Dr. Ralph DaCosta

Senior Scientist, Princess Margaret Cancer Center, University Health Network (Toronto, Canada)

Seeing Cancer in Motion: Intravital Optical Imaging as a Quantitative Analytical Platform for Cancer Biology and Drug Discovery

Advances in optical imaging now allow us to visualize cancer as a dynamic, evolving ecosystem rather than a static disease. My laboratory at the Princess Margaret Cancer Centre has pioneered intravital fluorescence microscopy (IVM) technologies that enable real-time, quantitative visualization of tumor, stromal, immune, vascular, and neuronal interactions deep within living tissues. These custom-engineered imaging windows — including our bone marrow, pancreatic, and cranial platforms — provide continuous access to the tumor microenvironment, capturing cellular behaviors, metabolic flux, and drug pharmacokinetics at subcellular resolution over time.

Our approach integrates principles of analytical chemistry with quantitative biology, where imaging itself is the key analytical instrument. Using multiplexed fluorescent probes, biosensors, and contrast agents, we directly measure signaling activity, oxygen tension, drug uptake, immune cell motility, and neural innervation dynamics in vivo. By coupling these optical readouts with complementary molecular and spatial analyses, we can correlate biochemical changes with dynamic cellular behaviors to reveal new mechanisms of tumor progression, neuro-immune modulation, and therapy response.

This talk will highlight how intravital “imaging” analytics can deconvolute mechanisms of therapeutic resistance, immune evasion, and metastatic spread in complex tumor niches, and how these insights can be operationalized to accelerate drug discovery. I will discuss emerging strategies to automate data extraction using AI-driven image analysis, enabling high-throughput phenotypic screening directly in living systems. Ultimately, integrating intravital imaging into preclinical development pipelines provides a transformative bridge between molecular  chemistry and functional biology — offering a powerful new paradigm for discovering, validating, and optimizing cancer therapeutics.

Biograph

Dr. Ralph DaCosta is an internationally recognized scientist and leader in developing, translating, and commercializing advanced optical imaging technologies for oncology and other diseases. With over 30 years of expertise in biophotonics and cancer molecular imaging, he is a Senior Scientist at the Princess Margaret Cancer Centre, where he leads a multidisciplinary program advancing cancer diagnosis and treatment through innovative molecular imaging technologies.

Dr. DaCosta’s lab pioneered intravital imaging, enabling the study of dynamic cancer cell interactions in living models of human cancers like pancreatic cancer and leukemia. This technology provides critical insights into tumor microenvironment remodeling, revealing how it hinders conventional therapies and inspires new treatment strategies as well as novel drug and immune therapies.

A Professor in Medical Biophysics at the Temerty Faculty of Medicine, University of Toronto, Dr. DaCosta has trained numerous graduate students and postdoctoral fellows, held the prestigious Cancer Care Ontario Chair in Cancer Imaging, and was named UHN Inventor of the Year in 2013 for his surgical oncology and infection imaging breakthroughs. He has led >15 single and multicenter clinical trials based on cancer imaging technologies, as well as an international multicenter randomized clinical trial involving an FDA-approved imaging drug with an intraoperative fluorescence imaging technology he invented for real-time margin assessment during breast cancer surgery.

Dr. DaCosta is an inventor on >320 patents worldwide. He is the Founder, Chief Scientific Officer and Board Director of MolecuLight Inc. (Toronto, Canada; Pittsburgh, USA), which commercialized his fluorescence imaging innovations in wound care and oncology.

Academic and Corporate Affiliations

• Senior Scientist, Princess Margaret Cancer Center, University Health Network (Toronto, Canada)
• 101 College Street, Unit 15-302, Toronto Mediacl Discovery Tower
• Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto (Toronto, Canada)
• Founder, Chief Scientist, Board Member, MolecuLight Inc. (Toronto, Canada)