About

Xing Shi Cai is an Assistant Professor of Mathematics at Duke Kunshan University, a position held since 2021. He completed his Ph.D. at McGill University in Canada in 2016. His professional role involves teaching and research within the field of mathematics, contributing to the academic community at Duke Kunshan University.

Research topics

• Biology
• Cell biology
• Genetics
• Biochemistry
• Medicine
• Computational biology
• Chemistry
• Internal medicine
• Immunology
• Cancer research
• Pathology
• Physics

Selected publications

• Arrhythmias across the tree of life: comparative insights for human electrophysiology

  Frontiers in Cardiovascular Medicine · 2026-01-06

  articleOpen access

  Introduction: Arrhythmias in non-human animals offer insights into human electrophysiology, yet physicians may be unaware of their occurrence and significance. This paper presents selected examples of arrhythmias in dogs, horses, and birds- as an invitation to human cardiologists to explore how animal models can illuminate mechanisms, genetics, and therapeutic approaches relevant to human electrophysiology. Methods: Leading veterinary cardiologists compiled overviews of common arrhythmias in dogs, cats, horses and birds. Genetic predisposition, natural history, therapeutic approaches, and epidemiology were compared across these species and humans, highlighting translational opportunities. Results: Common human arrhythmias including atrial fibrillation, bradycardia, ventricular tachycardia, and arrhythmogenic right ventricular cardiomyopathy occur naturally in dogs, cats, horses, and birds. Cross-species differences in disease expression provide unique insights into mechanisms of arrhythmia vulnerability and resistance. Dogs develop similar inherited arrhythmogenic diseases but with distinct phenotypes. Horses experience atrial fibrillation without thromboembolic complications, revealing potential protective pathways. They also demonstrate extreme exercise-induced arrhythmia susceptibility, isolating exercise as an arrhythmogenic trigger. Avian species exhibit remarkable adaptation to cardiac loading conditions that would be pathological in mammals. These comparative observations across species highlight novel mechanisms underlying both susceptibility and resistance to arrhythmias and conduction disorders, offering unexplored therapeutic targets for human patients. Discussion: Cross-species knowledge offers direct translational value for human electrophysiology-from genetic markers in Labrador Retrievers with supraventricular tachycardia to cardiac loading paradigms in broiler chickens. Breaking down disciplinary barriers through shared research initiatives and integrated training represents an essential, underutilized strategy for advancing arrhythmia diagnosis, treatment, and prevention in human patients.

  PublisherOA PDFDOI

• Orchestration of Endothelial and Osteogenic Marker Expression During Osteogenesis

  Preprints.org · 2026-04-02

  preprintOpen access

  Vascular endothelial cells (ECs) coordinate with osteogenic processes to establish the specialized vasculature of bone tissue, where endothelial cells and bone cells interact, and bone cells regulate EC proliferation and differentiation. However, it remains unclear how ECs and bone cells are coordinated during early bone formation and whether these interactions differ between endochondral ossification (e.g., femur) and intramembranous ossification (e.g., skull). To address this question, we analyzed endothelial and osteogenic marker expression in the femur and skull between postnatal days 3 and 39. We identified distinct expression patterns of endothelial markers (Endomucin, VE-cadherin and CD31) and osteogenic markers (Osterix, Cbfa1 and BGLP) during osteogenesis in these tissues. In the femurs, endothelial marker expression alternated with the expression of osteogenic markers, suggesting potential reciprocal regulation. In contrast, in the skull, endothelial and osteogenic markers exhibited similar temporal expression patterns without alternation. We also analyzed the expression of VEGF and its receptor FLK1. In the femur, VEGF expression paralleled osteogenic marker expression, whereas in the skull VEGF expression differed from both osteogenic and endothelial marker patterns. Together, these results demonstrate that the coordination of endothelial and osteogenic marker expression, as well as VEGF signaling, differs between endochondral and intramembranous ossification, suggesting distinct modes of interaction between endothelial and bone cells during the formation of long and flat bones.

