Klug Lab Other News

Spotlight by CU Innovations

In a recent interview with CU Innovations, Dr. Achim Klug, Professor of Physiology & Biophysics at CU Anschutz, shared exciting developments about a revolutionary treatment for age-related hearing loss that challenges everything we thought we knew about hearing restoration.

The Problem With Current Solutions

Dr. Klug's work addresses a widespread yet often misunderstood condition: central hearing loss, which affects the brain rather than the ears themselves. If you've ever struggled to follow a conversation in a noisy restaurant despite having "perfect hearing" according to traditional tests, you've experienced this phenomenon firsthand. The frustrating reality is that conventional hearing aids can't help with this condition because they're designed to amplify sound at the ear level, not address how the brain processes and filters auditory information.

This affects an astounding number of people—approximately one-third of adults between 40 and 65, and half of those 65 and older. That's millions of people who currently have no effective treatment options.

  • A Novel Approach: Drug Plus Sound

    What makes Dr. Klug's research particularly innovative is the treatment approach itself: a one-month combination therapy pairing medication with specially engineered sound. The goal isn't just temporary relief but lasting, long-term improvement in the brain's ability to isolate sounds of interest from background noise.

    The treatment is designed to be simple, non-invasive, and benign—critical factors for widespread adoption, especially among older populations who may already be managing multiple health conditions.

    From Bats to Breakthrough

    Dr. Klug's path to this discovery is as fascinating as the treatment itself. His career began studying echolocation in bats, drawn initially by scientific curiosity and the opportunity to work in exotic locations. But he recognized the profound medical relevance of these brain circuits in humans and pivoted to understanding what changes during aging—and crucially, how to reverse it.

    His motivation is deeply personal and urgent. As he notes in the interview, affected listeners consistently tell him to "work faster" because they desperately want this treatment. That human element drives the research forward.

    What's Next?

    The timeline is remarkably encouraging. Dr. Klug's team recently received FDA approval for Phase 2 clinical trials and planned to begin enrolling participants in October. The technology has been licensed to Parley Neurotech Inc., led by Dr. Sam Budoff as CEO, and the team is actively seeking venture capital investment to accelerate development and bring the treatment to market.

    Perhaps most exciting are the potential future applications. While the current focus is on age-related hearing loss, the same treatment may benefit people with autism, individuals who've experienced significant noise exposure (including factory workers and military veterans), and those suffering from tinnitus. Each of these populations represents millions more people who could potentially benefit from this groundbreaking approach.

    A Paradigm Shift in Hearing Medicine

    What stands out most about Dr. Klug's work is that it represents the first treatment for hearing loss caused by the brain rather than the ears. This isn't just an incremental improvement—it's a fundamental shift in how we approach hearing restoration, opening up an entirely new category of therapeutic intervention.

    For the millions of people who struggle to hear clearly in everyday situations despite normal ear function, this research offers genuine hope. The combination of solid science, FDA approval, and a clear path to commercialization suggests we may soon see a world where central hearing loss is no longer an untreatable condition but a manageable one.

    As Dr. Klug and his team move forward with clinical trials, they're not just developing a new treatment—they're potentially transforming the lives of millions of people who've been told there's nothing that can help them. That's the kind of innovation that deserves our attention and support.

    Here is the link to the interview.

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Celebrating Innovation: Dr. Benzheng Li's Emerging Research Grant Extended for Year Two

We are excited to announce that the Hearing Health Foundation (HHF.org) extended Dr. Benzheng Li's Emerging Research Grant for a second year, recognizing the promise of his groundbreaking work on sound localization in the brain. This continued investment underscores the innovative research that has the potential to transform hearing health outcomes for millions of people worldwide.

Tackling the Cocktail Party Problem

Dr. Li's research addresses one of the most persistent challenges in hearing science: how our brains successfully locate and focus on specific sounds in complex acoustic environments. If you've ever struggled to follow a conversation at a crowded restaurant or found yourself straining to hear a friend's voice over background chatter, you've experienced what researchers call the "cocktail party problem" firsthand.

  • For many individuals with hearing difficulties, these noisy environments present an even greater challenge. While hearing aids and cochlear implants can amplify sound, they often fall short when it comes to helping users distinguish between important speech signals and unwanted background noise. Dr. Li's work aims to uncover the fundamental brain circuits responsible for sound localization, laying the groundwork for more sophisticated solutions.

