Xinyue Zhang

All Publications

• Achieving inclusive healthcare through integrating education and research with AI and personalized curricula. Communications medicine Bahmani, A., Cha, K., Alavi, A., Dixit, A., Ross, A., Park, R., Goncalves, F., Ma, S., Saxman, P., Nair, R., Akhavan-Sarraf, R., Zhou, X., Wang, M., Contrepois, K., Li-Pook-Than, J., Monte, E., Rodriguez, D. J., Lai, J., Babu, M., Tondar, A., Schüssler-Fiorenza Rose, S. M., Akbari, I., Zhang, X., Yegnashankaran, K., Yracheta, J., Dale, K., Miller, A. D., Edmiston, S., McGhee, E. M., Nebeker, C., Wu, J. C., Kundaje, A., Snyder, M. 2025; 5 (1): 356

  Abstract

  Precision medicine promises significant health benefits but faces challenges such as complex data management and analytics, interdisciplinary collaboration, and education of researchers, healthcare professionals, and participants. Addressing these needs requires the integration of computational experts, engineers, designers, and healthcare professionals to develop user-friendly systems and shared terminologies. The widespread adoption of large language models (LLMs) such as Generative Pretrained Transformer (GPT) and Claude highlights the importance of making complex data accessible to non-specialists.We evaluated the Stanford Data Ocean (SDO) precision medicine training program's learning outcomes, AI Tutor performance, and learner satisfaction by assessing self-rated competency on key learning objectives through pre- and post-learning surveys, along with formative and summative assessment completion rates. We also analyzed AI Tutor accuracy and learners' self-reported satisfaction, and post-program academic and career impacts. Additionally, we demonstrated the capabilities of the AI Data Visualization tool.SDO demonstrates the ability to improve learning outcomes for learners from broad educational and socioeconomic backgrounds with the support of the AI Tutor. The AI Data Visualization tool enables learners to interpret multi-omics and wearable data and replicate research findings.SDO strives to mitigate challenges in precision medicine through a scalable, cloud-based platform that supports data management for various data types, advanced research, and personalized learning. SDO provides AI Tutors and AI-powered data visualization tools to enhance educational and research outcomes and make data analysis accessible to users from broad educational backgrounds. By extending engagement and cutting-edge research capabilities globally, SDO particularly benefits economically disadvantaged and historically marginalized communities, fostering interdisciplinary biomedical research and bridging the gap between education and practical application in the biomedical field.

  View details for DOI 10.1038/s43856-025-01034-y

  View details for PubMedID 40819118

  View details for PubMedCentralID 9108683

• Exposomics: a review of methodologies, applications, and future directions in molecular medicine. EMBO molecular medicine Wan, M., Simonin, E. M., Johnson, M. M., Zhang, X., Lin, X., Gao, P., Patel, C. J., Yousuf, A., Snyder, M. P., Hong, X., Wang, X., Sampath, V., Nadeau, K. C. 2025

  Abstract

  The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses. These molecular alterations can aid as biomarkers for the diagnosis, disease prediction, early detection, and treatment and offering new avenues for personalized medicine. Advances in high throughput omics and other technologies as well as increased computational analytics is enabling comprehensive measurement and sophisticated analysis of the exposome to elucidate their cumulative and combined impacts on health, which can enable individuals, communities, and policymakers to create programs, policies, and protections that promote healthier environments and people. This review provides an overview of the potential role of exposomics in molecular medicine, covering its history, methodologies, current research and applications, and future directions.

  View details for DOI 10.1038/s44321-025-00191-w

  View details for PubMedID 39870881

  View details for PubMedCentralID 8919561

• Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease. Cell host & microbe Zhou, X., Shen, X., Johnson, J. S., Spakowicz, D. J., Agnello, M., Zhou, W., Avina, M., Honkala, A., Chleilat, F., Chen, S. J., Cha, K., Leopold, S., Zhu, C., Chen, L., Lyu, L., Hornburg, D., Wu, S., Zhang, X., Jiang, C., Jiang, L., Jiang, L., Jian, R., Brooks, A. W., Wang, M., Contrepois, K., Gao, P., Rose, S. M., Tran, T. D., Nguyen, H., Celli, A., Hong, B. Y., Bautista, E. J., Dorsett, Y., Kavathas, P. B., Zhou, Y., Sodergren, E., Weinstock, G. M., Snyder, M. P. 2024

  Abstract

  To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.

