Integrative analysis of angiogenic signaling in obesity: capillary features and VEGF binding kinetics.

Obesity is a global health crisis, with its prevalence particularly severe in the United States, where over 42% of adults are classified as obese. Obesity is driven by complex molecular and tissue-level mechanisms that remain poorly understood. Among these, angiogenesis-primarily mediated by vascular endothelial growth factor (VEGF-A)-is critical for adipose tissue expansion but presents unique challenges for therapeutic targeting due to its intricate regulation.

Understanding the effects of oxytocin receptor variants on OXT-OXT receptor binding: A mathematical model.

Approximately half of U.S. women giving birth annually receive Pitocin, the synthetic form of oxytocin (OXT), yet its effective dose can vary significantly.

Quantification of surface-localized and total oxytocin receptor in myometrial smooth muscle cells.

Oxytocin acts through the oxytocin receptor (OXTR) to modulate uterine contractility. We previously identified OXTR genetic variants and showed that, in HEK293T cells, two of the OXTR protein variants localized to the cell surface less than wild-type OXTR. Here, we sought to measure OXTR in the more native human myometrial smooth muscle cell (HMSMC) line on both the cell-surface and across the whole cell, and used CRISPR editing to add an HA tag to the endogenous OXTR gene for anti-HA measurement.

Incorporating Diversity, Equity, and Inclusion Content Into Bioengineering Curricula: A Program-Level Approach.

Diversity, equity, and inclusion (DEI) are interconnected with bioengineering, yet have historically been absent from accreditation standards and curricula. Toward educating DEI-competent bioengineers and meeting evolving accreditation requirements, we took a program-level approach to incorporate, catalog, and assess DEI content through the bioengineering undergraduate program. To support instructors in adding DEI content and inclusive pedagogy, our team developed a DEI planning worksheet and surveyed instructors pre- and post-course.

Innovation and Entrepreneurship in Promotion and Tenure in Biomedical Engineering: Communication from the Biomedical Engineering Society Long Range Planning Committee.

Promotion and tenure (P&T) remain the central tenets of academia. The criteria for P&T both create and reflect the mission of an institution. The discipline of biomedical engineering is built upon the invention and translation of tools to address unmet clinical needs.

Toward Blood-Based Precision Medicine: Identifying Age-Sex-Specific Vascular Biomarker Quantities on Circulating Vascular Cells.

Introduction: Abnormal angiogenesis is central to vascular disease and cancer, and noninvasive biomarkers of vascular origin are needed to evaluate patients and therapies. Vascular endothelial growth factor receptors (VEGFRs) are often dysregulated in these diseases, making them promising biomarkers, but the need for an invasive biopsy has limited biomarker research on VEGFRs. Here, we pioneer a blood biopsy approach to quantify VEGFR plasma membrane localization on two circulating vascular proxies: circulating endothelial cells (cECs) and circulating progenitor cells (cPCs).

Correction: Innovation and Entrepreneurship in Promotion and Tenure in Biomedical Engineering.

[This corrects the article DOI: 10.1007/s12195-023-00767-x.].

Axl and Vascular Endothelial Growth Factor Receptors Exhibit Variations in Membrane Localization and Heterogeneity Across Monolayer and Spheroid High-Grade Serous Ovarian Cancer Models.

Vascular endothelial growth factor receptors (VEGFRs) and Axl are receptor tyrosine kinases (RTK) that are targeted in ovarian cancer therapy. Two-dimensional monolayer culture and three-dimensional spheroids are common models for RTK-targeted drug screening: monolayers are simple and economical while spheroids include several genetic and histological tumor features. RTK membrane localization dictates RTK signaling and drug response, however, it is not characterized in these models.

Absolute Quantification of Plasma Membrane Receptors Via Quantitative Flow Cytometry.

Plasma membrane receptors are transmembrane proteins that initiate cellular response following the binding of specific ligands (e.g., growth factors, hormones, and cytokines).

Pharmacological chaperones for the oxytocin receptor increase oxytocin responsiveness in myometrial cells.

Oxytocin is a potent uterotonic agent administered to nearly all patients during childbirth in the United States. Inadequate oxytocin response can necessitate Cesarean delivery or lead to uterine atony and postpartum hemorrhage. Thus, it may be clinically useful to identify patients at risk for poor oxytocin response and develop strategies to sensitize the uterus to oxytocin.

Naturally Occurring Genetic Variants in the Oxytocin Receptor Alter Receptor Signaling Profiles.

The hormone oxytocin is commonly administered during childbirth to initiate and strengthen uterine contractions and prevent postpartum hemorrhage. However, patients have wide variation in the oxytocin dose required for a clinical response. To begin to uncover the mechanisms underlying this variability, we screened the 11 most prevalent missense genetic variants in the oxytocin receptor () gene.

Fund Black scientists.

Our nationwide network of BME women faculty collectively argue that racial funding disparity by the National Institutes of Health (NIH) remains the most insidious barrier to success of Black faculty in our profession. We thus refocus attention on this critical barrier and suggest solutions on how it can be dismantled.

VEGF-A splice variants bind VEGFRs with differential affinities.

