My laboratory is interested in how epigenetic information shapes vertebrate development and influences disease pathology. In particular, we are interested in heterochromatin, a nucleoprotein structure associated with DNA compaction and transcriptional repression. Our main strategy employs zebrafish, which offer a powerful combination of genetic, molecular and cell biology based approaches to study epigenetics and chromatin regulation. Current projects in my laboratory focus on two areas:
1) Heterochromatin regulation during early development: External fertilization means that we have access to thousands of synchronously staged zebrafish embryos from the 1-cell stage onward. Using molecular approaches, we have found that markers associated with heterochromatin are completely absent from early stage zebrafish embryos. This unexpected finding provides a unique system to identify mechanisms that drive chromatin establishment during development. Current research is focused on identifying these mechanisms as well as understanding how early embryos are able to progress in the absence of heterochromatin.
2) Pericentromeric hypomethylation in malignancy: DNA methylation is an epigenetic modification that is enriched at heterochromatic sequences including the satellite repeats that surround chromosome centromeres. DNA methylation is lost at these sequences in most cancers, however it is unclear whether this loss is correlative or causative. Using genetic approaches, we have developed zebrafish models of pericentromeric hypomethylation. Current research is focused on using these models to understand the relationship between pericentromeric hypomethylation and cancer, as well as the mechanisms regulating methylation of pericentromeric satellite repeats.
- American Cancer Society Research Scholar, 2017-present
- March of Dimes Basil O’Connor Scholar, 2012-2014
- Louis V. Gerstner, Jr. Young Investigator, 2011-2014
- Damon Runyon Cancer Research Postdoctoral Fellow, 2007-2010
- Deans Award for Research Excellence, Columbia University, 2006
Current Grant Support:
- Heterochromatin in the developing vertebrate embryo, NIH/NIGMS
- Zbtb24 mutation and pericentromeric hypomethylation in malignancy, American Cancer Society
Li C., Evans T, Goll MG. (2016) Epigenetic Regulation of Hematopoietic Stem Cell Development. Methods in Cell Biology 135:431-48.
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.
Majoram L, Ashley A, Deerhake ME, Bagwell J, Mankiewicz J, Cocchiaro J, Beerman R, Willer J, Katsanis N, Tobin D, Rawls J, Goll MG, Bagnat M. (2015) Loss of uhrf1 function results in intestinal inflammation and IBD in zebrafish. Proceedings of the National Academy of Science U S A. USA 112(9):2770-5.
Wang WJ, Tay HG, Soni R, Perumal GS, Goll MG, Macaluso FP, Asara JM, Amack JD, Bryan Tsou MF. (2013) CEP162 is an axoneme-recognition protein promoting ciliary transition zone assembly at the cilia base. Nature Cell Biology 5(6):591-601.
Akitake CM., Macurak M, Halpern ME and Goll MG. (2011) Transgenerational analysis of transcriptional silencing in zebrafish. Developmental Biology 352(2): 191-201.
Feng S, Cokus SJ, Zhang X, Chen PY, Bostick M, Goll MG, Hetzel J, Jain J, Strauss SH, Halpern ME, Ukomadu C, Sadler KC, Pradhan S, Pellegrini M, Jacobsen SE. (2010) Conservation and divergence of methylation patterns in plants and animals. Proceedings of the National Academy of Science U S A. 107(19):8689-94.
Goll MG, Anderson RM, Stainier DY, Spradling AC, Halpern ME. (2009) Transcriptional Silencing and Reactivation in Transgenic Zebrafish. Genetics 182(3):747-55.
Anderson RM, Bosch JA, Goll MG, Hesselson D, Dong DS, Chi D, Shin D, Shin CH, Schlegel A, Verkade H, Halpern ME, Stainier DY. (2009) Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration. Developmental Biology 334(1):213-23.
Goll MG, Kirpekar F, Maggert K, Yoder J, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH. (2006) Methylation of tRNAAsp by the DNA methyltransferase homologue Dnmt2. Science 311(5759):395-8.
Goll MG and Bestor TH. (2005) Eukaryotic cytosine methyltransferases. Annual Review of Biochemistry 74:481-514
Goll MG and Bestor TH. (2002) Histone modification and replacement in chromatin activation. Genes and Development 16:1739-42.