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Helen Salz
Professor
Ph.D. Training Faculty
Department of Genetics
School of Medicine
Case Western Reserve University
Biomedical Research Building 626
2109 Adelbert Road
Cleveland, Ohio 44106-4955
Tel: (216) 368-2879
Fax: (216) 368-3432
E-mail: helen.salz@case.edu


About Helen Salz

Helen Salz received her PhD in Genetics at the University of California, Davis. She did her post-doctoral studies at Princeton University under the direction of Paul Schedl, PhD and Tom Cline, PhD. Helen joined the faculty at Case Western Reserve School of Medicine in 1987 and is now a Professor in the Department of Genetics and Genome Sciences with a secondary appointment in the Center for RNA Molecular Biology. The research in the Salz lab, focused on post-transcriptional gene regulation in development, has been funded by grants from the National Institutes of Health, the National Science Foundation and the American Cancer Society. She is a member of editorial boards for scientific journals, review panels for funding agencies, advisory groups for the Genetics Society of America and serves on the Board of Directors for the National Drosophila Society.


Research

Post-transcriptional gene regulation: Understanding tissue- and stage-specific gene regulation remains one of the central issues in developmental biology. Studies of developmentally important genes, such as those that specify and maintain cell fate, have revealed that many genes are regulated post-transcriptionally. Our work has established that sex determination in the fruit fly Drosophila melanogaster is a powerful tool for understanding tissue-specific post-transcriptional gene regulation in the living animal. Much of our work has focused on Sex-lethal (Sxl), the RNA binding protein encoding binary switch gene that regulates all aspects of female-specific development and behavior. Using experimental strategies that combine the strength of Drosophila genetics, cell biology and biochemistry, we elucidated how Sxl, once activated, controls its own expression by a positive feedback splicing mechanism. Current work in the laboratory is focused on understanding how Sxl controls expression of the downstream gene regulatory networks responsible for sexually dimorphic cellular fates and behaviors.

Adult stem cells and tumors: Information about adult stem cell behavior is not only necessary to understand how healthy cells replace damaged cells in adult tissues, but also for understanding the origins of cancer. In the healthy adult, tissue maintenance and repair depends on a stable population of stem cells that have the capacity to give rise to both self-renewing and differentiating daughter cells. Control of the self-renewal/differentiation process depends on cell autonomous determinants and on extrinsic cell-cell interactions with the cellular microenvironment. Regulated execution of the self-renewal/differentiation choice is critical because an excess of differentiation can lead to stem cell depletion and tissue senescence, whereas a failure to enter the differentiation pathway can lead to an accumulation of proliferating cells and tumor formation.

New studies emerging from our laboratory demonstrate a previously unknown role for Sxl in controlling the self-renewal/differentiation decision of germline stem cells in the adult ovary. We have observed that blocking stem cell differentiation leads to an ovary filled with tumorous germ cells. Current work in the laboratory is focused on providing information about the post-transcriptional regulatory strategy used by adult stem cells to make the self-renewal/differentiation switch during normal development and at developing an understanding of why the failure to make this switch triggers malignant transformation.

Translational Impact: The Drosophila ovary is a powerful genetic system for studying how stem cells behave in their natural environment because the stem cells can be easily located, genetically manipulated, and observed without destroying tissue architecture. Given the deep conservation of stem cell behavior and regulatory mechanisms across species, we are confidant that the information obtained from studies in the fly will reveal concepts important for understanding the mechanism underlying cancer and may, in the future, lead to the design of effective strategies to restrict tumor growth or even correct the errors that lead to cancer.


Selected Publications

Salz HK (2012)
Sex, stem cells and tumors in the Drosophila ovary.
Fly (Austin);7(1):
See PubMed abstract

Chau J, Kulnane LS, Salz HK (2012)
Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis.
Proc Natl Acad Sci U S A;:
See PubMed abstract

Salz HK (2011)
Sex determination in insects: a binary decision based on alternative splicing.
Curr Opin Genet Dev;:
See PubMed abstract

Johnson ML, Nagengast AA, Salz HK (2010)
PPS, a Large Multidomain Protein, Functions with Sex-Lethal to Regulate Alternative Splicing in Drosophila.
PLoS Genet;6(3):e1000872
See PubMed abstract

Salz HK, Erickson JW (2010)
Sex determination in Drosophila: The view from the top.
Fly (Austin);4(1):
See PubMed abstract

Chau J, Kulnane LS, Salz HK (2009)
Sex-lethal facilitates the transition from germline stem cell to committed daughter cell in the Drosophila ovary.
Genetics;182(1):121-32
See PubMed abstract

Penn JK, Graham P, Deshpande G, Calhoun G, Chaouki AS, Salz HK, Schedl P (2008)
Functioning of the Drosophila Wilms'-Tumor-1-Associated Protein Homolog, Fl(2)d, in Sex-Lethal-Dependent Alternative Splicing.
Genetics;178(2):737-48
See PubMed abstract

Salz HK (2007)
Male or female? The answer depends on when you ask.
PLoS Biol;5(12):e335
See PubMed abstract

Rajendra TK, Gonsalvez GB, Walker MP, Shpargel KB, Salz HK, Matera AG (2007)
A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle.
J Cell Biol;176(6):831-41
See PubMed abstract

Chaouki AS, Salz HK (2006)
Drosophila SPF45: A Bifunctional Protein with Roles in Both Splicing and DNA Repair
PLoS Genet;2(12):e178
See PubMed abstract

Salz HK, Mancebo RS, Nagengast AA, Speck O, Psotka M, Mount SM (2004)
The Drosophila U1-70K protein is required for viability, but its arginine-rich domain is dispensable
Genetics;168(4):2059-65
See PubMed abstract

Nagengast AA, Stitzinger SM, Tseng CH, Mount SM, Salz HK. (2003)
Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping.
Development.;130(3):463-71
See PubMed abstract

Nagengast AA, Salz HK. (2001)
The Drosophila U2 snRNP protein U2A' has an essential function that is SNF/U2B" independent.
Nucleic Acids Res.;29(18):3841-7
See PubMed abstract

Mount SM, Salz HK. (2000)
Pre-messenger RNA processing factors in the Drosophila genome.
J Cell Biol.;150(2):F37-44
See PubMed abstract

Stitzinger SM, Conrad TR, Zachlin AM, Salz HK. (1999)
Functional analysis of SNF, the Drosophila U1A/U2B" homolog: identification of dispensable and indispensable motifs for both snRNP assembly and function in vivo.
RNA.;5(11):1440-50.
See PubMed abstract