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 translational scientist whose work connects bioactive discovery with mechanism-driven biology. I study how natural products, endogenous metabolites, and peptides influence disease-relevant pathways, using experimental validation to move from “activity” to “mechanism.” My background spans marine bioactives, protein hydrolysates and peptide fractions, cell-based functional models, in vivo studies, and computational analysis (proteomics, bioinformatics, molecular docking). I currently work at the University of Alberta, applying these tools to peptide signaling and remodeling biology after myocardial infarction, and I like cross-disciplinary collaborations that turn molecular insights into testable interventions.

Research

I develop and test bioactive molecules from natural products and biopolymers to engineered peptides to understand how they reprogram cellular pathways in disease-relevant systems. My work connects molecular-level properties (stability, structure–function) to mechanisms, phenotypes, and translational potential through integrated wet-lab and data-driven approaches.

Current areas of focus include:

• Bioactives and biopolymers extraction/isolation, and linking structure to biological activity.
• Protein hydrolysates and bioactive peptide discovery - fractionation, functional screening, and mechanism-oriented validation
• Peptide therapeutics and stability engineering - design/testing of protease-resistant peptides.
• Protease-regulated signaling in tissue injury and repair - NEP biology and extracellular matrix [ECM] remodeling networks (MMPs [matrix metalloproteinases], TIMPs [tissue inhibitors of metalloproteinases], ADAMs [a disintegrin and metalloproteinases])
• Inflammation and immune-pathway modulation in disease models, including antiviral/inflammation contexts (SARS-CoV-2).
• Data-supported prioritization - proteomics, bioinformatics, and molecular docking to strengthen target and pathway inference. 
• Overall, I aim to build rigorous “molecule → mechanism → outcome” evidence that can guide practical therapeutic strategies.

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.

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
Collaboration & MentorshipI pursue collaborative research at the interface of natural product discovery and mechanistic biology. I welcome interdisciplinary partnerships in bioactive compounds, biopolymers, protein hydrolysates, bioactive peptides, and translational models that enable rigorous testing of molecular mechanisms underlying physiological and disease phenotypes. My work at the University of Alberta involves collaborative projects spanning cardiovascular biology, pharmacology, proteomics, and computational biology, with a focus on peptide signaling pathways, including neprilysin (NEP/MME)-mediated regulation and apelin–apelin receptor (APJ/APLNR) biology. 

Mentorship is central to my research program. I provide structured guidance in experimental design, assay optimization, quantitative data analysis, and scientific writing to develop independent researchers with strong technical skills, analytical rigor, and effective communication.

Teaching

I have experience teaching and mentoring undergraduate and graduate trainees in both wet-lab and data-driven research. My mentoring spans bioactive research workflows (e.g., polyphenols/biopolymers, protein hydrolysates and bioactive peptides), experimental design and troubleshooting, and quantitative data interpretation and figure generation. I also contribute to scientific service through manuscript peer review, collaborative grant and fellowship development, and outreach that promotes reproducible research practices and clear scientific communication.

• Publications