Engineering Leukocytes Generated from Human iPS Cells to Treat Human Disease

This project could lead to groundbreaking new clinical interventions for patients with neutropenia (an abnormally low level of neutrophils, a common type of white blood cell), antibiotic resistant infections, diabetes, autoimmune disease, cardiovascular disease, and cancer. It relies on the development of cutting-edge techniques for generating neutrophils and macrophages from induced pluripotent stem (iPS) cells and engineering iPSC lines that are more efficient at clearing infections or, in the future, have anti-tumor functions.

An increasing number of patients treated with chemotherapy or bone marrow transplantation develop neutropenia and are at risk for severe infections. Many of these bacterial and fungal infections are due to drug-induced neutropenia and are resistant to current antimicrobials. There is an increasing problem with drug resistance making it difficult to combat bacterial and fungal infections. The ability to specifically target and limit different types of inflammation by generating specific pro or anti-inflammatory innate immune cells represents a potentially exciting target for diverse human diseases including infection, cardiovascular disease, autoimmune disease and cancer.

The project will use CRISPR gene editing to generate a panel of iPS cell lines that lead to the production of neutrophil and macrophage populations that are expert killers of microbial pathogens.

Principal Investigator

• Anna Huttenlocher
  Professor of Pediatrics and Medical Microbiology and Immunology
  

Co-Principal Investigator

• Igor Slukvin
  Professor of Pathology and Laboratory Medicine
  

Co-Investigator

• David Beebe
  Professor of Biomedical Engineering

Collaborators

• Nancy Keller
  Professor of Medical Microbiology and Immunology
• JD Sauer
  Assistant Professor of Medical Microbiology and Immunology