Lu LIU

All Publications

• Harnessing iPSCs, 3D organoids, and multiomics to model rare vascular diseases: Emerging new approach methodologies. Vascular medicine (London, England) Liu, L., Wu, D., Tsao, P. S., Leeper, N. J., Sayed, N. 2026: 1358863X251394285

  Abstract

  Rare vascular diseases are a diverse group of life-threatening conditions defined by their low prevalence but profound impact on patient morbidity and quality of life. Diagnosing these disorders remains a significant clinical challenge due to their genetic heterogeneity, overlapping phenotypes, and limited patient populations. As such, the development of robust and human-relevant disease models is critical for elucidating pathogenic mechanisms and guiding therapeutic discovery. The advent of human induced pluripotent stem cell (iPSC) technology has opened new avenues for modeling rare vascular diseases by enabling the generation of patient-specific vascular cell types, including endothelial cells, smooth muscle cells, and fibroblasts, and the creation of both two-dimensional cultures and three-dimensional vascular organoids. Together with genome editing and next-generation multiomics, these platforms represent new approach methodologies (NAMs) that allow for detailed investigation of disease biology, facilitate the correction of pathogenic mutations, and enable high-throughput drug screening in a personalized context. In this review, we highlight the advancements in iPSC-derived vascular modeling, discuss the integration of gene editing and multiomics technologies, and explore their transformative potential for uncovering mechanisms and developing precision therapies for rare vascular diseases.

  View details for DOI 10.1177/1358863X251394285

  View details for PubMedID 41498403

• Multiscale profiling of tyrosine kinase inhibitor cardiotoxicity reveals mechanosensitive ion channel PIEZO1 as cardioprotective. Science translational medicine Manhas, A., Liu, Y., Noishiki, C., Wu, D., Tripathi, D., Mirza, S., Thomas, D., Liu, L., Guha, A., Nguyen, P. K., Chen, I. Y., Chitalia, V., Cheng, P., Sayed, D., Telli, M. L., Sallam, K., Wu, J. C., Sayed, N. 2025; 17 (829): eadv9403

  Abstract

  Tyrosine kinase inhibitors (TKIs) have improved cancer outcomes but are limited by cardiovascular toxicity, most notably hypertension and heart failure. The underlying mechanisms remain poorly understood, hindering the development of protective strategies. Here, we investigated the role of endothelial mechanotransduction in mediating vascular and cardiac injury caused by the vascular endothelial growth factor receptor-targeting TKI sunitinib. Using patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and a mouse model of TKI-induced hypertension, we identified down-regulation of piezo-type mechanosensitive ion channel component 1 (PIEZO1), a mechanically activated ion channel, as a driver of endothelial dysfunction. Restoring PIEZO1 expression, either pharmacologically with Yoda1, a selective agonist, or through inducible overexpression in iPSC-ECs, reversed sunitinib-induced endothelial dysfunction and mitigated its hypertensive effects, providing both mechanistic and genetic validation of PIEZO1's protective role against vascular toxicity. In mice, cotreatment with sunitinib and Yoda1 prevented the long-term cardiac dysfunction observed after sunitinib exposure and normalized elevations in circulating cardiac stress biomarkers. Single-nucleus multiomic profiling of mouse hearts revealed that sunitinib exposure activated chromatin remodeling and fibrogenic programs, which were reversed with PIEZO1 activation. Human engineered cardiac organoids further demonstrated that sunitinib impaired cardiomyocyte function only in the presence of endothelial cells, confirming a role for disrupted endothelial-cardiomyocyte cross-talk in TKI cardiotoxicity. Together, these findings identify endothelial PIEZO1 as a mediator of TKI-induced hypertension and cardiac dysfunction and highlight PIEZO1 activation as a potential therapeutic strategy for protecting cardiovascular health during cancer therapy.

  View details for DOI 10.1126/scitranslmed.adv9403

  View details for PubMedID 41406242

• Generation of an induced pluripotent stem cell line from a patient with Varicose veins. Stem cell research Noishiki, C., Manhas, A., Adkar, S. S., Tripathi, D., Wu, D., Sadat, S., Liu, L., Sallam, K., Leeper, N. J., Fukaya, E., Sayed, N. 2025; 89: 103850

  Abstract

  Chronic venous disease is among the most common vascular diseases globally. Varicose veins (VV), characterized by permanent dilation, elongation, and tortuosity of superficial veins, is a manifestation of chronic venous disease. Here, we generated an induced pluripotent stem cell (iPSC) line from PBMCs obtained from a patient with VV. The iPSC line exhibited typical morphology, maintained undifferentiated hPSC state markers, demonstrated a normal karyotype, and successfully differentiated into all three germ layers. This iPSC line provides a valuable platform to model VV pathogenesis and investigate the molecular mechanisms underlying venous dysfunction.

  View details for DOI 10.1016/j.scr.2025.103850

  View details for PubMedID 41075513

• Generation of induced pluripotent stem cell line from a patient with long COVID. Stem cell research Wu, D., Manhas, A., Noishiki, C., Tripathi, D., Liu, L., Turbes, N., Thomas, D., Sallam, K., Lee, J. T., Sayed, N. 2025; 83: 103652

  Abstract

  Long COVID, or post-acute sequelae of SARS-CoV-2 infection, leads to vascular dysfunction, which contributes to the chronic multi-organ damage often seen in affected patients. Long COVID, a global health concern is associated with increased thrombotic risk, also known as COVID-19-associated coagulopathy (CAC). Here, we derived an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a long COVID patient. This iPSC line showed normal morphology, maintained pluripotency, had a stable karyotype, and demonstrated the ability to differentiate into the three germ layers (ectoderm, endoderm, and mesoderm). This line provides a valuable tool for modeling long COVID and exploring mechanisms underlying multi-organ dysfunction.

  View details for DOI 10.1016/j.scr.2025.103652

  View details for PubMedID 39823918

• Generation of two iPSC lines from vascular Ehlers-Danlos Syndrome (vEDS) patients carrying a missense mutation in COL3A1 gene. Stem cell research Manhas, A., Tripathi, D., Noishiki, C., Wu, D., Liu, L., Sallam, K., Lee, J. T., Fukaya, E., Sayed, N. 2024; 79: 103485

  Abstract

  Vascular Ehlers-Danlos Syndrome (vEDS) is an inherited connective tissue disorder caused by COL3A1 gene, mutations that encodes type III collagen, a crucial component of blood vessels. vEDS can be life-threatening as these patients can have severe internal bleeding due to arterial rupture. Here, we generated induced pluripotent stem cell (iPSC) lines from two vEDS patients carrying a missense mutation in the COL3A1 (c.226A > G, p.Asn76Asp) gene. These lines exhibited typical iPSC characteristics including morphology, expression of pluripotency markers, and could differentiate to all three germ layer. These iPSC lines can serve as valuable tools for elucidating the pathophysiology underlying vEDS.

  View details for DOI 10.1016/j.scr.2024.103485

  View details for PubMedID 38944978