Claudia L. Kleinman & Dr. Nada Jabado

Unraveling Childhood Brain Tumors, in Quebec’s top ten 2020 research

One of the strengths of the Ludmer Centre is its cadre of transdisciplinary researchers. We are proud to count Dr. Claudia Kleinman, who leads a computational research lab at the Jewish General Hospital’s Lady Davis Institute, among our most innovative, as well as most active in the training of new researchers. Quebec Science in its 28th edition of Top 10 Discoveries agrees with us.

A study led by Dr. Kleinman and Dr. Nada Jabado, at the Research Institute of the McGill University Health Centre (RI-MUHC), has been recognized as one of Quebec’s top 10 research findings of 2020. Published in Nature Genetics, the paper “Stalled developmental programs at the root of pediatric brain tumors” significantly advances understanding of pediatric tumors, notably their prenatal origin. The transdisciplinary team developed and exploited big-data approaches to study several types of highly aggressive and, ultimately, fatal pediatric brain tumors. Tracing their origin to early brain development, they noted that the genetic events that triggers these tumors happen in the very earliest phases of cellular development, most likely prenatally.

The research was highlighted in a number of November 2019 articles, notably Pediatric Brain Cancer Clues Drawn from Developing Brain Cell Transcriptomes in GenomeWeb and Origin of Childhood Brain Tumors Discovered in Genetic Engineering & Biotechnology News (GEN).

The Québec Science’s top 10 discoveries of 2020 were selected by a jury of scientists and journalists; however, per tradition, the general public is invited to vote and chose their favorite among the final 10.

VOTE ON YOUR FAVORITE !

Visit this page to vote for your favorite: https://www.quebecscience.qc.ca/decouverte2020 . Dr. Kleinman’s research team is listed under the title “Incursion inédite dans les tumeurs du cerveau”, number 10 in the list.

RESEARCH CONTINUES, NEW TUMOUR PUBLICATION

The 2020 brain tumor publication was only the latest in over a decade of collaborative research led by Dr. Kleinman and Dr. Jabado, which has already led to another, more recent publication in the Dec. 2020 issue Cell, Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.

As detailed in the December 2020 publication, Drs Kleinman and Jabado discovered that high-grade gliomas, which are deadly brain tumors and a leading cause of mortality in children and young adults, originate in a specific type of neuronal stem cell. Their team employed new technologies that measure the levels of every gene in thousands of individual cells to generate a “big data” resource. As described by Selin Jessa, a Quantitative Life Sciences (QLS) PhD student in the Kleinman lab and co-first author on the study, the team used single cell analyses to create an atlas of the healthy developing brain, identifying hundreds of cell types and their traits. According to Dr. Kleinman, “Since these brain tumors retain a memory, or footprint, of the cell in which they originated, we could then pinpoint the most similar cell type for these tumors in the atlas, in this case, inhibitory neuronal progenitors that arise during fetal development or after birth in specific structures of the developing brain.” For more details, see the recent McGill Reporter article: Researchers identify the origin of a deadly brain cancer.

Left to right: Dre Nada Jabado, Selin Jessa, and Claudia Kleinman. Image: Donald Robitaille

Dr. Kleinman and Dr. Jabado are hopeful that their cumulative ongoing research will lead to new therapeutics to treat deadly brain cancers in children, teens and young adults.

Drs Nada Jabado, Selin Jessa, and  Claudia Kleinman. (Image: Donald Robitaille)

NEXT STEPS

According to Dr. Kleinman, “The next step is to use this novel information to design more accurate tumor models and to devise strategies to revert the developmental blockade in these tumors. Like Peter Pan in Neverland, tumors conserve their progenitor-like state, ultimately leading to oncogenesis; reverting this state may lead to therapeutic strategies for these deadly tumors.”

Learn more about Claudia Kleinman’s research.

FUNDERS

Contact the Ludmer Centre for information on how you can support Dr. Kleinman’s work. To date, vital funding has been provided by Genome Canada, Genome Québec, the Fonds de la recherche en santé Québec, the Canadian Foundation for Innovation, the Canadian Institutes of Health Research, and the Canadian Cancer Society Research Institute.

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