Dr. Salz received her PhD in Genetics at the University of California, Davis and did her post-doctoral studies at Princeton University. She joined the CWRU faculty in 1987 and is now a Professor in the Department of Genetics and Genome Sciences. She holds a secondary appointment in the in the Center for RNA Science and Therapeutics and is a member of the Molecular Oncology Program, Case Comprehensive Cancer Center. Dr. Salz has served on editorial boards for scientific journals, on advisory committees for the Genetics Society of America, on the National Drosophila Society Board of Directors, and on grant review panels for the American Cancer Society, National Science Foundation and National Institutes of Health
We are interested in sex determination and germ cell biology. Our experimental approaches are broad, bringing together advanced genomic, molecular and genetic technologies.
Germs cells are the cells that give rise to sperm or eggs. In most sexually reproducing animals, the cells that will become germ cells are set-aside during embryogenesis. Germ cells then migrate to the developing gonad, which will form ovaries in females and testes in males. There, germ cells will ultimately differentiate into sperm or eggs. Whether germ cells succeed in making eggs or sperm depends on a number of factors, including preservation of sexual identity. In humans, defects in sex-specific programming interferes with germ cell development, leading to infertility and germ cell tumors. Although rare, germ cell tumors are the most frequent cause of cancer in young men and represent the majority of ovarian malignancies in young women. Despite its importance to human health and reproduction, how germ cell sexual identity is secured is poorly understood.
We have chosen to study germ cell development in Drosophila to take advantage of the many genetic, molecular and cell biological tools available in this system. Fly and human germ cells face many of the same developmental issues, and are likely to solve problems in similar ways. Our studies in the fly will therefore inform our understanding of how human germ cells maintain their sexual identity, and why errors in this process leads to infertility and germ cell tumors. The knowledge gained from our studies may also lead to the design of effective strategies to restrict tumor growth or even correct the errors that lead to germ cell tumors.
We are interested in understanding how sex is determined and maintained in germ cells. We have projects centered around our discovery that female germ cells secure their sexual identity through a mechanism that includes formation of H3K9me3 silencing islands on a select set of euchromatic genes. This work provides an elegant illustration that forms of context-dependent repressive chromatin other than canonical Polycomb controlled H3K27me3 domains, are used to control the expression of genes important for cell fate maintenance.
We are also interested in understanding why defects in sex-specific programming cause germ cell tumors. We have projects centered around our discovery that inappropriate expression of a single testis-specific protein, called Phf7, is largely responsible for destabilizing female fate and causing germ cell tumors. This finding provides the ground work for a new set of studies focused on understanding how pathological reprogramming drives tumorigenesis. Germ cells are the ultimate stem cell, therefore discovering the key events that drive sex-fate reprogramming in the fly germline will inform strategies to improve the quality, ease and efficiency of directed stem cell fate reprogramming for regenerative medicine applications.