  PublisherOA PDFDOI

• 26-A-15307-ACC ASSOCIATION OF SUBCLINICAL CARDIAC REMODELING WITH INCIDENT CANCER IN THE MESA STUDY

  Journal of the American College of Cardiology · 2026-03-27

  article
  PublisherDOI

• Baseline cardiac biomarkers as predictors of future cancer: a new frontier in preventive cardio-oncology

  European Journal of Preventive Cardiology · 2025-11-11

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson’s disease

  The Journal of Cell Biology · 2025-04-25 · 10 citations

  articleOpen access

  Parkinson's disease results from degeneration of dopaminergic neurons in the midbrain, but the underlying mechanisms are unclear. Here, we identify novel crosstalk between depolarization-induced entry of Ca2+ and lysosomal cation release in maintaining dopaminergic neuronal function. The common disease-causing G2019S mutation in LRRK2 selectively exaggerated Ca2+ entry in vitro. Chemical and molecular strategies inhibiting the lysosomal ion channel TPC2 reversed this. Using Drosophila, which lack TPCs, we show that the expression of human TPC2 phenocopied LRRK2 G2019S in perturbing dopaminergic-dependent vision and movement in vivo. Mechanistically, dysfunction required an intact pore, correct subcellular targeting and Rab interactivity of TPC2. Reducing Ca2+ permeability with a novel biased TPC2 agonist corrected deviant Ca2+ entry and behavioral defects. Thus, both inhibition and select activation of TPC2 are beneficial. Functional coupling between lysosomal cation release and Ca2+ influx emerges as a potential druggable node in Parkinson's disease.

  PublisherOA PDFDOI

• Baseline Cardiac Biomarker Levels as Predictors of Cancer Risk in the MESA Cohort

  JACC Advances · 2025-06-16 · 2 citations

  articleOpen access1st authorCorresponding

  BACKGROUND: Assessing the association between baseline levels of cardiac biomarkers and future cancer risk is critical to understand the cross talk between cardiovascular disease and cancer. OBJECTIVES: The authors aimed to determine the association between baseline levels of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cancer risk in the prospective MESA (Multi-Ethnic Study of Atherosclerosis) cohort. METHODS: We analyzed data from 6,244 MESA participants free of self-reported cancer and cardiovascular disease at baseline. Incident cancer was identified using International Classification of Diseases-9th Revision codes from hospitalizations. Cox proportional hazards models were employed to evaluate the associations of hs-cTnT and NT-proBNP with cancer risk. Likelihood ratio tests assessed whether these associations differed by race/ethnicity or sex. RESULTS: The median age was 61.0 years, with 52.7% being female. Over a median follow-up period of 17.8 years, there were 820 incident cancer events, with an incidence rate of 91.2 cases per 10,000 person-years. Higher incidence rates for all cancers were generally associated with higher baseline hs-cTnT and NT-proBNP levels, especially in the highest quartiles. For all-cancer endpoints, the HRs of hs-cTnT and NT-proBNP, calculated based on the SDs for continuous covariates after standardization, were statistically significant in fully adjusted models (HR: 1.18; 95% CI: 1.09-1.27; P < 0.001; and HR: 2.41; 95% CI: 1.30-4.49; P = 0.006, respectively). Sex and race/ethnicity did not significantly affect any of these associations. CONCLUSIONS: In the MESA cohort, higher baseline levels of hs-cTnT and NT-proBNP predicted an increased risk of incident cancer, with no significant differences by race/ethnicity or sex.

  PublisherDOI

• Regulating the cell differentiation trajectory of progenitor cells in adipose tissue fibrosis

  Molecular Metabolism · 2025-08-06 · 2 citations

  articleOpen access

  OBJECTIVE: Adipose fibrosis signifies pathological remodeling of white adipose tissue (WAT) associated with insulin resistance, diabetes, and cardiovascular disease. Matrix Gla protein (MGP) balances bone morphogenetic protein (BMP) and transforming growth factor β (TGFβ) signaling but has an unclear role in WAT. METHODS: To study the role of MGP in WAT, we used mice with global or platelet-derived growth factor receptor α (Pdgfra)-Cre-mediated Mgp deletion in adipose progenitor cells (APCs) together with single cell RNA sequencing (scRNA-seq), characterization on adipose and fibrotic phenotypes, and BMP and TGFβ signaling studies. RESULTS: Our results showed that Mgp deletion promotes fibrosis and impairs adipogenesis in mice with global or Pdgfra-Cre-mediated Mgp deletion in APCs. ScRNA-seq showed two new adipose-derived stem cells (ASC) populations, ASC1 and ASC4, emerging after Mgp deletion. Trajectory analysis found that ASC1 and ASC4 were derived from ASC2, which normally undergo adipogenesis but instead had diverted to fibrogenic differentiation. All three ASCs expressed Pdgfra and dipeptidyl peptidase-4 (Dpp4). Inhibition of TGFβ signaling or DPP4 activity in mice with Pdgfra-Cre-mediated Mgp deletion reduced the size of the PDGFRα+; DPP4+ cell population and rescued the WAT from unwanted fibrosis. CONCLUSIONS: MGP is essential for appropriate balance between adipogenic differentiation and fibroblast activation. Dysregulation of PDGFRα+; DPP4+ cells may signal early adipose fibrosis.

