Research Interests

My lab studies transcriptional circuits that control gene expression and cell phenotype within cells and in complex tissues and tumors. We develop experimental and computational tools for this task, and apply them in mammalian cells, especially from the immune system and cancer. We have developed and applied an extensive experimental and computational toolbox in the context of these studies. Experimentally, this includes novel methods to profile RNA, proteins and their interactions, especially in single cells, nanotechnology-based delivery to primary cells, and combined strategies to monitor the effect of hundreds of thousands of perturbations on genomic profiles. Computationally, we have pioneered sophisticated algorithms to reconstruct dynamic circuit models from time course and perturbation data, to design time course, perturbation and signature experiments, and to facilitate analysis of large scale genomics datasets, especially transcript assembly from RNA-Seq, and single cell RNA-Seq analysis. We have successfully applied these approaches to reconstruct dynamic circuits in a variety of systems and time scales, especially in immune cell differentiation and function. These include the circuits that control the gene expression response to pathogens in dendritic cells, the dynamic network controlling Th17 cell differentiation, the regulatory networks that control hematopoiesis, and the roles of chromatin regulators and lincRNA in the ES cell circuit. We have pioneered experimental and computational approach for single cell and single nucleus RNA-Seq. We have showed how these can be applied for reconstructing intra- and inter-cellular circuits in immune cells, performed the first single cell RNA-Seq study in cancer tissue, developed computational strategies for mapping of single cells to their location in complex tissues, and invented a droplet based strategy for massively-parallel single cell and single nucleus RNASeq. We have been a key member of the development and application of mapping techniques in the brain, including as part of the BRAIN initiative and in the SpaceTX pilot project. Most recently, we combined scRNA-Seq with perturbation screens, including combinatorially. I co-lead the International Initiative to build a Human Cell Atlas.

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Primary Section

Section 43: Immunology and Inflammation

Secondary Section

Section 29: Biophysics and Computational Biology