Dr. John Whetstine, also known as John W, discovered his passion for science while attending Bolton Agricultural High School in Tennessee, where he earned his high school degree. Despite moving frequently as a child, Bolton became the place where he delved into the world of science, particularly captivated by Punnett squares. Although unsure about the path of a scientist, his high school teacher's influence ignited a love for discovery. Pursuing undergraduate degrees in recombinant genetics and chemistry at Western Kentucky University, he later obtained his PhD in the Pharmacology Department at Wayne State University in Michigan, combining his interests in gene control and chemistry. His postdoctoral fellowship at Harvard Medical School in Massachusetts led him to become part of the team that discovered histone lysine demethylases, a subject he continues to study at the molecular and translational levels. Dr. Whetstine then joined Massachusetts General Hospital and Harvard Medical School, rising to the position of associate professor and Tepper Family Scholar, as well as vice chair of the epigenetics center. Recruited to Fox Chase Cancer Center in December 2018, he is now the Jack Schultz Basic Science Endowed Professor, Director of the Cancer Epigenetics Institute, Co-leader of the Nuclear Dynamics and Cancer Program, and Director of the Genomics Resource. His research has unveiled the role of chromatin factors in driving extrachromosomal DNA amplification, linking these regions to aggressive tumors and drug resistance. Dr. Whetstine's lab has significantly impacted our understanding of DNA replication regulation and copy number control, identifying new biomarkers and therapeutic targets. He has mentored and contributed to the development of the next generation of scientists at various academic levels, with his trainees achieving success at prestigious institutions and in leading pharmaceutical companies. The accomplishments of his trainees stand out as the most cherished stories of his career.