  View details for DOI 10.1016/j.chom.2024.02.012

  View details for PubMedID 38479397

• California Stress, Trauma, and Resilience Study (CalSTARS) protocol: A multiomics-based cross-sectional investigation and randomized controlled trial to elucidate the biology of ACEs and test a precision intervention for reducing stress and enhancing resilience. Stress (Amsterdam, Netherlands) Kim, L. Y., Schüssler-Fiorenza Rose, S. M., Mengelkoch, S., Moriarity, D. P., Gassen, J., Alley, J. C., Roos, L. G., Jiang, T., Alavi, A., Thota, D. D., Zhang, X., Perelman, D., Kodish, T., Krupnick, J. L., May, M., Bowman, K., Hua, J., Liao, Y. J., Lieberman, A. F., Butte, A. J., Lester, P., Thyne, S. M., Hilton, J. F., Snyder, M. P., Slavich, G. M. 2024; 27 (1): 2401788

  Abstract

  Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes of death in the United States. Despite this fact, our mechanistic understanding of how ACEs impact health is limited. Moreover, interventions for reducing stress presently use a one-size-fits-all approach that involves no treatment tailoring or precision. To address these issues, we developed a combined cross-sectional study and randomized controlled trial, called the California Stress, Trauma, and Resilience Study (CalSTARS), to (a) characterize how ACEs influence multisystem biological functioning in adults with all levels of ACE burden and current perceived stress, using multiomics and other complementary approaches, and (b) test the efficacy of our new California Precision Intervention for Stress and Resilience (PRECISE) in adults with elevated perceived stress levels who have experienced the full range of ACEs. The primary trial outcome is perceived stress, and the secondary outcomes span a variety of psychological, emotional, biological, and behavioral variables, as assessed using self-report measures, wearable technologies, and extensive biospecimens (i.e. DNA, saliva, blood, urine, & stool) that will be subjected to genomic, transcriptomic, proteomic, metabolomic, lipidomic, immunomic, and metagenomic/microbiome analysis. In this protocol paper, we describe the scientific gaps motivating this study as well as the sample, study design, procedures, measures, and planned analyses. Ultimately, our goal is to leverage the power of cutting-edge tools from psychology, multiomics, precision medicine, and translational bioinformatics to identify social, molecular, and immunological processes that can be targeted to reduce stress-related disease risk and enhance biopsychosocial resilience in individuals and communities worldwide.

  View details for DOI 10.1080/10253890.2024.2401788

  View details for PubMedID 39620249

• Pharmacologic Targeting of the C-Terminus of Heat Shock Protein 90 Improves Neuromuscular Function in Animal Models of Charcot Marie Tooth X1 Disease ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE Kaur, S., Zhang, X., Patel, S., Rodriguez, Y. A., Luther, K. J., Alghafli, G., Lang, R. M., Abrams, C. K., Dobrowsky, R. T. 2023: 306-319

