About

Yifan Zheng is an assistant professor in the Department of History at the University of Washington, specializing in the social, legal, and institutional history of ancient China. His research examines how legal and administrative practices shaped the lives and identities of people across the social spectrum in the Warring States, Qin, and Han periods, with particular attention to marginalized groups and frontier regions. He is currently working on a manuscript for his first book, which analyzes excavated manuscripts, transmitted texts, and archaeological materials to explore how early imperial governments identified, categorized, and managed populations. The book aims to reconstruct state mechanisms such as registration systems, penal labor regimes, and frontier control, illustrating how these groups navigated state authority and reshaped societal boundaries in early Chinese society. Zheng's approach adopts a bottom-up, periphery-to-center perspective, using case studies of peripheral towns to explore the practical implementation of imperial policies. He joined the University of Washington in Autumn 2025 after serving as a Postdoctoral Fellow at the National University of Singapore. His previous academic experiences include visiting scholar positions at Kyoto University and the Yuelu Academy. His future research plans involve integrating geographical, economic, and environmental factors and extending his chronological scope into the early medieval period to develop a broader understanding of ancient Chinese history.

Research topics

• Cardiology
• Medicine
• Internal medicine
• Pathology
• Biology

Selected publications

• Protocol for studying dynamics of parasite-host-mediated endothelial inflammation in 3D engineered brain microvessels

  STAR Protocols · 2025-10-31

  articleOpen accessSenior author

  .

  PublisherDOI

• Assessing the accuracy of eplet mismatching using imputed HLA typing

  Human Immunology · 2025-09-01

  article
  PublisherDOI

• The LTB4-BLT1 axis attenuates influenza-induced lung inflammation by suppressing NLRP3 activation

  Cell Death Discovery · 2025-04-06 · 4 citations

  articleOpen access

  The mortality associated with influenza A virus (IAV) infection typically results from excessive immune responses, leading to immunopathological lung damage and compromised pulmonary function. Various immunomodulators are seen beneficial when used in conjunction with direct anti-infection treatment. Leukotriene B4 (LTB4) is a derivative of arachidonic acid (AA) and has been shown to be advantageous for numerous infectious diseases, allergies, and autoimmune disorders. Nonetheless, the function of LTB4 in influenza infection remains unclear. This study demonstrates that LTB4 and its primary receptor BLT1, as opposed to the secondary receptor BLT2, act as a protective immune modulator during influenza infection in bone marrow-derived macrophages and mouse models. Mechanistically, LTB4 promotes K27-linked and K48-linked polyubiquitination of the NLRP3 protein at its K886 and K1023 sites via a cAMP/PKA-dependent pathway, which inhibits NLRP3 inflammasome assembly and thereby diminishes subsequent NLRP3 inflammasome activation. The consequent decline in the release of IL-1β and IL-18 leads to a reduction in inflammation caused by viral infection. Furthermore, the administration of a LTB4 treatment in a fatal IAV infection model can mitigate the excessive NLRP3 inflammasome activation and reduce IAV-induced severe pulmonary damage. These findings illustrate the protective function of LTB4 in fatal IAV infection by mitigating the severe inflammation induced by the virus.

  PublisherOA PDFDOI

• Microvascularization in 3D Human Engineered Tissue and Organoids

  Annual Review of Biomedical Engineering · 2025-05-01 · 8 citations

  reviewOpen access

  The microvasculature, a complex network of small blood vessels, connects systemic circulation with local tissues, facilitating the nutrient and oxygen exchange that is critical for homeostasis and organ function. Engineering these structures is paramount for advancing tissue regeneration, disease modeling, and drug testing. However, replicating the intricate architecture of native vascular systems-characterized by diverse vessel diameters, cellular constituents, and dynamic perfusion capabilities-presents significant challenges. This complexity is compounded by the need to precisely integrate biomechanical, biochemical, and cellular cues. Recent breakthroughs in microfabrication, organoids, bioprinting, organ-on-a-chip platforms, and in vivo vascularization techniques have propelled the field toward faithfully replicating vascular complexity. These innovations not only enhance our understanding of vascular biology but also enable the generation of functional, perfusable tissue constructs. Here, we explore state-of-the-art technologies and strategies in microvascular engineering, emphasizing key advancements and addressing the remaining challenges to developing fully functional vascularized tissues.

