About

Liang Fang is a faculty member at the Cornell Duffield Engineering, specifically associated with the Meinig School of Biomedical Engineering. He holds the position of Postdoctoral Associate and is part of the Jiang Lab. His work is conducted within a highly collaborative and dynamic intellectual community known for excellence in educating students, pursuing groundbreaking research, and advancing technological innovations that impact people, communities, and the world. The community emphasizes a commitment to education, research, and technological development, contributing to the broader mission of Cornell Engineering.

Research topics

• Biology
• Cell biology
• Medicine
• Immunology
• Chemistry

Selected publications

• APOA1 binding protein promotes lymphatic cell fate and lymphangiogenesis by relieving caveolae-mediated inhibition of VEGFR3 signaling

  Nature Communications · 2025-10-21 · 3 citations

  articleOpen accessSenior authorCorresponding

  The lymphatic system maintains tissue fluid balance, and its dysfunction can result in lymphedema. Although cholesterol is essential for cellular function, its role in lymphatic development has remained unknown. Here, we identify APOA1 binding protein (AIBP) as a key regulator that promotes lymphatic endothelial cell fate specification and lymphangiogenesis. Mechanistically, AIBP reduces plasma membrane cholesterol content, thereby enhancing VEGFR3 signaling by disrupting caveolae—small plasma membrane invaginations formed by the scaffolding protein caveolin-1 (CAV-1)—and relieving CAV-1–mediated inhibition. In zebrafish and mice, AIBP loss impairs VEGFR3 signaling and lymphatic development, defects that can be rescued by CAV-1 deletion or by a VEGFR3 mutant (VEGFR3AAA) lacking CAV-1 binding. Administration of recombinant AIBP augments VEGFC-induced lymphangiogenesis and accelerates the resolution of secondary lymphedema in adult mice. These findings define the AIBP–CAV-1 axis as a regulator of VEGFR3 signaling and lymphatic growth, offering potential therapeutic opportunities for treating lymphatic dysfunction. Lymphatics maintain lipid transport, immunity, and fluid balance. Kim J and Chaudhary S et al. reveal an AIBP-driven cholesterol efflux mechanism that regulates lymphangiogenesis via VEGF signaling.

  PublisherOA PDFDOI

• AIBP-LRP2–mediated HDL uptake restricts CXCR4 ⁺ stemlike capillary expansion and collateral circulation

  Science Advances · 2025-10-15 · 1 citations

  articleOpen accessCorresponding

  The tissue environment governs vascular remodeling, a key determinant of collateral circulation (CC) in ischemic disease, yet the mechanisms driving CC in adults remain unclear. Plasma profiling from patients with peripheral artery disease (PAD) and ischemic murine muscle revealed dysregulated lipid metabolism, including elevated APOA1 binding protein (AIBP), with levels positively correlating with PAD severity. Myeloid cells enriched at CC sites increased AIBP expression postischemia. Genetic deletion of AIBP expanded CXCR4⁺ capillary endothelial cells (CECs) with stemlike and proliferative properties that remodeled into functional collaterals, a process blocked by CXCR4 inhibition. Mechanistically, AIBP bound the endocytic receptor LRP2 to promote endothelial uptake of high-density lipoprotein (HDL)-associated miR-223, a repressor of CXCR4. Disruption of this AIBP-LRP2-HDL-miR-223 axis restored CXCR4 and rescued CC growth. These findings define a two-phase mechanism in which stemlike CECs first expand and then transition to arterial fates, establishing a therapeutic strategy for revascularization in ischemic vascular disease.

  PublisherDOI

• A visual–omics foundation model to bridge histopathology with spatial transcriptomics

  Nature Methods · 2025-05-29 · 60 citations

  articleOpen access

  Artificial intelligence has revolutionized computational biology. Recent developments in omics technologies, including single-cell RNA sequencing and spatial transcriptomics, provide detailed genomic data alongside tissue histology. However, current computational models focus on either omics or image analysis, lacking their integration. To address this, we developed OmiCLIP, a visual-omics foundation model linking hematoxylin and eosin images and transcriptomics using tissue patches from Visium data. We transformed transcriptomic data into 'sentences' by concatenating top-expressed gene symbols from each patch. We curated a dataset of 2.2 million paired tissue images and transcriptomic data across 32 organs to train OmiCLIP integrating histology and transcriptomics. Building on OmiCLIP, our Loki platform offers five key functions: tissue alignment, annotation via bulk RNA sequencing or marker genes, cell-type decomposition, image-transcriptomics retrieval and spatial transcriptomics gene expression prediction from hematoxylin and eosin-stained images. Compared with 22 state-of-the-art models on 5 simulations, and 19 public and 4 in-house experimental datasets, Loki demonstrated consistent accuracy and robustness.

