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“Children with brain cancers are one of the toughest groups of patients to treat with conventional treatment options. My work is directed at connecting new discoveries that we make in the lab to options for children with brain tumors.”

Dr. John Prensner was a senior in college studying English Literature at Tufts University when he was introduced to a young woman dying of brain cancer. That chance encounter inspired him to pursue medical school at the University of Michigan. Today, the self proclaimed “genome nerd” combines his passion for cancer science with his love for working with kids. Dr. Prensner was awarded a ChadTough Defeat DIPG New Investigator Grant in 2023 for his work studying how genomes (or the complete set of genes or genetic material present in a cell) impact cancer cells. We had a chance to talk to Dr. Prensner about his work, his passion for finding a cure for DIPG, and his fantastic sense of humor that surely helps him through the hardest parts of his job.

CTDDF: Can you tell me a bit about yourself and how you decided to work in the world of brain cancer research?

Dr. Prensner: I always think of myself as an accidental physician-scientist. I went to college first to study classics, but as a first-year student all of the courses that I wanted were full with juniors and seniors. So I went into English literature and assumed that was my future path. But then I decided to take organic chemistry and just fell in love with science. I started working in my professor’s organic chemistry lab, but it turns out that I was so bad at first that I broke a lot of lab material. (I still feel guilty about that.)  So I decided to think about medicine. When I was a senior in college I spent a week or two visiting a local intensive care unit every day to hear the medical team, and I was introduced to a 36 year old woman who was dying in the ICU with brain cancer. I was so shocked. So I went to medical school planning to be an adult cancer doctor. When I matriculated, the first and second years of medical school were separated by a 3 month summer break (many schools don’t do this anymore). So I decided to try a few months in a cancer science lab. I just loved it! (And, I didn’t break anything!) I continued working in that lab and ultimately ended up getting a PhD with the University of Michigan in addition to the MD degree. As a doctor-in-training, however, I learned pretty quickly that I liked working with children more than adult patients. I got to use coloring books with children and hold babies in the clinic. (The adult patients were, well, less interested in me cuddling them.) And so I started down my current path of combining my love of cancer science with childhood brain cancer patients.

CTDDF: Can you tell me about your latest work and what you have learned so far?

Dr. Prensner: I am a genome nerd. The genome is the full set of DNA genetic material that you inherit from your biological parents. The genome has about 3 billion DNA base-pairs, which are the individual letters in the genetic code. That’s a whole lot. But only 1.5 or 2% of these letters are used to make the genes known to exist in humans.  What my lab studies is how childhood brain cancers use the other 98%, which is sometimes called the “dark genome”. We are learning that each childhood brain cancer uses certain parts of this 98% to facilitate the aggressive behavior of the cancer cells.  We are really excited to learn more about this topic in diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), because these two cancer types are known to have a lot of abnormal activity happening in this 98% of the dark genome, but nobody really knows exactly what is happening or why. My lab has been finding out that these cancers may be producing previously-undescribed genome products from these regions, and we are learning how they may impact how the cancer cells behave. 

CTDDF: Is there any specific research happening in the world of childhood brain cancer that you find particularly exciting?

Dr. Prensner: I am excited about so many things! One thing that comes to mind in the lab is the increasing focus on proteomics to study key protein pathways that may not be obvious in the genomics data. I know I said I’m a genome nerd, but I really find this other area fascinating. I am also super excited that we are now using some of these new research methods to figure out new medicine combinations that might be major breakthroughs for patients. At the University of Michigan and elsewhere around the country and globe, we are studying new drug combinations that are developed because we are understanding the proteomics and the genomics of DIPG now. That’s really special to me.

CTDDF: As a ChadTough New Investigator grant recipient, what do you feel is the importance of private funding in moving the field of DIPG forward?

Dr. Prensner: There are not a lot of federal funding resources to fuel the scientific discoveries that are needed for kids who get cancer. Private funding and foundations are essential to keep research on childhood cancer moving forward. I’ve been so astonished, thankful, and inspired by the work of the DIPG community to raise money and invest in early-career scientists like myself. Groups like the ChadTough Defeat DIPG Foundation truly enable me to do the work that I want to do. It’s not an overstatement to say that I couldn’t be where I am without the generosity and dedication of DIPG families and foundations.

ChadTough Defeat DIPG Foundation is proud to have helped foster the exciting work of Dr. John Prensner and his team at Michigan Medicine. We look forward to learning more about his findings in the world of childhood brain cancer throughout his project.