Dr. Sujatha Venkataraman, a researcher at the University of Colorado, was awarded a New Investigator grant jointly funded by The ChadTough Foundation and Michael Mosier Defeat DIPG Foundation. The New Investigator grant allows funding for either newly independent DIPG researchers in establishing new DIPG research labs or established researchers who have not previously conducted brain tumor research to encourage them to start DIPG research.
We had the opportunity to talk with Dr. Venkataraman to get a more in-depth look at her research and the inspiration behind her work.
Q) We understand you were inspired to switch your research focus from adult breast and prostate cancer to pediatric cancer after you lost your child to the horrible disease. What inspired you to focus your energy on DIPG?
SV: My son was a happy 2-year-old when he was diagnosed with a devastating cancer — stage 4 neuroblastoma. During that time, I was doing my postdoctoral fellowship at the University of Iowa investigating the role of reactive oxygen species and hypoxia in adult prostate and breast tumors. The diagnosis took a toll on our family. He was given many rounds of chemotherapy and radiation, and he went through a bone marrow transplant, all in vain.
After each chemotherapy round, I had to give him an injection to increase his white blood cell count, and those were the hardest moments in my life. The instant he saw the needle in my hand, he used to scream and cry, “Mummy, please no!” He wouldn’t come to me for hours after I gave him the shot. My heart shattered into pieces. I tried to stay strong and think “one day,” when he becomes free from cancer and grows up into a big boy, he will understand that I was only trying to help him. That day never came.
Cancer is terrifying, and when it is diagnosed in children, it is devastating. As a mother who lost her young son to cancer, I say it’s the parent’s worst nightmare. I felt numb to everything. The tragic loss of my loving son changed my life. I don’t want any parent to go through this pain. That is when I decided I want to continue my research in pediatric cancer.
When we moved to Denver and after I joined the University of Colorado’s pediatric neuro-oncology division, I attended a neuro-oncology conference where I learned about the devastating brain tumor called DIPG, which affects children and has a median survival of only 11 months. I didn’t have any DIPG tumor lines to work with, so I contacted many centers where DIPG work was in progress, received cell lines, and started my research work in studying DIPG tumorigenesis. If, through my research work, I could save at least one child and one parent from losing their child, I have achieved my goal in life.
Q) Your current work centers on identifying the genes that cause DIPG and to identify the pathways that make the DIPG tumor aggressive after relapse from radiation treatment. Can you tell us a little more about this work and what you have discovered thus far?
We have performed studies to identify pathways that are upregulated by radiation. We find that DIPG cells undergo senescence (loss of a cell’s power of division and growth) but not complete cell death after radiation. These senescent cells then reactivate and become more resistant to therapy. We have identified two specific pathways that drive the increased aggressiveness of the DIPG cells. We are now testing several new agents to target these pathways.
Q) What do you hope will be the conclusion of your research? How might the findings in your research impact DIPG patients? Will it drive changes in treatment?
We hope that by the end of this project we will have established that several specific pathways drive DIPG cell aggressiveness in the face of radiation. We hope to show that suppressing these pathways resensitizes DIPG cells to radiation and other therapies. We plan to generate the preclinical data needed to justify additional large-scale studies and early-phase clinical trials for these new agents.
Q) What do you think have been some of the biggest breakthroughs in DIPG research over the last few years?
In my opinion, the most significant breakthrough in DIPG biology was the discovery of characteristic mutations in the histone H3 protein, found in more than 80% of DIPG patient tumors and associated with a poor prognosis. The identification of H3K27M mutations and the resulting epigenetic changes now present numerous and promising druggable targets. Similarly, the identification of mutations that accompany the H3K27M mutation, like the ACVR1 receptor kinase mutation in a subset of DIPG tumors, presents opportunities for intervention. A recent study tracing the origin of DIPG tumor cells using single-cell RNA sequencing and another targeting cell surface antigens on DIPG tumor cells promise to reveal druggable targets. But even with the increasing number of breakthroughs in understanding the biology of DIPG, the standard of treatment has not changed, and there is still no improvement in patient survival.
Q) How important is private funding, such as the Defeat DIPG ChadTough New Investigator grant, in moving forward with your research?
Brain tumors are the leading cause of death in children, but pediatric brain tumor research is acutely underfunded. Only 4 percent of federal funding is dedicated to childhood cancer research, and only a fraction of that is allocated to pediatric brain tumor research. This lack of funding hinders many of the critical studies that are needed to improve the outcome of children with brain cancer.
Private funding from foundations like The ChadTough Foundation and Michael Mosier Defeat DIPG Foundation is critically important as it enables more researchers to explore their innovative hypotheses and helps them obtain federal funding to move their ideas from the bench to the bedside. Without the funding, our project would likely have not been performed at the speed that it was. We will have a publication submitted describing data funded by the foundation within the next 6 months. The funding was critical as it enabled us to develop robust preclinical proof of principle data that will form the basis of additional NIH grants. We are hopeful that the successful completion of this work will form the basis of a clinical trial through the Pediatric Brain Tumor Consortium (PBTC) phase 1 trials.