High-Throughput Identification of Novel Treatments for Liver Cirrhosis and Hepatocarcinoma

Summary

• Liver cirrhosis and chronic liver disease such as hepatocellular carcinoma (HCC) are global health problems that affect over 100 million adults and account for >2 million deaths worldwide per year
• Other than liver transplantation, there is no cure for these diseases
• Furthermore, while the rates of cirrhosis and HCC have increased, there has been no advancement of clinical therapies largely due to the lack of available clinically annotated biological samples and patient-derived models to better understand the disease and its associated characteristics
• The EIPM, in conjunction with Weill Cornell Medicine-New York Presbyterian (WCM-NYP), are working collaboratively to couple cutting edge profiling and ex vivo modeling technologies with clinical expertise and access to samples

Technical Overview

• The EIPM has a 3-aim approach to better perturb the biology of cirrhosis and HCC and leverage that information to develop novel therapies
• Aim 1: Molecular characterization of the progression of liver cirrhosis - They will use single cell and spatial-omic technologies to study the complexity of cirrhosis at each stage of disease progression (see figure)
• Aim 2: Generation of pre-clinical models of liver cirrhosis and HCC to identify novel targets and therapies - The EIPM has developed patient derived 3D models of normal livers in order to generate pre-clinical models of different stages of liver cirrhosis and HCC in order to test novel treatment options (see figure)
• Aim 3: Elucidate and evaluate potential drivers of cirrhosis progression using novel therapies - Culmination of Aims 1 & 2, providing a complete understanding of drug response across disease states

Market Opportunity

• This work will provide a translational tool kit of complementary approaches to characterize the complex molecular dynamics of cirrhosis and develop novel treatments in tandem
• The project will produce an unprecedented resource to study cirrhosis and HCC and offers the opportunity to greatly improve both diagnostics and treatment of both conditions

Partnering Opportunity

Weill Cornell Medicine is seeking a strong industrial partner with a market leading franchise in the liver space

Figure 1: Left: Mass cytometric analysis of liver tissue after liver injury. Right: Representative pictures of PM1230 colorectal organoids at 63X magnification.