About

Xinzhong Dong is a Professor of Neuroscience, Neurosurgery, and Dermatology at The Solomon H Snyder Department of Neuroscience, Johns Hopkins School of Medicine. His profile is listed among former members of the department, indicating his previous affiliation and contributions to the field. The page provides information about his academic background, research focus, and professional trajectory, but does not include a detailed personal biography or specific descriptions of his research interests or key contributions.

Research topics

• Medicine
• Neuroscience
• Biology
• Immunology
• Cell biology
• Dermatology

Selected publications

• Ectopic engraftment of nociceptive neurons derived from hPSCs for pain relief and joint homeostasis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-19

  articleOpen accessSenior authorCorresponding

  SUMMARY Chronic pain arises from the interplay of inflammatory signals that activate and sensitize nociceptors within injured tissues. Most analgesics fail clinically due to their mono-targeted mechanisms. Here, we apply human pluripotent stem cell–derived nociceptive neurons (hPSC-NNs) as therapeutic agents for osteoarthritis, targeting both pain and joint degeneration. We generated sensory neurons from hPSCs and identified CD200 as a nociceptor marker. Transcriptomic and functional profiling revealed that CD200 high hPSC-NNs closely resemble human nociceptors, expressing pain-relevant receptors and ion channels. Strikingly, ectopic transplantation of CD200 high hPSC-NNs into the knee joint of osteoarthritic mice reduced pain and promoted bone and cartilage repair, whereas CD200 low cells exhibited no benefit. Mechanistically, human and mouse proteomics suggest that CD200 high hPSC-NNs act as decoys by sequestering inflammatory ligands while secreting reparative factors in joint tissues. These findings uncover a fundamental role of nociceptors in tissue repair, providing a multi-targeted, disease-modifying strategy for OA and chronic pain. GRAPHIC ABSTRACT HIGHLIGHTS hPSC-derived nociceptors (hPSC-NNs) as Decoy Engraftment for Cellular Interception and Repair (DECIR) when transplanted into the knee joint, extending beyond conventional regenerative strategies CD200 serves as a clinically actionable surface marker for the purification of hPSC-NNs Ectopic grafting of CD200 high hPSC-NNs delivers dual benefits, alleviating pain and modulating the neuro-immune environment within joint tissues Proteomic analyses reveal that CD200 high hPSC-NNs sequester inflammatory mediators and secrete reparative factors to support joint homeostasis

  PublisherDOI

• Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force

  Cell · 2025-03-24 · 37 citations

  articleOpen access
  PublisherOA PDFDOI

• Local B cell maturation and mast cell regulation of choroid plexus function in early life.

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-01

  preprintOpen access

  Abstract Postnatal development is a critical period for the maturation of the nervous and immune systems. The choroid plexus (CP) within the brain ventricles guides brain development through the production of cerebrospinal fluid and responds to stimuli from its local immune microenvironment. Here, using single-cell sequencing, we chart the establishment of the immune niche within the CP from birth to adulthood. We demonstrate that the CP is an active site for the development of B cells from early pro-B cells to mature B cells. We also characterize a transient population of CP mast cells that is highly abundant in the perinatal period. Single activation of these cells shortly after birth led to activation of serotonin-dependent secretion from the CP epithelial cells and resulted in cognitive impairment later in life. Our findings highlight the crucial nature of the CP as a neuroimmune interface, where cellular crosstalk regulates key functions of CP activity, thereby guiding brain development.

  PublisherOA PDFDOI

• Epicutaneous Staphylococcus aureus initiates cross-tissue IL-36R signaling for neutrophilic lung inflammation in a model of the atopic march

  Cell Reports · 2025-07-24 · 4 citations

  articleOpen access

  Patients with atopic dermatitis exhibit abundant Staphylococcus aureus skin colonization and an increased risk of atopic march diseases, including allergic rhinitis, food allergies, and asthma. We have previously shown that S. aureus skin exposure exacerbates allergic lung inflammation in an interleukin-36 receptor (IL-36R)-dependent manner. However, the cellular and molecular mechanisms by which S. aureus skin exposure and IL-36R signaling orchestrate the progression from skin to lung inflammation are unclear. Using a preclinical model of the atopic march, we found that S. aureus skin exposure promoted robust neutrophilic lung inflammation via keratinocyte- and lung epithelia-specific IL-36R signaling. Unexpectedly, neutrophil IL-36R signaling triggered neutrophil extracellular trap (NET) formation and augmented lung pathology. Importantly, anti-IL-36R monoclonal antibody (mAb) treatment prevented the development of neutrophilic lung inflammation. Collectively, our findings suggested that S. aureus skin exposure exacerbates lung inflammation via distinct IL-36R signaling mechanisms on epithelia and neutrophils, which has therapeutic potential in halting the progression of the atopic march.

