Erika Bach, Ph.D.

Assistant Professor
Graduate Director, Molecular Pharmacology Training Program, Sackler Institute
New York University School of Medicine
erika.bach@nyu.edu

Stem cells have the unique property of producing multiple types of specialized cells. They can regenerate damaged tissues throughout the lifetime of an individual; they are the building blocks of life. After a stem cell divides, one descendent will become a stem cell, while the other one becomes a specialized cell type. Understanding how a stem cell offspring chooses between becoming a stem or a specialized cell holds great potential for breakthroughs in cancer treatment. Human tumors have so-called “cancer stem cells” that survive even the most brutal therapeutic regimens and then establish new, often more aggressive tumors.

Critical regulators of stem cell numbers in mammals are a group of proteins called JAKs and STATs. In normal cells, the activity of JAKs and STATs is regulated and they work together in a coordinated manner to relay a signal from the outside of a stem cell to its interior. Continuous activity of JAKs and STATs cause human blood cancers and has been implicated in more than 50% of breast, prostate and lung cancers, 50% of multiple myeloma, and 95% of head and neck cancers. Recently, scientists showed that reducing the activity of one STAT protein significantly impairs the survival of human lymphoma cancer cells. These results indicate that JAKs and STATs are good candidates for therapeutic intervention in a clinical setting.

The normal and cancer-causing activities of JAKs and STATs are not well understood. We propose to use the power of fruit fly genetics to unravel these functions. JAK and STAT genes exist in very similar forms in other organisms such as the fruit fly, Drosophila. The fruit fly is an excellent model genetic organism that has been used for many years and with great success to identify and characterize genes involved in human diseases. In my lab, we have shown that persistent activation of JAK and STAT proteins in the fly eye and testis leads to dramatic overgrowths that consist of stem cells and that resemble human tumors. Furthermore, when these proteins do not work, stem cells in the eye and testis are lost. We have identified some of the genes that JAKs and STATs turn on, including cyclin E, which regulates the division of cells, dmyc, which regulates the size of cells, and chinmo, which allows a stem cell offspring to become a stem cell.

Our study is designed to discover how JAK and STAT proteins control the number of stem cells in Drosophila. First, we will address whether these proteins increase the number of times a stem cell can divide by controlling the level of Cyclin E. Second, we will ask if JAKs and STATs increase the size of a stem cell by augmenting dMyc expression. Lastly, we will focus our attention on how Chinmo allows a stem cell offspring to become a stem cell and not a specialized cell. Our results will provide critical insights into the functions of human JAK and STAT proteins. In a broader sense, our study should result in better therapeutics for human patients.

Select Publications

Flaherty MS, Zavadil J, Ekas LA, Bach EA. Genome-wide expression profiling in the Drosophila eye reveals unexpected repression of notch signaling by the JAK/STAT pathway. Dev Dyn. 2009 Jun 4.

Kim BH, Yin CH, Guo Q, Bach EA, Lee H, Sandoval C, Jayabose S, Ulaczyk-Lesanko A, Hall DG, Baeg GH. A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells. Mol Cancer Ther. 2008 Sep;7(9):2672-80.

Ayala-Camargo A, Ekas LA, Flaherty MS, Baeg GH, Bach EA. The JAK/STAT pathway regulates proximo-distal patterning in Drosophila. Dev Dyn. 2007 Oct;236(10):2721-30.

Bach EA, Ekas LA, Ayala-Camargo A, Flaherty MS, Lee H, Perrimon N, Baeg GH. GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. Gene Expr Patterns. 2007 Jan;7(3):323-31.

Ekas LA, Baeg GH, Flaherty MS, Ayala-Camargo A, Bach EA. JAK/STAT signaling promotes regional specification by negatively regulating wingless expression in Drosophila. Development. 2006 Dec;133(23):4721-9.

Arbouzova NI, Bach EA, Zeidler MP. Ken & Barbie selectively regulates the expression of a subset of Jak/STAT pathway target genes. Curr Biol. 2006 Jan 10;16(1):80-8.

Read RD, Bach EA, Cagan RL. Drosophila C-terminal Src kinase negatively regulates organ growth and cell proliferation through inhibition of the Src, Jun N-terminal kinase, and STAT pathways. Mol Cell Biol. 2004 Aug;24(15):6676-89.

Bach EA, Vincent S, Zeidler MP, Perrimon N. A sensitized genetic screen to identify novel regulators and components of the Drosophila janus kinase/signal transducer and activator of transcription pathway. Genetics. 2003 Nov;165(3):1149-66.

Ghiglione C, Bach EA, Paraiso Y, Carraway KL 3rd, Noselli S, Perrimon N. Mechanism of activation of the Drosophila EGF Receptor by the TGFalpha ligand Gurken during oogenesis. Development. 2002 Jan;129(1):175-86.

Bach EA, Tanner JW, Marsters S, Ashkenazi A, Aguet M, Shaw AS, Schreiber RD. Ligand-induced assembly and activation of the gamma interferon receptor in intact cells. Mol Cell Biol. 1996 Jun;16(6):3214-21.

Meraz MA, White JM, Sheehan KC, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenlund AC, Campbell D, Carver-Moore K, DuBois RN, Clark R, Aguet M, Schreiber RD. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell. 1996 Feb 9;84(3):431-42.

Bach EA, Szabo SJ, Dighe AS, Ashkenazi A, Aguet M, Murphy KM, Schreiber RD. Ligand-induced autoregulation of IFN-gamma receptor beta chain expression in T helper cell subsets. Science. 1995 Nov 17;270(5239):1215-8.