The Single-Cell Analysis Technologist

Burroughs Wellcome Fund honors Charles Gawad’s genomics mission for pediatric biology

More on Gawad and Single-Cell Analysis

Video | Charles Gawad on childhood leukemia breakthroughs
Learn about Charles Gawad’s advances at Stanford University’s Lucile Packard Children's Hospital. In this video, a Fluidigm C1™ system specialist examines how single-cell DNA sequencing is leading to new discoveries in pediatric blood cancer.

Webinar | ‪Single-cell DNA sequencing‬ and pediatric cancer‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬
Revealing Hidden VariationWatch this archive webinar to learn how researchers are sequencing somatic mutations in heterogeneous samples to make breakthrough discoveries in pediatric blood cancer.

Video | Top experts on the significance of single-cell DNA sequencing
Revealing Hidden MutationsResearchers around the world are using single-cell DNA sequencing to explore the causes, origins and relapse drivers of cancer.

Publication | Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics
In this PNAS publication, Gawad and his collaborators report findings on DNA sequencing for cancer research.

Publication | Noninvasive in vivo monitoring of tissue-specific global gene expression in humans
Gawad and team focused on tissue-specific genes to identify their contributions to circulating RNA and monitored changes during tissue development and in neurodegenerative disease states.

Single-cell biology’s time has officially arrived. It’s genuinely thrilling that this year’s Burroughs Wellcome Fund Career Award for Medical Scientists  (BWF CAMS) was awarded to Charles Gawad, MD, PhD. A program designed to support the studies of academic physician scientists, CAMS promotes the nation’s most promising early-career investigators.

Burroughs Wellcome Fund award

An independent private foundation dedicated to advancing biomedical sciences through research and education, BWF pursues its mission in part by supporting scientists as they develop into independent investigators. The organization’s goal is to advance underfunded fields while facilitating growth and spurring innovation.

This award signifies the BWF scientific committee’s recognition of the impact single-cell analysis stands to have on advancing oncology research. The organization has honored Gawad for his advances at Stanford University using single-cell genomics to define the cellular and genetic origins of childhood lymphoblastic leukemia as well as his promise to make lasting contributions to the field of cancer biology.

A promising researcher

In his current role as a pediatric scientist in the departments of Oncology and Computational Biology at St. Jude Children’s Research Hospital, Gawad splits his time between running his lab and seeing children with leukemia. The research explores the etiology and pathogenesis of childhood leukemias, with a focus on leveraging new information obtained with single-cell genomics.

Cancers are triggered by and develop through complex interactions between the genomes of individual cells and their environments. Tumor biology is currently studied primarily at the level of large groups of malignant cells. One of the next steps is to detect the size and frequency of biological processes heterogeneously expressed within those tumors by breaking them down into their cellular building blocks.

Single-cell genomics research targets leukemia

Single-cell analysis was instrumental in his decoding of the order of genetic events that result in pediatric acute lymphoblastic leukemia (ALL), the most common malignancy diagnosed in children. According to Medscape, the disease accounts for more than one in four pediatric cancer cases. 

He and his colleagues developed new technological and computational tools to better understand how pediatric leukemia develops. Their approach enabled them to determine that childhood leukemia is initiated by genomic structural variation, which is followed by single-nucleotide variant acquisition that appears to be mediated by APOBEC proteins and results in the outgrowth of co-dominant clonal populations. Gawad further characterized other biological processes of leukemia that could only be resolved at the single-cell level.

Identifying characteristics of pediatric leukemia is vital to the development of more effective diagnostics and treatments—and one day, possibly even prevention. For that reason, his key areas of investigative focus include:
Studying cancerous clonal population changes during treatment
Identifying cellular origins of pediatric cancer using single-cell RNA sequencing
Defining how viruses and antiviral APOBEC proteins contribute to childhood leukemia

A progressive vision

Gawad’s goal for the research supported by the award is to use single-cell DNA and RNA sequencing to further characterize the cellular and genetic origins of pediatric leukemias.

“I believe that single-cell genomics is going to transform our understanding of cancer,” Gawad said. “Having my proposal looked upon favorably by the Burroughs Wellcome Fund scientific review board made me feel encouraged and excited that such an accomplished group also believes in and supports my vision.”

Gawad uses a combination of targeted and exome single-cell sequencing in his research, which includes a focus on treatment resistance. “By resolving the clonal structures of the leukemias, we can order the genetic changes and mutational processes that occur as those malignancies develop and respond to treatment,” he explained. 

Doing it for the kids

His patients motivate Gawad and his work. “The two questions families always ask me when their child is diagnosed with leukemia are, one, why did my child develop this, and two, are you going to cure it?"

By dissecting the malignancy into its cellular building blocks, Gawad hopes to better predict patient outcomes. “We believe this new knowledge will provide opportunities to intervene so patients can receive less toxic treatments.”

Gawad holds the strong conviction that single-cell analysis will transform many life science fields. “Breaking complex organisms down into their cellular building blocks provides a higher-resolution view of what were previously thought to be homogeneous tissues, including the diseases that develop when that normal biology is perturbed.” 

It’s now possible to detect and study the genomic, transcriptomic and phenotypic heterogeneity within tissues. “I believe the discoveries that have been made thus far are just the beginning of what we are going to learn by studying biology at single-cell resolution,” he added.

“This type of information could further tailor patient-directed cancer therapy beyond what we can now do with bulk sequencing. These types of applications of single-cell genomics seem far in the future, but I think they will be rapidly integrated into clinical care once we overcome some of the technical challenges and are able to clearly establish the clinical value.”
—Charles Gawad, MD, PhD

Single-cell analysis as clinical care guide

In time, Gawad believes it will be possible to rapidly sequence tens of thousands or even millions of a cancer patient’s cells to have a deep understanding of the underlying mutations and mutational processes driving their instance of the disease. “We will be able to deeply sample the population genetic diversity of the malignancy to predict treatment response and resistance,” he explained.

“This type of information could further tailor patient-directed cancer therapy beyond what we can now do with bulk sequencing. These types of applications of single-cell genomics seem far in the future, but I think they will be rapidly integrated into clinical care once we overcome some of the technical challenges and are able to clearly establish the clinical value.”

Upcoming publication

Gawad was pleased to learn that Nature Reviews Genetics plans to publish his latest paper providing an overview of single-cell genome sequencing. “We discuss the technical challenges as well as applications where the field has provided important new insights into previously inaccessible areas of biology.”

The intersection of single-cell analysis with translational research and industry holds great potential for collaboration. “Once initial data motivates investors,” he said, “we’ll begin to see companies creating products around technologies that show the potential to improve clinical care.”

A single-cell champion

Gawad is an inspiration, and so is his groundbreaking research. Engaging with expert scientists like him continually informs us about emerging medical innovations and applications and ways to make more empowering and revolutionary products.

An exemplar of the next-generation researcher, Gawad is at home with technology. He’s prepared to take risks with novel methods that make many scientists and clinicians uncomfortable. With single-cell DNA sequencing, for example, Gawad recognized its implications from the start of an experiment all the way through to the biological interpretation, so he became an expert on the chemistry.

We admire his willingness to get his hands dirty examining the data. Gawad and his colleagues wrote their own analysis tools to process and interpret their sequencing data. He is a scientist with a quiet, soft-spoken demeanor, but he is blazing new trails and setting cancer research afire. 

At Fluidigm, we look forward to watching Charles Gawad’s career grow and embracing the opportunities we’ll have to support him along the way.

October 2015