Associate Professor of Otolaryngology – Head & Neck Surgery University of Michigan
Panelist
Chad Brenner, PhD
Chad Brenner, PhD, is an associate professor of otolaryngology – head & neck surgery at the University of Michigan, with joint appointments in pharmacology and membership in the Center for Computational Medicine and Bioinformatics. He directs the Michigan Otolaryngology and Translational Oncology research laboratories, the Translational Innovations Pathology CLIA Laboratory, the Head & Neck Oncology Program and the Cellular and Molecular Biology program. His research focuses on HPV-positive head and neck cancer, circulating tumor DNA diagnostics, HPV integration genomics, and precision oncology approaches to improve cancer detection, monitoring, and treatment response assessment. Brenner’s group developed and clinically implemented MyHPVscore, a Bio-Rad ddPCR-based assay for detecting circulating tumor HPV DNA in patients with HPV-associated cancers.
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Human papillomavirus (HPV)-associated cancers, which target the skin and mucus membranes, account for a growing proportion of malignancies worldwide, particularly in the head and neck region. Minimally invasive technologies like circulating tumor DNA (ctDNA) testing are emerging as promising tools for supporting diagnosis, monitoring treatment response, and detecting recurrence. Advances in assay development and PCR platforms are defining how HPV ctDNA tests can be integrated into clinical workflows.
In this IPM webinar, Chad Brenner, PhD, will describe the development, validation, and clinical implementation of MyHPVscore, a droplet digital PCR-based circulating tumor HPV DNA assay performed on the Bio-Rad QX200 platform. He will highlight the role of HPV ctDNA testing in patients with HPV-positive cancers, including applications for diagnosis support, recurrence surveillance, and clinical monitoring. He will also emphasize the operational experience of establishing and running the assay in a CLIA laboratory, including workflow optimization, assay performance, sample processing, quality control, and integration into clinical and translational research programs. Lastly, his talk will go over ongoing efforts to expand HPV ctDNA testing applications, including future opportunities for broader clinical deployment.
A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelist.
Brain organoids created in the lab using patient cells have allowed researchers based at the Wilhelmina Children’s Hospital in Utrecht to find out more about the progression of an ultra-rare type of childhood Parkinson’s disease.
Notably, as reported at the European Society of Human Genetics meeting in Gothenburg this week, the study also identified that an affordable and readily available form of vitamin B3 could help improve symptoms in these children.
Irena Muffels, MD, PhD, a clinical genetics resident at the Wilhemina Children’s Hospital, was working at the Icahn School of Medicine at Mount Sinai, New York, when the study began. Two parents contacted the lab where she was working to ask if they could look into the condition their children had been diagnosed with, a rare form of early Parkinson’s caused by mutations in the DHDDS gene.
“They contacted Professor Eva Morava, for whom I was then working. We started creating mini-brains—tiny blobs of brain tissue grown in the lab from patients’ own cells—thus avoiding the need to take samples directly from the children’s brains,” she explained.
Muffels and colleagues observed these mini brains in the lab and found there were significant signs of deterioration after four months mirroring that seen in the brains of children with this rare condition.
In healthy cells, DHDDS helps make dolichol, a small fat-like molecule that acts as a platform for attaching sugars to proteins. When DHDDS doesn’t work properly, dolichol levels fall. As a result, cells struggle to attach sugar chains, called glycans, to proteins in the usual way.
Those glycans are important because they help proteins fold correctly, reach the right place in the cell, and function as they should. In the patient‑derived mini brains, the team could see that these sugar chains were formed incorrectly.
Low dolichol also disrupts overall lipid regulation and causes cholesterol to build up in astrocytes, the brain’s supportive cells. “This accumulation builds over time, and this is why we think the disease progresses,” said Muffels, “since the accumulation of cholesterol leads to mitochondrial dysfunction, leading in turn to reduced energy production.”
Perlara, a rare‑disease biotech public benefit corporation that runs phenotypic screens in simple ‘patient avatar’ organisms, helped Muffels and colleagues identify nicotinamide mononucleotide, a naturally occurring type of vitamin B3, in a yeast‑based assay as a potential modifier of DHDDS‑driven cellular stress.
The vitamin appeared to have positive effects on the mini brains, and when the families of patients heard about it, they began using the supplement as it is readily available without a prescription and known to be safe. Within a few weeks, the patient’s walking got better and they had more energy and less tremors.
“The word about nicotinamide mononucleotide reached more DHDDS patients, and we currently have 12 patients taking it. We recently received funding from Congenital Disorders of Glycosylation UK… to start an international trial for nicotinamide mononucleotide supplementation in DHDDS-related disease,” said Muffels.
