About

Victoria L. Bautch is a Beverly Long Chapin Distinguished Professor in the UNC Department of Biology, affiliated with the Program in Molecular Biology & Biotechnology. Her research focuses on the growth and interactions of cells within their natural environment—the animal—and how these interactions are modified in disease. She studies the mechanisms that control blood vessel formation, which is crucial for development and is involved in diseases such as cancer and diabetes. Her work involves developing models of developmental blood vessel formation using genetically altered mice and cells derived from those mice, including a cell culture model to study the cross-talk between cellular processes like cell division and sprouting migration to expand vessel networks. Bautch's research includes using mouse embryonic stem cells to differentiate into structures containing embryonic tissues, including primitive blood vessels, with visualization of blood vessel formation through GFP reporter genes and time-lapse imaging. She employs genetic manipulation and inhibitors to dissect the role of signaling pathways such as VEGF in these processes. Her studies also investigate the role of a novel gene that activates cellular homologs of oncogenes like Ras, which is not required for development but is necessary for vessel response to tumor-promoting agents, indicating its importance in diseases like cancer and diabetes. Additionally, she explores how blood vessels determine their migration patterns during development by using chimeric embryos with genetically manipulated mouse tissue, uncovering the crucial role of VEGF in vessel patterning around the neural tube, which contributes to the formation of the brain and spinal cord.

Research topics

• Cell biology
• Genetics
• Biology
• Cancer research
• Chemistry
• Biochemistry

Selected publications

• Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-20

  articleOpen accessSenior authorCorresponding

  ABSTRACT Vascular endothelial cells respond to environmental forces to remodel vessels during development and to achieve homeostasis, and mis-regulated responses lead to vascular dysfunction and disease. The nucleus participates in force transduction to cell-matrix junctions via the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that resides in the nuclear envelope, but how these forces are regulated and relayed is incompletely understood. We found that the LINC complex protein SUN2 is required for proper endothelial cell-matrix interactions that occur far from the nucleus and affect angiogenic expansion, vascular responses to flow, and barrier integrity. Endothelial cells lacking SUN2 had inappropriate flow responses and reduced expression of flow-mediated transcription factors in vitro and in vivo . Expression of several matrix and adhesion genes was reduced in SUN2-depleted cells, leading to defective extracellular matrix, dysmorphic focal adhesions resistant to dynamic turnover, and disturbed cell-matrix force distribution. Mechanistically, nuclear SUN2 affected dynamic regulation of the microtubule cytoskeleton that correlated with matrix metalloprotease-dependent barrier dysfunction. These findings indicate that nuclear SUN2 establishes and maintains blood vessel homeostasis by controlling microtubule-mediated effects on focal adhesion turnover and extracellular matrix properties, with implications for cardiovascular aging and diseases such as Marfan syndrome that affect vessel wall integrity.

  PublisherDOI

• Impact of ligand binding on VEGFR1, VEGFR2, and NRP1 localization in human endothelial cells

  PLoS Computational Biology · 2025-07-16 · 2 citations

  articleOpen access

  The vascular endothelial growth factor receptors (VEGFRs) bind to cognate ligands to facilitate signaling pathways critical for angiogenesis, the growth of new capillaries from existing vasculature. Intracellular trafficking regulates the availability of receptors on the cell surface to bind ligands, which regulate activation, and the movement of activated receptors between the surface and intracellular pools, where they can initiate different signaling pathways. Using experimental data and computational modeling, we recently demonstrated and quantified the differential trafficking of three VEGF receptors, VEGFR1, VEGFR2, and coreceptor Neuropilin-1 (NRP1). Here, we expand that approach to quantify how the binding of different VEGF ligands alters the trafficking of these VEGF receptors and demonstrate the consequences of receptor localization and ligand binding on the localization and dynamics of signal initiation complexes. We include simulations of four different splice isoforms of VEGF-A and PLGF, each of which binds to different combinations of the VEGF receptors, and we use new experimental data for two of these ligands to parameterize and validate our model. We show that VEGFR2 trafficking is altered in response to ligand binding, but that trafficking of VEGFR1 is not; we also show that the altered trafficking can be explained by a single mechanistic process, increased internalization of the VEGFR2 receptor when bound to ligand; other processes are unaffected. We further show that even though the canonical view of receptor tyrosine kinases is of activation on the cell surface, most of the ligand-receptor complexes for both VEGFR1 and VEGFR2 are intracellular. We also explore the competition between the receptors for ligand binding, the so-called 'decoy effect', and show that while in vitro on the cell surface minimal such effect would be observed, inside the cell the effect can be substantial and may influence signaling. We term this location dependence the 'reservoir effect' as the size of the local ligand reservoir (large outside the cell, small inside the cell) plays an integral role in the receptor-receptor competition. These results expand our understanding of receptor-ligand trafficking dynamics and are critical for the design of therapeutic agents to regulate ligand availability to VEGFR1 and hence VEGF receptor signaling in angiogenesis.

