PARTICIPATING RESEARCHERS

Three dimensional organoid culture of primary human tissues is an enabling technology for basic biology, disease modeling and therapeutic development. Many tissues are poorly accessible through conventional tissue procurement routes, such as surgery, endoscopy, or interventional radiology. In contrast, research autopsy provides an opportunity to obtain such organs. Tissues from the RACS will facilitate organoid generation from difficult-to-obtain primary human tissues and tumors, either as simple organoids that solely contain epithelium, or more complex organoids that propagate epithelium together with stromal components such as fibroblasts and immune cells.

Calvin Kuo, MD PhD
Maureen Lyles D'Ambrogio Professor of Medicine (Hematology)

> Visit the Calvin Kuo Lab

Our research seeks to understand the diversity of human tissue-resident immune cells using single cell genomics. This project builds on our previous work, which discovered that people with a premalignant condition called CHIP have a 30-50% reduction in risk of Alzheimer's disease (AD) – a reduction in risk comparable to carrying an APOE ε2 allele. We found that these CHIP carriers have a substantial number of somatically mutated, bone marrow-derived myeloid cells in their brains, which may contribute to the reduced incidence of AD (Bouzid et. al., 2023). However, our prior work was limited to frozen brain nuclei, which precluded deeper analysis or functional studies of these cells. Thus, we are very excited to team up with Dr. Hooper's team and the Research Autopsy Center in order to obtain access to fresh human tissues, which enables us to isolate tissue-resident immune cells, including microglia, directly from human tissues. We hope that a deeper understanding of these cells and their role in disease will inform therapeutic strategies for AD.

Julia Belk, MD
Postdoctoral Scholar, Dermatology

> Visit the Jaiswal Lab

> Visit the Chang Lab

Stem cells are powerful agents of tissue repair, but also vulnerable to becoming malignant when hijacked by cancer-causing mutations. The human brain is challenging to understand from a stem cell perspective. Breakthroughs in our knowledge of human neural stem cell function rely on donated human brain tissue recovered as quickly as possible – on similar timescales to organs recovered for transplantation into living donors. With this tissue, our lab is able to isolate rare populations of candidate stem cells and analyze their behavior in the laboratory. We also transplant human stem cells into the brains of laboratory mice, allowing us to follow their fate in a setting that more closely mimics their natural tissue environment. From these experiments, we learn 1) how quickly or slowly the candidate stem cells divide; 2) whether they maintain their stem cell identity over time; 3) what kinds of mature brain cells they give rise to; and 4) what factors cause important changes to stem cell behavior. Answering these questions is fundamental to understanding the human brain’s capacity for recovery after injury, as well as revealing early molecular events on the road toward cancer, that we hope can help facilitate the discovery of new treatments.

The Weissman Lab has long been at the forefront of stem cell research, contributing needle-moving discoveries relevant to both cancer and regeneration. Anna is a postdoctoral scholar in the Weissman Lab helping lead these efforts.

Anna Eastman, PhD
Postdoctoral Scholar

> Visit the Dr. Irving L. Weissman Lab