Research Interest
During mammalian development, transcription factors and microRNAs both provide input to direct gene expression and determine lineage decisions. Some of these same pathways are recapitulated during oncogenesis and metastasis. Transcription factors controlling epithelial-mesenchymal transition are important both during development and in cancer. MiRNAs are critical for control of gene expression and thus cell fate decisions and are often involved in temporal switches in lineage decisions. These two classes of developmental regulators have been shown to influence one another, but their mutual regulatory functions are not completely understood. In the Unternaehrer lab we use tissue culture and mouse models to study the interplay between EMT factors and miRNAs in development and in cancer. We are modeling gastrulation by differentiating mouse embryonic stem cells (ESC) to the primitive streak fate. We have characterized several ovarian cancer cell lines for their epithelial vs. mesenchymal phenotype, and for their expression of stem cell markers. We are using an orthotopic patient-derived ovarian cancer xenograft (PDX) model to study the roles of EMT transcription factors including Snail, and miRNAs including let-7, in ovarian cancer progression and metastasis. The PDX is being used as a preclinical model to test manipulation of these factors as a therapy for ovarian cancer.
A major focus of our research is the mechanism by which stemness is regulated. Loss of let-7 miRNA is a contributor to the cancer stem cell (CSC) phenotype in many cancers. The mechanisms that decrease let-7 expression in cancer are incompletely understood, and we are examining regulation at transcriptional and epigenetic levels.
During postdoctoral studies at Harvard Medical School, Dr. Unternaehrer studied the mechanism of reprogramming mouse and human somatic cells to pluripotency. Surprisingly, factors involved in EMT are upregulated and play a positive role in the early stages of the induced pluripotent stem (iPS) cell generation process. The miRNA let-7 is downregulated at time points when these factors are increased, and Snail binds the promoter of several let-7 family members.
Dr. Unternaehrer studied the initiation of immune responses during Ph.D. studies at Yale, where she described molecular details of the interactions between dendritic cells and naïve CD4 T cells.
University of California, Riverside, Stem Cell Center Appointment
During mammalian development, transcription factors and microRNAs both provide input to direct gene expression and determine lineage decisions. Some of these same pathways are recapitulated during oncogenesis and metastasis. Transcription factors controlling epithelial-mesenchymal transition are important both during development and in cancer. MiRNAs are critical for control of gene expression and thus cell fate decisions and are often involved in temporal switches in lineage decisions. These two classes of developmental regulators have been shown to influence one another, but their mutual regulatory functions are not completely understood. In the Unternaehrer lab we use tissue culture and mouse models to study the interplay between EMT factors and miRNAs in development and in cancer. We are modeling gastrulation by differentiating mouse embryonic stem cells (ESC) to the primitive streak fate. We have characterized several ovarian cancer cell lines for their epithelial vs. mesenchymal phenotype, and for their expression of stem cell markers. We are using an orthotopic patient-derived ovarian cancer xenograft (PDX) model to study the roles of EMT transcription factors including Snail, and miRNAs including let-7, in ovarian cancer progression and metastasis. The PDX is being used as a preclinical model to test manipulation of these factors as a therapy for ovarian cancer.
A major focus of our research is the mechanism by which stemness is regulated. Loss of let-7 miRNA is a contributor to the cancer stem cell (CSC) phenotype in many cancers. The mechanisms that decrease let-7 expression in cancer are incompletely understood, and we are examining regulation at transcriptional and epigenetic levels.
During postdoctoral studies at Harvard Medical School, Dr. Unternaehrer studied the mechanism of reprogramming mouse and human somatic cells to pluripotency. Surprisingly, factors involved in EMT are upregulated and play a positive role in the early stages of the induced pluripotent stem (iPS) cell generation process. The miRNA let-7 is downregulated at time points when these factors are increased, and Snail binds the promoter of several let-7 family members.
Dr. Unternaehrer studied the initiation of immune responses during Ph.D. studies at Yale, where she described molecular details of the interactions between dendritic cells and naïve CD4 T cells.
University of California, Riverside, Stem Cell Center Appointment