    Bridging Engineering and Neuroscience

    What makes Dr. Li's approach particularly exciting is his unique interdisciplinary background. As an electrical engineer who has expanded into auditory neuroscience, he brings a fresh perspective to longstanding questions in the field. This combination of technical engineering expertise and deep neuroscientific inquiry positions him to not only understand how the brain processes spatial hearing but also to envision practical applications of that knowledge.

    "Dr. Li's engineering background allows him to approach these complex neural circuits with a different lens," notes the research team. "He's not just asking how these systems work, but how we might eventually replicate or enhance their function through innovative prosthetic devices."

    The Path to Better Treatments

    The fundamental research Dr. Li is conducting today is a crucial foundation for tomorrow's breakthroughs. By mapping the precise neural pathways involved in sound localization and focusing on brain areas that have been understudied, his work will help researchers understand why current prosthetic devices sometimes struggle in noisy environments and how future generations of hearing technology might overcome these limitations.

    Dr. Li's long-term vision extends to developing novel prosthetic solutions for patients whom current hearing aids and cochlear implants cannot adequately help. These might include individuals with complex hearing loss patterns or those who need enhanced spatial hearing abilities for their daily activities and quality of life.

    Supporting the Next Generation

    The Hearing Health Foundation's Emerging Research Grant program specifically targets early-career investigators like Dr. Li who bring fresh ideas and innovative approaches to hearing research. By providing multi-year support, HHF enables these promising researchers to pursue ambitious projects that might otherwise be considered too risky or long-term for traditional funding mechanisms.

    This research represents exactly the kind of innovative, interdisciplinary work that can lead to unexpected breakthroughs in hearing health.

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NIH Awards Multi-PI R01 to Study Mechanisms of Central Hearing Loss

The National Institutes of Health has awarded a multi-principal investigator R01 grant to a collaborative research team consisting between our lab and the laboratory of Dr. Dan Tollin, investigating one of hearing science's most complex puzzles: understanding the distinct mechanisms that contribute to central hearing loss.

The Challenge of Central Hearing Loss

Central hearing loss occurs when the problem isn't in the ear itself, but in how the brain processes auditory information. Unlike peripheral hearing loss, where damaged hair cells or structural problems in the ear are the culprit, central hearing loss involves disruptions in the neural pathways that carry and process sound information in the brain.

  • For patients experiencing central hearing loss, the symptoms can be particularly frustrating. They may be able to detect sounds but struggle to understand speech, especially in noisy environments. Traditional hearing aids, which work by amplifying sound, often provide limited benefit because the underlying problem lies in neural processing rather than sound detection.

    Three Mechanisms, One Complex Problem

    The research team will focus on rigorously investigating three key neural mechanisms that have been proposed as contributors to central hearing loss:

    Synaptopathy refers to damage or dysfunction in the synaptic connections between hair cells and auditory nerve fibers. These tiny connection points are crucial for transmitting sound information accurately, and when they're missing, the brain receives distorted or incomplete auditory signals.

    Demyelination involves the breakdown of myelin sheaths that surround nerve fibers. Myelin acts like insulation on electrical wires, ensuring that neural signals travel quickly and efficiently. When demyelination occurs in auditory pathways, it can slow or disrupt the precise timing that's essential for sound processing.

    High-frequency hearing loss affects the ability to hear higher-pitched sounds and can have cascading effects on central auditory processing. When the brain consistently receives incomplete frequency information, it may reorganize in ways that further compromise hearing function.

    The Diagnostic Dilemma

    One of the greatest challenges in treating central hearing loss is that patients typically present with a combination of all three mechanisms. This creates a diagnostic puzzle: determining which factor is the primary driver of a patient's hearing difficulties and which might be secondary consequences.

    Making this determination even more complex is the fact that these mechanisms can influence each other. For instance, synaptopathy might lead to secondarily to demyelination. Similarly, demyelination in one part of the auditory system might place additional stress on synaptic connections elsewhere.

    "Currently, it's extremely difficult to assess these factors in a rigorous way," explains the research team. "When a patient comes in with central hearing loss symptoms, typically all three mechanisms are involved to some degree, making treatments very difficult."

    A Rigorous Experimental Approach

    What sets this R01 project apart is its systematic approach to discriminating between these three mechanisms. Rather than studying them in isolation or as a combined phenomenon, the research team has designed experiments that will carefully dissect each mechanism from the others.

    This methodical approach involves developing animal models where each mechanism can be studied independently, advanced imaging techniques to visualize changes in neural structures, and sophisticated behavioral testing to understand how each mechanism specifically affects hearing function.

