How do tumors become drug resistant and what can we do about it?

Dr. Hangauer has performed research for 25 years across diverse fields including organic chemistry and chemical biology, genomics and cancer biology. His Ph.D. thesis work leveraging bioorthogonal chemistry to design fluorogenic reagents to image glycans and other non-genetically encoded biomolecules (Angewandte Chemie 2008, JACS 2012) contributed to his Ph.D. mentor Carolyn Bertozzi’s 2022 Nobel Prize. As a postdoc, he discovered that >85% of the human genome is transcribed in at least one tissue type and uncovered tens of thousands of novel long intergenic noncoding RNAs (PLOS Genetics 2013). Then, also as a postdoc, he initiated his ongoing focus on how tumors become therapy resistant with a particular interest in the subpopulation of cancer “persister” cells which reversibly enter a drug tolerant, quiescent cell state and utilize non-genetic survival mechanisms. Persister cells are present in a wide range of tumor types and constitute a cell reservoir, also known as minimal residual disease (MRD), from which overtly drug resistant cells can emerge to drive tumor recurrence. As a postdoc, he discovered that while persister cells resist apoptotic death, they are hypersensitized to death by ferroptosis (Nature 2017). Partially based on this finding, multiple commercial drug development efforts are underway to induce ferroptosis in cancer. He started his independent lab at UCSD in 2018 where he has focused on the molecular mechanisms of acquired therapy resistance both for immunotherapy and targeted therapies. His lab is particularly currently interested in the consequences of sublethal apoptotic signaling which occurs in stressed persister cells including how this results in genetic and nongenetic adaptation to drugs and immune therapy.