  Abstract

  Charcot-Marie-Tooth X1 (CMTX1) disease is an inherited peripheral neuropathy that arises from loss-of-function mutations in the protein connexin 32 (Cx32). CMTX1 currently lacks a pharmacologic approach toward disease management, and we have previously shown that modulating the expression of molecular chaperones using novologue therapy may provide a viable disease-modifying approach to treat metabolic and demyelinating neuropathies. Cemdomespib is an orally bioavailable novologue that manifests neuroprotective activity by modulating the expression of heat shock protein 70 (Hsp70). We examined if 1 to 5 months of daily cemdomespib therapy may improve neuropathic symptoms in three mouse models of CMTX1 (Cx32 deficient (Cx32def), T55I-Cx32def, and R75W-Cx32 mice). Daily drug therapy significantly improved motor nerve conduction velocity (MNCV) and grip strength in all three models, but the compound muscle action potential was only improved in Cx32def mice. Drug efficacy required Hsp70 as improvements in MNCV, and the grip strength was abrogated in Cx32def × Hsp70 knockout mice. Five months of novologue therapy was associated with improved neuromuscular junction morphology, femoral motor nerve myelination, reduction in foamy macrophages, and a decrease in Schwann cell c-jun levels. To determine if c-jun may be downstream of Hsp70 and necessary for drug efficacy, c-jun expression was specifically deleted in Schwann cells of Cx32def mice. While the deletion of c-jun worsened the neuropathy, cemdomespib therapy remained effective in improving MNCV and grip strength. Our data show that cemdomespib therapy improves CMTX1-linked neuropathy in an Hsp70-dependent but a c-jun-independent manner and without regard to the nature of the underlying Cx32 mutation.

  View details for DOI 10.1021/acsptsci.2c00223

  View details for Web of Science ID 000924937300001

  View details for PubMedID 36798471

  View details for PubMedCentralID PMC9926526

• Charting the landscape of the environmental exposome IMETA Wei, X., Huang, Z., Jiang, L., Li, Y., Zhang, X., Leng, Y., Jiang, C. 2022; 1 (4)

  View details for DOI 10.1002/imt2.50

  View details for Web of Science ID 001136692200004

• Precision environmental health monitoring by longitudinal exposome and multi-omics profiling. Genome research Gao, P., Shen, X., Zhang, X., Jiang, C., Zhang, S., Zhou, X., Schüssler-Fiorenza Rose, S. M., Snyder, M. 2022

  Abstract

  Conventional environmental health studies have primarily focused on limited environmental stressors at the population level, which lacks the power to dissect the complexity and heterogeneity of individualized environmental exposures. Here, as a pilot case study, we integrated deep-profiled longitudinal personal exposome and internal multi-omics to systematically investigate how the exposome shapes a single individual's phenome. We annotated thousands of chemical and biological components in the personal exposome cloud and found they were significantly correlated with thousands of internal biomolecules, which was further cross-validated using corresponding clinical data. Our results showed that agrochemicals and fungi predominated in the highly diverse and dynamic personal exposome, and the biomolecules and pathways related to the individual's immune system, kidney, and liver were highly associated with the personal external exposome. Overall, this data-driven longitudinal monitoring study shows the potential dynamic interactions between the personal exposome and internal multi-omics, as well as the impact of the exposome on precision health by producing abundant testable hypotheses.

  View details for DOI 10.1101/gr.276521.121

  View details for PubMedID 35667843

• Human exposome assessment platform. Environmental epidemiology (Philadelphia, Pa.) Merino Martinez, R., Muller, H., Negru, S., Ormenisan, A., Arroyo Muhr, L. S., Zhang, X., Trier Moller, F., Clements, M. S., Kozlakidis, Z., Pimenoff, V. N., Wilkowski, B., Boeckhout, M., Ohman, H., Chong, S., Holzinger, A., Lehtinen, M., van Veen, E., Bala, P., Widschwendter, M., Dowling, J., Tornroos, J., Snyder, M. P., Dillner, J. 1800; 5 (6): e182

  Abstract

  The Human Exposome Assessment Platform (HEAP) is a research resource for the integrated and efficient management and analysis of human exposome data. The project will provide the complete workflow for obtaining exposome actionable knowledge from population-based cohorts. HEAP is a state-of-the-science service composed of computational resources from partner institutions, accessed through a software framework that provides the world's fastest Hadoop platform for data warehousing and applied artificial intelligence (AI). The software, will provide a decision support system for researchers and policymakers. All the data managed and processed by HEAP, together with the analysis pipelines, will be available for future research. In addition, the platform enables adding new data and analysis pipelines. HEAP's final product can be deployed in multiple instances to create a network of shareable and reusable knowledge on the impact of exposures on public health.