    The Promise of Precision Medicine

    The ultimate goal of this research extends far beyond understanding these mechanisms in the laboratory. By clearly identifying which neural factors are driving a patient's central hearing loss, clinicians could eventually develop more precise treatment approaches.

    For instance, if synaptopathy is identified as the primary issue, treatments might focus on protecting or restoring synaptic connections. If demyelination is the main culprit, therapeutic approaches could target myelin repair. For cases primarily driven by high-frequency hearing loss, interventions might focus on preventing or reversing the secondary central changes.

    As this research progresses over the coming years, it promises to provide the detailed mechanistic insights that have long been missing from our understanding of central hearing loss. For the millions of people who struggle with this condition, this work represents hope for more effective treatments that address the root causes rather than just the symptoms.

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Welcoming Dr. Sam Budoff: Bridging Spatial Vision and Spatial Hearing

We're excited to announce that our lab has welcomed Dr. Sam Budoff—a recent PhD graduate whose research journey perfectly complements our mission to understand how the brain processes spatial information.

From Retina to Cochlea: A Natural Progression

Sam recently defended his doctoral thesis, "A Complete Spatial Map of Mouse Retinal Ganglion Cells Reveals Density and Gene Expression Specializations," which revealed how different retinal cell types are spatially organized to support various visual functions. This groundbreaking work used cutting-edge spatial transcriptomics and machine learning to map the complete distribution of retinal ganglion cells—the neurons that transmit visual information from eye to brain.

  • The connection to our lab's hearing research isn't coincidental. Both spatial vision and spatial hearing rely on similar computational principles: the brain must integrate information from multiple sensors (photoreceptors or hair cells) distributed across space (the retina or cochlea) to create meaningful perceptions of our environment.

    A Track Record of Innovation

    Before entering academia, Sam demonstrated exceptional leadership as the 13th employee at Modern Meadow, a biotechnology company that uses biofabrication to create sustainable materials. There, they built the biochemical analytics and high-throughput cell engineering departments from scratch—experience that proves invaluable for scaling innovative biotechnology solutions.

    Their educational foundation spans multiple disciplines crucial for our work: a Master's in Applied Statistics, a Master's in Neuroengineering, and an undergraduate degree from Vanderbilt University combining Genetics and Neuroscience with Human and Organizational Development on the leadership track.

    Introducing Parley Neurotech

    Sam will serve as the new Chief Executive Officer of our spin-out company, Parley Neurotech. This startup addresses a critical need: helping the 800 million people who struggle to hear in crowded rooms but don't qualify for traditional hearing aids. This challenge—often called the "cocktail party problem"—affects many listeners, especially as they age, and has everything to do with how the brain processes spatial audio information rather than simple hearing acuity.

    Sam has been working closely with Dr. Klug since before defending their thesis and joined full-time in April 2025 to lead both fundraising efforts and strategic development for this promising venture.

    What's Coming Next

    Starting next week, we'll launch a weekly blog series exploring the fascinating parallels between spatial vision and spatial hearing. These posts will dive into how both sensory systems solve similar computational challenges and what this teaches us about developing better treatments for hearing difficulties in noisy environments.

    The intersection of spatial vision research and auditory neuroscience represents a powerful approach to understanding how our brains make sense of complex sensory environments—and how we can help when these systems don't work optimally.

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Klug Lab Awarded SPARK Grant for Groundbreaking Hearing Restoration Research

Research team receives funding to advance innovative solutions for age-related hearing loss

The Klug Laboratory has been awarded a prestigious SPARK Grant from the State of Colorado Office of Economic Development and International Trade (OEDIT) Advanced Industries grant program. This award will accelerate the translation of the lab's research on hearing restoration into marketable solutions that address one of the most common challenges of age-related hearing loss.

  • Bridging Research and Real-World Application

    Age-related hearing loss affects millions of people worldwide, with one of its most debilitating aspects being the difficulty in following conversations in noisy environments. Unlike conventional hearing loss that simply reduces volume, this specific form of impairment—often called the "cocktail party problem"—compromises a person's ability to distinguish between competing sounds, making social gatherings particularly challenging.

    The Klug Lab's approach targets the neural mechanisms responsible for auditory signal processing, offering hope for those who struggle with speech comprehension in crowded settings. The SPARK Grant will provide crucial resources to bridge the gap between laboratory research and commercial applications, potentially transforming how this form of age-related hearing loss is treated.

    From Laboratory to Marketplace

    This support from Colorado's Advanced Industries grant program will be transformative. While traditional hearing aids amplify all sounds, this new technology specifically addresses the brain's diminished capacity to filter and focus on relevant speech in noisy environments—a capability that naturally declines with age.

