Using Neuroscience to Uncover Clues About Pediatric Cancer
The Pattwell Lab studies the genes and processes involved in normal neurodevelopment and how they are hijacked in the context of cancer. A better understanding of normal developmental processes can help scientists pinpoint exactly when and where certain processes go wrong in tumors. This can inform our knowledge of tumor biology— with the ultimate goal of creating more targeted cancer treatments with fewer side effects.
Using RCAS/tv-a technology to study tumor biology
This research examines how normal developmental processes can go haywire and lead to cancer. RCAS/tv-a technology allows for the expression of a specific gene or protein in a particular cell type of genetically engineered mice. This enables researchers to model different pediatric tumors and explore their genetics, microenvironment, and response to treatment in mice that have a functional immune system. This research will shed light on why certain pediatric tumors develop and may help scientists understand what goes wrong when cancer arises both within and outside the central nervous system (CNS).
Using next generation sequencing to study normal development and tumor biology
This research utilizes single cell analysis to explore organ development during embryogenesis, neonatal, juvenile and adolescent time periods. By examining the expression patterns of various genes in different cell populations across time in mouse models, the lab can compare developing tissue to tumors originating from similar organ sites. This work has the potential to shed light on the cell of origin for various pediatric cancers, as well as offer clues into when during development certain cells may go down the wrong path towards oncogenesis.
Exploring the role of the alternative splicing and neurotrophin biology in development and cancer
Fundamental neuroscience research has uncovered a wealth of knowledge about brain development. Sometimes, when a gene is read, it can make different versions of a protein from the same starting material. These variations in proteins, while made from the same DNA strand, have different arrangements of RNA, and are known as splice variants.
Understanding the unique genetic makeup of proteins in normal brain compared to brain tumors is one main focus of the lab. Important for establishing the developing nervous system, a family of proteins called the neurotrophin receptors are very tightly regulated at the DNA, RNA, and protein level. Recent work from Dr. Pattwell’s group has shown that a particular change at the RNA level results in a unique variation of a neurotrophin receptor called tropomyosin receptor kinase B, or TrkB. This particular TrkB variant is expressed at very high levels in adult and pediatric cancers, including brain tumors. Forced expression of this receptor splice variant causes multiple cancer types in our mouse model, suggesting that it is both a marker and driver of oncogenesis – and a potentially druggable target.
Understanding the effects of chemotherapy and radiation on brain development
With a background in developmental neuroscience and subsequent training in cancer biology, Dr. Pattwell has long been interested the brain's capacity for change. Combining these distinct yet overlapping fields, her lab utilizes genetic mouse models to explore both normative and aberrant developmental plasticity and the link between these processes in tumors of the central nervous system (CNS). The Pattwell Lab seeks to learn more about how undergoing chemotherapy or radiation for cancer impacts child brain development, and how those impacts might be different in childhood versus in adolescence. This work includes building learning and memory assays to better understand potential cognitive, learning and memory changes associated with chemotherapy and radiation. The overarching goal is to better understand these side effects and work to mitigate them.
Examining the effects of COVID-19 on the developing brain
The Pattwell Lab is working to better understand how COVID-19 may impact the brain. The lab is interested in studying the effects of “long COVID” and the cognitive effects seen in some patients after they have recovered. In particular, they are interested in how the COVID-19 spike protein may cause inflammatory, cognitive or other effects in the child and adolescent brain. Through molecular, developmental, and behavioral neuroscience techniques, the lab aims to address this question using a mouse model system.
About Dr. Pattwell
Siobhan Pattwell, PhD
Siobhan Pattwell, PhD, is an assistant professor at the University of Washington School of Medicine in the Department of Pediatrics. She is a principal investigator in the Ben Towne Center for Childhood Cancer Research at Seattle Children's Research Institute. Dr. Pattwell completed her graduate work under the mentorship of Dr. Francis Lee at Weill Cornell Graduate School of Medical Sciences, Cornell University, where she studied neurodevelopment and the brain’s capacity for change across childhood, adolescence, and early adulthood. Expanding upon her background in developmental and molecular neuroscience, Dr. Pattwell continued her training in cancer genetics, alternative splicing, and preclinical mouse modeling as a postdoctoral fellow in the lab of Dr. Eric Holland at Fred Hutchinson Cancer Research Center. Combining her expertise in normal and aberrant neurodevelopment, Dr. Pattwell started her independent laboratory at Seattle Children’s in October 2021. Her lab focuses on the intersection between neuroscience and cancer biology in an effort to better understand what developmental processes are hijacked by tumor cells and how these pathways may be targeted by novel therapeutics.
Ben Towne Center for Childhood Cancer Research
1100 Olive Way
Seattle, WA 98101