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Murphy Lab

Welcome to the Murphy Lab

 

The Murphy lab investigates the mechanisms that activate or silence genes as cells transition from one state to another. In very early embryos, stem cells begin to divide and change. Through this process, called differentiation, tissues start to form, and all the cell types of the organism begin to arise. Differentiation relies on a highly coordinated series of gene activation and silencing events. As cells divide during differentiation, changes in gene expression provide each cell type with a specific identity and function. In a similar sense, when the gene expression patterns of normal adult cells change inappropriately, the cell identity also changes, and this can lead to carcinogenesis. Presently, it is unknown what molecular machinery allows a cell to transition from one gene expression state to another.

In the Murphy laboratory, we use the zebrafish model, mammalian stem cells, and human cancer cell lines, to investigate how epigenetic marks control gene expression patterns, and drive cell state transitions. This work relies on classic genetics and developmental biology methods, new DNA sequencing technologies, and bioinformatics applications, to map the genomic locations of various proteins and epigenetic marks as they change during cell state transitions. 

Fish

For many reasons, the zebrafish model is a powerful tool for studying various aspects of vertebrate diseases and normal developmental processes. These fish have a short generation time, are small, and are highly manipulatable for functional studies. Additionally, zebrafish are transparent as embryos. For these reasons as well as others, zebrafish have become a prevailing model for studying cell state transitions during vertebrate differentiation and in carcinogenesis. More recently, zebrafish have emerged as incredibly valuable when combined with genomics and biochemical studies. This is largely because zebrafish fertilization and early organismal development occur ex utero, and a single breeding pair can produce over 200 offspring per mating. Therefore, many thousands of cells can be harvested for complex studies that would be costly, and require dissection, if other vertebrate models were used.

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Patrick Murphy

Patrick Murphy

Principal Investigator

Epigenomics-Chromatin.org

Selected Publications

Murphy PJ, Wu SF, James CR, Wike CL, Cairns BR; Placeholder nucleosomes underlie germline-to-embryo DNA methylation reprogramming. Cell. 2018 Feb 22;172(5):993-1006.e13. Recommended by Faulty 1000

Guo J, Grow EJ, Yi C, Mlcochova H, Maher GJ, Lindskog C, Murphy PJ, Wike CL, Carrell DT, Goriely A, Hotaling JM, Cairns BR.; Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development. Cell Stem Cell. 2017 Oct 5;21(4):533-546.

Jenkins TG, James ER, DF Alonso DF, Hoidal JR, Murphy PJ, Hotaling JM, Cairns BR, Carrell DT, Aston KI; Cigarette Smoking Significantly Alters Sperm DNA Methylation Patterns. Andrology. 2017 Sep 26. [Epub ahead of print]

Murphy PJ & Cairns BR, Genome-Wide DNA Methylation Profiling in Zebrafish. Methods Cell Biol. 2016 Jun: 135:345-59.

Murphy KE, Murphy PJ, and Carrell DT; Chapter 5 - Epigenetic Changes in the Paternal Germline. In Transgenerational Epigenetics : Evidence and Debate, T. Tollefsbol, ed. (Oxford: Academic Press), 2014. 43–55.

Murphy PJ, Cipriany BR, Wallin C, Ju CY, Benítez JJ, Szeto K, Hagarman JA, Craighead HG, Soloway PD; Single-Molecule Analysis of Combinatorial Epigenomic States in Normal and Tumor Cells. Proc Natl Acad Sci. USA 2013 May 7;110(19):7772-7. Recommended by Faulty 1000

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Contact Us

  Murphy Lab
601 Elmwood Ave
Rochester, NY 14642