“Patients will take nicotinamide mononucleotide for a year and will be evaluated every three months. Although I have now left the U.S., I hope that the Wilhemina Hospital in Utrecht will be one of the official sites and that I may continue to work with these patients.”
An international collaboration led by researchers at the University of Barcelona, Spain, have identified why the two most common forms of non-small cell lung cancer (NSCLC)—lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC)—respond differently to anti-angiogenic therapies that target the blood vessels tumors need to grow. The study found that fibroblasts within the tumor microenvironment play a central role in shaping blood vessel formation, oxygen availability, and treatment response. The findings, published in the journal Cell Death & Disease, could pave the way for treatment decisions that are guided not only by tumor type but also by characteristics of the tumor microenvironment.
“The study reveals that the fibroblast-rich tumor microenvironment is not merely a spectator but a key player that shapes the tumor’s progression. Tumor-associated fibroblasts can influence the vascular network, the availability of oxygen and nutrients and, potentially, also metastatic dissemination and the immune response,” said senior author Jordi Alcaraz, PhD, a professor at the University of Barcelona’s Faculty of Medicine and Health Sciences and researcher at the Institute for Bioengineering of Catalonia.
The new study provides additional evidence that can be used to ascertain the viability of combining anti-angiogenic treatments with immunotherapy. Interest in this potential combination therapy has been growing over the past several years, to address the limited success of immunotherapy alone in treating NSCLC. Anti-angiogenic treatments are of interest since blood vessel growth has been shown to contribute to immune suppression and treatment resistance. But while anti-angiogenic drugs have shown benefits in lung adenocarcinoma, their efficacy has been limited or have produced toxicity as a treatment for squamous cell carcinoma.
“These contrasting outcomes and the limited overall therapeutic benefits attained by anti-angiogenic drugs in LUAD (adenomcarcinoma) underscore the need for a more nuanced understanding of the histotype-dependent complexity of angiogenesis regulation in NSCLC,” the researchers wrote.
For this study, the international team analyzed markers of angiogenesis and hypoxia across multiple patient cohorts. They used a combination of transcriptomic analyses in both lab and animal studies to examined how tumor-associated fibroblasts regulate blood vessel formation in the two major lung cancer subtypes.
The data showed clear differences between the two cancers. Adenocarcinoma tumors had greater angiogenesis, larger vessel lumens, higher oxygen availability, and less necrosis and hypoxia, while squamous cell carcinomas exhibited poorer blood vessel formation, increased hypoxia, and more necrotic tissue.
The investigators determined that fibroblasts from adenocarcinoma tumors produced a pro-angiogenic secretome characterized by elevated levels of vascular endothelial growth factor A (VEGF-A) and tissue inhibitor of metalloproteinases-1 (TIMP-1). “The LUAD-TAF secretome was primed for angiogenesis through SMAD3-dependent overproduction of key regulators, particularly TIMP-1 and VEGF-A,” the researchers wrote adding that “we also uncovered a novel function for TIMP-1 in promoting endothelial cell hyperbranching over basal VEGF signaling.” The findings showed that TIMP-1 amplified VEGF-driven angiogenesis and increased formation of the branching vascular networks commonly associated with tumors.
In squamous cell carcinoma, however, fibroblasts behaved differently. “By contrast,” Alcaraz said, “in squamous cell carcinoma, blood vessel formation is inefficient due to molecular changes in the associated fibroblasts resulting from higher tobacco exposure, resulting in tumors with lower oxygen levels, that is, more hypoxic.”
The findings may also help explain differences in disease progression between the two cancers. Because metastasis depends on tumor cells gaining access to blood vessels, the more developed vascular networks in adenocarcinoma likely play a role to its tendency to spread earlier than squamous cell carcinoma.
These finding could influence new approaches for stratification and treatment selection of patients with NSCLC. Potential biomarkers include the SMAD3/SMAD2 ratio, TIMP-1 levels, VEGF-A expression, and hypoxia-associated fibroblast signatures. The researchers suggest that adenocarcinoma patients may benefit from therapies targeting stromal SMAD3 signaling or TIMP-1, while patients with squamous cell carcinoma may benefit more from treatments designed to counter hypoxia, acidosis, or other features of the tumor microenvironment.
Future research will focus on validating biomarkers such as TIMP-1 in larger patient populations and prospective studies, better understanding the molecular interactions that link SMAD3, VEGF-A, and TIMP-1, and developing treatments that target these pathways. As Alcaraz noted, the challenge now is to identify robust biomarkers, validate them prospectively, and demonstrate that modifying the tumor microenvironment can improve therapeutic responses.
