Biology subjects

Patel, P. R.

Publications and source records attributed to Patel, P. R..

17 recordsLinked to original sources

bioRxiv2026

A Sac7-Rho1 axis at the plasma membrane controls clathrin-independent endocytosis

In eukaryotes, our understanding of clathrin-independent endocytosis (CIE) lags far behind that of clathrin-mediated endocytosis (CME). CIE plays key roles in internalizing receptors, viruses, bacterial toxins, and pathogens; thus, deeper mechanistic insights are critical for understanding cellular strategies for plasma membrane regulation. Yeast CIE requires a signal relay between the stress sensor Mid2, the guanine nucleotide exchange factor (GEF) Rom1, the Rho1 GTPase, and the formin Bni1. While GEFs promote GTPase activity, GTPase-activating proteins (GAPs) conversely stimulate nucleotide hydrolysis and GTPase inactivation. Here, we provide new insight into CIE, adding the RhoGAP Sac7 as a regulator. SAC7 deletion in CME-deficient cells improved cargo internalization, and Sac7 localizes primarily to the mother cortex. Cells lacking SAC7 accumulate active Rho1 and retain Bni1 at the plasma membrane, where Bni1 retention may subsequently enhance actin assembly needed for CIE. Our results thus demonstrate that Sac7 negatively regulates CIE by restricting cortical Rho1 activity.

cell biology↗

bioRxiv2025

A method for efficient, rapid, and minimally invasive implantation of individual non-functional motes with penetrating subcellular-diameter carbon fiber electrodes into rat cortex

ObjectiveDistributed arrays of wireless neural interfacing chips with 1-2 channels each, known as "neural dust", could enhance brain machine interfaces (BMIs) by removing the wired connection through the scalp and increasing biocompatibility with their submillimeter size. Although several approaches for neural dust have emerged, a procedure for implanting them in batches that builds upon the safety and performance of currently used electrodes remains to be demonstrated. ApproachHere, we demonstrate the feasibility of implanting batches of wireless motes that rest on the cortical surface with carbon fiber electrodes of subcellular diameter (6.8-8.4 {micro}m) that penetrate to a target brain depth of 1 mm without insertion aids. To simulate their implantation, we assembled more than 230 mechanically equivalent motes and affixed them to insertion tools with polyethylene glycol (PEG), a quickly dissolvable and biocompatible material. Then, we implanted mote grids of multiple configurations into rat cortex in vivo and evaluated insertion success and their arrangement on the brain surface using photos and videos captured during their implantation. Main ResultsWhen placing motes onto the insertion device, we found that they aggregated in molten PEG such that the array pitch was only 5% wider than the dimensions of the mote bases themselves (240 x 240 {micro}m). Overall, we found that motes with this arrangement could be inserted into rat cortex with a high success rate, as 171/186 (92%) motes in 4x4 (N=4) and 5x5 (N=5) square grid configurations were successfully inserted using the insertion device alone. After implantation, measurements of how much motes tilted (22{+/-}9{degrees}, [X]{+/-}S) and had been displaced relative to their original positions were smaller than those measured for devices implanted inside the brain in the literature. SignificanceCollectively, these data establish the viability of safely implementing motes with ultrasmall electrodes and epicortically-situated chips for use in future BMIs.

bioengineering↗

bioRxiv2024

Self-Assembled Origami Neural Probes for Scalable, Multifunctional, Three-Dimensional Neural Interface

Flexible intracortical neural probes have drawn attention for their enhanced longevity in high-resolution neural recordings due to reduced tissue reaction. However, the conventional monolithic fabrication approach has met significant challenges in: (i) scaling the number of recording sites for electrophysiology; (ii) integrating of other physiological sensing and modulation; and (iii) configuring into three-dimensional (3D) shapes for multi-sided electrode arrays. We report an innovative self-assembly technology that allows for implementing flexible origami neural probes as an effective alternative to overcome these challenges. By using magnetic-field-assisted hybrid self-assembly, multiple probes with various modalities can be stacked on top of each other with precise alignment. Using this approach, we demonstrated a multifunctional device with scalable high-density recording sites, dopamine sensors and a temperature sensor integrated on a single flexible probe. Simultaneous large-scale, high-spatial-resolution electrophysiology was demonstrated along with local temperature sensing and dopamine concentration monitoring. A high-density 3D origami probe was assembled by wrapping planar probes around a thin fiber in a diameter of 80[~]105 m using optimal foldable design and capillary force. Directional optogenetic modulation could be achieved with illumination from the neuron-sized micro-LEDs (LEDs) integrated on the surface of 3D origami probes. We could identify angular heterogeneous single-unit signals and neural connectivity 360{degrees} surrounding the probe. The probe longevity was validated by chronic recordings of 64-channel stacked probes in behaving mice for up to 140 days. With the modular, customizable assembly technologies presented, we demonstrated a novel and highly flexible solution to accommodate multifunctional integration, channel scaling, and 3D array configuration.

