Zohreh Gholizadeh-Siahmazgi: Furthering induced pluripotent stem cell research

The following story was written in Fall 2025 by Eli Speechley in ​ENGL ​4824​: Science Writing ​as part of a collaboration among the English department, the Center for Communicating Science, and the U.S. National Science Foundation COMPASS Center. The COMPASS Center is tackling the grand challenge of uncovering the genetic, molecular, cellular, and chemical rules of life underlying virus-host interactions through community-based and ethically grounded research. It is one of four Predictive Intelligence for Pandemic Prevention (PIPP) centers funded by the National Science Foundation.

In the city of Rasht, Northern Iran, just twenty minutes away from the Caspian Sea, Zohreh Gholizadeh-Siahmazgi believed she knew what she might want to do with her life. 

    “I was more interested in physics, but one day by chance, I started reading The Double Helix by Francis Crick,” she recalls. She reminisced about reading of Francis Crick's and James Watson’s discovery, stating that it “completely changed my perspective, my ideas, and inspired me to explore biology.”

    This led her to Azad University in Tehran in 2016, where she completed both her master’s degree in microbiology and Ph.D in cellular and molecular biology. Gholizadeh-Siahmazgi first began working with compounds from plants and applying them to bacteria and later moved on to studying cancer biology. 

    Through her studies, she eventually encountered a problem using primary cells for research. 

    “Primary cells have a major limitation, like a short life span,” she explains. Donor viability can also affect the quality of the primary cell and its suitability for research, she says. 

    This is why Gholizadeh-Siahmazgi began working on induced pluripotent stem cells (or iPSCs), which do not have these problems. Induced pluripotent stem cells are cells that have been reprogrammed to represent cells in an embryonic-like state. These cells can then be made to become a variety of different cell types in the human body through the process of differentiation. This was first described in a famous paper in 2006, she says, where Shinya Yamanaka and his colleagues showed they could induce cells with a combination of different factors, now called Yamanaka factors (Takahashi & Yamanaka, 2006).

    This interest in iPSCs led Gholizadeh-Siahmazgi to work at the Wake Forest University School of Medicine in North Carolina, where she is part of a research team working on various projects. Gholizadeh-Siahmazgi uses iPSCs to form organoids of brains, livers, and some other organs. This is done by spinning the cells in a flask with small molecule compounds, media, and growth factors. The cells then aggregate and self organize into spheroids. Then “the cells mimic an organ,” says Gholizadeh-Siahmazgi, and act like “mini brains.” This can then be made more complex by fusing two or more organoids together to create assembloids, allowing for the modeling of interactions between organs or between different regions of the same organ.

    The research team is led by Colin Bishop, who has worked on iPSCs and organoids for years and uses them for research in drug discovery, cerebral malaria, and pathogenicity.

    Gholizadeh-Siahmazgi and other researchers at Wake Forest send organoids to various universities with which they collaborate, allowing these researchers to study diseases using the organoids. They send some of these organoids to two researchers at Virginia Tech, X.J. Meng and Kylene Kehn-Hall, who then examine the effects of pathogens such as the hepatitis E virus, encephalitic alphaviruses, and Rift Valley virus on the organoids. Both Wake Forest and Virginia Tech are part of the U.S. NSF COMPASS Center (National Science Foundation Center for Community Empowering Pandemic Prediction and Prevention from Atoms to Societies), a collaboration of six universities aimed at predicting and preventing future pandemics as well as minimizing their effects.

    Induced pluripotent stem cells and organoids show great promise at reducing the use of animals in research. In fact, Gholizadeh-Siahmazgi believes that iPSC-derived organoids could mostly replace animal models in the future. Over a hundred million animals are used in research each year, so if the need to use animals can be reduced through new technology, many animal lives could be saved (Mayir et al., 2016).

    However, new technologies come with their own limitations. For instance, iPSCs are much more representative of embryonic cells, not mature adult cells, making genomic stability and response to stimuli variable. Additionally, organoids do not represent multiple organs, which may have different reactions when exposed to the same stimulus. This can be mitigated by using assembloids, Gholizadeh-Siahmazgi says. While these systems cannot replicate the complexity of a fully sized organism, they will have a much more nuanced response to a disease or when compared to an iPSC model.

    The future of iPSCs is very exciting and can contribute to advances in growing organs, the development of new drugs, the creation of better disease models, and regenerative medicine. Gholizadeh-Siahmazgi continues to work as part of a research team at the forefront of research into iPSCs, alongside Bishop and Anthony Atala at the COMPASS Center, contributing to current and future innovative projects in iPSC-based organoid development.