  PublisherDOI

• The role of 8-OxoG and its repair systems in liver diseases progression: responsible mechanisms and promising natural products

  Chinese Journal of Natural Medicines · 2025-07-01

  review1st author
  PublisherDOI

• Pressure Points: Endothelial Responses to Shear Stress and Pressure in Health and Pulmonary Arterial Hypertension

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-02

  preprintOpen access

  Background: Hemodynamic forces exert a profound influence on endothelial signaling and, when abnormal, contribute centrally to human vascular disease. Pulmonary arterial hypertension (PAH) is characterized by both hemodynamic derangement and pulmonary arterial endothelial cell (PAEC) dysfunction. Despite importance in disease initiation and progression, the combined effects of shear and pressure forces on PAEC biology remain incompletely understood, particularly in the context of PAH. Methods: ) shear stress under either low or elevated (60 mmHg) pressure. After 24 hours, we assessed cellular morphology and performed transcriptomic analysis via bulk RNA sequencing, incorporating analyses of PAH subtype and donor sex. Results: Morphologically, PAECs (n=18 donors) aligned with flow under high, but not low, shear, and alignment was not significantly altered by disease state or pressure. As expected, shear stress fundamentally reorganized the PAEC transcriptome. The "dose-response" to increasing shear differed across biological pathways in six statistically significant patterns. Increasing shear led to divergence in transcription between control and PAH cells, particularly in pathways involved in immune activation, stress signaling, and vascular remodeling, with subtype differences also observed. Pressure had modest effects on transcription, with CHD-PAH PAECs notably displaying pressure-induced stress and inflammatory signaling. We identified sexual dimorphism in the endothelial shear response, including that male cells under shear enriched for proliferative and angiogenic pathways and female cells for fatty acid metabolism and stress responses. Conclusions: We provide a systems-level overview of how shear and pressure shape PAEC transcription, revealing divergent responses across disease state, PAH subtype, and donor sex. These findings highlight the need for further investigation into mechanosensitive pathways in PAH as potential novel therapeutic targets.

  PublisherOA PDFDOI

• Targeting USP18 overcomes acquired resistance in hepatocellular carcinoma by regulating NCOA4 deISGylation and ferroptosis

  Cell Death and Disease · 2025-06-13 · 7 citations

  articleOpen access

  Targeted therapy resistance has become a major challenge for hepatocellular carcinoma (HCC) treatment. Triggering ferroptosis emerges as a promising strategy to overcome therapeutic resistance. Here, we have identified ubiquitin-specific protease 18 (USP18), a member of the deubiquitinating enzyme family, contributing to HCC resistance by inhibiting sorafenib-induced ferroptosis. Nuclear receptor coactivator 4 (NCOA4), a crucial regulator of ferroptosis, turned out to be a novel downstream effector of USP18 and is posttranslationally suppressed. Such regulation is based on the USP18-mediated deISGylation and degradation process. Additionally, we have demonstrated that sorafenib promotes USP18 accumulation in HCC via the STING/IRF3/ISG15 axis. Importantly, we screened and identified hyperoside (HYP) as a new USP18 enzyme activity inhibitor, which sensitizes cancer cells to existing targeted therapies (sorafenib and regorafenib) by inhibiting USP18 and following deISGylation of NCOA4. Collectively, our study has uncovered a novel mechanism of acquired sorafenib resistance and offers a promising combination therapy strategy for overcoming therapeutic resistance in HCC.

  PublisherOA PDFDOI

• Under pressure: integrated endothelial cell response to hydrostatic and shear stresses

  Vascular Biology · 2025-01-01

  articleOpen accessSenior author

  Blood flow within the vasculature is a critical determinant of endothelial cell (EC) identity and functionality, yet the intricate interplay of various hemodynamic forces and their collective impact on endothelial and vascular responses is not fully understood. Specifically, the role of hydrostatic pressure in the EC flow response is understudied, despite its known significance in vascular development and disease. To address this gap, we developed in vitro models to investigate how pressure influences EC responses to flow. Our study demonstrates that elevated pressure conditions significantly modify shear-induced flow alignment and increase EC density. Bulk and single-cell RNA sequencing analyses revealed that, while shear stress remains the primary driver of flow-induced transcriptional changes, pressure modulates shear-induced signaling in a dose-dependent manner. These pressure-responsive transcriptional signatures identified in human ECs were conserved during the onset of circulation in early mouse embryonic vascular development, where pressure was notably associated with transcriptional programs essential to arterial and hemogenic EC fates. Our findings suggest that pressure plays a synergistic role with shear stress on ECs and emphasize the need for an integrative approach to EC mechanotransduction, one that encompasses the effects induced by pressure alongside other hemodynamic forces.

