Vivekanand Yadav, PhD
Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Cancer Biology, University of Kansas School of Medicine
Full Biography
Vivekanand Yadav, PhD, Hematology/Oncology, received a one and a half year, $193,002 grant from the ChadTough Defeat DIPG Foundation.
Dr. Yadav’s study, “Epigenetically activated ID1 is a key transcriptional regulator of DIPG invasion and is targetable with cannabidiol,” will explore the gene responsible for the lethal pediatric brain tumor known as diffuse intrinsic pontine glioma (DIPG) with the goal of opening the door for potential new therapies.
There are no effective therapies for DIPGs other than radiation. As a result, most of the patients die within 1.5 years of diagnosis. Dr. Yadav recognizes that there is an urgent need for new therapies for this pediatric brain tumor.
“Inhibitor of DNA-binding (ID) proteins are key transcriptional regulators of tissue and lineage-specific gene differentiation during embryogenesis, he explained. “Also, higher expression of ID1 is associated with aggressive and invasive behavior of tumor cells, correlating with poor clinical outcomes of multiple human cancers.”
Over 80 percent of DIPGs harbor K27M mutations in the genes encoding histone H3.1 (H3F3A) or H3.3 (HISTIH3B) variants and often with concurrent mutation in Activin A receptor, type I (ACVR1). Previous reports show upregulation of ID1 with H3K27M and ACVR1 mutations. However, the impact of ID1 on DIPG tumorigenesis has not yet been validated in human DIPG samples and no attempts have been made to target this pathway in DIPG.
“Our preliminary data suggest that the ID1 gene is epigenetically activated in DIPG and ID1 is upregulated in human DIPG tumor cells and tissues. We observed that genetic knockdown of ID1 reduces DIPG cell invasion and migration while significantly improving the survival of DIPG tumor-bearing mice, indicating that ID1 upregulation is essential for primary features of DIPG,” said Dr. Yadav. “We found that cannabidiol (CBD), a clinically available non-toxic and non-psychotropic cannabinoid, is effective in reducing ID1 levels and viability of cultured DIPG cells.”
CBD treatment (off trial, non-prescribed) is an increasingly popular and controversial therapy among DIPG patients. However, it is entirely un-studied in this setting, with no pre-clinical efficacy data or understanding of its potential mechanism in targeting DIPG cells. Therefore, Dr. Yadav explains that there is a need to investigate the underlying mechanisms of ID1-driven invasion/migration in DIPG and the impact of patient-specific genetic features (e.g. H3 or ACVR1 mutation) on CBD efficacy.
Dr. Yadav’s study will determine the epigenetic mechanism of ID1 activation and its role in DIPG invasiveness as well as the impact of H3F3A/ACVR1 mutation on CBD-mediated ID1 inhibition in DIPG.
This study will lay the groundwork for potential future clinical trials for testing the efficacy of CBD treatment in a rational manner.