In March 2014, a team of researchers led by Sue O’Shea, Ph.D., and Melvin McInnis, M.D., published a report of the first stem cell lines (iPSC) generated from patients with bipolar disorder.
K. Sue O’Shea, Ph.D., the Crosby-Kahn Collegiate Professor of Cell and Developmental Biology and director (retired) of the University of Michigan Center for Pluripotent Stem Cell Research, is a leader in research using induced pluripotent stem cells (iPSCs) to model bipolar disorder at the cellular level. Our community’s generous philanthropy has helped Dr. O’Shea recruit some of the best and brightest in the field for this work. These experts changed how we see bipolar disorder.
The O’Shea lab sampled skin tissue from adults living with bipolar disorder and those without. Then, after turning the skin cells to stem cells (iPSCs) in the lab, the team became the first in the world to grow brain cells from these stem cells. This allowed researchers to examine, for the first time, how brain cells derived from people with and without bipolar disorder look and behave when analyzed under a microscope. With donor support, the team was able to dig even deeper and use this “brain in a dish” model to study inhibitory and excitatory neurons and astrocytes, vital support cells in the brain.
A long held theory is that when neurons malfunction, it can contribute to bipolar disorder. In an effort to examine the differences between control neurons and bipolar neurons, the team identified a difference in the respective content of small particles called exosomes, which appear to influence the development and function of neurons. Dr. O’Shea led experiments that introduced bipolar exosomes into the medium populated with iPSC-derived brain cells from control groups. Researchers in O’Shea’s lab demonstrated that the introduced bipolar exosomes caused a reduction of the electrical activity of neurons, indicating that these particles have the potential to be a site of medical intervention, possibly leading to new treatments and a testable biomarker of bipolar disorder.
Dr. O’Shea’s lab has laid the foundation for critical knowledge of bipolar disorder and trained a new generation of thoughtful medical scientists who are tackling some of the most important questions in bipolar and mood disorder research. Dr. O’Shea retired in 2024, but her research has set the stage for work on the next frontier of bipolar cell biology.
Nerve cells from a bipolar patient. The branches (red) are the cables that run through the nervous system carrying nerve signals. The bright yellow spots are synapses and show where cells communicate with each other. The nerve signals in bipolar nerve cells are stronger and longer compared to non-bipolar nerve cells.
