Seminar - “Heart-on-a-plate for Drug Discovery and Disease Modeling” by Milica Radisic, Department of Chemical Engineering & Applied Chemistry, University of Toronto

Thursday, October 27, 2016 3:30 pm - 3:30 pm EDT (GMT -04:00)

ABSTRACT:  The current drug development process is both very slow (15 year average) and costly ($1.5B/drug average). Despite this hefty investment, inefficiencies in the drug screening process routinely result in the withdrawal of drugs from the market due to serious toxicities and adverse cardiovascular effects. Safety screen assessments performed on cell cultures and animal models do not always correlate with clinical risk. Specifically, this entire framework predicts only 75-90% of the effects of a drug in a human patient, resulting in the abandonment of many promising drugs early in development and enabling some cardiotoxic drugs go to market. A potential explanation is that much of the safety and efficacy testing has relied upon animal studies and little information has been gathered from human preparations. The applicability of animal studies is limited by the fundamental cardiovascular differences amid species. Similarly, cardiac ion channel in vitro screens frequently involve non-cardiac cells (Chinese hamster ovary, CHO or human embryonic kidney, HEK) that have been engineered to overexpress an individual target ion channel, most commonly the human ether-a-go-go (hERG) channel (IKr current). However, interference with other currents may also contribute to cardiac complications necessitating an assessment protocol that evaluates the effect of a drug on the collective behaviour of cardiac ion channels.

Organ-on-a-chip devices hold a promise to revolutionize the way drugs are discovered and tested when used in conjunction with cardiomyocytes derived from human pluripotent stem cells. Current devices are limited by the presence of non-physiological materials such as glass and drug-absorbing PDMS as well as the necessity for specialized equipment such as vacuum lines and fluid pumps that inherently limit their throughput. An overview of two new technologies, Biowire and AngioChip that overcome some of the limitations above will be presented. Biowires and AngioChips are situated in an open-concept plate-like platform compatible with current liquid handling practices that involve pipetting or pipetting robots. The use of these technologies in maturation of cardiomyocytes derived from pluripotent stem cells, their perfusion, drug testing and disease modelling will be presented.

Dr. Milica Radisic is Professor at the University of Toronto and Canada Research Chair (Tier 2) in Functional Cardiovascular Tissue Engineering. She obtained B.Eng. from McMaster University in 1999, and Ph.D. form the Massachusetts Institute of Technology in 2004, both in Chemical Engineering. Dr. Radisic received numerous awards and fellowships, including MIT Technology Review Top 35 Innovators under 35.  In 2010, she was named “The One to Watch” by the Scientist and the Toronto Star; she also received McMaster Arch Award. She was a recipient of the Professional Engineers Ontario-Young Engineer Medal in 2011, Engineers Canada Young Engineer Achievement Award in 2012, Queen Elizabeth II Diamond Jubilee Medal in 2013 and NSERC E.W.R Steacie Fellowship in 2014.  In 2014 she was elected to the Royal Society of Canada, College of New Scholars, Artists and Scientists and in 2015 she was the recipient of Hatch Innovation Award by CSChE. The long term objective of Dr. Radisic’s research is to enable cardiovascular regeneration through tissue engineering and development of new biomaterials.  Her research interests also include microfluidic cell separation and development of in vitro models for drug testing. Currently, Dr. Radisic holds research funding from CIHR, NSERC, CFI, ORF, NIH, and the Heart and Stroke Foundation. She is an Associate Editor for ACS Biomaterials Science & Engineering and a member of Editorial Board of Tissue Engineering. She serves on CIHR BME panel. She is actively involved with BMES (Cardiovascular Track Chair in 2013 and 2104) and TERMIS-AM (Council member, Chair of the Membership Committee). Her research findings were presented in over 100 research papers, reviews and book chapters with h-index of 44 and over 6750 citations.  She is a co-founder of a start-up company TARA Biosystems focused on the use of engineered tissues in drug development.