European biotechs presented a range of interesting technologies and novel therapeutic biotechs at the recent BioTrinity conference, organized by BioUK, formerly OBN. The meeting highlighted a spectrum of cell and protein-based therapies, as well as novel delivery methods, with eye-catching investments and partnering opportunities.
One of the stand-out technologies discussed by U.K.-based University of Southampton spin-out Renovos Biologics was the use of synthetic nanoclays. However, these are not being used for their traditional application of controlling drug release, but rather, for medical delivery. According to Agnieszka Janeczek, PhD, “We are developing an injectable, biodegradable nanoclay for use with bone morphogenetic protein 2 (BMP-2), a crucial growth factor in bone regeneration. We intend to use this on patients who have had spinal fusions after trauma or sports injuries.”
Current treatments to encourage bone growth after spinal fusion, such as BMP-2 in its current formulations, are poorly retained around the spine, causing inflammation or, worse, bone growth outside the spine. This often leads to patients needing revision surgery at a cost of up to $50,000. “BMP-2 was used around fusions in the cervical spine, but the growth of bone and inflammation caused some patients to develop breathing difficulties and has resulted in a black box warning against using BMP-2 for this application,” noted Janeczek.
To overcome these issues, the company has developed a synthetic nanoclay that provides a localized environment conducive to cell infiltration. The nanoclay retains the BMP-2 bioactive molecule until newly regenerated tissue gradually replaces it.
“We have used RENOVITE® with BMP-2 so that this protein is injectable with a 23-gauge needle to deliver BMP-2 in a gel to allow precise templating of new bone formation, and therefore safer and more efficient bone fusion,” she continued. “Using our nanoclay, we see better quality bone growth as the bone grows evenly around and through the fusion, unlike BMP-2 on its own, which can sometimes initiate bone growth around the fusion to create an eggshell effect with bone only on the outside.”
Renovos Biologics, which is developing an injectable, biodegradable nanoclay for use with bone morphogenetic protein 2, intends to use this crucial growth factor in patients who have had spinal fusions after trauma or sports injuries. [Vadym Terelyuk/Getty Images]
The Renovos nanoclay retains the BMP-2 protein more readily around the fusion. As a result, it is possible to administer BMP-2 in a lower dosage, giving it the potential benefit of use in lower-cost markets, said Janeczek, and concluded that “Twenty-one percent of lumbar fusions are in patients that are younger than 45 years old, and the market for bone fusion could be worth $24.5 billion by 2035. Our lead asset RENOVITE BMP-2 will enter first-in-human trials by 2027, and we welcome investment to help assess this game-changing product in the clinic.”
Patching up wounds
Thomas Hafner, CEO of Onya Therapeutics, based in Ebbw Vale, U.K., stated that “For 25 years, wound care has been an innovation desert because therapies are difficult to scale and are not easy to adapt. This is not a glamorous area, but it is a massive opportunity.”
To address this issue, several companies are developing devices, artificial skin, or anti-microbials. Others are developing sponges for managing exuding wounds, making them thicker for better absorption. As Hafner pointed out, they are doing this without asking, “Is this the right approach? “Wound care is a massive problem. For example, 30% of patients with diabetic foot ulcers will lose a limb within five years. Globally, there are triple the number of patients with chronic wounds as there are with cancer—wound care is a $400 billion crisis in plain sight.”
Currently, with wound care, 90% of the costs are for the labor to manage the wound and only 6% for the products themselves. To address this, Onya says it is developing a treatment that could collapse the 90% costs of wound management by accelerating healing. The company calls it active exudate therapy.
“In chronic wounds, the amount of exudate increases, and so instead of mopping up the exudate with dressings, we have found a way of turning off the tap. By doing this, we encourage healing and reduce amputations, potentially saving billions of dollars,” Hafner noted.
Onya, which closed a £2.6 million seed financing round in 2025, is utilizing a compound known as OTX-PP01, based on potassium permanganate, a molecule with long-established clinical safety and broad antimicrobial and astringent action. This compound is delivered via a patch. “Unlike other wound management treatments, we don’t absorb the fluid; instead, our OTX-PP01 patch supports reduction of excessive exudate by addressing chronic inflammation, and creating the conditions for healing to restart,” said Hafner.
Onya Therapeutics’ OTX-PP01 patch supports reduction of excessive exudate by addressing chronic inflammation, and creating the conditions for healing to restart. [Victor Golmer/Getty Images]
The compound does this in two ways: first, it targets exudate with an astringent action that can reduce excessive wound fluid at the source, targeting the inflammatory cycle that can stall healing. Second, it addresses inflammation using a broad-spectrum antimicrobial action targeting pathogens through oxidation.