  PublisherDOI

• Abstract 1785 Mechanisms of VEGF Receptor Trafficking Dynamics and Regulation

  Journal of Biological Chemistry · 2025-05-01

  articleOpen access

  Vascular endothelial growth factor (VEGF) controls the growth and regression of blood vessels. While some successes have been achieved in inhibition of VEGF to disrupt blood vessel growth in cancer and retinopathy, over a dozen clinical trials of VEGF delivery to increase vascular growth in patients with ischemic diseases have failed. The inability to successfully bridge treatment from animals to humans demonstrates that our understanding of the VEGF system is far from complete. We have developed and validated a molecularly-detailed computational model of VEGFR1, VEGFR2, and Neuropilin-1 trafficking in endothelial cells.

  PublisherOA PDFDOI

• Mechanistic computational modeling of sFLT1 secretion dynamics

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-17 · 1 citations

  preprintOpen access

  Abstract Constitutively secreted by endothelial cells, soluble FLT1 (sFLT1 or sVEGFR1) binds and sequesters extracellular vascular endothelial growth factors (VEGF), thereby reducing VEGF binding to VEGF receptor tyrosine kinases and their downstream signaling. In doing so, sFLT1 plays an important role in vascular development and in the patterning of new blood vessels in angiogenesis. Here, we develop multiple mechanistic models of sFLT1 secretion and identify a minimal mechanistic model that recapitulates key qualitative and quantitative features of temporal experimental datasets of sFLT1 secretion from multiple studies. We show that the experimental data on sFLT1 secretion is best represented by a delay differential equation (DDE) system including a maturation term, reflecting the time required between synthesis and secretion. Using optimization to identify appropriate values for the key mechanistic parameters in the model, we show that two model parameters (extracellular degradation rate constant and maturation time) are very strongly constrained by the experimental data, and that the remaining parameters are related by two strongly constrained constants. Thus, only one degree of freedom remains, and measurements of the intracellular levels of sFLT1 would fix the remaining parameters. Comparison between simulation predictions and additional experimental data of the outcomes of chemical inhibitors and genetic perturbations suggest that intermediate values of the secretion rate constant best match the simulation with experiments, which would completely constrain the model. However, some of the inhibitors tested produce results that cannot be reproduced by the model simulations, suggesting that additional mechanisms not included here are required to explain those inhibitors. Overall, the model reproduces most available experimental data and suggests targets for further quantitative investigation of the sFLT1 system. Author Summary Proteins that are typically found outside cells are initially made inside cells, and later secreted into extracellular space. Many of these secreted proteins have important functions outside the cell that are well-studied; however, usually much less is known about the pre-secretion life of these molecules. Many computational models only represent the extracellular versions of secreted proteins, reducing all production and secretion steps into a single modeled process. Here, we develop a mechanistic model of the production and secretion of a specific secreted protein, sFLT1, which inhibits blood vessel growth by acting as an extracellular sponge for another set of secreted proteins, the vascular endothelial growth factors. We compare several models to existing experimentally-measured sFLT1 data, and we show that the data are most simply explained by including a delay between intracellular sFLT1 production and sFLT1 transport or degradation. This is consistent with the biology of the cell’s secretory pathway, where immature proteins are gradually processed into mature forms over minutes to hours. Our approach could be incorporated into improved models for any pathway involving secreted proteins, including sFLT1-regulated models of blood vessel biology.

