Oncology and Pathology

Faculty of Medicine | Lund University

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Functional Genomics

The human genome contains ~3 billion base-pairs. Although as much as 90% of the genome is transcribed into various forms of RNA transcripts, only a fraction is responsible for the ~23000 protein-coding genes and ~17000 non-coding transcripts which are presumed to have biological functions. These genes and functional RNAs, through interactions with each other, with lipids and carbohydrates, and with the genome itself, regulate the delicate balance between cell proliferation, cell differention, and cell death. When this critical balance is disturbed by inherited and acquired changes to the genome of cells, cancer can arise. In the Canceromics Branch Functional Genomics Unit, our goals are to elucidate the processes by which aberrantly regulated genes contribute to breast tumorigenesis. By using in vitro and in vivo model systems combined with genetic methods such as site-directed mutagenesis and genomic techniques such as microarrays and next-generation sequencing, we study the effect and function of modified genes, their interactions with biological processes and the genome, and how they influence responses to pharmacological agents. These mechanistic studies may provide significant and clinically relevant insights into the variable tumor behavior and responses cancer patients show to drug therapy.

Currently our main focus is on the Notch signaling pathway. The Notch family of receptor-transcription factors are involved in signal transduction pathways which control cell proliferation, cell differentiation, and cell-fate decisions. This pathway has received increasing interest in cancer biology due to accumulating evidence that activated Notch signaling plays an important role in several human malignancies including breast cancer.  Therefore, therapies that target activation of Notch signaling, such as gamma-secretase inhibitors, may be an effective treatment for Notch-dependent cancers. The four human Notch homologues, Notch1-4, are transmembrane proteins with two components: an extracellular component that, upon interaction with their ligands such as delta-like or jagged presented by neighboring cells, triggers a cleavage process, releasing the activated intracellular transcription factor component which translocates into the nucleus where it modifies the expression of target genes. We aim to further characterize the role and effects of Notch signaling in breast cancer, identify downstream effector genes, and test whether therapeutics against Notch activation in combination with other pathway drugs can be a viable strategy to mediate the development of treatment-resistance.

Contact

sofia gruvberger

Sofia Gruvberger, Ph.D.
Head, Functional Genomics Unit
Asst. Professor, Div. of Oncology
Phone: +46 46 2221575
E-mail: sofia.gruvberger@med.lu.se
 

Funding

  • BioCARE Research Program
  • Berta Kamprad Foundation

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