neuroscience↗

bioRxiv2023

Sex Dependent Regional Differences in Dopamine Release Determined by Chronic Fast-Scan Cyclic Voltammetry in Nucleus Accumbens and Dorsal Striatum

We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation (ES; 60Hz) induced DA release was recorded in the NAc of single or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than in males. Finally, DA release following ES of the medial forebrain bundle at 60Hz was studied over four weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo. Significance StatementDopamine release is not uniform or fixed. In the nucleus accumbens, pair housing, compared with individual housing, is shown to differentially affect dopamine responsiveness to stimulation in a sex-dependent and region-specific way. There are also sex differences in stimulated dopamine release in the dorsolateral striatum of intact rats, which are not seen in gonadectomized rats, indicating the hormone dependence of this sex difference. However, reuptake of dopamine was slower in females than in males, independent of gonadal hormones. Importantly, the electrical stimulation-induced dopamine release in the dorsolateral striatum of gonadectomized rats demonstrated sensitization of dopamine release in vivo within animals for the first time. Thus, stimulated dopamine release exhibits sex-specific neuroplasticity that is modified in females by the housing conditions.

neuroscience↗

bioRxiv2022

Profiling neurons surrounding subcellular-scale carbon fiber electrode tracts enables modeling recorded signals

Characterizing the relationship between neuron spiking and the signals electrodes record is vital to defining the neural circuits driving brain function and informing computational modeling. However, electrode biocompatibility and precisely localizing neurons around the electrodes are critical to defining this relationship. Here, we show the ability to localize post-explant recording tips of subcellular-scale carbon fiber electrodes and surrounding neurons. Immunostaining of astrocyte, microglia, and neuron markers confirmed improved tissue health. While neurons near implants were stretched, their number and distribution were similar to control, suggesting that these minimally invasive electrodes demonstrate the potential to sample naturalistic neural populations. This motivated prediction of the spikes produced by neurons nearest to the electrodes using a model fit with recorded electrophysiology. These simulations show the first direct evidence that neuron placement in the immediate vicinity of the recording site influences how many spike clusters can be reliably identified by spike sorting.

neuroscience↗

bioRxiv2022

Utah Array Characterization and Histological Analysis of a Multi-Year Implant in Non-Human Primate Motor and Sensory Cortices

The Utah array is widely used in both clinical studies and neuroscience. It has a strong track record of safety. However, it is also known that implanted electrodes promote the formation of scar tissue in the immediate vicinity of the electrodes, which negatively impacts the ability to record neural waveforms. This scarring response has been primarily studied in rats and mice, which may have a very different response than primate brain. Here, we present a rare nonhuman primate histological dataset (n=1 rhesus macaque) obtained 848 and 590 days after implantation in two brain hemispheres. For 2 of 4 arrays that remained within the cortex, NeuN was used to stain for neuron somata at 3 different electrode depths. Images were filtered and denoised, with neurons then counted in the vicinity of the arrays as well as a nearby section of control tissue. Additionally, 3 of 4 arrays were imaged with a scanning electrode microscope (SEM) to evaluate any materials damage that might be present. Overall, we found a 63% percent reduction in the number of neurons surrounding the electrode compared to control areas. In terms of materials, the arrays remained largely intact with metal and Parylene C present, though tip breakage and cracks were observed on many electrodes. Overall, these results suggest that the tissue response in the nonhuman primate brain shows similar neuron loss to previous studies using rodents. Electrode improvements, for example using smaller or softer probes, may therefore substantially increase the neuronal recording yield in primate cortex.

bioengineering↗

bioRxiv2022

Automated assembly of high-density carbon fiber electrode arrays for single unit electrophysiological recordings

