In the world of oncology research, Dr. Charalampos (Harris) A. Lazaris stands out as a beacon of innovation. As a Senior Expert in Oncology Data Science at Novartis Biomedical Research in Cambridge, Massachusetts, Harris is dedicated to understanding how cancer cells manipulate gene regulation to survive and proliferate. His work focuses on the dependencies these cells develop, offering new avenues for targeted therapies.
Harris’s journey began in Greece, where he witnessed firsthand the impact of serious illness on his family. Initially aspiring to become a medical doctor, his path took an unexpected turn when he did not gain admission to medical school. This setback, however, proved to be a blessing in disguise. “That door closing turned out to be one of the best things that ever happened to me,” he reflects. Instead, he pursued biology at the University of Ioannina, where he discovered a passion for gene regulation and the intricate mechanisms that govern cellular identity.
Unraveling the Complexities of Gene Regulation
Harris’s fascination with gene regulation stems from its fundamental role in development. He explains, “An embryo goes from a single fertilized egg to hundreds of specialized cell types, each arriving at precisely the right place at precisely the right time.” This intricate process, he believes, is one of the most profound puzzles in science. Combining his love for biology with his affinity for computers, Harris earned a Master’s in Bioinformatics at the University of Edinburgh. This intersection of disciplines provided him with the tools to study gene regulation at an unprecedented scale.
Cancer, in Harris’s view, is a disease of disrupted gene regulation. His research focuses on two forms of dependency: oncogenic addiction where cancer cells become reliant on overactive cancer genes, and non-oncogenic addiction where they co-opt stress-response or survival pathways. By understanding these dependencies, Harris aims to identify vulnerabilities that can be targeted for therapy.
Pioneering Research in Cancer Dependencies
Harris’s work has shed light on the intricate relationship between genome architecture and cancer dependencies. In a study published in Nature Communications he demonstrated that strong chromatin boundaries preferentially wall off super-enhancers, large clusters of regulatory elements that act as control hubs for gene expression. This finding suggested that losing such insulation could lead to uncontrolled gene activation. Subsequent research in Nature Genetics confirmed this hypothesis, showing that the loss of insulating chromatin boundaries in T-cell acute lymphoblastic leukemia allows a super-enhancer to upregulate c-MYC, a gene commonly activated in cancer.
In another groundbreaking study published in Nature Medicine Harris and his team revealed how the oncogenic driver NOTCH1 sustains leukemia by hijacking the cell’s own stress-response machinery. This interplay between oncogenic and non-oncogenic dependencies presents a potential vulnerability that can be exploited for therapeutic purposes. “Cancer cells can become ‘hooked’ on gene-expression programs that drive their growth and survival—and those dependencies are precisely the vulnerabilities we can target,” Harris explains.
Advancing Cancer Research at Novartis
In his current role at Novartis, Harris focuses on transcriptional dependencies in solid tumors. By integrating genomics, epigenomics, and transcriptomics, he aims to understand these dependencies better and develop more effective therapies. His work could lead to more precise patient selection for therapies and longer-lasting responses for people living with cancer.
Harris’s contributions extend beyond his research. As a Keystone Symposia Fellow, he has played an active role in shaping the scientific community. At the Scientific Advisory Board (SAB) meeting in Boulder, Colorado, in, Harris had the opportunity to contribute his perspective on various topics, including science advocacy and outreach. He emphasizes the importance of mentorship in developing resilient scientists and credits his own mentors for shaping his career.
Harris’s advice to early-career scientists is to overcome shyness and seize opportunities. “Don’t let shyness hold you back,” he advises. “Approach the speaker after the talk; send the cold email. The worst anyone can say is no.” He encourages young researchers to engage with established scientists, as they often enjoy connecting with curious minds. Harris himself mentors students in molecular and computational biology and serves as President of the NYU Graduate School of Arts and Science Doctoral Alumni Association.
Looking ahead, Harris aims to continue his rigorous research while playing an active role in deciding which questions the scientific community tackles. His journey from Greece to Cambridge, marked by leaps into the unknown, has shaped his unique perspective on science. “Science looks different depending on where you’re standing,” he reflects, underscoring the importance of diverse viewpoints in driving innovation.