  View details for DOI 10.1097/EE9.0000000000000182

  View details for PubMedID 34909561

• Decoding personal biotic and abiotic airborne exposome. Nature protocols Jiang, C., Zhang, X., Gao, P., Chen, Q., Snyder, M. 2021

  Abstract

  The complexity and dynamics of human diseases are driven by the interactions between internal molecular activities and external environmental exposures. Although advances in omics technology have dramatically broadened the understanding of internal molecular and cellular mechanisms, understanding of the external environmental exposures, especially at the personal level, is still rudimentary in comparison. This is largely owing to our limited ability to efficiently collect the personal environmental exposome (PEE) and extract the nucleic acids and chemicals from PEE. Here we describe a protocol that integrates hardware and experimental pipelines to collect and decode biotic and abiotic external exposome at the individual level. The described protocol has several advantages over conventional approaches, such as exposome monitoring at the personal level, decontamination steps to increase sensitivity and simultaneous capture and high-throughput profiling of biotic and abiotic exposures. The protocol takes ~18 h of bench time over 2-3 d to prepare samples for high-throughput profiling and up to a couple of weeks of instrumental time to analyze, depending on the number of samples. Hundreds to thousands of species and organic compounds could be detected in the airborne particulate samples using this protocol. The composition and complexity of the biotic and abiotic substances are heavily influenced by the sampling spatiotemporal factors. Basic skillsets in molecular biology and analytical chemistry are required to carry out this protocol. This protocol could be modified to decode biotic and abiotic substances in other types of low or ultra-low input samples.

  View details for DOI 10.1038/s41596-020-00451-8

  View details for PubMedID 33437065

• The Exposome in the Era of the Quantified Self ANNUAL REVIEW OF BIOMEDICAL DATA SCIENCE, VOL 4 Zhang, X., Gao, P., Snyder, M. P. edited by Altman, R. B. 2021; 4: 255-277

  View details for DOI 10.1146/annurev-biodatasci-012721-122807

  View details for Web of Science ID 000677831600013

• Targeting Heat Shock Protein 70 to Ameliorate c-Jun Expression and Improve Demyelinating Neuropathy ACS CHEMICAL NEUROSCIENCE Zhang, X., Li, C., Fowler, S. C., Zhang, Z., Blagg, B. S. J., Dobrowsky, R. T. 2018; 9 (2): 381-+

  Abstract

  Increased expression of the c-jun transcription factor occurs in a variety of human neuropathies and is critical in promoting Schwann cell (SC) dedifferentiation and loss of the myelinated phenotype. Using cell culture models, we previously identified KU-32 as a novobiocin-based C-terminal heat shock protein 90 (Hsp90) inhibitor that decreased c-jun expression and the extent of demyelination. Additional chemical optimization has yielded KU-596 as a neuroprotective novologue whose mechanistic efficacy to improve a metabolic neuropathy requires the expression of Hsp70. The current study examined whether KU-596 therapy could decrease c-jun expression and improve motor function in an inducible transgenic model of a SC-specific demyelinating neuropathy (MPZ-Raf mice). Treating MPZ-Raf mice with tamoxifen activates the MAPK kinase pathway, increases c-jun expression and produces a profound demyelinating neuropathy characterized by a loss of motor function and paraparesis. KU-596 therapy did not interfere with MAPK activation but reduced c-jun expression, significantly improved motor performance, and ameliorated the extent of peripheral nerve demyelination in both prevention and intervention studies. Hsp70 was necessary for the drug's neuroprotective efficacy since MPZ-Raf × Hsp70 knockout mice did not respond to KU-596 therapy. Collectively, our data indicate that modulating Hsp70 may provide a novel therapeutic approach to attenuate SC c-jun expression and ameliorate the onset of certain demyelinating neuropathies in humans.

  View details for DOI 10.1021/acschemneuro.7b00377

  View details for Web of Science ID 000426144000028

  View details for PubMedID 29120605

  View details for PubMedCentralID PMC5821551