What we do

Our group leverages state-of-the-art induced pluripotent stem cell (iPSC) technology to improve the understanding of liver physiology and disease. We generate iPSCs from patients and combine this with bioengineering and gene editing to generate cell, organoid and animal models. We also apply this approach toward the creation of novel cell therapies. Finally, to better understand which patients are most likely to benefit from such therapies, we leverage disease registries and electronic health records to precisely characterise the natural history of disease.

Why it is important

The liver is a large and complex organ. Its functions are essential to life. Some of these functions include: carbohydrate, fat and protein metabolism, drug detoxification and bile excretion. Because of its vital regulatory function, disruption to the liver can ultimately lead to liver failure and death. Liver disease accounts for approximately 2 million deaths per year worldwide and since 1970s the deaths due to liver disease have increased by 400%. Currently, the only curative treatment for patients with liver failure is orthotopic liver transplantation, so alternative treatment options are urgently required. However, research into liver diseases, including studies of the molecular pathological mechanisms and research into novel and more effective therapeutics, is hindered by a lack of hepatic models that can faithfully recapitulate complex disease phenotypes. Therefore, there is a strong need to generate better in vivo human hepatocyte models, which is what our lab does using iPSCs. Furthermore, the ability to generates patient-specific iPSCs, and their unlimited self-renewal ability, makes iPSC-derived hepatocytes a good source for future cell therapy.

How it can benefit patients

Our iPSC-hepatocyte models allow us to study the molecular mechanisms underpinning liver diseases. We use this understanding to discover more effective therapeutics for these diseases. Furthermore, the iPSC-hepatocytes themselves are potential candidates for liver cell therapy. Ultimately, our work aims to provide patients with liver disease with more effective treatment options.

Therapeutic applications of iPSC-hepatocytes

Summary of current research

The purpose of our research is to better understand and treat liver disease. Examples of diseases we are approaching in this way include:

• Alpha-1 antitrypsin deficiency (AATD)
• Genetic cholestasis
• Wilson’s Disease
• NAFLD
• Acute liver failure

Prospective PhD students, please email for more information about PhD positions in our lab.

Key publications

Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells.
Rashid T*, Corbineau S.*, Hannan N, Marciniak S, Miranda E, Alexander G, Huang-Doran I, Griffin J, Ahrlund-Richter L, Skepper J, Semple R, Weber A, Lomas DA & Vallier L. Journal of Clinical Investigation 2010. https://doi.org/10.1172/JCI43122 

Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells.
Rashid ST*, Yusa K*, Strick-Marchand H, Varela I, Liu P-Q, Paschon D, Miranda E, Ordóñez A, Hannan N, Rouhani F, Darche S, Alexander G, Marciniak S, Fusaki N, Hasegawa M, Holmes M, Di Santo J, Lomas DA, Bradley A & Vallier L. Nature 2011. https://doi.org/10.1038/nature10424 

Validation of cGMP-compliant human pluripotent stem cell-derived hepatocytes for cell-based therapy
Blackford, SJI, Ng, SS, Segal, JM, King, A, Kent, DH, Moore, J, Sheldon, M, Ilic, D, Dhawan, A, Mitry, R& Rashid, ST. Stem Cells Translational Medicine 2018. https://doi.org/10.1002/sctm.18-0084 

Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold.
Ng SS, Saeb-Parsy, K, Segal, JM, Serra, MP, No, DY, Frank, CW, Cho, NJ, Nakauchi, H, Glenn, JS& Rashid, ST. Biomaterials 2018. https://doi.org/10.1016/j.biomaterials.2018.07.043

Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors
Segal, JM, Kent, DH, Wesche, D, Ng, SS, Serra M, Teichmann S, Quake, S, *Nakauchi, H& *Rashid, ST. Nature Communications 2019. https://doi.org/10.1038/s41467-019-11266-x

Sulfated Alginate Reduces Pericapsular Fibrotic Overgrowth on Encapsulated  cGMP-Compliant hPSC-Hepatocytes in Mice
Syanda, A.M, Kringstad, V.I, Blackford, S.J.I, Kjesbu, J.S, Ng, S.S, Ma, L, Xiao, F, Coron, A.E, Rokstad, A.M.A, Modi, S, et al*Rashid, ST. Front Bioeng Biotechnol 2021. https://doi.org/10.3389/fbioe.2021.816542