Associate Professor Ph.D. (2006) Columbia University Packaging of DNA into open regions of euchromatin and condensed regions of heterochromatin is critical for genome integrity and transcriptional regulation. The Goll lab seeks to understand the mechanisms that drive the initial establishment of these chromatin states during the earliest stages of embryogenesis and to understand how aberrant chromatin states can contribute to disease pathology. We use a combination of genetic, genomic, molecular, and cell biology-based approaches to address these questions in the context of vertebrate development. Our favorite model is the zebrafish! Our research is currently supported by : NIGMS 1R35GM139556 Heterochromatin in the developing vertebrate embryo NIEHS 1R21ES032503 Environmental stress and epigenetic repression in the developing embryo Education Education: BA. Cornell University PhD. Columbia University Postdoc, Carnegie Institution for Science Research Research Interests: Our Mission: Research in our laboratory integrates molecular, cell, developmental, genetic and genomic data to understand fundamental processes related to DNA packaging, transcriptional regulation and epigenetic inheritance in the context of early vertebrate development and disease. Our Model: We primarily use the zebrafish as a model for our research. Most processes are well conserved between zebrafish and other vertebrates (including humans). The large numbers of synchronously dividing, externally fertilized embryos produced from zebrafish crosses enable molecular and genomic studies of early embryogenesis that can be difficult to perform in mammalian systems. At the same time the small size, rapid development and clarity of the zebrafish embryo facilitates imaging-based approaches to monitor chromatin dynamics in vivo across all stages of development. Primary Research Focuses: CHROMATIN REGULATION IN EARLY EMBRYOGENESIS: Segregation of eukaryotic genomes into open regions of euchromatin and condensed regions heterochromatin represents one of the most fundamental processes in eukaryotic biology. Failure to package DNA into these distinct states during early embryogenesis can have profound consequences for transcriptional regulation, genome stability and normal development. Yet, despite its fundamental importance, the mechanisms that drive the fractionation of genomes into these distinct domains remain unclear. Current research in our laboratory is aimed at understanding the mechanisms that drive the de novo segregation of genomes into these distinct compartments, and the developmental consequences of shifting the timing of this event. DNA METHYLATION LOSS IN DISEASE (CANCER AND ICF SYNDROME): The epigenetically modified DNA base 5-methylcytosine (DNA methylation, 5mC) is essential for vertebrate development and abnormal DNA methylation patterns are common in diseases. In particular, the pericentromeric satellite repeats that flank chromosome centromeres are highly enriched in 5mC. Specific loss of 5mC at these sequences is common in cancer and is also a hallmark of the rare human disease, Immunodeficiency, Centromere and Facial abnormalities (ICF) syndrome. Our laboratory has generated the first viable animal models that faithfully recapitulate selective hypomethylation of pericentromeres and hallmarks of ICF syndrome. Current research in our laboratory uses these models to understand the relationship between pericentromeric methylation loss and cancer, how pericentromeric methylation loss contributes to ICF syndrome pathology, and the mechanisms that regulate methylation at pericentromeres. Selected Publications Selected Publications: Calvird AE, Broniec MN, Duval KL, Higgs AN, Arora V, Ha LN, Schouten EB, Crippen AR, McGrail M, Laue K, Goll MG (2022). Uncovering Regulators of Heterochromatin Mediated Silencing Using a Zebrafish Transgenic Reporter. Front Cell Dev Biol. 10:832461. Akdogan-Ozdilek B, Duval KL, Meng FW, Murphy PJ, Goll MG. (2021) Identification of chromatin states during zebrafish gastrulation using CUT&RUN and CUT&Tag. Dev Dyn. 251(4):729-742. Laue K, Rajshekar S, Courtney AJ, Lewis ZA, Goll MG. (2019) The maternal-to-zygotic transition regulates genome-wide heterochromatin establishment in the zebrafish embryo. Nature Communications 10(1):1551. Rajshekar S, Yao J, Arnold PK, Payne SG, Zhang Y, Bowman TV, Schmitz, RJ, Edwards JR, Goll MG. (2018) Pericentromeric hypomethylation elicits an interferon response in an animal model of ICF syndrome. eLife 7:e39658. Li C, Lan Y, Schwartz-Orbach L, Korol E, Tahiliani M, Evans T, Goll MG. (2015) Overlapping requirements for Tet2 and Tet3 in normal development and hematopoietic stem cell emergence. Cell Reports 12(7):1133-43.
