John Quackenbush, Henry Pickering Walcott Professor at Harvard T.H. Chan School of Public Health, is uncovering how gene regulatory networks - not DNA sequence alone- drive cancer progression. In 2012, his team introduced PANDA, a method that “reverse engineers” which of 1,600 regulatory proteins control gene activity by integrating expression data. PANDA revealed the underlying control mechanisms that differentiate healthy from diseased cells.

Applying PANDA to colon cancer, they discovered sex-specific regulatory differences: men and women modulate immune responses and drug metabolism differently. These insights have already guided personalized chemotherapy strategies in mouse models.

Building on this, Quackenbush developed PHOENIX, which charts how the regulation of all 25,000 human genes shifts as cells progress from normal to malignant. Recognized by the National Cancer Institute as a 2024 breakthrough, PHOENIX aims to identify regulatory “tipping points” and drugs that can arrest cancer before it fully develops.

Quackenbush stresses that these advances and the training of over 100 biomedical scientists via open-source tools - depend on sustained NIH funding. He warns that recent federal grant terminations risk stalling this work and undermining U.S. leadership in computational biology and cancer research.