Cardiovascular biology
The Mukhopadhyay lab has several areas of investigation related to angiogenesis and cardiovascular conditions.
Angiogenesis
We study angiogenesis to better understand the mechanisms behind impaired tissue repair, chronic inflammation and disease progression. Angiogenesis, the process by which new blood vessels grow from existing ones, is essential for healing wounds and restoring blood flow after injury.
We use transgenic zebrafish models with fluorescently labeled blood vessels, allowing us to watch blood vessels form, branch and remodel in real time at the level of individual cells. This powerful approach helps us observe how vessel growth changes under both normal and disease conditions. By combining live imaging with genetic experiments and drug-based experiments, we identify how vascular growth is disrupted in a variety of conditions, including neurodegenerative disorders and cardiovascular injury.
Our goal is to uncover the key molecular pathways controlling these changes and find new therapeutic targets to restore healthy blood vessel function.
Zebrafish embryos in angiogenesis studies
Confocal images show the dorsal side of two-day-old Tg(fli:EGFP) zebrafish larvae. The blood vessels are labeled with enhanced green fluorescent protein (EGFP) in control wild type (WT) on the left and morpholino knockdown (morphant) on the right. The green threadlike structures represent the developing blood vasculature in the head region of the larvae. Images were acquired using an LSM 880 confocal microscope at the core facility, with excitation at 488 nanometers (nm) and a 20x objective lens. Scale bar is 200 micrometers (µm).
Zebrafish embryo and vascular development
Confocal images show the lateral side of the anterior region of a 2-day-old transgenic Tg(Fli:EGFP) zebrafish larva control WT on the left and morphant on the right. The green structure represents the blood vasculature in the head and the intersegmental vessels. This image was captured using the LSM 880 confocal microscope at the core facility using the 488 laser and the 10x objective. Scale bar is 200 micrometers (µm).
Zebrafish embryo in vascular permeability studies
This is a confocal image of the lateral trunk region of a 3-day-old transgenic zebrafish larva. The top section is the control with no heat shock showing no extravasation of red dye. The bottom is with heat shock-induced chronic vascular permeability, with red dye visible in the intersegmental space between intersegmental vessels. Green represents the blood vasculature and intersegmental vessels. Red indicates 70 kDa dextran dye. Images were acquired using an LSM 880 confocal microscope at the core facility with a 488 nanometer laser and a 10x objective. Scale bar is 100 micrometers (µm).
Cardiovascular biology
Our cardiovascular research focuses on understanding the role of VEGF receptors in heart disease and repair.
We investigate how these receptors regulate vascular growth, cardiomyocyte survival and tissue remodeling. We also study how their dysregulation contributes to the development and progression of heart failure. Our main interest lies in the role of VEGF receptor signaling in promoting cardiomyocyte remodeling in dilated cardiomyopathy and heart regeneration after myocardial infarction. This includes the influence of VEGF receptor signaling on angiogenesis, inflammation resolution and scar remodeling.
Using genetic mouse models with cell type-specific VEGF receptor manipulations, alongside zebrafish cardiac injury models, we apply high-resolution imaging techniques, such as confocal and two-photon microscopy combined with molecular and transcriptomic profiling. This integrated approach enables us to visualize and quantify cellular dynamics in real time, identify key molecular pathways, and evaluate therapeutic strategies aimed at harnessing VEGF signaling to improve heart repair and functional recovery.
Comparison of heart morphology
This image shows a comparison of heart morphology between wild-type mice on the left (A and C) and smooth muscle protein 22-NRP1 knockout mice on the right (B and D). In the knockout mice, NRP1 is selectively deleted in cardiomyocytes and smooth muscle cells, leading to structural abnormalities. Notably, knockout hearts exhibit marked enlargement of the right ventricle, indicative of altered cardiac remodeling and potential functional impairment. Images A and B represent heart tissue dissected, and C and D represent a histological section of the heart.
Echocardiographic images comparing cardiac structure and function
This image shows echocardiographic images comparing cardiac structure and function between wild-type mice on the left and smooth muscle protein 22α (SM22α)-NRP1 knockout mice on the right. The knockout mice lack NRP1 specifically in cardiomyocytes and smooth muscle cells, resulting in significant alterations in cardiac morphology and performance. Notably, the knockout hearts exhibit enlarged right ventricles, reflecting remodeling changes that may impact cardiac output and function. These echocardiographic findings underscore the critical role of NRP1 signaling in maintaining normal heart structure and highlight its importance in cardiovascular health and disease. The images show the left ventricle (LV) and the right ventricle (RV). The scale is 2 millimeters (mm).