    The OEDIT Advanced Industries grant program was designed precisely for initiatives like this—supporting research with clear commercial potential that can strengthen Colorado's position in innovative industries while addressing significant health challenges.

    The lab will now begin the process of developing prototypes and conducting targeted trials necessary to bring their technology to market, potentially creating new jobs in Colorado's growing biotechnology sector.

    Looking Ahead

    As the lab moves forward with commercialization efforts, their work stands to benefit an aging population increasingly affected by communication difficulties in social settings. For millions who have withdrawn from social interactions due to hearing challenges, this technology represents more than just medical innovation—it offers the possibility of renewed connection and improved quality of life.

    The SPARK Grant's support of this hearing restoration technology exemplifies the important role that targeted public funding can play in advancing solutions to pressing health challenges while simultaneously fostering economic development in Colorado's advanced industries. The official start date of this two year project is May 1, 2025.

    Click here for more details on SPARK.

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New Publication Alert: Klug Lab Unveils Novel Sapphire Optrode in International Collaboration

In an exciting development for neuroscience research, the Klug Lab has published a new paper detailing an innovative sapphire optrode that promises to enhance optogenetic experiments. This work represents an international collaboration between research teams from Macau, Guangzhou, UC Denver, and the Klug Lab at CU Anschutz.

  • A Transparent Yet Durable Solution

    The newly developed device combines neural recording capabilities across multiple channels with precise light stimulation through miniature LEDs embedded directly in a sapphire substrate. What makes this optrode particularly remarkable is the sapphire material itself—transparent like glass but with exceptional hardness that enhances both safety and targeting accuracy during experiments.

    Flexible Design for Customized Research

    One of the most significant advantages of this new technology is the ability to arrange recording sites and LED locations in arbitrary configurations. This flexibility will allow researchers in the future to customize the optrode layout for specific experimental requirements, potentially opening doors to novel experimental paradigms that were previously impossible to implement.

    Enhancing Optogenetic Research

    For those working in optogenetics—a technique that uses light to control cells in living tissue, typically neurons that have been genetically modified to express light-sensitive ion channels—this development represents a substantial leap forward. The integration of both recording and stimulation capabilities in a single, highly durable probe will enable more sophisticated experiments with greater precision.

    The combination of multi-channel neural recording with targeted light delivery through integrated LEDs addresses a critical challenge in the field: simultaneous stimulation and recording at precise locations in neural tissue.

    Citation:

    Yanyan Xu, Ben-Zheng Li, Xinlong Huang, Yuebo Liu, Zhiwen Liang, Xien Yang, Lizhang Lin, Liyang Wang, Yu Xia, Matthew Ridenour, Yujing Huang, Zhen Yuan, Achim Klug, Sio Hang Pun, Tim C. Lei, Baijun Zhang:

    Sapphire-Based Optrode for Low Noise Neural Recording and Optogenetic Manipulation

    ACS Chemical Neuroscience Vol 16, 628-641, 2025.

    https://pubs.acs.org/doi/10.1021/acschemneuro.4c00602

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Dr. Benzheng Li Awarded Prestigious Hearing Health Foundation Emerging Research Grant

We are excited to announce that Dr. Benzheng Li has been awarded a Hearing Health Foundation Emerging Research Grant for his innovative work in computational neuroscience.

  • Dr. Li's research focuses on developing complex mathematical models and neural decoders to explore the neural mechanisms behind sound localization. His work bridges the gap between theoretical neuroscience and hands on experimental approaches, potentially leading to improved hearing technologies and interventions.

    The Hearing Health Foundation's Emerging Research Grant program supports promising scientists in the early stages of their careers who demonstrate exceptional potential to advance our understanding of hearing disorders. This competitive grant will provide crucial funding for Dr. Li to continue his groundbreaking work.

    This grant represents an important opportunity to advance our understanding of how the brain processes spatial auditory information. By developing more accurate models of neural circuits involved in sound localization, better treatments for those with hearing impairments can be facilitated.

    Dr. Li's interdisciplinary approach combines computational modeling, signal processing, and neuroscience wet alb approaches to understand the neural activity patterns associated with hearing in noise processing. His research has implications not only for hearing health but also for broader applications in neural engineering and sensory augmentation technologies.

    For more information about Dr. Li and this award, visit:

    https://hearinghealthfoundation.org/meet-the-researcher/ben-zheng-li-2025

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