Cell fate specification is among the most fundamental processes in biology and is exerted physiologically during stem cell differentiation, pathologically during cancer stem cell formation, and can be engineered with reprogramming approaches.

All these processes involve activation of target programs and inhibition of donor cell programs and are controlled by sequence-specific DNA binding transcription factors (TFs) and their diverse interactions with the chromatin landscape.

We aim to understand how TFs decode mammalian genomes to generate the diverse cell identities that arise during development, cellular reprogramming and pathological conditions. To this end we employ multi-omic approaches, genome engineering, single cell tool development and bioinformatic analysis to delineate the TF-driven mechanisms that determine cell fate specification. Our ultimate goal is to engineer customized stem cells and their differentiated progeny for clinical applications while exploring the mechanisms that govern organ aging and regeneration and tumor growth.

Current Interests include

1. A roadmap of mammalian development
   How are pluripotent stem cells “programmed” to generate all bodily cell types during development, and how can somatic cells be “reprogrammed” to an ESC-like state?
   We develop and apply innovative genomic technologies to map the epigenetic and transcriptomic events that drive cell fate decisions during early ESC differentiation and somatic to iPS reprogramming.
2. Reprogramming transcription factors and gene regulation
   How can transcription factors identify and select cell type-specific genomic targets from thousands of potential binding sites?
   Current research in the lab is aimed at understanding how reprogramming transcription factors facilitate the loss or destabilization of somatic cell identities and the activation of new target programs at single cell resolution
3. Engineering customizable cell fates
   How can we engineer clinically relevant cell types to alleviate pathological conditions?
   We use computational and systems biology approaches to define novel reprogramming TF combinations that can contribute to the generation of Hematopoietic Stem, Progenitor and Mature blood cell types with the ultimate goal of transplantation therapy and to understand mechanisms that contribute to blood diseases.

• Norn Group -Impetus Grant Funding Mechanism. Defining a chromatin-state clock to measure and reverse hematopoietic stem cell aging  – PI:Chronis
• NHLBI –R01HL170286 Reprogramming Gene Regulatory Networks to a Hematopoietic Stem Cell State –  PI:Chronis
• NHLBI –P01 HL160469 The lung endothelium as an instructive niche for the innate immune system during vascular injury  –  Epigenetics and Transcriptomics Core Lead: Chronis
• High-Resolution Ensemble 3DStructures of Genome across Tissues  INCITE award – Argonne National Labs – Co-PI: Chronis