  PublisherOA PDFDOI

• Demyelination-Related Pain: Role of Lysophosphatidic Acid in Satellite Glial Cell-Neuron Crosstalk

  Research Square · 2025-09-11

  preprintOpen access
  PublisherOA PDFDOI

• A mouse model of classical trigeminal neuralgia via intradural compression of the trigeminal nerve

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-26

  preprintOpen access

  Introduction: Trigeminal neuralgia (TN) is a debilitating orofacial pain condition that adversely affects quality of life. Although heterogeneous, the most common form of TN is classical TN, characterized by paroxysmal bouts of pain in response to otherwise innocuous stimuli. It is believed that classical TN results from neurovascular compression of the trigeminal nerve. However, the underlying pathophysiology of TN is not well understood, thus limiting the development of targeted therapies. Current animal models lack translational relevance, particularly in their inability to replicate intradural nerve root compression, a core anatomic component of TN. Methods: We developed a TN mouse model that achieves intradural nerve root compression via a retro-orbital approach confirmed by anatomic dissection and magnetic resonance imaging. To assess behavioral outcomes, we measured orofacial pain through facial wiping and interaction with a reward stimulus. Pharmacological responsiveness was tested using carbamazepine administration. Mechanistic studies included calcium imaging of trigeminal ganglia (TG), electrophysiologic recordings to measure resting membrane potential and rheobase, and immunohistochemical analysis of the TG. Results: The model elicited orofacial neuropathic pain, substantiated by increased facial wiping and reduced interaction with a reward stimulus, behaviors that suggest both spontaneous and evoked pain. Carbamazepine attenuated these behaviors, suggesting pharmacologic relevance to current TN treatment. Calcium imaging showed heightened spontaneous activity in the TG, and electrophysiologic recordings revealed an increased resting membrane potential and a reduced rheobase. Finally, immunohistochemical studies showed infiltration of CD45+ cells, demyelination and an increase in CGRP expression in the TG, supporting the presence of neuroinflammation after nerve root compression. Conclusion: These findings show that our approach replicates the anatomy and clinical presentation of classical TN in humans. This model may represent a new and robust platform for future mechanistic studies of TN and subsequent preclinical evaluation of therapies in mice.

  PublisherOA PDFDOI

• An interorgan neuroimmune circuit promotes visceral hypersensitivity

  Research Square · 2025-03-17 · 3 citations

  preprintOpen access
  PublisherOA PDFDOI

• Vascular motion in the dorsal root ganglion sensed by Piezo2 in sensory neurons triggers episodic pain

  Neuron · 2025-03-29 · 12 citations

  articleOpen access
  PublisherOA PDFDOI

• Specific Stimulation and Multiplex Secretion Analysis of T Cells Using a Suspendable Hydrogel Platform Enables Immunophenotyping at the Single-Cell Scale

  ACS Nano · 2025-06-20 · 1 citations

  article

  The ability to characterize and separate cells based on their surface marker expression profiles using flow cytometry revolutionized our understanding of the immune system at the level of single cells. However, the use of surface protein quantification to functionally evaluate T cells following stimulation fails to capture important outcomes of T cell activation, most prominently, cytokine secretion. This key limitation hinders elucidation of the mechanistic correlates of T cell function, which in turn limits our ability to design effective cell therapies for diseases such as cancer and autoimmune disorders. Here, we employ a single-cell microparticle-based technology (termed nanovials) to assess both the cell surface expression profiles and the protein secretion behavior of stimulated T cells. Using protein-conjugated nanovials, we demonstrated the capacity to stimulate ovalbumin-specific primary mouse CD8+ T cells, both nonspecifically by coating anti-CD3 and anti-CD28 antibodies on the particle, and specifically by coating ovalbumin peptide-loaded major histocompatibility complexes and anti-CD28 antibody on the particle. We further showed that nanovials could simultaneously capture secretions of multiple cytokines from single cells and that viable T cells contained within the nanovials could be sorted based on cytokine secretion levels. We applied this platform to characterize the phenotypic profile of resting T cells that would go on to secrete the interferon gamma (IFNγ) cytokine following activation on nanovials by staining cells for surface marker expression prior to on-particle stimulation. Overall, the nanovial platform and assays developed herein help elucidate the functional properties of T cells, which will inform the engineering of future cell therapies.

  PublisherDOI

• Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis

  Diabetes Care · 2025-07-29 · 10 citations

  articleOpen access

  OBJECTIVE: In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use. RESEARCH DESIGN AND METHODS: Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persistent ≥50% eGFR reduction from baseline, kidney failure, or death from kidney/CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended. RESULTS: Effects were analyzed by baseline MRA use (n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse (n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P-interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups (P-interaction > 0.7). Albuminuria at 104 weeks was reduced from baseline with semaglutide by 15% (95% CI -41, 31) in MRA users and 33% (26, 39) in nonusers versus placebo (P-interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide (P-interaction = 0.71). The safety profile of semaglutide was comparable between subgroups. CONCLUSIONS: In participants with T2D and CKD, consistent benefits of semaglutide on major kidney outcomes, MACE, and all-cause mortality were observed regardless of baseline MRA use.

  PublisherOA PDFDOI

Recent grants

• Interdisciplinary Training in Biobehavioral Pain Research

  NIH · $3.6M · 2005–2026

• Functional Analysis of Mrgpr Family in itch sensation

  NIH · $2.9M · 2007–2029

• Characterization of a dendritic cell specific receptor critical for SJS

  NIH · $1.6M · 2018–2023

• NIH Grant R03DA033176

  NIH · $82k · 2013

• JHU Center for Neuroscience Research

  NIH · $21.8M · 2005–2021

Frequent coauthors

• Yun Guan

  Johns Hopkins University

  289 shared

• Srinivasa N. Raja

  134 shared

• Qian Xu

  Johns Hopkins Medicine

  123 shared

• Shao-Qiu He

  Johns Hopkins Medicine

  106 shared

• Nathachit Limjunyawong

  Johns Hopkins University

  98 shared

• Fei Yang

  Jinan Central Hospital

  92 shared

• Vinod Tiwari

  85 shared

• Qian Huang

  Johns Hopkins Medicine

  81 shared

Labs

• Xinzhong Dong LabPI

  Not provided

Education

• PhD, Biological Chemistry

  University of California, Los Angeles

  1998

• BA

  College of the Holy Cross

  1992