Jennifer Rhodes, PhD
Office Phone: 215-728-3829
My laboratory is interested in understanding how the specialized cells found in the blood normally develop, a process called hematopoiesis, and how disturbances in this process can contribute to blood cell transformation and cancer. Our research makes use of zebrafish, Danio rerio, a small freshwater fish that has the same spectrum of blood cell types that are present in people and mice. The transparent embryos develop outside the mother's body, each growing from a fertilized egg to an embryo with a beating heart in just 25 hours. We can easily manipulate the genetics of the zebrafish, by inducing random mutations in the DNA, knocking down expression of individual genes, or overexpressing genes of interest. Together, these characteristics make it easy to experimentally manipulate and analyze hematopoiesis, and make zebrafish an ideal model for our studies.
Cancerous cells of hematopoietic origin often have chromosomal deletions, which are thought to contribute to the development of the disease by removing one or more tumor suppressor genes. However, the deleted regions are often very large making it difficult to identify the critical gene or genes. A growing body of evidence has shown that factors essential for the normal development of mature hematopoietic cells can also function as tumor suppressors in blood cell cancers. My laboratory uses the power of zebrafish genetics to discover novel genes that are essential for normal blood cell development and to test their potential to act as tumor suppressors. This strategy allows us to expand our current knowledge about the biology of blood cells and explore zebrafish models of hematopoietic disease, with the goal of revealing important insights to the genesis and progression of blood cell cancers.
Currently, we are exploring four interrelated areas of interest:
- Hematopoietic gene discovery using random induction of mutations in the genome and assessing the role of the mutated genes in blood cell development
- Examining genetic networks involved in the development of blood cell cancers by combining different genetic lesions and interrogating the effects on embryonic and adult zebrafish hematopoiesis
- Developing transgenic zebrafish that label specific subsets of cells with a fluorescent protein, allowing us to study the live development of these cells or purify this population for experimentation
- Payne EM, Bolli N, Rhodes J, Abdel-Wahab OI, Levine R, Hedvat CV, Stone R, Khanna-Gupta A, Sun H, Kanki JP, Gazda HT, Beggs AH, Cotter FE, Look AT. Ddx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AML. Blood. 2011 Jul 28;118(4):903-15. PubMed
- Bolli N, Payne EM, Rhodes J, Gjini E, Johnston AB, Guo F, Lee JS, Stewart RA, Kanki JP, Chen AT, Zhou Y, Zon LI, Look AT. cpsf1 is required for definitive HSC survival in zebrafish. Blood. 2011 Apr 14;117(15):3996-4007. PubMed
- Rhodes J*^, Amsterdam A, Sanda T, Moreau LA, McKenna K, Heinrichs S, Ganem NJ, Ho KW, Neuberg DS, Johnston A, Ahn Y, Kutok JL, Hromas R, Wray J, Lee C, Murphy C, Radtke I, Downing JR, Fleming MD, MacConaill LE, Amatruda JF, Gutierrez A, Galinsky I, Stone RM, Ross EA, Pellman DS, Kanki JP, Look AT. Emi1 maintains genomic integrity during zebrafish embryogenesis and cooperates with p53 in tumor suppression. Mol Cell Biol. 2009 Nov;29(21):5911-22. *Corresponding author. ^Cover image selected for publication by journal. PubMed
- Rhodes J, Hagen A, Hsu K, Deng M, Liu TX, Look AT, Kanki JP. Interplay of pu.1 and gata-1 determines myelo-erythroid progenitor cell fate in zebrafish. Dev Cell. 2005 Jan;8(1):97-108. PubMed
- Liu TX, Howlett NG, Deng M, Langenau DM, Hsu K, Rhodes J, Kanki JP, D’Andrea AD, Look AT. Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis. Dev Cell. 2003 Dec;5(6):903-14. PubMed