Presidential Lectures

In this lecture, Leonardo Rastelli will overview the bootstrap approach, the idea that theory space can be determined from the general principles of symmetry and quantum mechanics. This strategy provides a new unifying language for QFT and has allowed researchers to make predictions for physical observables even in strongly coupled theories. Rastelli will illustrate the general framework in a few examples, ranging from the concrete (boiling water) to the abstract (supersymmetric theories in various spacetime dimensions).

In this lecture, Paola Arlotta will focus on the cerebral cortex and present the challenges and opportunities of modeling human brain development using pluripotent stem cells within 3D human brain organoids. Building on developmental work in mice, such organoids promise a better understanding of complex neurodevelopmental conditions such as autism spectrum disorder. She will discuss her recent work on the generation and long-term development of human brain organoids and the study of their developmental trajectories, cellular diversities and neuronal network features.

What’s the longest sequence of steps you can create while guaranteeing your safety? If you’re two steps from death, the answer is 11. For three steps, the answer is 1,161. But what about for other numbers? This conundrum, the Erdős discrepancy problem, was conjectured by mathematician Paul Erdős in around 1932 and had gone unsolved for more than seven decades. In this lecture, Terence Tao will discuss his general solution to the problem, published last year, and its connections to the Chowla and Elliot conjectures in number theory. The solution incorporates mathematical tools from probability, number theory and information theory.

In this lecture, Dr. David Ledbetter will describe Geisinger Health System’s Precision Health Center. The center makes available more than 20 years’ worth of electronic health data for research and innovation. In partnership with Regeneron Genetics Center, Geisinger now has exome sequence data for more than 92,000 patient-participants, with an ultimate goal of 250,000. Those data have already led to the successful identification of new drug targets, improved prevalence estimates of the most common Mendelian disorders (FH, BRCA, Lynch) and the identification of autism spectrum and neuropsychiatric CNV disorders in 0.8 percent of the dataset’s adult participants. These results are already having a positive impact on individual participants, their family members and their primary care physicians.

In this lecture, Arnold Levine will discuss how recent studies have illuminated a great deal about the human immune system and its complexities. Methods for sequencing T cell receptors and quantifying their diversity have been developed. Antigens recognized by these T cell receptors can be identified by matching amino acid sequences to mutations in the DNA sequences of cancers and the microbiome. Algorithms are being developed to identify responders and non-responders, identify tumor antigens and explore the vitality and functionality of the immune system.

In this lecture, Dr. Charles Sawyers will discuss this important area of research using prostate cancer as an example. Recent evidence, for instance, suggests that while more potent inhibitors deliver superior clinical efficacy, they can lead to more diverse mechanisms for cancer cells to escape treatment. Prostate cancers treated with the drug enzalutamide can develop resistance through mutations in the androgen receptor, via bypass of the androgen receptor blockade by signaling through the glucocorticoid receptor, or by lineage plasticity. During lineage plasticity, androgen-dependent luminal epithelial cells undergo an identity change to more basal-like epithelial cells. The complexity underlying these adaptive responses to targeted therapy reinforces the importance of combination therapy to achieve long-term clinical benefit.