“OTX-PP01 is not a new molecule. It has over 150 years of safe clinical use, but the delivery method is new,” explained Hafner. “The patch is easy to fit, and a nurse can put it on the wound and leave it on for 15 minutes for the compound to absorb and do its job of healing. After removing the patch, a nurse can then redress the wound.”
Onya has designed its OTX-PP01 patch product to treat diabetic foot ulcers, venous leg ulcers, and pressure ulcers. It does not have to undertake Phase I studies as these were waived based on the established safety profile of the active compound. “We have a Phase II/III adaptive trial design, which we hope to complete in the next four to five years. Our aim with OTX-PP01 is to transform wound management to wound healing,” said Hafner.
Eyes on the prize
Therapies for treating ophthalmic diseases were also noteworthy at BioTrinity, with StemSight and Link Biologics presenting data on their promising clinical candidates. StemSight, based in Tampere, Finland, is a biotech company spun out from Tampere University. The firm is developing off-the-shelf induced pluripotent stem cell (iPSC) therapies to cure corneal blindness.
According to Laura Koivusalo, PhD, CEO and founder of StemSight, the market value of regenerative medicine products across a variety of indications was $63 billion in 2026. However, the bottleneck for making these therapies widely available is manufacturing and scaleup. Koivusalo said that “Recently in Japan, the first iPSC treatments have been approved for use, and the advantage of using iPSCs combined with biomaterials is that they provide efficient and durable therapies.”
Her company is developing a therapy to treat limbal stem cell deficiency (LSCD), a rare disease that causes blurry vision due to corneal epithelium loss and eventually blindness. There are over 240,000 sufferers worldwide, and there are currently no treatments for this condition available for most patients.
“The only treatment option for LSCD is available only to patients with one healthy eye,” Koivusalo explained. “Scientists can harvest limbal stem cells from the healthy eye and transplant them into the diseased one to restore the damaged surface cells. The therapy proves that the cell transplantation approach works, but this is a personalized autologous treatment. Additionally, if both eyes have LSCD, and the patient is truly blind, this treatment is not possible as there are no healthy stem cells available to harvest. That’s where the high value of cure is really measured.”
StemSight is developing an allogenic limbal stem cell therapy, which uses gene-edited iPSCs to reduce immunogenicity. Currently, the firm can produce one hundred patient doses per batch using a GMP-compliant process. It then freezes these cells until their delivery on a biomaterial carrier for patients.
StemSight and Link Biologics presented data in their talks on their promising clinical candidates for ophthalmic diseases. [Shironosov/Getty Images]
“Our process produces high-quality stem cells for a low cost of goods,” continued Koivusalo. “We are currently in late preclinical development with our lead product, STE-101, and have shown that we can regenerate corneal epithelium in rodent models using imaging and histology. These are objective measures of efficacy, as we cannot ask rodents if they can read a chart.”
StemSight is aiming to treat ten patients in a Phase I/II study starting early 2028.
Unlike StemSight, Link Biologics, a U.K.-based spin-out from the University of Manchester, is developing first-in-class biologics to treat Dry Eye Disease (DED) and Wet Age-related Macular Degeneration (AMD). The firm is developing therapies based on TSG-6 (Tumor Necrosis Factor-α-Stimulated Gene/Protein-6), a secreted glycoprotein that has an endogenous role to protect tissues from inflammatory damage and promote repair. Link’s TSG-6-based therapies have enhanced activities compared to the native protein and thus have a unique combination of anti-inflammatory, tissue-protective, and tissue-reparative properties.
Reuben Dawkins, CEO and co-founder of Link Biologics, stated that “We are using these protein biologics to treat DED and wet AMD because these are billion-dollar markets where there are limited treatment options available. Current standard of care for DED, for example, involves cyclosporine, which has a 15% response rate, or Xiidra, where 50% of pivotal trials did not show improvement in key efficacy measures vs no treatment. Overall, nine in ten DED patients stop using their initial medication within one year.”
The company’s lead candidate, LB001, is in preclinical development for the treatment of DED. Dawkins presented data to show that in mouse models, twice daily administration of LB001 for seven days reduced corneal epithelial damage and suppressed inflammatory markers compared to a branded cyclosporine (Restasis).
“Unlike other treatments, LB001 has a dual tissue-repair and anti-inflammatory action which may make this molecule more effective than current therapies,” noted Dawkins. “We have completed CMC so are able to manufacture LB001 to GMP standards, and it is stable as an eye drop formulation. We will be taking LB001 into a 180-patient Phase I/II clinical trial, which we aim to commence in 2027.”
