Dr. Daniel Pomeranz Krummel, PhD, has joined UNC Health’s Department of Neurosurgery as a research faculty member. He will work alongside his wife, UNC Health physician-scientist Dr. Soma Sengupta, in a shared lab researching malignant brain tumors.
Dr. Pomeranz Krummel went to Yale for his graduate work. During that time, he worked on an RNA enzyme alongside his mentor, Dr. Sidney Altman, a recipient of the Nobel Prize for Chemistry (1989). It was at Yale that Dr. Pomeranz Krummel first crossed paths with his future life partner and research collaborator, Dr. Sengupta. He then went to work at the Laboratory of Molecular Biology in Cambridge, U.K. The Laboratory of Molecular Biology has a storied history – it was a research home for many greats of 20th century science, including Max Perutz (Nobel 1963), Aaron Klug (Nobel 1982), Cesar Milstein (Nobel 1984), and Sidney Brenner (Nobel 2002). “What made this institute unique was significant internal funding, which created a supportive environment to set ambitious goals”, said Dr. Pomeranz Krummel.
Dr. Pomeranz Krummel went to Cambridge to obtain the first structural insight into an integral part of a very large complex called the spliceosome. According to Dr. Pomeranz Krummel, many doubted at the time that he could achieve his research goal. But after eight years he and his colleagues reported in an article in the scientific journal Nature that they had solved the structure. “It was a big deal at the time and provided molecular insight into a complex that is fundamental to all advanced life,” said Dr. Pomeranz Krummel.
While he found this research thrilling, over time Dr. Pomeranz Krummel grew more interested in doing research that he felt may directly impact patients. His conversations with Dr. Sengupta at the dinner table led to deeper conversations about brain tumor research. “I decided to do more work that directly impacted patients,” said Dr. Pomeranz Krummel. He wanted to be involved in drug development for adult and pediatric patients diagnosed with primary brain tumors.
Dr. Sengupta’s early lab-based research in Boston focused on how to stop cancer growth in a pediatric brain cancer. Her discovery that an important neurotransmitter receptor called the GABA-A receptor was functional in pediatric cancer cells led her to explore a new way treating this cancer. “When Soma told me about this interesting discovery, I was blown away. I was heavily involved in RNA, but I told her I wanted to collaborate and get involved,” said Dr. Pomeranz Krummel.
Dr. Pomeranz Krummel recalls the transition from basic research to translational cancer research, stating that it was much smoother than one would think, however, at the time many questioned his pedigree in cancer research. “My work in 2015 was not cancer-related at all, but I collaborated with Dr. Sengupta,” said Dr. Pomeranz Krummel. “She was in Boston then and I was about a 30-minute drive away, and it was not easy to collaborate to the extent we wanted.” In addition to running two separate laboratories, Dr. Sengupta and Dr. Pomeranz Krummel were raising their two young daughters and Dr. Sengupta’s clinical demands had increased. In 2016, they decided to relocate to Emory University, solidified their collaboration, and began working in the same lab.
While at Emory, they discovered in collaboration with a senior medicinal chemist at the University of Wisconsin-Milwaukee, James Cook, a class of drugs that can turn cancer cells poorly responsive to various treatment modalities, including immunotherapy, responsive. “We discovered that this class of drugs can sensitize tumors to radiation, certain chemotherapies, and immunotherapy,” said Dr. Pomeranz Krummel. “We are now pursuing this drug and evaluating the game-changing roles it can play in different cancers.”
For Dr. Pomeranz Krummel, his research became personal after he lost his mother to brain metastases caused by lung cancer. “After surgery and all kinds of drugs, drug resistance, and side effects, she had radiation to the brain, and within a week, she went from being very sharp mentally to no longer there cognitively,” recalled Dr. Pomeranz Krummel. “It was a horrible, painful experience for my father, her children, and grandchildren.” At the time, Dr. Pomeranz Krummel had written grants on the effects of radiation on the brain and cognitive deficits due to chemotherapy. But this personal experience was a significant wake up call.
His research alongside Dr. Sengupta looks at ways to make radiation, chemotherapy, and immunotherapy effective or more effective while reducing toxic side effects. “The thing that happens with cancer treatments is that the cancer treatment itself devastates the body,” said Dr. Pomeranz Krummel. “It is often not that the treatment is un-effective, but that the treatment itself becomes toxic.”
Over the past two years, Dr. Pomeranz Krummel has worked alongside Dr. Sengupta, focusing significant effort on metastatic brain tumors. Their discovery of a new class of drugs may lead to an increase in life expectancy for patients diagnosed with malignant brain tumors as well as reduced toxicity. Their main objective is to get support to advance to clinical trials.
Dr. Pomeranz Krummel explains that this class of drugs can potentially make brain cancer a disease that is managed and treated. “Cancer is always evolving,” said Dr. Pomeranz Krummel. “It is never really eradicated. More kept at bay. It evolves, and then you find an alternative or another treatment approach. It is a constant battle.”
Dr. Pomeranz Krummel looks forward to joining UNC. “UNC Health has a powerful cancer center,” said Dr. Pomeranz Krummel. “There are excellent investigators in immunology and immuno-oncology to form potential collaborations with and learn from. There is a strong and very established ecosystem to support biotech and research collaboration opportunities in the Triangle region. Few places in the U.S. have that aspect for biomedical research.”
Both Dr. Sengupta and Dr. Pomeranz Krummel want to alleviate toxic side effects, making the treatment period less painful and easier for cancer patients. “This would be a major achievement,” said Dr. Pomeranz Krummel. Driven by personal experience, Dr. Pomeranz Krummel hopes their promising research will someday make this a reality for cancer patients.
Written by: Makenzie Hardy, Marketing Coordinator, UNC Health Department of Neurosurgery