UTHealth Grows Lab 'Mini Brains' from Skin Cells to Uncover Causes of Schizophrenia

UTHealth scientists grow pea‑sized brain organoids from skin to study schizophrenia

Researchers at the University of Texas Health Science Center at Houston are turning forearm skin samples into living brain organoids to investigate how schizophrenia and other psychiatric disorders develop. Using gene reprogramming, the team converts skin cells into induced pluripotent stem cells (iPSCs) and then into three‑dimensional organoids — tiny structures smaller than a pea that retain the donor's DNA and contain functioning brain cells.

Why organoids matter: Postmortem brains provide important information but cannot reveal how cells behaved while the person was alive. Organoids let scientists observe cellular signaling, electrical activity and subtle genetic differences in living brain tissue, offering clues about how genetic mutations and early environmental events may alter brain development.

From family story to laboratory mission: Principal investigator Consuelo Walss‑Bass leads the UTHealth Houston Brain Collection for Research in Psychiatric Disorders. Her interest is personal: more than two decades ago her mother and sister were diagnosed with schizophrenia while other siblings — including Walss‑Bass — were not. That question drove her to pursue research despite early skepticism from mentors.

The science behind the work: The lab's process builds on two landmark advances: the Human Genome Project, which improved researchers' ability to connect genes to disorders, and the 2012 discovery that mature cells can be reprogrammed into stem cells. The team inserts a set of genes that revert skin cells to iPSCs; those cells are then directed to become neurons and, in successful cases, organized into complex organoids. Creating a single organoid-ready culture typically takes about six months and demands daily, sterile care.

How the program operates: Research coordinator Kendall Farrell works with families and the Harris County medical examiner's office to obtain consent for brain donation, which is separate from organ donation. Since 2017, the lab has obtained permission to study 175 brains from donors with conditions such as schizophrenia, bipolar disorder and substance use disorder; roughly 40 donors had no mental‑health diagnosis and serve as controls. When a brain is accepted, researchers also collect blood and a forearm skin sample — the latter provides the cells for organoid production.

Research scientist Laura Stertz manages the daily cell culture work, including feeding and maintaining sterile conditions. Once enough skin cells are available, the team inserts the reprogramming genes and guides the cells through stages from iPSCs to neurons and then to three‑dimensional organoids. The lab has produced three organoids so far and aims to generate approximately 10 from people with schizophrenia and 10 from unaffected donors to enable statistically meaningful comparisons.

Early results and future goals: In 2020, Walss‑Bass and colleagues published a study using neurons derived from siblings in Costa Rica that revealed subtle differences in cell signaling between affected and unaffected family members. The organoids offer a next step — allowing investigators to test how prenatal infections, early‑life toxins, or specific genetic variants influence brain development and to screen potential medications in a human‑cell context.

"We have to be like detectives and follow the signals. And sometimes they're very subtle," Walss‑Bass said. "In the next few years, I expect we'll be getting a lot of new findings."

The research is still scaling up: producing sufficient organoids to draw robust conclusions will take time and resources, but the approach provides a promising path toward understanding why only some family members develop schizophrenia and toward identifying new targets for treatment.