Vascular endothelial growth factor A (VEGF-A) and its binding to VEGFRs is an important angiogenesis regulator, especially the earliest-known isoform, VEGF-A. Yet several additional splice variants play prominent roles in regulating angiogenesis in health and in vascular disease, including VEGF-A and an anti-angiogenic variant, VEGF-A. Few studies have attempted to distinguish these forms from their angiogenic counterparts, experimentally.

Systems Biology Will Direct Vascular-Targeted Therapy for Obesity.

Healthy adipose tissue expansion and metabolism during weight gain require coordinated angiogenesis and lymphangiogenesis. These vascular growth processes rely on the vascular endothelial growth factor (VEGF) family of ligands and receptors (VEGFRs). Several studies have shown that controlling vascular growth by regulating VEGF:VEGFR signaling can be beneficial for treating obesity; however, dysregulated angiogenesis and lymphangiogenesis are associated with several chronic tissue inflammation symptoms, including hypoxia, immune cell accumulation, and fibrosis, leading to obesity-related metabolic disorders.

Author Correction: Discovery of High-Affinity PDGF-VEGFR Interactions: Redefining RTK Dynamics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sex differences in cancer mechanisms.

We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels.

The Convergence of Cell-Based Surface Plasmon Resonance and Biomaterials: The Future of Quantifying Bio-molecular Interactions-A Review.

Cell biology is driven by complex networks of biomolecular interactions. Characterizing the kinetic and thermodynamic properties of these interactions is crucial to understanding their role in different physiological processes. Surface plasmon resonance (SPR)-based approaches have become a key tool in quantifying biomolecular interactions, however conventional approaches require isolating the interacting components from the cellular system.

Multiplexing Angiogenic Receptor Quantification via Quantum Dots.

Clinical and biomedical research seeks single-cell quantification to better understand their roles in a complex, multicell environment. Recently, quantification of vascular endothelial growth factor receptors (VEGFRs) provided important insights into endothelial cell characteristics and response in tumor microenvironments. However, existing technologies for quantifying plasma membrane receptor tyrosine kinases (RTKs) lack multiplexing capabilities, limiting detailed characterization.

Characterizing Glioblastoma Heterogeneity via Single-Cell Receptor Quantification.

Dysregulation of tyrosine kinase receptor (RTK) signaling pathways play important roles in glioblastoma (GBM). However, therapies targeting these signaling pathways have not been successful, partially because of drug resistance. Increasing evidence suggests that tumor heterogeneity, more specifically, GBM-associated stem and endothelial cell heterogeneity, may contribute to drug resistance.

VEGFR1 promotes cell migration and proliferation through PLCγ and PI3K pathways.

The ability to control vascular endothelial growth factor (VEGF) signaling offers promising therapeutic potential for vascular diseases and cancer. Despite this promise, VEGF-targeted therapies are not clinically effective for many pathologies, such as breast cancer. VEGFR1 has recently emerged as a predictive biomarker for anti-VEGF efficacy, implying a functional VEGFR1 role beyond its classically defined decoy receptor status.

Discovery of High-Affinity PDGF-VEGFR Interactions: Redefining RTK Dynamics.

Nearly all studies of angiogenesis have focused on uni-family ligand-receptor binding, e.g., VEGFs bind to VEGF receptors, PDGFs bind to PDGF receptors, etc.

Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a Dimeric-cRGD Peptide for Targeted Imaging of α β Integrin Activity.

Cyclic peptides containing the Arg-Gly-Asp (RGD) sequence have been shown to specifically bind the angiogenesis biomarker α β integrin. We report the synthesis, chemical characterization, and biological evaluation of two novel dimeric cyclic RGD-based molecular probes for the targeted imaging of α β activity (a radiolabeled version, Cu-NOTA-PEG-cRGD, for PET imaging, and a fluorescent version, FITC-PEG-cRGD, for in vitro work). We investigated the performance of this probe at the receptor, cell, organ, and whole-body levels, including its use to detect diabetes associated impairment of ischemia-induced myocardial angiogenesis.

Integrative meta-modeling identifies endocytic vesicles, late endosome and the nucleus as the cellular compartments primarily directing RTK signaling.

Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms.

qFlow Cytometry-Based Receptoromic Screening: A High-Throughput Quantification Approach Informing Biomarker Selection and Nanosensor Development.

Nanosensor-based detection of biomarkers can improve medical diagnosis; however, a critical factor in nanosensor development is deciding which biomarker to target, as most diseases present several biomarkers. Biomarker-targeting decisions can be informed via an understanding of biomarker expression. Currently, immunohistochemistry (IHC) is the accepted standard for profiling biomarker expression.

A Method of Targeted Cell Isolation via Glass Surface Functionalization.

One of the limiting factors to the adoption and advancement of personalized medicine is the inability to develop diagnostic tools to probe individual nuances in expression from patient to patient. Current methodologies that try to separate cells to fill this niche result in disruption of physiological expression, making the separation technique useless as a diagnostic tool. In this protocol, we describe the functionalization and optimization of a surface for the cellular capture and release.