TITLE: "A quantitative view of strategies to engineer cell-selective ligand binding" ABSTRACT: Selective binding to specific target cells is a critical property of many therapies. To enhance selectivity in specific situations, a series of new strategies have been proposed in the drug development literature, including affinity, valency, multi-specificity, and other alterations to target cell binding. […]
TITLE: "Organoid Maturation by Circadian Entrainment " ABSTRACT: Stem cell-derived tissues that recap endogenous physiology are key for regenerative medicine. Yet, most methods yield products that function like fetal, not adult tissues. Organoids are typically grown in constant environments, while our tissues mature along with behavioral cycles. I show that inducing circadian rhythms in pancreatic islet organoids, […]
TITLE: "Building an integrated framework for tissue morphogenesis with the zebrafish inner ear" ABSTRACT: How simple tissues give rise to geometrically complex organs with robust shapes and functions is a fundamental question in biology with important implications in disease and translational medicine. The current mechanistic framework explains how upstream genetic and biochemical information pattern cellular mechanics […]
TITLE: "Understanding how environmental cues regulate Neuro-Mesodermal progenitor cells in development and disease" ABSTRACT: The trunk and tail of vertebrates arise from the addition of mesodermal (i.e., muscle and vertebrae) and neural (i.e., spinal cord) cells from the progenitor zone in the tailbud. This developmental program is critical for the proper formation of the posterior body […]
TITLE: "Cellular plasticity and fate choices in developing tissues and single cancer cells" ABSTRACT: While cellular processes are often reproducible and precise, cells may also alter their molecular states and adopt new fates in response to stimuli, a phenomena referred to as “plasticity”. I am interested in understanding the control principles governing cellular plasticity and fate […]
TITLE: "Exploration of human genetic and phenotypic diversity through cell villages" ABSTRACT: Our species is characterized by an immense diversity in neurological and psychological traits. Common and rare genetic variants have been linked to trait differences and disease risk in human populations, though the underlying biology is poorly understood and difficult to study at large scales. […]
TITLE: "Imaging-based genetic recording of developmental histories" ABSTRACT: Systems-level understanding of cell fate decisions has been hampered by limitations of the existing methods to capture developmental history of the cells. Synthetic recording, which uses genome editing to create sequence diversity in genetic barcodes, is emerging as a promising approach for mapping cell lineage and molecular history. […]
TITLE: "Genomewide supervised prediction of activating and repressive regions in over hundred cell and tissue types" ABSTRACT: While the vast majority of variants associated with common disease risk are distributed across the non-coding genome, our understanding of the regulatory elements contained within remains notably incomplete. Strategies for identifying and characterizing these regulatory elements, such as […]
TITLE: "XIST controls X chromosome dampening and autosomal genes in early human development" ABSTRACT: Female human pre-implantation embryos and naïve human pluripotent stem cells (hPSCs) equalize X-linked gene expression with males via X-chromosome dampening (XCD), a unique strategy of dosage compensation in mammals. The mechanisms controlling XCD are unknown. Here, we show that the long non-coding […]
TITLE: "Fast estimation of genetic correlation for Biobank-scale data" ABSTRACT: Genetic correlation is an important parameter in understanding the shared genetic basis across pairs of complex traits with applications ranging across disease subtyping, genetic prediction, and causal inference. The availability of genome-wide genetic data has led to a number of methods that aim to estimate genetic […]