ObjectiveCarbon fiber (CF) is good for chronic neural recording due to the small diameter (7 {micro}m), high Youngs modulus, and low electrical resistance, but most high-density carbon fiber (HDCF) arrays are manually assembled with labor-intensive procedures and limited by the accuracy and repeatability of the operator handling. A machine to automate the assembly is desired. ApproachThe HDCF array assembly machine contains: 1) a roller-based CF extruder, 2) a motion system with three linear and one rotary stages, 3) an imaging system with two digital microscope cameras, and 4) a laser cutter. The roller-based extruder automatically feeds single CF as raw material. The motion system aligns the CF with the array backend then places it. The imaging system observes the relative position between the CF and the backend. The laser cutter cuts off the CF. Two image processing algorithms are implemented to align the CF with the support shanks and circuit connection pads. Main resultsThe machine was capable of precisely handling 6.8 m carbon fiber electrodes. Each electrode was placed into a 12 m wide trenches in a silicon support shank. Two HDCF arrays with 16 CF electrodes populated on 3 mm shanks (with 80 m pitch) were fully assembled. Impedance measurements were found to be in good agreement with manual assembled arrays. One HDCF array was implanted in the motor cortex in an anesthetized rat and was able to detect single unit activity. SignificanceThis machine can eliminate the manual labor-intensive handling, alignment and placement of single carbon fiber during assembly, providing a proof-of-concepts towards fully automated HDCF array assembly and batch production.

bioengineering↗

bioRxiv2022

Chromatin-associated lncRNA Malat1 regulates Th17 effector program and promotes intestinal inflammation

Interleukin IL-17 cytokines are central regulators of mucosal homeostasis and disease. In mouse models of colonic tissue injury, IL-17A promotes epithelial barrier functions and restricts local inflammation. Here, we report that IL-17A production by the diverse T lymphocyte subsets is dynamically regulated at different stages of colitis pathogenesis. During the onset and peak of the disease, T{gamma}{delta}17 cells are the major IL-17A producers, while Th17 activity is temporally restricted by long non-coding RNA (lncRNA) Malat1. In response to IL-6 and TGF{beta} signaling, Malat1 is recruited to the Th17-specific cis-regulatory elements, CNS3 and CNS4, of the Il17a locus to fine-tune bivalent super-enhancer activities and repress local transcription. During the resolution phase of inflammation, Malat1 expression is down-regulated to enhance Th17 activities, allowing Th17 cells to emerge as the main producers of IL-17A in the colonic lamina propria. Genetic ablation of Malat1 potentiates IL-17A production in Th17 cells and improves disease outcomes in mouse models of colitis. These findings uncover a surprising role of a chromatin-associated lncRNA in regulating colonic Th17-specific responses to control the timing of inflammation resolution. Significance StatementT cells are critical modulators of mucosal barrier function and inflammation. The function of long-noncoding RNAs (lncRNAs) in T cells and their role in mucosal inflammation remain elusive. Here, we identify an essential role of the lncRNA Malat1 restricting transcription of the Il17a locus in Th17 cells encoding a cytokine implicated in epithelial barrier function post-injury. By controlling the activity of the bivalent super-enhancer at the Il17a locus, Malat1 regulates the timing of inflammation resolution in the intestine. The Malat1-Il17a pathway reveals new targets for combating mucosal diseases. Graphic Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

immunology↗

bioRxiv2022

Ultra-flexible and Stretchable Intrafascicular Peripheral Nerve Recording Device with Axon-dimension, Cuff-less Microneedle Electrode Array

Peripheral nerve mapping tools with higher spatial resolution are needed to advance systems neuroscience, and potentially provide a closed-loop biomarker in neuromodulation applications. Two critical challenges of microscale neural interfaces are (i) how to apply them to small peripheral nerves, and (ii) how to minimize chronic reactivity. We developed a flexible microneedle nerve array (MINA), which is the first high-density penetrating electrode array made with axon-sized silicon microneedles embedded in low-modulus thin silicone. We present the design, fabrication, acute recording, and chronic reactivity to an implanted MINA. Distinctive units were identified in the rat peroneal nerve. We also demonstrate a long-term, cuff-free, and suture-free fixation manner using rose bengal as a light-activated adhesive for two timepoints. The tissue response at 1-week included a sham (N=5) and MINA-implanted (N=5) group, and the response at 6-week also included a sham (N=3) and MINA-implanted (N=4) group. These conditions were quantified in the left vagus nerve of rats using histomorphometry. Micro-CT was added to visualize and quantify tissue encapsulation around the implant. MINA demonstrated a reduction in encapsulation thickness over previously quantified interfascicular methods. Future challenges include techniques for precise insertion of the microneedle electrodes and demonstrating long-term recording.

