Dineth Nagahawatta, PhD

Availability

Status: Open to research collaborations, trainee mentoring, and seminar/guest lectures. Meeting windows (MT): Mon–Fri, 10:00–16:00 (by appointment). Location: Department of Medicine (Cardiology), Faculty of Medicine & Dentistry, University of Alberta, Edmonton.

Area of Study / Keywords

Cardiovascular Biology; Heart Failure & Myocardial Infarction; ECM Remodeling; Neprilysin (MME)–Apelin/APJ Signaling; Peptide Therapeutics; Proteomics & Bioinformatics; Molecular Docking; Antiviral/Inflammation (SARS-CoV-2); Marine Polyphenolics

About

I am a Postdoctoral Research Fellow in Cardiology at the University of Alberta (Oudit Lab). My work centers on NEP (MME)–apelin/APJ signaling and extracellular matrix (ECM) remodeling in heart failure and myocardial infarction. During my Ph.D. and M.Sc. at Jeju National University, I identified therapeutic candidates for SARS-CoV-2 and chronic inflammatory diseases using marine polyphenolic compounds, exploring how they modulate viral entry, proliferation, and cytokine storms. These experiences spanning bioactive compound isolation, cell culture, animal models, proteomics, and molecular docking sparked my interest in how proteases (MMPs, TIMPs, ADAMs) govern ECM turnover and tissue injury/repair. I now integrate in vivo models, advanced imaging, multi-omics, and peptide engineering to map actionable targets for cardioprotection.

Research

I am a Postdoctoral Research Fellow in Cardiology at the University of Alberta (Oudit Lab, Department of Medicine, Faculty of Medicine & Dentistry). My research program focuses on how neprilysin (NEP/MME)–apelin/APJ signaling and extracellular matrix (ECM) protease networks (MMPs, TIMPs, ADAMs) coordinate cardiomyocyte–stromal–vascular crosstalk during myocardial infarction (MI), and heart failure. I combine in vivo disease models with mechanistic cell biology, multi-omics profiling, and peptide/drug engineering to define actionable targets for cardioprotection and improved post-MI remodeling.

My scientific foundation was built during my Ph.D. and M.Sc. at Jeju National University, where I investigated bioactive marine polyphenolic compounds as therapeutic candidates for SARS-CoV-2 infection and chronic inflammatory diseases. That work spanned bioactive compound isolation, cell culture, animal models, proteomics, and molecular docking, and probed how polyphenols modulate viral entry, replication dynamics, and cytokine storm responses. These projects sharpened my interest in how molecular interactions translate to system-level outcomes, and they led me to the cardiovascular ECM, where proteases and their inhibitors (MMPs/TIMPs), alongside ADAM family metalloproteinases, orchestrate matrix turnover, mechanotransduction, and growth-factor/cytokine bioavailability during injury, repair, and fibrosis.

Today, my work at UAlberta integrates three synergistic themes:

1. NEP–Apelin/APJ Signaling in Cardioprotection NEP (MME) regulates many vasoactive peptides; our focus is its intersection with apelin/APJ, a pro-survival, pro-angiogenic pathway with compelling roles in endothelial function, fibrosis attenuation, and ventricular remodeling. I use mouse MI models (including genetic lines and pharmacologic perturbations) to dissect how NEP activity modulates apelin bioavailability and downstream signaling (Akt, ERK, AMPK, eNOS), and how those signals influence fibroblast phenotype, microvascular integrity, and ventricular remodeling. A translational thrust involves NEP-resistant apelin analogs and small-molecule modulators to improve post-ischemic recovery.

2. ECM Proteases and Growth-Factor Networks: I map how MMPs/TIMPs/ADAMs shape the pericellular microenvironment after MI—regulating collagen dynamics, matricellular cues, and latent growth factors (e.g., TGF-β axis) that drive myofibroblast activation and scar quality. By coupling label-free/DIA proteomics with bulk and single-cell transcriptomics, I chart protease–substrate and protease–cytokine networks over time, then validate key interactions using primary cardiac fibroblasts, endothelial cells, and co-culture systems. The goal is to pinpoint drug-gable nodes that recalibrate ECM remodeling without compromising mechanical stability.

3. Therapeutic Design and Data-Driven Discovery Bridging mechanism to therapy, I collaborate on peptide engineering (e.g., stabilizing apelin motifs against NEP cleavage) and apply molecular docking/computational chemistry and AI-aided screening to prioritize analogs and small molecules. Leads are tested in acute signaling assays, migration/angiogenesis readouts, and in vivo efficacy metrics (function, fibrosis, vessel density). I emphasize reproducibility, quantitative rigor, and open, well-documented analysis pipelines.

Approach & Methods.
My lab practice blends careful in vivo physiology with deep phenotyping. Tools include MI/vascular injury models, echocardiography/functional endpoints, confocal microscopy, flow cytometry, Western blotting, ELISA/multiplex secretome analysis, gelatin zymography (MMP-2/9), qPCR, immunostaining and histopathology, and multi-omics (proteomics, transcriptomics, occasionally metabolomics). On the computation side, I work with R/tidyverse/ggplot2, Python, and established proteomics pipelines; I’m comfortable integrating public datasets (e.g., Human Protein Atlas, Expression Atlas) with our own data to strengthen inference and reproducibility.

Scientific Vision
Acute MI sets off parallel cascades—ischemia, inflammation, ECM remodeling, angiogenesis, and neurohumoral activation. Many therapies target single nodes, yet patients vary widely in matrix biology and peptide signaling. By elucidating how NEP–apelin signaling intersects with ECM protease activity and growth-factor bioavailability, we can design precision interventions that preserve microvascular function, temper pathological fibrosis, and improve contractile recovery. My long-term aim is to translate this systems-level map into peptide therapeutics and rational combination strategies for heart failure and vascular disease.

Prior Work & Its Impact on My Current Focus
My Ph.D./M.Sc. research on marine polyphenolics taught me to move fluidly between molecular mechanisms and disease-scale readouts. Dissecting how compounds influence receptor–ligand interactions, membrane dynamics, and immune signaling in viral and inflammatory contexts prepared me to study cardiovascular stress responses, where ECM remodeling and inflammatory circuits are tightly interwoven. 
The same disciplined pipeline—hypothesis → mechanistic assays → in vivo validation → omics integration → therapeutic iteration—now underpins my cardiovascular work.

Collaboration & Mentorship
I actively collaborate across cardiology, pharmacology, proteomics, and computational biology, and I welcome partnerships on ECM proteases, apelin/APJ biology, vascular biology, and peptide/drug design. I value trainee development and provide hands-on mentorship in experimental design, data analysis, and scientific communication, aiming to cultivate independent, rigorous scientists.

Teaching

I have experience teaching/mentoring at the undergraduate and graduate levels and enjoy guest lecturing on molecular pharmacology, omics workflows, and statistics/data visualization. I contribute to manuscript reviewing, collaborative grant development, and community outreach emphasizing open science and reproducibility.

• Publications