  PublisherDOI

• Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution

  Communications Biology · 2025-08-05 · 2 citations

  articleOpen access

  Ovarian clear cell carcinoma (OCCC) represents a rare and aggressive subtype of epithelial ovarian cancer with distinctive clinical and molecular characteristics. However, the identification, origin, and molecular features of the malignant epithelial cells in OCCC remain poorly studied. We establish an OCCC-associated transcriptional landscape using single-cell RNA sequencing and investigated the properties of epithelial cells in tissues from normal ovaries, ovarian endometriosis, primary OCCC and recurrent OCCC to assess the status of malignant epithelial cells. We identify a specific subcluster of malignant epithelial cells and further analyze them to discover 173 candidate factors associated with OCCC. Regulon and pseudotime trajectory analyses reveal six transcription factors (TFs) and their corresponding targets among these candidate factors, highlighting their roles in OCCC onset and reoccurrence. Through experimental validation, we confirm the crucial involvement of STAT3, KLF5, and TRIM28 in the proliferation and migration of OVISE cells. Silencing these three TFs also results in the down-regulation of their associated TF targets linked to OCCC. Overall, we characterize complex malignant-like cell populations at single-cell resolution and highlighted several TFs and their targets, providing essential resources for understanding the regulatory mechanisms underlying OCCC initiation and recurrence.

  PublisherOA PDFDOI

• Multi-omics integration reveals Vha68-3 as a testicular aging-specific factor that coordinates spermatid elongation through mitochondrial metabolic homeostasis

  Cellular & Molecular Biology Letters · 2025-05-09 · 4 citations

  articleOpen access

  BACKGROUND: Testicular aging has profound effects on spermatogenesis, sperm function, and the spermatogenic microenvironment, contributing to reduced male fertility. However, the precise molecular mechanisms by which mitochondria influence spermiogenesis during aging still remain largely unclear. METHODS: Vha68-3 KO flies were generated using the CRISPR/Cas9 technique. Testicular phenotypes and functions were mainly observed through immunofluorescence staining and transmission electron microscopy. Multi-omics study was mainly conducted through single-cell RNA sequencing and transcriptome-metabolomics association analysis. Vha68-3 binding proteins were identified via liquid chromatography-tandem mass spectrometry. The therapeutic potential of modulating mitochondrial metabolism for testicular aging mainly relied on the dietary intake of related compounds in fruit flies. RESULTS: In this study, we identified Vha68-3, a testis-specific subunit of the V-type adenosine triphosphate (ATP) synthase, predominantly localized in the tails of elongated spermatids, as a key age-related regulator of male fertility and spermatid elongation in Drosophila testes. Crucially, Vha68-3 deficiency impaired mitochondrial homeostasis in elongated spermatids during testicular aging. Through a multi-omics approach, including single-cell transcriptomics, protein interaction mapping of Vha68-3, and transcriptome-metabolome integration, we identified pyruvate metabolism as a critical pathway disrupted by Vha68-3 deficiency. Moreover, dietary supplementation with pyruvate (PA), S-lactoylglutathione (SLG), and phosphoenolpyruvate (PEP) effectively alleviated mitochondrial dysfunction and testicular aging linked to Vha68-3 deficiency. CONCLUSIONS: Our findings uncover novel mechanisms by which mitochondrial metabolism regulates spermatid elongation and propose potential therapeutic strategies to combat mitochondrial metabolic disorders in aging testes.

  PublisherOA PDFDOI

Recent grants

• Rebuilding the glomerular filtration barrier by regenerating adult podocytes

  NIH · $855k · 2015–2017

• 3D human-based microvessel bed for the study of Plasmodium falciparum interacting with vessel wall

  NIH · $2.3M · 2015–2020

• Rebuilding the glomerular filtration barrier by regenerating adult podocytes

  NIH · $858k · 2015–2020

• A Microfluidic Bone Marrow Niche for the Study of Hematopoiesis

  NIH · $2.6M · 2013–2018

• Perfusable 3D human cardiac constructs for heart regeneration

  NIH · $3.3M · 2018–2023

Frequent coauthors

• Triantafyllos Chavakis

  50 shared

• Carl G. Gahmberg

  University of Helsinki

  49 shared

• Thalia Papayannopoulou

  University of Washington

  49 shared

• Stefanie Dimmeler

  Goethe University Frankfurt

  49 shared

• Eun Young Choi

  Seoul National University

  49 shared

• DaRue A. Prieto

  49 shared

• Christian Weber

  49 shared

• Line Fraemohs

  RWTH Aachen University

  49 shared

Education

• PhD, Biomedical Engineering

  University of Michigan

  2008

• B.S, Engineering Thermophysics

  University of Science and Technology of China

  2002

Awards & honors

• Tang Post-Doctoral Research Award, Tang Center for Early Chi…
• Townsend Dissertation Fellowship, Townsend Center for the Hu…
• Koo Fellowship for Outstanding Graduate Students in East Asi…
• Chiang King-kuo Foundation Doctoral Dissertation Fellowship,…
• David N. Keightley Fellowship for Early China, Graduate Divi…