Humanized Mice in Biomedicine: Challenges and Innovations

Course Overview

In the last decade, several new genetically modified immune deficient mouse strains have been developed. They allowed high levels of engraftment of the human immune system, tissues and tumours. These models have become highly relevant for basic research to understand the function of the human immune system and the development of human pathologies (infections and cancer) in vivo. They are also being increasingly used as potency and safety models to evaluate new therapies and approaches in regenerative medicine prior to testing in humans.

This course will cover all aspects of the topic, including conceptual and technical classes on human stem cell transplantation and immune reconstitution, infections with human-specific pathogens (EBV, HIV, HCV, HBV, Ebola, Adenovirus), in vivo modelling using patient-derived xenografts (PDX) of solid tumours and leukaemia models as well as regenerative approaches for the liver.

The Jackson Laboratory will provide additional support for the course, which will take place at the EMBL Advanced Training Centre in Heidelberg, which provides state-of-the-art laboratory space in an exciting academic environment. Besides presenting lectures, the speakers will be involved in wet-lab activities with the PhD students and Post-docs using humanized mice: isolation of cells and tissues, analysis of cell panels by flow cytometry, as well as histological and molecular analyses. Finally, we will discuss the value and impact of these models on the biology and therapy of human diseases.

Audience

Junior faculty, post-docs and pre-docs in the field, who will be selected based on their letter of motivation, level of pre-education and training in the fields of immunology, infectious diseases, oncology, pharm-tox. The goal is to promote their intellectual and practical training in the development and analyses of predictive humanised mouse models.

Modules/Resources

Mouse strains optimised for humanisation

Engraftment of human hematopoietic stem cells, human tissues and human malignancies

Human innate and adaptive immune reconstitution in vivo

Modelling infections with human pathogens in vivo

Modelling human malignancies in vivo

Proof-of-concepts for regenerative medicine

Regulatory aspects of non-clinical and pharm-tox studies in humanised mice

Learning Outcomes

Material and technical requirements for setting up humanized mouse models

Dynamics of human immune reconstitution in humanized mice and functional assays

Outcome of human infections in humanized mice and testing therapies

Outcome of human malignancies in humanized mice and testing therapies

Requirements for reproducibility of data for predictive dynamic models

For an impression of the course check the 2017 course programme.

Speakers

Karl-Dimiter Bissig

Duke University Medical Center

USA

Dominique Bonnet

The Francis Crick Institute

Michael Brehm

University of Massachusetts Medical School

USA

Carol Bult

The Jackson Laboratory

USA

James Di Santo

Institut Pasteur

France

Julia Dickow

BioLegend GmbH

Germany

Silvia Guionaud

AstraZeneca

Shanna Hogeling

University Medical Center Groningen

The Netherlands

Kristina Howard

U.S. Food and Drug Administration

USA

Roos Houtsma

University Medical Center Groningen

The Netherlands

Scott Kitchen

University of California Los Angeles

USA

Florian Klein

Centre for Molecular Medicine Cologne

Germany

Terrence Meehan

EMBL-EBI Hinxton

Christian Münz

University of Zurich

Switzerland

Estefania Rodriguez-Burgos

The Heinrich Pette Institute, Leibniz Institute for Experimental Virology

Germany

Kourosh Saeb-Parsy

University of Cambridge

Johannes Sam

Roche Zurich

Switzerland

J.J. Schuringa

University of Groningen

The Netherlands

Amar Sharma

Hannover Medical School

Germany

Leonard Shultz

The Jackson Laboratory

USA

Renata Stripecke

Hannover Medical School

Germany

Andreas Trumpp

German Cancer Research Center

Germany

Livio Trusolino

University of Torino Medical School

Italy

Anja Wege

University Hospital Regensburg

Germany

Trainers

David Agorklu

Miltenyi Biotec

Germany

Corinna Klein

HI-STEM

Germany

Diana Ordonez

EMBL Heidelberg

Germany

Yvonne Petersen

EMBL Heidelberg,

Germany

Brian Soper

The Jackson Laboratory

USA

Sebastian Theobald

Hannover Medical School

Germany

Ross Thorne

EMBL-EBI Hinxton

Kanika Vanshylla

Center for Molecular Medicine Cologne

Germany

Carsten Wiethe

BioLegend

Germany

Li-Chin Yao

The Jackson Laboratory

USA