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Molecular Biology and Genetics.
855 N. Wolfe St
Baltimore, MD 21205
Genomics, Synthetic Biology, Developmental Biology
My lab operates at the interface of biology and technology to investigate important questions in biomedical sciences. We develop and apply molecular engineering, genome engineering, and computational approaches to better understand mammalian epigenetics and development. For instance, we engineer cells with molecular devices that label their genomes with unique barcodes. Such barcoding enables tracking cellular identity, behavior, and history. The barcoding devices comprise homing guide RNAs (hgRNAs) which target their own loci to create random heritable mutations. We have established a unique mouse model, known as MARC1 (Mouse for Actively Recording Cells!), which carries multiple hgRNA loci distributed across its genome. Activating these hgRNAs in the zygote results in their mutagenesis throughout gestation, creating developmentally barcoded mice in which lineage information is recorded in hgRNA barcodes. To complement this strategy for recording cellular histories in their genomes, we work on in situ sequencing technologies that allow for high throughput readout of these barcodes directly from cells and tissue sections. We also develop the theoretical and computational approaches to analyze barcoding outcomes. We use these strategies to study early and extraembryonic development, as well as the development of the central nervous system.
Lee HH*, Kalhor R*, Goela N*, Bolot J, Church GM. Terminator-free template-independent enzymatic DNA synthesis for digital information storage. Nat Commun. 2019 Jun 3;10(1):2383. PMID: 31160595.
Kalhor R†, Kalhor K, Mejia L, Leeper K, Graveline A, Mali P, Church GM†. Developmental barcoding of whole mouse via homing CRISPR. Science. 2018 Aug 31;361(6405). pii: eaat9804. PMID: 30093604.
Kalhor R, Mali P, Church GM. Rapidly evolving homing CRISPR barcodes. Nat Methods. 2017 Feb;14(2):195-200. PMID: 27918539.
Lee JH, Daugharthy ER, Scheiman J, Kalhor R, Yang JL, Ferrante TC, Terry R, Jeanty SS, Li C, Amamoto R, Peters DT, Turczyk BM, Marblestone AH, Inverso SA, Bernard A, Mali P, Rios X, Aach J, Church GM. Highly multiplexed subcellular RNA sequencing in situ. Science. 2014 Mar 21;343(6177):1360-3. PMID: 24578530.
Kalhor R, Tjong H, Jayathilaka N, Alber F, Chen L. Genome architectures revealed by tethered chromosome conformation capture and population-based modeling. Nat Biotechnol. 2012 Jan;30(1):90-8. PMID: 22198700.