Deanne Taylor is pushing researchers to prioritize children\u2019s health, starting at a cellular level.<\/p>\n
In 2017, Deanne Taylor attended a presentation at the University of Pennsylvania, just a short walk from her office. A researcher was there to unveil the Human Cell Atlas, an ambitious project that aimed to map every cell in the human body. Taylor was floored, and then concerned. As details emerged, she discovered that the project\u2019s researchers had only made plans to study adults. \u201cThat\u2019s when my little alarm went off,\u201d she says. \u201cNot again.\u201d<\/p>\n
Since joining the Children\u2019s Hospital of Philadelphia (CHOP) as the director of bioinformatics three years earlier, Taylor had been disappointed by the lack of investment in medical research focused on children. The dominant view, she says, was that children are exactly like small adults. They\u2019re not. Children\u2019s cells are different from grownups\u2019 cells in the way they express genes\u2014switching them on and off or turning them up or down. Those variations can cause drastically different and even deadly responses to drugs that adults tolerate well.\u00a0<\/p>\n
The 2017 talk was the moment Taylor didn\u2019t know she\u2019d been waiting for. She quickly channeled her concern into a campaign, joining the Human Cell Atlas\u2019s volunteer team and helping write a section on children for a white paper outlining the group\u2019s goals and plans. She then rallied a cross-hospital coalition of pediatric researchers to contribute to the project and spearheaded a 2019 paper that outlined the case for studying children\u2014a bid to attract more interest and funding to the field. \u201cIt put a flag in the ground,\u201d she says. \u201cWhy don\u2019t we have healthy models of children\u2019s development?\u201d<\/p>\n
So far, the push has paid off. In 2021 the NIH awarded a $38.5 million grant to the Developmental Genotype-Tissue Expression Project (dGTEx), a major initiative aimed at establishing the first comprehensive database of healthy pediatric tissue. The project banks samples collected from otherwise healthy children who have died and whose parents agreed to donate their bodies, and maps how genes across all the major organ systems are expressed. Taylor and her team curate and standardize the information associated with each tissue donation, including family history and details about the samples. A separate group does analysis on the samples themselves, and then all the information is combined to create a database\u00ad\u2014a baseline of what gene expression looks like in children. It\u2019s the first step to enabling research that could advance our knowledge of normal development, disease, drug effectiveness, and other phenomena.\u00a0<\/p>\n
The dGTEx team will eventually feed its data into the Human Cell Atlas, which, thanks to Taylor and many of the coauthors of the 2019 paper, now includes a pediatric section.<\/p>\n
Taylor\u2019s primary responsibility may be collecting and organizing data for dGTEx, but colleagues say she\u2019s also the glue holding diverse research projects together. That\u2019s especially important for the Human Cell Atlas, which depends on contributions from a loose coalition of researchers, all pursuing their own objectives. \u201cDeanne took a big-picture view and said, We don\u2019t just need to understand the pediatric kidney or the pediatric brain or the pediatric immune system. We need a holistic view of pediatric development,\u201d says Sarah Teichmann, a cofounder of the Human Cell Atlas. \u201cShe embodies that interdisciplinary spirit.\u201d\u00a0<\/p>\n
Taylor describes her career as a \u201crandom walk,\u201d driven by a singular intensity she now attributes to undiagnosed autism and ADHD. At five, she began reading her mom\u2019s medical texts. By 12, she was checking out physics books from the library. Physics provided mysteries to solve, and she wanted to understand how things worked.\u00a0<\/p>\n
Taylor got her PhD in biophysics, in 2001, but was inspired by the then-active Human Genome Project to change gears and take on a postdoc at Pfizer, writing code to handle complex data in rare-disease research. Then she moved to reproductive medicine, where she worked on some of the first computer programs to screen embryos for chromosomal abnormalities\u2014many of which are still in use today.<\/p>\n
Despite this seemingly winding road, Taylor says her focus has always been on understanding why the same illness hits people differently. How can two people carry the same disease-\u00adassociated gene variant, but only one get sick?\u00a0<\/p>\n
The Human Cell Atlas\u2014including all the data feeding into it from dGTEx and other projects\u2014could at last help researchers find answers. The effort is a natural extension of the Human Genome Project. That initiative, which wrapped up in 2003, helped researchers link specific genes to specific diseases. But a map of the genome is a bit like a DIY kit with all the parts and no assembly manual. It doesn\u2019t tell you where and how cells use each gene throughout the body.<\/p>\n
After all, \u201cwe\u2019re just older kids,\u201d Taylor says. \u201cBy ignoring the pediatric side of things, I think people are missing a window of intervention in human disease.\u201d<\/p>\n
For that, you need to know how the genes are expressed. Gene expression generally involves making a protein that does a specific job in the body, like building tissue or sending signals. Unlike DNA, which largely remains the same throughout our lives, the way the genes in DNA are expressed changes as we develop.\u00a0<\/p>\n
Differences in gene expression can determine whether a therapy will work\u2014or could harm more than it helps. Because of the way cardiac genes are expressed in children, chemotherapy drugs can attack not only tumors but also children\u2019s 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.<\/p>\n
The dGTEx database aims to create a baseline for gene expression in children\u2014a molecular map of how the body\u2019s roughly 20,000 genes do their work in healthy tissue cells. It is only one of the collaborations Taylor manages. She\u2019s a principal investigator for the Kids First Data Resource Center, which sequences diseased tissues collected from children enrolled in other studies nationwide. And she has been collaborating with researchers on HubMAP, an effort that\u2019s building a resource complementary to the Human Cell Atlas, to secure funding to create 3D maps of children\u2019s cells like the ones it\u2019s already made for adults.<\/p>\n