In 2017, Deanne Taylor attended a presentation at the University of Pennsylvania, a short distance from her office. A researcher was presenting the Human Cell Atlas Map, an ambitious project that sought to map every cell in the human body. Taylor was surprised and then concerned. When she learned the details, she discovered that the researchers had only planned to study adults. "That's when my alarm went off," she says. "Again."
Since joining Children's Hospital Philadelphia as director of bioinformatics three years earlier, Taylor had been disappointed by the lack of investment in medical research focused on children. The prevailing view, according to her, was that children were exactly like smaller adults. They are not. Children's cells differ from those of adults in the way they express genes—turning them on and off or increasing and decreasing their intensity. These variations can cause drastically different and even lethal responses to drugs that adults tolerate well.
The 2017 presentation was the moment Taylor did not know she had been waiting for. She quickly channelled her concern into a campaign, joining the volunteer team of the Human Cell Atlas Map and helping to write a section on children for a document that outlined the group's objectives and plans. She then assembled a coalition of paediatric researchers from various hospitals to contribute to the project and led a 2019 paper that made the case for studying children—an effort to attract more interest and funding to the field. "It was planting a flag in the ground," she says. "Why don't we have healthy models of children's development?"
So far, the push has paid off. In 2021, the National Institutes of Health awarded a 38.5-million-dollar grant to the Developmental Genotype-Tissue Expression (dGTEx) Project, a major initiative aimed at establishing the first comprehensive database of healthy paediatric tissue. The project stores samples collected from generally healthy children who have died and whose parents agreed to donate their bodies, and maps how genes are expressed across all major organ systems. Taylor and her team curate and standardise the information associated with each tissue donation, including family history and details about the samples. A separate group performs analysis on the samples themselves, and then all the information is combined to create a database—a baseline of what gene expression looks like in children. It is the first step toward enabling research that can advance our knowledge of normal development, disease, drug effectiveness and other phenomena.
The dGTEx team will eventually feed its data into the Human Cell Atlas Map, which, thanks to Taylor and many of the coauthors of the 2019 paper, now includes a paediatric section.
Although Taylor's primary responsibility may be collecting and organising data for dGTEx, colleagues say she is also the glue that holds diverse research projects together. That is especially important for the Human Cell Atlas Map, which depends on contributions from a flexible coalition of researchers, all pursuing their own objectives. "Deanne took a bird's-eye view and said: We don't just need to understand the paediatric kidney or the paediatric brain or the paediatric immune system. We need a holistic vision of paediatric development," says Sarah Teichmann, cofounder of the Human Cell Atlas Map. "She embodies that interdisciplinary spirit."
Taylor describes her career as a "random walk", driven by a singular intensity that she now attributes to undiagnosed autism and ADHD. At five years old, she began reading her mother's medical textbooks. At 12, she was checking physics books out of the library. Physics presented her with mysteries to solve, and she wanted to understand how things worked.
Taylor earned her doctorate in biophysics in 2001, but was inspired by the then-active Human Genome Project to change direction and undertake a postdoctoral fellowship at Pfizer, writing code to handle complex data in rare disease research. She then moved into reproductive medicine, where she worked on some of the first computer programmes to screen embryos for chromosomal abnormalities—many of which are still used today.
Despite this apparently winding path, Taylor says her focus has always been on understanding why the same disease affects people differently. How can two people carry the same genetic variant associated with disease, but only one get sick?
The Human Cell Atlas Map—including all the data flowing into it from dGTEx and other projects—could finally help researchers find answers. The effort is a natural extension of the Human Genome Project. That initiative, which concluded in 2003, helped researchers link specific genes to specific diseases. But a genome map is somewhat like a do-it-yourself kit with all the parts and no assembly manual. It doesn't tell you where and how cells use each gene throughout the body.
After all, "we're just older children," Taylor says. "By ignoring the paediatric side of things, I think people are missing a window of intervention in human disease."
For that, you need to know how genes are expressed. Gene expression generally involves making a protein that performs a specific job in the body, such as building tissue or sending signals. Unlike DNA, which largely remains the same during our lives, the way genes are expressed in DNA changes as we develop.
Differences in gene expression can determine whether a therapy will work—or could cause more harm than good. Because of the way cardiac genes are expressed in children, chemotherapy drugs can attack not only tumours but also children's developing hearts, potentially causing lifelong damage. Other treatments can affect the entire body, sometimes triggering a reversible but potentially fatal immune system reaction called cytokine release syndrome.
The dGTEx database aims to create a baseline for gene expression in children—a molecular map of how approximately 20,000 genes in the body function in healthy tissue cells. It is just one of the collaborations Taylor manages. She is principal investigator of the Kids First Data Resource Center, which sequences diseases.