detection of viruses associated with human disease.



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In anticipation of RNA Day (on August 1), GEN invites you to join our exciting Spotlight virtual event on RNA Therapeutics on Wednesday, July 29.

We are living in a “post-genomic” world where RNA is no longer just a messenger but a programmable drug and molecular therapeutic. From the global impact of mRNA vaccines to advances in RNA editing and the potential of circular RNA, the field of RNA therapeutics is truly taking off. RNA is rapidly becoming a universal software for precision medicine.

Over 2.5 hours, this GENSpotlight on RNA Therapeutics brings you three interlinked sessions that feature outstanding researchers exploring various aspects of RNA biology and therapeutics, including:

  • A keynote panel including two founding members of the AIRFoundry (Artificial Intelligence-driven RNA BioFoundry) at the University of Pennsylvania—Zachary Ives, PhD, and Nobel laureate Drew Weissman, MD, PhD

  • A talk from Silvi Rouskin, PhD, a leading microbiologist at Harvard Medical School, presenting new research on alternative RNA structures and their relevance in health and disease

  • Presentations from our two sponsors, 4basebio and Aldevron

  • Registration to our Spotlight on RNA Therapeutics is entirely free. We look forward to celebrating RNA Day with you (a few days early).

Produced with support from:

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Microglia derived from human induced pluripotent stem cells are regulated by osteopontin, an endogenous extracellular matrix protein maintaining immune homeostasis

IntroductionMicroglia are brain-resident immune cells responsible for maintaining homeostasis, coordinating responses to injury and disease, and mediating regeneration. Upon activation, they undergo dynamic changes in morphology, gene expression, and function, reflecting the nature and context of the stimuli encountered. Although pharmacological modulation of microglia holds great promise for treating various neurological disorders, its development is hampered by a major translational roadblock: Human microglial cell lines commonly used in preclinical studies, as well as primary rodent microglia, substantially limit the translatability of results. Here, we aimed to generate microglia from human induced pluripotent stem cells (hiPSCs) and to demonstrate their physiological responsiveness to the brain-endogenous, context-relevant ligand osteopontin (OPN).Materials and methodsMicroglia generated from two healthy hiPSC lines were stimulated with OPN, lipopolysaccharide (LPS), or their combination for 24 h and subsequently analyzed. Microglial identity and the expression of the phagocytic cell marker cluster of differentiation 68 (CD68) were determined by immunocytochemistry. Cell viability was assessed by propidium iodide (PI)/Hoechst staining, morphological activation was evaluated using Sholl analysis, and inflammatory gene expression changes were assessed by RT-qPCR.ResultshiPSC-derived microglia acquired a native central nervous system (CNS)-specific immunophenotype, expressing the microglia-specific markers ionized calcium-binding adapter molecule 1 (IBA1), transmembrane protein 119 (TMEM119), PU.1, and Spalt-like transcription factor 1 (SALL1), while remaining negative for Myb and membrane-spanning 4-domains, subfamily A, member 7 (MS4A7) at the protein level. Exposure to LPS led hiPSC-derived microglia to adopt a rounded, process-retracted shape and to increase CD68 protein intensity, a surrogate marker of lysosomal and phagocytic activity, while downregulating the anti-inflammatory marker cluster of differentiation 206 (CD206) at the transcriptional level. OPN induced a distinct microglial functional state characterized by intermediate morphology, increased CD68 intensity, and reduced homeostatic gene expression, without eliciting robust inflammatory gene expression. Intriguingly, OPN prevented LPS-induced microglial cell death, and when hiPSC-derived microglia exposed to LPS were additionally treated with OPN, the morphological effects of LPS were reversed.ConclusionOPN induced a distinct early response profile in hiPSC-derived microglia, characterized by intermediate morphological remodeling, increased CD68 intensity, and reduced homeostatic gene expression, without overt pro-inflammatory gene expression. These findings support the role of OPN as a physiological priming signal in microglia and highlight hiPSC-derived microglia as a model for studying regulators of microglial modulation.
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Global trends and neurobiological frontiers of manual therapy in sleep disorders: integrating bibliometrics with clinical evidence

BackgroundSleep disorders not only impair nocturnal rest but also significantly compromise daytime functioning, emotional regulation, and overall mental well-being. Beyond conventional pharmacological treatments, manual therapy has emerged as a promising non-pharmacological intervention. Specifically, emerging evidence suggests its benefits may extend to alleviating psychological distress and enhancing mood. This study employs a bibliometric approach to systematically investigate the current status, research hotspots, and future trends of manual therapy for sleep disorders, with an emphasis on its psycho-physiological outcomes.MethodsPublications related to manual therapy for sleep disorders were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric visualizations and analyses were conducted using VOSviewer and CiteSpace. Furthermore, clinical trial records from PubMed were extracted to assess the translational and clinical advancements in this field.ResultsThe analysis included 594 publications originating from 321 institutions across 63 countries. The overall trend demonstrates a consistent annual increase in both publication volume and citation impact, reflecting escalating academic interest. Keyword and literature co-occurrence analyses indicate that exploring neurobiological mechanisms and circadian rhythm regulation are the predominant research frontiers.ConclusionBibliometric evidence indicates that research on manual therapy for sleep disorders is evolving toward multidimensional and interdisciplinary integration. Manual therapy increasingly emerges as a key complementary treatment, exerting therapeutic effects via the regulation of 5-hydroxytryptamine (5-HT) and the Hypothalamic-Pituitary-Adrenal axis (HPA axis). Its safety and efficacy represent distinct advantages; however, future clinical translation necessitates multi-center validation and standardized sham-controlled protocols.