Biology subjects

Luu, C.

Publications and source records attributed to Luu, C..

5 recordsLinked to original sources

bioRxiv2026

Manipulating speech perception with amplitude-modulated kilohertz magnetic perturbation (AM-kTMP)

Speech perception has been hypothesized to exploit neural activity that entrains to the rhythmic properties of the utterance. Perceptual sensitivity varies with the phase of oscillatory activity induced by speech, and with an external oscillatory perturbation induced by transcranial alternating current stimulation (tACS) over the temporal lobe. Here we used a new form of non-invasive brain stimulation (NIBS), kilohertz transcranial magnetic perturbation (kTMP), in which a low frequency perturbation is created by the amplitude modulation (AM) of a continuous high-frequency carrier signal (3.5 kHz). As a magnetic induction method, kTMP can produce much higher electrical fields at the cortical surface than tACS and reduces cutaneous co-stimulation. Human participants (n=40) listened to sequences of rhythmic speech while receiving kTMP with an AM component of 3.125 Hz. The phasic modulation of perceptual sensitivity was greater during AM-kTMP than during sham stimulation, suggesting that AM-kTMP entrains neural activity underlying speech perception. Participants ratings of rhythmic sensations and other side effects did not differ between AM-kTMP and sham stimulation. Together with its reduced peripheral stimulation, our results highlight kTMP as a promising NIBS method for modulating frequency-specific brain dynamics in speech perception.

neuroscience↗

bioRxiv2026

Amplitude-Modulated Kilohertz Stimulation Targeting Beta-Band Activity Disrupts Motor Learning

Sensorimotor learning is associated with the modulation of neural rhythms in the primary motor cortex (M1). Beta-band activity ("beta"; 15-30 Hz) is suppressed during learning, while delta oscillations (1-4 Hz) become increasingly correlated with movement kinematics as skill improves. These observations have been complemented by experimental manipulations designed to perturb oscillatory activity with externally applied electric fields (E-fields). In non-human primates, invasive beta stimulation has been shown to disrupt motor learning whereas delta stimulation enhanced motor recovery in a stroke model. Causal evidence in humans remains limited, partly because established non-invasive methods cannot achieve continuous, narrowband E-fields at sufficient amplitude in the brain. To address this gap, we employed kilohertz transcranial magnetic perturbation (kTMP), a non-invasive magnetic induction technique that delivers continuous narrowband kilohertz E-fields which can be amplitude-modulated (AM) to target cortical rhythms. We applied AM-kTMP to test the functional relevance of beta and delta activity in human motor learning. In a double-blind mixed design, 40 participants performed a force-control task while receiving AM-kTMP at E-field amplitudes of 8 V/m in M1. We targeted either beta or delta, each paired with a sham condition. AM-kTMP influenced motor performance in a frequency-dependent manner: Beta-kTMP suppressed performance gains relative to both delta-kTMP and sham, whereas delta-kTMP showed no effect. These results suggest that increased beta activity in human M1 can interfere with motor learning. More broadly, kTMP offers a novel approach to probe frequency-specific cortical dynamics.

neuroscience↗

bioRxiv2025

Optimization of AAV tools to target Muller glial cells for retinal gene therapy

Reprogramming of Muller glial (MG) cells into retinal neurons has the potential to treat vision loss by regenerating the retina. Development of efficient gene delivery systems to target the MG cells is critical. Adeno-associated virus (AAV) serotypes and promoter specificity are important factors that influence AAV transduction profile in the retina. However, studies that optimize these parameters to specifically target MG cells are limited, in particular in rats which are commonly used for eye research. Here we tested 4 AAV serotypes and 14 promoters to optimize gene delivery to human MG cells in vitro and/or rat MG cells in vivo. We showed that the combinatorial use of MG-specific serotypes and promoters achieved high specificity for MG cell targeting, with ShH10Y serotype and the GFAP (gfaABC1D) promoter as the best performing tool to target rat MG cells in vivo. We developed new AAV vectors using known and novel MG-specific promoters and engineered short promoter variants to improve the cargo capacity of AAV delivery. Our results highlighted a number of promoters that can target MG cells in vitro or in vivo. This study further expands the AAV toolbox to target MG cells, which has important implications for retinal gene therapy development.

molecular biology↗

bioRxiv2022

Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells

Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. Here we report the generation of a stable human RPE cell line with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. We conducted functional studies on the POLDIP2 knockout cell line and showed that they retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells. Our results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. We showed that loss of POLDIP2 causes a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology.

neuroscience↗

bioRxiv2019

In-Depth Characterization and Validation in BRG1-Mutant Lung Cancers Define Novel Catalytic Inhibitors of SWI/SNF Chromatin Remodeling

Members of the ATP-dependent SWI/SNF chromatin remodeling complexes are among the most frequently mutated genes in cancer, suggesting their dysregulation plays a critical role. The synthetic lethality between SWI/SNF catalytic subunits BRM/SMARCA2 and BRG1/SMARCA4 has instigated great interest in targeting BRM. Here we have performed a critical and in-depth investigation of novel dual inhibitors (BRM011 and BRM014) of BRM and BRG1 in order to validate their utility as chemical probes of SWI/SNF catalytic function, while obtaining insights into the therapeutic potential of SWI/SNF inhibition. In corroboration of on-target activity, we discovered compound resistant mutations through pooled screening of BRM variants in BRG1-mut cancer cells. Strikingly, genome-wide transcriptional and chromatin profiling (ATAC-Seq) provided further evidence of pharmacological perturbation of SWI/SNF chromatin remodeling as BRM011 treatment induced specific changes in chromatin accessibility and gene expression similar to genetic depletion of BRM. Finally, these compounds have the capacity to inhibit the growth of tumor-xenografts, yielding important insights into the feasibility of developing BRM/BRG1 ATPase inhibitors for the treatment of BRG1-mut lung cancers. Overall, our studies not only establish the feasibility of inhibiting SWI/SNF catalytic function, providing a framework for SWI/SNF therapeutic targeting, but have also yielded successful elucidation of small-molecule inhibitors that will be of importance in probing SWI/SNF function in various disease contexts.

cancer biology↗