  PublisherDOI

• CDK1 inhibition reduces osteogenesis in endothelial cells in vascular calcification

  JCI Insight · 2024-01-23 · 5 citations

  articleOpen access

  Vascular calcification is a severe complication of cardiovascular diseases. Previous studies demonstrated that endothelial lineage cells transitioned into osteoblast-like cells and contributed to vascular calcification. Here, we found that inhibition of cyclin-dependent kinase (CDK) prevented endothelial lineage cells from transitioning to osteoblast-like cells and reduced vascular calcification. We identified a robust induction of CDK1 in endothelial cells (ECs) in calcified arteries and showed that EC-specific gene deletion of CDK1 decreased the calcification. We found that limiting CDK1 induced E-twenty-six specific sequence variant 2 (ETV2), which was responsible for blocking endothelial lineage cells from undergoing osteoblast differentiation. We also found that inhibition of CDK1 reduced vascular calcification in a diabetic mouse model. Together, the results highlight the importance of CDK1 suppression and suggest CDK1 inhibition as a potential option for treating vascular calcification.

  PublisherDOI

• Two-step regulation by matrix Gla protein in brown adipose cell differentiation

  Molecular Metabolism · 2024-01-04 · 4 citations

  articleOpen access

  OBJECTIVE: Bone morphogenetic protein (BMP) signaling is intricately involved in adipose tissue development. BMP7 together with BMP4 have been implicated in brown adipocyte differentiation but their roles during development remains poorly specified. Matrix Gla protein (MGP) inhibits BMP4 and BMP7 and is expressed in endothelial and progenitor cells. The objective was to determine the role of MGP in brown adipose tissue (BAT) development. METHODS: The approach included global and cell-specific Mgp gene deletion in combination with RNA analysis, immunostaining, thermogenic activity, and in vitro studies. RESULTS: The results revealed that MGP directs brown adipogenesis at two essential steps. Endothelial-derived MGP limits triggering of white adipogenic differentiation in the perivascular region, whereas MGP derived from adipose cells supports the transition of CD142-expressing progenitor cells to brown adipogenic maturity. Both steps were important to optimize the thermogenic function of BAT. Furthermore, MGP derived from both sources impacted vascular growth. Reduction of MGP in either endothelial or adipose cells expanded the endothelial cell population, suggesting that MGP is a factor in overall plasticity of adipose tissue. CONCLUSION: MGP displays a dual and cell-specific function in BAT, essentially creating a "cellular shuttle" that coordinates brown adipogenic differentiation with vascular growth during development.

  PublisherDOI

• Inhibition of endothelial histone deacetylase 2 shifts endothelial-mesenchymal transitions in cerebral arteriovenous malformation models

  Journal of Clinical Investigation · 2024-05-23 · 6 citations

  articleOpen access

  Cerebral arteriovenous malformations (AVMs) are the most common vascular malformations worldwide and the leading cause of hemorrhagic strokes that may result in crippling neurological deficits. Here, using recently generated mouse models, we uncovered that cerebral endothelial cells (ECs) acquired mesenchymal markers and caused vascular malformations. Interestingly, we found that limiting endothelial histone deacetylase 2 (HDAC2) prevented cerebral ECs from undergoing mesenchymal differentiation and reduced cerebral AVMs. We found that endothelial expression of HDAC2 and enhancer of zeste homolog 1 (EZH1) was altered in cerebral AVMs. These alterations changed the abundance of H4K8ac and H3K27me in the genes regulating endothelial and mesenchymal differentiation, which caused the ECs to acquire mesenchymal characteristics and form AVMs. This investigation demonstrated that the induction of HDAC2 altered specific histone modifications, which resulted in mesenchymal characteristics in the ECs and cerebral AVMs. The results provide insight into the epigenetic impact on AVMs.

  PublisherOA PDFDOI

Frequent coauthors

• Neil J. Freedman

  Duke Medical Center

  20 shared

• Xiangbing Wang

  Taiyuan University of Technology

  20 shared

• David E. Clapham

  Howard Hughes Medical Institute

  16 shared

• Yucheng Yao

  University of California, Los Angeles

  15 shared

• Kristina I. Boström

  University of California, Los Angeles

  15 shared

• Jiao‐Hui Wu

  Duke Medical Center

  12 shared

• Xiuju Wu

  12 shared

• Xiaojing Qiao

  11 shared