neuroscience↗

bioRxiv2021

Carbon Fiber Electrodes for Intracellular Recording and Stimulation

To understand neural circuit dynamics, it is critical to manipulate and record from many neurons, ideally at the single neuron level. Traditional recording methods, such as glass microelectrodes, can only control a small number of neurons. More recently, devices with high electrode density have been developed, but few of them can be used for intracellular recording or stimulation in intact nervous systems, rather than on neuronal cultures. Carbon fiber electrodes (CFEs) are 8 micron-diameter electrodes that can be organized into arrays with pitches as low as 80 {micro}m. They have been shown to have good signal-to-noise ratios (SNRs) and are capable of stable extracellular recording during both acute and chronic implantation in vivo in neural tissue such as rat motor cortex. Given the small fiber size, it is possible that they could be used in arrays for intracellular stimulation. We tested this using the large identified and electrically compact neurons of the marine mollusk Aplysia californica. The cell bodies of neurons in Aplysia range in size from 30 to over 250 {micro}m. We compared the efficacy of CFEs to glass microelectrodes by impaling the same neurons cell body with both electrodes and connecting them to a DC coupled amplifier. We observed that intracellular waveforms were essentially identical, but the amplitude and SNR in the CFE were lower than in the glass microelectrode. CFE arrays could record from 3 to 8 neurons simultaneously for many hours, and many of these recordings were intracellular as shown by recording from the same neuron using a glass microelectrode. Stimulating through CFEs coated with platinum-iridium had stable impedances over many hours. CFEs not within neurons could record local extracellular activity. Despite the lower SNR, the CFEs could record synaptic potentials. Thus, the stability for multi-channel recording and the ability to stimulate and record intracellularly make CFEs a powerful new technology for studying neural circuit dynamics.

neuroscience↗

bioRxiv2021

Serine 182 on RORγt regulates T helper 17 and regulatory T cell functions to resolve inflammation

Intestine homeostasis is maintained by the delicate balance of Th17 effector cells and Treg cells. Dysregulation of these cell populations contributes to inflammation, tissue damage, and chronic conditions. ROR{gamma}t is essential for the differentiation of Th17 and a subset of Treg (ROR{gamma}t+ Treg) cells involved in intestinal inflammation. ROR{gamma}t belongs to the nuclear receptor family of transcription factors with hinge regions that are highly flexible for co-activator/co-repressor interactions. Serine 182 at the hinge region of ROR{gamma}t is phosphorylated. This study aims to uncover how S182 on ROR{gamma}t contributes to mucosal homeostasis and diseases. We used CRISRP technology to generate a phosphor-null knock-in mutant mouse line (ROR{gamma}tS182A) to assess its role in intestine physiology. scRNA-seq was performed on WT and ROR{gamma}tS182A cohoused littermates to evaluate colonic T cell heterogeneity under steady state and colitis settings. Single-cell transcriptomics revealed that ROR{gamma}tS182 maintains colonic T cell heterogeneity under steady state, without interfering T cell development and differentiation. In inflamed tissues, ROR{gamma}tS182 simultaneously restricts IL-1{beta}-mediated Th17 activities and promotes anti-inflammatory cytokine IL-10 production in LT-like Treg cells. Phospho-null ROR{gamma}tS182A knock-in mice challenged with DSS induced colitis and EAE experienced delayed recovery and exacerbated pathology. The double switch role of ROR{gamma}tS182 is critical in resolving T cell-mediated inflammation and provides a potential therapeutic target to combat autoimmune diseases.

immunology↗

bioRxiv2021

Benchtop Carbon Fiber Microelectrode Array Fabrication Toolkit

BackgroundConventional neural probes are primarily fabricated in a cleanroom, requiring the use of multiple expensive and highly specialized tools. New methodWe propose a cleanroom "light" fabrication process of carbon fiber neural electrode arrays that can be learned quickly by an inexperienced cleanroom user. This carbon fiber electrode array fabrication process requires just one cleanroom tool, a parylene-c deposition machine, that can be learned quickly or outsourced to a commercial processing facility at marginal cost. Our fabrication process also includes hand-populating printed circuit boards, insulation, and tip optimization. ResultsThe three different tip optimizations explored here (Nd:YAG laser, blowtorch, and UV laser) result in a range of tip geometries and 1kHz impedances, with blowtorched fibers resulting in the lowest impedance. While previous experiments have proven laser and blowtorch electrode efficacy, this paper also shows UV laser cut fibers can record neural signals in vivo. Comparison with existing methodsExisting carbon fiber arrays either do not have individuated electrodes in favor of bundles or require cleanroom fabricated guides for population and insulation. The proposed arrays use only tools that can be used at a benchtop for fiber population. ConclusionsThis carbon fiber electrode array fabrication process allows for quick customization of bulk array fabrication at a reduced price compared to commercially available probes.