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• A visual–omics foundation model to bridge histopathology image with transcriptomics

  Research Square · 2025-04-16 · 1 citations

  preprintOpen access
  PublisherOA PDFDOI

• Flow Upregulated Scap Dictates Hematopoiesis

  Blood · 2024-11-05

  articleOpen access1st authorCorresponding

  Surbhi Chauhary1, Michihiro Kobayashi2, Pamela Wenzel3, Momoko Yoshimoto2, Longhou Fang1,4 1Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute. Houston Methodist, 6550 Fannin Street, Texas 77030, USA. 2Center for Immunology, Department of Investigative Medicine, Western Michigan University Homer Stryker MD School of Medicine 3Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States. 4Physiology, Biophysics, and Systems Biology Program, Weill Cornell Medical College, Cornell University, New York 10065, USA. Deficiencies in hematopoietic stem cell (HSC) donor sources are a significant cause of poor engraftment outcomes in patients with myelodysplasia and other hematopoietic disorders. The imperative to enhance HSC quality has driven extensive research into the developmental processes of HSCs, particularly through the endothelial-to-hematopoietic transition. Among the myriad regulators of hematopoiesis, mechanoregulatory pathways have emerged as pivotal players in HSC development. Within the anatomical hotspots of HSC specification, blood flow-generated forces activate two closely related mechanosensitive transcriptional cofactors, Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ). While YAP and TAZ can function independently, YAP has been reported to support HSC specification1. However, the role of TAZ in HSC specification remains unknown. Our preliminary studies have established a functional role for TAZ in HSC specification. This HSC fate determination occurs from hemogenic endothelial cells (HECs), a rare population of endothelial cells with hematopoietic potential. We found that blood flow activates TAZ in HECs, which in turn upregulates SCAP, a chaperone that binds and activates sterol regulatory element-binding protein 1 (SREBP1). SCAP subsequently increases the expression of SREBP1-regulated polyunsaturated fatty acid (PUFA) target genes2. Functionally, we demonstrated that the knockout of TAZ, SCAP, or SREBP1 impairs hematopoiesis in mice and zebrafish. These preliminary studies and existing literature suggest an essential signaling pathway in HSC specification, wherein flow-activated TAZ promotes SCAP/SREBP1-mediated PUFA biosynthesis. Understanding these regulatory mechanisms will reveal a novel innate pathway-endogenous PUFA biosynthesis-for HSC specification. Our research team has pioneered the study of biomechanical forces3, 4 and cholesterol metabolism5 in hematopoiesis. We recently showed that SREBP2, the master transcription factor of cholesterol biosynthesis, which is also activated by SCAP, controls HSC specification. Surprisingly, cholesterogenic activity remains unchanged or even suppressed in HECs under flow conditions4. Thus, our project focusing on SREBP1-regulated PUFA biosynthesis aims to uncover previously unknown mechanisms dictating HSC fate. Insights gained from this research could pave the way for novel therapeutic strategies in HSC generation. References 1 Lundin, V. et al. YAP Regulates Hematopoietic Stem Cell Formation in Response to the Biomechanical Forces of Blood Flow. Dev Cell52, 446-460 e445 (2020). https://doi.org/10.1016/j.devcel.2020.01.006 2 Goldstein, J. L., DeBose-Boyd, R. A. & Brown, M. S. Protein sensors for membrane sterols. Cell124, 35-46 (2006). https://doi.org/10.1016/j.cell.2005.12.022 3 Adamo, L. et al. Biomechanical forces promote embryonic haematopoiesis. Nature459, 1131-1135 (2009). https://doi.org/10.1038/nature08073 4 Diaz, M. F. et al. Biomechanical forces promote blood development through prostaglandin E2 and the cAMP-PKA signaling axis. J Exp Med212, 665-680 (2015). https://doi.org/10.1084/jem.20142235 5 Gu, Q. et al. AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate. Science363, 1085-1088 (2019). https://doi.org/10.1126/science.aav1749