Sue Pearson, PhD, is a freelance writer based in the U.K.
<![CDATA[Explore today’s schizophrenia treatments, comparing first-, second-, and newer antipsychotics, clozapine’s role, and how side effects and adherence drive medication choices.]]>
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<![CDATA[Clinicians weigh diagnosis clarity, side effects, and adherence when choosing antipsychotic formulations, often starting oral therapy then switching to long-acting injectables.]]>
IntroductionThe clinical translation of magnetic stimulation for central nervous system trauma is severely hindered by “parameter ambiguity”—the lack of evidence-based screen of stimulation protocol. Repetitive trans-spinal magnetic stimulation (rTSMS) holds therapeutic promise, yet its frequency-dependent effects on the complex spinal microenvironment remain poorly understood. To address this gap, this study aimed to decode the frequency-response relationship of rTSMS and establish an optimal, evidence-based frequency standard to orchestrate immune-fibrotic remodeling and promote functional recovery following spinal cord injury (SCI).MethodsUtilizing novel in vivo label-free second-harmonic generation (SHG) imaging to visualize the real-time microglia activation, we performed a high-fidelity close-loop screen of various rTSMS frequencies (10 Hz, 40 Hz, and 80 Hz). In an adult mice SCI model, we integrated transcriptomic profiling, morphological analysis, electrophysiological recordings, and behavioral assessments to comprehensively evaluate the neuroregenerative potential.ResultsWe identified 40 Hz as a privileged therapeutic frequency that specifically modulates microglia and the extracellular matrix. Unlike 10 Hz or 80 Hz regimens, 40 Hz rTSMS uniquely reprogrammed the transcriptomic landscape, driving microglia toward a restorative M2 phenotype, and most importantly, suppressing collagen fibrillogenesis. This targeted modulation effectively attenuated fibrotic scarring and preserved mitochondrial dynamics and axonal integrity. Consequently, the 40 Hz protocol significantly enhanced corticospinal tract conduction and drove robust, long term sensorimotor recovery.ConclusionOur findings define 40 Hz as the critical therapeutic standard for coupling immune modulation with fibrotic remodeling in SCI. By overcoming the barrier of inconsistent parameters, this study provides a precise, clinically translatable framework for the application of rTSMS in neurorestorative medicine.
IntroductionUnderstanding how neurotransmitter systems organize into large-scale networks is essential for elucidating the mechanisms through which drugs, diseases, and behavioral states alter brain function. Existing imaging modalities such as functional MRI (fMRI) and positron emission tomography (PET) provide measures of hemodynamic and metabolic connectivity, but cannot noninvasively map neurotransmitter-associated networks with high spatial resolution. Herein, we introduce a chemical exchange saturation transfer (CEST) MRI-based framework for mapping glutamate-associated molecular connectivity and apply it to characterize nicotine-induced network reorganization in the mouse brain.MethodsMale C57BL/6 mice underwent dynamic glutamate-weighted CEST (gluCEST) MRI before and after seven days of nicotine exposure. Regional glutamate-weighted CEST time series were extracted from 51 brain regions, and connectivity was evaluated using within-subject temporal correlation and inter-subject covariance analyses.ResultsGraph theory analyses identified four baseline glutamate-associated modules involving frontal-sensorimotor, cortico-hippocampal, intra-hippocampal, and cortico-striatal circuits. Nicotine exposure attenuated these baseline networks in analyses performed without global signal regression (GSR) and with conditional GSR, whereas full GSR reduced the apparent magnitude of these effects. Nicotine also reduced nodal strength in the CA1 and insular cortex. In contrast, nicotine selectively strengthened a thalamo-striato-motor circuit involving the motor cortex, mediodorsal and ventral thalamic nuclei, and caudoputamen. This pattern remained evident even under full GSR. Subject-level covariance analysis confirmed widespread nicotine-induced attenuation of glutamate-associated connectivity and revealed a distinct sensory-limbic module involving the lateral geniculate nucleus, amygdala, and piriform cortex that was selectively disrupted following nicotine exposure.DiscussionThese results demonstrate the feasibility of dynamic gluCEST MRI for mapping glutamate-associated molecular connectivity in vivo and detecting pharmacologically induced network remodeling. This approach provides a noninvasive platform for investigating glutamatergic dysregulation in addiction, neuropsychiatric disorders, and therapeutic response.
Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation.
, a Bio-Rad ddPCR-based assay for detecting circulating tumor HPV DNA in patients with HPV-associated cancers.