  PublisherOA PDFDOI

• Resolving the design principles that control post-natal vascular growth and scaling

  Cell Systems · 2025-07-01 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Mechanistic computational modeling of sFLT1 secretion dynamics.

  UNC Libraries · 2025-09-04

  articleOpen access

  Constitutively secreted by endothelial cells, soluble FLT1 (sFLT1 or sVEGFR1) binds and sequesters extracellular vascular endothelial growth factors (VEGF), thereby reducing VEGF binding to VEGF receptor tyrosine kinases and their downstream signaling. In doing so, sFLT1 plays an important role in vascular development and in the patterning of new blood vessels in angiogenesis. Here, we develop multiple mechanistic models of sFLT1 secretion and identify a minimal mechanistic model that recapitulates key qualitative and quantitative features of temporal experimental datasets of sFLT1 secretion from multiple studies. We show that the experimental data on sFLT1 secretion is best represented by a delay differential equation (DDE) system including a maturation term, reflecting the time required between synthesis and secretion. Using optimization to identify appropriate values for the key mechanistic parameters in the model, we show that two model parameters (extracellular degradation rate constant and maturation time) are very strongly constrained by the experimental data, and that the remaining parameters are related by two strongly constrained constants. Thus, only one degree of freedom remains, and measurements of the intracellular levels of sFLT1 would fix the remaining parameters. Comparison between simulation predictions and additional experimental data of the outcomes of chemical inhibitors and genetic perturbations suggest that intermediate values of the secretion rate constant best match the simulation with experiments, which would completely constrain the model. However, some of the inhibitors tested produce results that cannot be reproduced by the model simulations, suggesting that additional mechanisms not included here are required to explain those inhibitors. Overall, the model reproduces most available experimental data and suggests targets for further quantitative investigation of the sFLT1 system.

  PublisherDOI

• Sleep and circadian rhythms in cardiovascular resilience: mechanisms, implications, and a Roadmap for research and interventions

  Nature Reviews Cardiology · 2025-09-18 · 5 citations

  reviewOpen access
  PublisherOA PDFDOI

• Mechanistic computational modeling of sFLT1 secretion dynamics

  PLoS Computational Biology · 2025-08-18

  articleOpen accessCorresponding

  Constitutively secreted by endothelial cells, soluble FLT1 (sFLT1 or sVEGFR1) binds and sequesters extracellular vascular endothelial growth factors (VEGF), thereby reducing VEGF binding to VEGF receptor tyrosine kinases and their downstream signaling. In doing so, sFLT1 plays an important role in vascular development and in the patterning of new blood vessels in angiogenesis. Here, we develop multiple mechanistic models of sFLT1 secretion and identify a minimal mechanistic model that recapitulates key qualitative and quantitative features of temporal experimental datasets of sFLT1 secretion from multiple studies. We show that the experimental data on sFLT1 secretion is best represented by a delay differential equation (DDE) system including a maturation term, reflecting the time required between synthesis and secretion. Using optimization to identify appropriate values for the key mechanistic parameters in the model, we show that two model parameters (extracellular degradation rate constant and maturation time) are very strongly constrained by the experimental data, and that the remaining parameters are related by two strongly constrained constants. Thus, only one degree of freedom remains, and measurements of the intracellular levels of sFLT1 would fix the remaining parameters. Comparison between simulation predictions and additional experimental data of the outcomes of chemical inhibitors and genetic perturbations suggest that intermediate values of the secretion rate constant best match the simulation with experiments, which would completely constrain the model. However, some of the inhibitors tested produce results that cannot be reproduced by the model simulations, suggesting that additional mechanisms not included here are required to explain those inhibitors. Overall, the model reproduces most available experimental data and suggests targets for further quantitative investigation of the sFLT1 system.