bioengineering↗

bioRxiv2021

Sharpened and mechanically robust carbon fiber electrode arrays for neural interfacing

Bioelectric medicine treatments target disorders of the nervous system unresponsive to pharmacological methods. While current stimulation paradigms effectively treat many disorders, the underlying mechanisms are relatively unknown, and current neuroscience recording electrodes are often limited in their specificity to gross averages across many neurons or axons. Here, we develop a novel, durable carbon fiber electrode array adaptable to many neural structures for precise neural recording. Carbon fibers were sharpened using a reproducible blowtorch method that uses the reflection of fibers against the surface of a water bath. The arrays were developed by partially embedding carbon fibers in medical-grade silicone to improve durability. We recorded acute spontaneous electrophysiology from the rat cervical vagus nerve (CVN), feline dorsal root ganglia (DRG), and rat brain. Blowtorching resulted in fibers of 72.3 {+/-} 33.5 degree tip angle with 146.8 {+/-} 17.7 m exposed carbon. Silicone-embedded carbon fiber arrays were durable with 87.5% of fibers remaining after 50,000 passes. Observable neural clusters were recorded using sharpened carbon fiber electrodes from rat CVN (41.8 Vpp), feline DRG (101.1 Vpp), and rat brain (80.7 Vpp). Recordings from the feline DRG included physiologically-relevant signals from increased bladder pressure and cutaneous brushing. These results suggest that this carbon fiber array is a uniquely durable and adaptable neural recording device. In the future, this device may be useful as a bioelectric medicine tool for diagnosis and closed-loop neural control of therapeutic treatments and monitoring systems.

bioengineering↗

bioRxiv2020

Lentiviral interleukin-10 gene therapy preserves fine motor circuitry and function after a cervical spinal cord injury in male and female mice

In mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading onto an implantable biomaterial scaffold, into a left-sided hemisection at the C5 vertebra in mice. We hypothesized that improved behavioral outcomes associated with anti-inflammatory treatment are due to the sparing of fine motor circuit components. We examined behavioral recovery using a ladder beam, lower motor neuron apoptosis and muscle innervation using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2 weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12 weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons and muscle innervation at 2 weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ratios and peak-to-peak amplitudes more similar to that of uninjured controls than to that of control injured animals at 2 weeks post-injury. These data show that gene therapy using anti-inflammatory interleukin-10 can significantly reduce lower motor neuron loss, muscle denervation, and subsequent motor deficits after a spinal cord injury. Together, these results suggest that early modulation of the injury response can preserve muscle function with long-lasting benefits.

neuroscience↗

bioRxiv2020

Cellular-scale silicon probes for high-density, precisely-localized neurophysiology

Neural implants with large numbers of electrodes have become an important tool for examining brain functions. However, these devices typically displace a large intracranial volume compared to the neurons they record. This large size limits the density of implants, provokes tissue reactions that degrade chronic performance, and impedes the ability to accurately visualize recording sites within intact circuits. Here we report next-generation silicon-based neural probes at cellular-scale (5x10{micro}m cross-section), with ultra-high-density packing (as little as 66{micro}m between shanks) and 64 or 256 closely-spaced recording sites per probe. We show that these probes can be inserted into superficial or deep brain structures and maintain high-quality spike recordings in freely behaving rats for many weeks. Finally, we demonstrate a slice-in-place approach for the precise registration of recording sites relative to nearby neurons and anatomical features, including striatal {micro}-opioid receptor patches. This scalable technology provides a valuable tool for examining information processing within neural circuits, and potentially for human brain-machine interfaces.

bioengineering↗

bioRxiv2020

Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array

Autonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8-9 m in diameter, 150-250 m in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1-91.7 V and signal-to-noise ratios of 2.0-8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7-4.4 m/sec) and efferent (0.7-8.8 m/sec) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.

bioengineering↗

bioRxiv2020

DDX5 targets tissue-specific RNAs to promote intestine tumorigenesis

Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that an RNA binding protein DDX5 augments C3 and FABP1 expressions post-transcriptionally to promote tumorigenesis in the colon and small intestine, respectively. Mice with epithelial-specific knockout of DDX5 are protected from intestine tumorigenesis. The identification of DDX5 as the common upstream regulator of tissue-specific oncogenic molecules provides a new therapeutic target for intestine cancers.

cancer biology↗