Shinichiro Ogawa

Shinichiro Ogawa is an affiliate scientist at the McEwen Stem Cell Institute, University Health Network.

He obtained his MD in Japan. After finishing his residency, he served as a staff surgeon at Shinshu University, specializing hepatobiliary- pancreatic malignancy and liver transplantation.

He also completed a PhD at the Shinshu University, studying liver regeneration and hepatocyte differentiation from stem cells, followed by postdoctoral training in the laboratory of Dr Gordon Keller’s Lab at McEwen Stem Cell Institute, in Toronto.

His research interests have been focused on the molecular pathways responsible for liver associated cell differentiation from human pluripotent stem cells in liver injury and regeneration.

Research Synopsis

It is reported that over three million Canadians are affected by liver diseases, and many of them progress to liver failure.

Currently, liver transplantation is the only available and curative treatment for the end stage of liver diseases.

As the demand for liver transplantation far exceeds the number of available donor organs, there is an unmet medical need to search for an alternative treatment for liver failure.

The regeneration and repair of damaged and diseased liver through the transplantation of liver cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) offers a potential new therapy.

Our research focus is to understand molecular mechanisms that promote the development of all cell types in the liver from human pluripotent stem cells by translating knowledge of human liver development to the differentiation culture system.

Hepatocyte and cholangiocyte are of particular importance as they are responsible to maintain liver function.

Based on current advances, our group established differentiation protocols that promote the efficient generation of both cell types displaying many characteristics and properties found in the adult liver.

With access to hPSCs derived liver cells, our lab is establishing in vivo transplantation assay, using mice engineered to undergo liver failure as pre-clinical models to restore liver function.

Through the multidisciplinary collaborative approach, we are developing new in vitro liver tissue and liver organoids including functional biliary structures with hPSCs derived liver cells.

These studies are also focused on developing models to study Cystic Fibrosis Liver Disease (CFLD), which impairs the function of bile ducts in the liver.

To test the function of hPSCs derived liver tissue and liver organoids, we are employing in vivo assay to develop extracorporeal liver support system in liver failure using small and large pre-clinical animal models.

The ultimate goal is to translate the stem cell biology to therapeutic interventions for liver diseases.

The Ogawa Lab

The Ogawa Lab is located downtown Toronto at the MaRS Centre, Max Bell Research Centre (MBRC).

We work on stem cell cultures from human pluripotent stem cells on daily basis along with molecular studies including:

• qPCR
• immunostaining
• ELIZA
• flow cytometry analysis and gene modification
• cloning.

We also utilize high resolution confocal microscopy, electron microscopy.

Pre-clinical animal transplantation studies have been performed at ARC facility (Animal Resources Centre) which locates in the same building.

We use high-throughput plate reader assay, RNA-seq and single cell RNA in close collaboration.

Selected Publications

MacParland S, Liu Zhong X, Innes B, Bartczak A, Gage B, Manuel J, Khuu N, Echeverri J, Linares I, Gupta R, Cheng M, Liu L, Camat D, Chung S, Seliga R, Shao Z, Lee E, Ogawa S, Ogawa M, Wilson M, Fish J, Selzner M, Ghanekar A, Grant D, Greig P, Sapisochin G, Selzner N, Winegarden N, Adieu O, Keller G, Bader G, McGilvray I. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nature Communications. 2018 Oct 22;9 (1).

Zhang B, Montgomery M, Chamberlain D, Ogawa S, Koroji A, Wells L, Aric P, Masse S, Kim J, Reis L, Abdulah L, Nunes S, Wheeler A, Nanthakumar K, Keller G, Sefton M, Radisic M. Angiochip: a biogradable scaffold with built in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nature Material. 2016; 15, 669-678.

Ogawa M, Ogawa S, Bear CE, Ahmadi S, Chin S, Li B, Grompe M, Keller G, Kamath BM, Ghanekar A. Directed differentiation of cholangiocytes from human pluripotent stem cells. Nat Biotechnol. 2015 Aug; 33(8): 853-61.

Holtzinger A, Streeter P, Sarangi F, Hillborn S, Niapour S, Ogawa S, Keller G. New markers for tracking endoderm induction and hepatocyte differentiation from human pluripotent stem cells. Development. 2015 Dec15;142(24):4253-65.

Ogawa S, Surapisitchat J, Virtanen C, Ogawa M, Niapour M, Sugamori KS, Wang S, Tamblyn L, Guillemette C, Hoffmann E, Zhao B, Strom S, Laposa RR, Tyndale RF, Grant DM, Keller G. Three-dimensional culture and cAMP signaling promote the maturation of human pluripotent stem cell-derived hepatocytes. Development. 2013 Aug; 140(15): 3285-96.