The role of single cell research in the treatment of childhood acute lymphoblastic leukemia

Since its inception, the Burroughs Wellcome Foundation has been dedicated to promoting the academic research of medical scientists, especially in areas where funding is underfunded, and giving the world's most promising researchers strong support to pioneer innovative research in the unknown.

This year, the organization awarded the Doctor of Medicine (BWF CAMS) to Dr. Charles Gawad. In recognition of his research project at Stanford University - the use of single-cell genomics to determine the cellular and genetic origins of childhood acute lymphoblastic leukemia and his commitment to continue research in the field of cancer biology. This means that the impact of single-cell analysis on advancing oncology research has been recognized by the scientific committee, and it also means that the era of single-cell biology has officially arrived.

Dr. Charles Gawad, Department of Oncology and Computational Biology, St. Jude Children's Research Hospital

Single-cell genomics research

According to Medscape, a well-known professional medical search engine in the United States, the incidence of childhood acute lymphoblastic leukemia caused by single cell decoding of genetic events accounts for about a quarter of the common childhood malignancies. Single-cell analysis plays an important role in studying its pathogenesis and processes.

Gawad and his colleagues have developed new techniques and computational tools to better understand the development of childhood leukemia. Their findings suggest that the onset of childhood leukemia begins with genomic structural variation, followed by single nucleotide mutations caused by APOBEC proteins and leads to the growth of codominant clonal subpopulations. Subsequently, Gawad further explored the characteristics of other biological processes in childhood leukemia, and this research can only be done at the single cell level. Therefore, Gawad focused his research on the following aspects:

1. Study the changes between different tumor clonal subpopulations during the course of treatment.

2. Identify the origin of tumor cells in pediatric cancer using single-cell RNA sequencing.

3. Analysis of the role of viral and antiviral APOBEC proteins in childhood leukemia

a new field of research

Gawad's goal is to further understand the cellular and genetic origins of childhood leukemia using single-cell DNA and RNA sequencing. This goal has been rewarded by BWF CAMS.

“I believe that single-cell genomics will change our understanding of cancer,” Gawad said. “I am encouraged and excited by the BWF Scientific Committee's support and recognition of my research project.” In Gawad's research, he combined single-cell sequencing of targeting sequences and exons, focusing on therapeutic research of disease. . "By addressing the structure of leukemia clones, we can regulate the genetic mutations and processes that occur during cancer development and treatment," he explained.

Do something for the kids

Gawad's patient inspired him and his work. “When a child is diagnosed with leukemia, parents often ask me two questions, why is my child getting sick? Will you cure it?”

By dissecting tumor cell masses, Gawad hopes to more clearly predict the patient's prognosis. “We believe that this new knowledge will help us find better ways to treat leukemia, so that patients can reduce traditional toxicity treatments.”

Gawad believes that single-cell analysis will change many areas of life sciences. “The breakdown of complex organisms into their cell masses and in-depth study of single cells provides us with a clearer view.” Detecting and studying genomic, transcriptional and phenotypic heterogeneity in human tissue Sex has now become possible. "I believe that the findings that have been made so far are only the beginning. Through research at the single-cell level, we will learn and understand biology more deeply," he said.

"This single-cell type of information greatly exceeds the information we have obtained from the sequencing of population cells we are doing now, and further helps us optimize the means of cancer treatment. The application of single-cell genomics seems to be far away, but I think Once we overcome some technical challenges and have clear clinical application value, they will quickly integrate into clinical treatment."

— Charles Gawad, MD, PhD

Single cell analysis as a guide to clinical treatment

Gawad believes that through single-cell genome testing, rapid sequence analysis can be performed on cells of tens of thousands or even millions of cancer patients to gain insight into the mechanisms of deeper mutations and mutations in cancer cells in clinical cases. He explained: "We will be able to further study the genetic diversity of malignant tumors to predict the response and side effects of patients in treatment."

Gawad's findings in single-cell genome sequencing will be published in the well-known journal Nature Reviews Genetics. “Our discussion of the challenges and applications of this technology provides important insights into the application of this technology in the field of disease treatment, helping us to enter the biological field that was previously inaccessible.”

With the rapid development of translational medicine and single-cell research, there is potentially a great opportunity for cooperation between the two. “Once the initial data can introduce a lot of investment,” he said, “we will see products built around the technology that will show a strong ability to improve clinical treatment.”

Pioneer of single cell research

Gawad's groundbreaking research has greatly inspired people. Scientists like him are constantly bringing more and more revolutionary products to us based on their innovative medical methods, applications and technologies.

As a model for a new generation of researchers, Gawad is prepared to take risks. For example, through single-cell DNA sequencing, Gawad and his colleagues also wrote their own analysis tools to process and interpret their sequencing data. He is a quiet scientist who speaks fluently, but he has pioneered a new field of cancer research.