  PublisherOA PDFDOI

• Mitigating Vascular Inflammation by Mimicking AIBP Mechanisms: A New Therapeutic End for Atherosclerotic Cardiovascular Disease

  International Journal of Molecular Sciences · 2024-09-25 · 4 citations

  reviewOpen accessSenior author

  Atherosclerosis, characterized by the accumulation of lipoproteins and lipids within the vascular wall, underlies a heart attack, stroke, and peripheral artery disease. Endothelial inflammation is the primary component driving atherosclerosis, promoting leukocyte adhesion molecule expression (e.g., E-selectin), inducing chemokine secretion, reducing the production of nitric oxide (NO), and enhancing the thrombogenic potential. While current therapies, such as statins, colchicine, anti-IL1β, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, target systemic inflammation, none of them addresses endothelial cell (EC) inflammation, a critical contributor to disease progression. Targeting endothelial inflammation is clinically significant because it can mitigate the root cause of atherosclerosis, potentially preventing disease progression, while reducing the side effects associated with broader anti-inflammatory treatments. Recent studies highlight the potential of the APOA1 binding protein (AIBP) to reduce systemic inflammation in mice. Furthermore, its mechanism of action also guides the design of a potential targeted therapy against a particular inflammatory signaling pathway. This review discusses the unique advantages of repressing vascular inflammation or enhancing vascular quiescence and the associated benefits of reducing thrombosis. This approach offers a promising avenue for more effective and targeted interventions to improve patient outcomes.

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• Abstract 13674: AIBP-Mediated Cholesterol Efflux Controls Lymphangiogenesis

  Circulation · 2023-11-07

  articleSenior author

  Background: Lymphangiogenesis give rise to lymphatic vessels that are essential for maintenance of tissue fluid homeostasis. Lymphatic vessel formation requires lymphatic endothelial cell (LEC) specification from the venous ECs and subsequent LEC proliferation and migration, all of which are regulated by the VEGFC/VEGFR3 signaling. Cholesterol is essential for cell functions and organ development yet the molecular mechanism by which it controls lymphangiogenesis is unknown. Hypothesis: In this study, we hypothesize the role of apoA-I binding protein (AIBP)-regulated cholesterol metabolism in lymphangiogenesis. Aim: We aim to dissect the role of AIBP mediated cholesterol efflux on caveolin-1 (CAV-1) disruption and its effect on VEGFC/VEGFR3 signaling and lymphangiogenesis. Methods: We utilized the mouse embryonic stem cell differentiation model to assess the role of AIBP-CAV-1-VEGFR3 axis in LEC fate determination. We used AIBP and CAV-1 knockout (KO) to assess the role of this signaling circuit in developmental lymphangiogenesis using zebrafish and in adult lymphangiogenesis using the mouse corneal lymphangiogenesis model. We used CAV-1 KO neonatal mice to study tail lymphangiogenesis. Results: We found that AIBP dictates lymphatic vessel formation by accelerating cholesterol efflux. Loss of Aibp2, the zebrafish paralog of human AIBP, impairs lymphangiogenesis. Recombinant AIBP protein induces mouse embryonic stem cell differentiation to LECs. Mechanistically, CAV-1 suppresses VEGFR3 activation, but cholesterol efflux by AIBP disrupts lipid rafts/caveolae and reduces CAV-1 bioavailability, which abolishes the CAV-1 inhibition of VEGFR3 signaling, thereby augmenting VEGFR3 activation in human LECs. Loss of CAV-1 increases LEC progenitor specification in zebrafish, and rescues lymphangiogenesis in Aibp2-deficient animals. CAV-1 KO neonatal mice significantly augmented tail lymphangiogenesis. Further, AIBP expression is reduced in the epidermis of human lymphedema. Conclusion: Our study elucidates a novel role of AIBP-mediated cholesterol efflux in lymphatic vessel formation and provides new therapeutic targets for the treatment of lymphatic dysfunctions.

