Research Interests: Notch receptor signaling and chemo-mechanical regulation of vascular barrier, molecular regulation of endothelial cell morphodynamics during angiogenic sprouting and in cerebral small vessel disease, cardiac myocyte sarcomerogenesis, and angiocrine niche contribution to parenchymal tissue development, cancer, and infectious disease progression. Summary: Research in the Kutys Lab is focused on achieving a molecular and physical understanding of biological mechanisms that interact across time and length scales to enable emergent, tissue morphogenic behaviors. Central to our efforts is the development and application of biomimetic microphysiological culture models, organ-on-chip systems, that incorporate three-dimensional (3D) organotypic architectures and permit the study of human tissue development, regeneration, and pathogenesis with unprecedented resolution and biological control. Combining these models with innovative molecular technologies and high content microscopy, a major focus of my laboratory is understanding orchestration of tissue morphogenic behavior and cell fate specification by cell-cell and cell-extracellular matrix (ECM) adhesion complexes during cardiovascular development and disease. Current projects in the lab focus on: Notch receptor signaling and chemo-mechanical regulation of vascular barrier, molecular regulation of endothelial cell morphodynamics during angiogenic sprouting and in cerebral small vessel disease, cardiac myocyte sarcomerogenesis, and angiocrine niche contribution to parenchymal tissue development, cancer, and infectious disease progression.
Publications
The Notch1 intracellular domain orchestrates mechanotransduction of fluid shear stress.
Perivascular matrix densification dysregulates angiogenesis and activates pro-inflammatory endothelial cells.
Quantitative comparison of fluorescent proteins using protein nanocages in live cells.
Editorial overview: Cell dynamics across biological length scales.
Doublecortin reinforces microtubules to promote growth cone advance in soft environments.
Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain.
Arp2/3 complex activity enables nuclear YAP for naïve pluripotency of human embryonic stem cells.
Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion.
A 3D biomimetic model of lymphatics reveals cell-cell junction tightening and lymphedema via a cytokine-induced ROCK2/JAM-A complex.
'Chip'-ing away at morphogenesis - application of organ-on-chip technologies to study tissue morphogenesis.
A convolutional neural network STIFMap reveals associations between stromal stiffness and EMT in breast cancer.
Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation.
Microphysiological model of PIK3CA-driven vascular malformations reveals a role of dysregulated Rac1 and mTORC1/2 in lesion formation.
Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion.
Adherens junctions organize size-selective proteolytic hotspots critical for Notch signalling.
Conversation before crossing: dissecting metastatic tumor-vascular interactions in microphysiological systems.
3D mesenchymal cell migration is driven by anterior cellular contraction that generates an extracellular matrix prestrain.
Uncovering mutation-specific morphogenic phenotypes and paracrine-mediated vessel dysfunction in a biomimetic vascularized mammary duct platform.
Extracellular matrix alignment dictates the organization of focal adhesions and directs uniaxial cell migration.
Force Generation via β-Cardiac Myosin, Titin, and α-Actinin Drives Cardiac Sarcomere Assembly from Cell-Matrix Adhesions.
Forces and mechanotransduction in 3D vascular biology.
An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.
Dimensions in cell migration.
Regulation of cell adhesion and migration by cell-derived matrices.
Ubiquitylation of phosphatidylinositol 4-phosphate 5-kinase type I γ by HECTD1 regulates focal adhesion dynamics and cell migration.
Micro-environmental control of cell migration--myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics.
Monte Carlo analysis of neck linker extension in kinesin molecular motors.
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