Abstract: Cellular plasticity is emerging as an important driving force underlying cancer progression and drug resistance. In this talk, I will discuss the concept of cancer cell states present in the tumor prior to treatment, as well as those that accompany resistance to increasing drug doses. In particular, I will discuss work published in our recent manuscript 'Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment' and recent developments in this project. Second, I will discuss our new work of 'Drug-induced adaptation along a resistance continuum in cancer cells'. In this work we provide evidence that the dose and treatment duration together drive the resistance of ovarian cancer cells to targeted therapy along a trajectory of cellular adaptation, that we denote the ‘resistance continuum’. We report that gradual dose exposure and prolonged treatment promote a continuous increase in fitness, and show that this process is mediated by evolving transcriptional, epigenetic and genetic changes that promote multiple cell state transitions. The resistance continuum is underpinned by the assembly of gene expression programs and epigenetically reinforced stress response regulation. Using both in vivo and in vitro models, we found that this process involves widespread reprogramming of cell survival pathways, including interferon response, lineage reprogramming, metabolic rewiring and oxidative stress regulation. Together, the resistance continuum reveals the dynamic nature of cellular adaptation, and carries implications for cancer therapies, as initial exposure to lower doses primes cells over time for increased resistance to higher doses.

In addition to this special seminar, Dr. Yanai will lead a GradFUTURES workshop over dinner at 6 pm in Prospect House Garden Room titled “What is the Question?” focused on the creative side of scientific research. In this workshop, he will highlght that a discovery is unexpected- an unknown unknown- and often does not fit neatly into a ‘knowledge gap’. A crucial step in many discoveries is the invention or the refocusing of the research question, and we will explore ways in which questions may be formulated or rephrased for research progress.  We invite graduate students, postdocs and faculty to attend.

Itai Yanai is a Professor at the NYU Grossman School of Medicine, where his studies dynamic biological processes through the lens of gene regulation and systems biology. His work has led to many contributions in the fields studying the evolution of developmental gene expression programs, spatial and single-cell transcriptomics, cancer cell states & tumor heterogeneity, and genome evolution and the genetic basis of genotype-environment interactions.

Along with Dr. Martin Lercher, Dr. Yanai co-authored the popular science book The Society of Genes, which discusses how genes compete and cooperate in our genome. Also in collaboration with Dr. Lercher, Dr. Yanai discusses the exciting and significant parts of scientific research that occur behind the scenes, called “night science” and explores the creative side of scientific thinking in a collection of editorials in Genome Biology and associated podcasts. 

Dr. Yanai earned PhD in Bioinformatics from Boston University and pursued postdoctoral training at Weizmann Institute of Science in Israel and Harvard University. He served as Assistant and Associate Professor of Biology at Technion -Israel Institute of Technology between 2008-2016. In 2016, he joined NYU Langone Health.