  PublisherDOI

• Publisher Correction: Epigenetic landscape reveals MECOM as an endothelial lineage regulator

  Nature Communications · 2023-05-18

  erratumOpen access
  PublisherOA PDFDOI

• Epigenetic landscape reveals MECOM as an endothelial lineage regulator

  Nature Communications · 2023-04-25 · 47 citations

  articleOpen access

  A comprehensive understanding of endothelial cell lineage specification will advance cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures preferentially regulate cell identity genes. We thus systematically investigate the epigenetic landscape of endothelial cell lineage and identify MECOM to be the leading candidate as an endothelial cell lineage regulator. Single-cell RNA-Seq analysis verifies that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide endothelial cells derived from induced pluripotent stem cells. Our experiments demonstrate that MECOM depletion impairs human endothelial cell differentiation, functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate endothelial cell identity genes. Further, we identify and verify the VEGF signaling pathway to be a key target of MECOM. Our work provides important insights into epigenetic regulation of cell identity and uncovered MECOM as an endothelial cell lineage regulator.

  PublisherOA PDFDOI

• Free Cholesterol Bioavailability and Atherosclerosis

  Current Atherosclerosis Reports · 2022-03-25 · 31 citations

  reviewOpen access

  PURPOSE OF REVIEW: As both a cholesterol acceptor and carrier in the reverse cholesterol transport (RCT) pathway, high-density lipoprotein (HDL) is putatively atheroprotective. However, current pharmacological therapies to increase plasma HDL cholesterol (HDL-c) concentration have paradoxically failed to prevent or reduce atherosclerosis and cardiovascular disease (CVD). Given that free cholesterol (FC) transfer between surfaces of lipoproteins and cells is reversible, excess plasma FC can be transferred to the cells of peripheral tissue sites resulting in atherosclerosis. Here, we summarize potential mechanisms contributing to this paradox and highlight the role of excess free cholesterol (FC) bioavailability in atherosclerosis vs. atheroprotection. RECENT FINDINGS: Recent findings have established a complex relationship between HDL-c concentration and atherosclerosis. Systemic scavenger receptor class B type 1 (SR-B1) knock out (KO) mice exhibit with increased diet-induced atherosclerosis despite having an elevated plasma HDL-c concentration compared to wild type (WT) mice. The greater bioavailability of HDL-FC in SR-B1 vs. WT mice is associated with a higher FC content in multiple cell types and tissue sites. These results suggest that dysfunctional HDL with high FC bioavailability is atheroprone despite high HDL-c concentration. Past oversimplification of HDL-c involvement in cholesterol transport has led to the failures in HDL targeted therapy. Evidence suggests that FC-mediated functionality of HDL is of higher importance than its quantity; as a result, deciphering the regulatory mechanisms by which HDL-FC bioavailability can induce atherosclerosis can have far-reaching clinical implications.

  PublisherOA PDFDOI

Recent grants

• AIBP Mediates a Novel Interplay between Cholesterol Metabolism and Lymphangiogenesis

  NIH · $2.7M · 2016–2022

• NIH Grant R00HL114734

  NIH · $738k · 2018

• NIH Grant K99HL114734

  NIH · $238k · 2014

Frequent coauthors

• Yury I. Miller

  University of California, San Diego

  105 shared

• McKenna J. Geary

  University of California, San Diego

  64 shared

• Po‐Hsun Huang

  Taipei Veterans General Hospital

  64 shared

• Ting-Yang Lin

  Keelung Chang Gung Memorial Hospital

  64 shared

• Jaw‐Wen Chen

  Taipei Veterans General Hospital

  64 shared

• Liang Wen

  South China Normal University

  64 shared

• John Y.‐J. Shyy

  University of California, San Diego

  64 shared

• David A. Johnson

  64 shared

Labs

• Jiang LabPI

Education

• Postdoc/Assist Proj Sci, Medicine

  University of California San Diego

  2014

• Ph.D, Institute of Biochmestry and Cell Biology

  Shanghai Institutes for Biological Sciences

  2007

• B.S, Biology

  Anhui Normal University

  2000

Awards & honors

• SPROUT Awards
• EPICC Awards
• Research, Teaching, and Advising Awards
• Distinguished Alumni Award