  PublisherOA PDFDOI

• Differential endothelial cell cycle status in postnatal retinal vessels revealed using a novel PIP-FUCCI reporter and zonation analysis

  Angiogenesis · 2024-05-25 · 4 citations

  articleOpen accessSenior author

  Cell cycle regulation is critical to blood vessel formation and function, but how the endothelial cell cycle integrates with vascular regulation is not well-understood, and available dynamic cell cycle reporters do not precisely distinguish all cell cycle stage transitions in vivo. Here we characterized a recently developed improved cell cycle reporter (PIP-FUCCI) that precisely delineates S phase and the S/G2 transition. Live image analysis of primary endothelial cells revealed predicted temporal changes and well-defined stage transitions. A new inducible mouse cell cycle reporter allele was selectively expressed in postnatal retinal endothelial cells upon Cre-mediated activation and predicted endothelial cell cycle status. We developed a semi-automated zonation program to define endothelial cell cycle status in spatially defined and developmentally distinct retinal areas and found predicted cell cycle stage differences in arteries, veins, and remodeled and angiogenic capillaries. Surprisingly, the predicted dearth of S-phase proliferative tip cells relative to stalk cells at the vascular front was accompanied by an unexpected enrichment for endothelial tip and stalk cells in G2, suggesting G2 stalling as a contribution to tip-cell arrest and dynamics at the front. Thus, this improved reporter precisely defines endothelial cell cycle status in vivo and reveals novel G2 regulation that may contribute to unique aspects of blood vessel network expansion.

  PublisherOA PDFDOI

• Life at the crossroads: the nuclear LINC complex and vascular mechanotransduction

  Frontiers in Physiology · 2024-05-20 · 15 citations

  articleOpen accessSenior authorCorresponding

  Vascular endothelial cells line the inner surface of all blood vessels, where they are exposed to polarized mechanical forces throughout their lifespan. Both basal substrate interactions and apical blood flow-induced shear stress regulate blood vessel development, remodeling, and maintenance of vascular homeostasis. Disruption of these interactions leads to dysfunction and vascular pathologies, although how forces are sensed and integrated to affect endothelial cell behaviors is incompletely understood. Recently the endothelial cell nucleus has emerged as a prominent force-transducing organelle that participates in vascular mechanotransduction, via communication to and from cell-cell and cell-matrix junctions. The LINC complex, composed of SUN and nesprin proteins, spans the nuclear membranes and connects the nuclear lamina, the nuclear envelope, and the cytoskeleton. Here we review LINC complex involvement in endothelial cell mechanotransduction, describe unique and overlapping functions of each LINC complex component, and consider emerging evidence that two major SUN proteins, SUN1 and SUN2, orchestrate a complex interplay that extends outward to cell-cell and cell-matrix junctions and inward to interactions within the nucleus and chromatin. We discuss these findings in relation to vascular pathologies such as Hutchinson-Gilford progeria syndrome, a premature aging disorder with cardiovascular impairment. More knowledge of LINC complex regulation and function will help to understand how the nucleus participates in endothelial cell force sensing and how dysfunction leads to cardiovascular disease.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL083262

  NIH · $1.4M · 2011

• Mechanisms of neovascularization in response to ischemia

  NIH · $1.5M · 2014–2018

• Molecular Control of Angiogenesis

  NIH · $7.1M · 1989–2020

• NIH Grant R21HL071993

  NIH · $652k · 2006

• NIH Grant R01HL086564

  NIH · $1.4M · 2013

Frequent coauthors

• William P. Dunworth

  92 shared

• Suk-Won Jin

  Yale University

  76 shared

• Heon‐Woo Lee

  Chosun University

  74 shared

• Diana C. Chong

  University of North Carolina at Chapel Hill

  54 shared

• John C. Chappell

  46 shared

• William L. Stanford

  Ottawa Hospital

  45 shared

• Maneesha S. Inamdar

  Jawaharlal Nehru Centre for Advanced Scientific Research

  43 shared

• Michihiro Hidaka

  Kumamoto Medical Center

  42 shared