Research Interests
Our research focuses on acute leukemia. Our acute myeloid leukemia project involves a multi-omics study comparing the leukemic cells collected at time of initial diagnosis with the ones collected at relapse, to identify alterations likely conveying the chemotherapy resistance commonly seen at relapse in this disease. We combine whole genome- and RNA sequencing with proteomic and epigenomic analyses. By integrating the different data sets we aim to get a more complete picture of the leukemic cells that previously never has been generated. Hypotheses generated from these analyses will be functionally evaluated by biochemical analyses, cellular studies and mouse modelling, followed by potential therapeutic studies.
Our acute lymphoblastic leukemia (ALL) project investigates mutations I previously identified in pediatric high-risk ALL in the epigenetic regulator Polycomb Repressive Complex 2 (PRC2), which trimethylates histone H3 at Lysine 27 (H3K27), leading to transcriptional repression. For a better understanding of the effect these mutations have on tumor formation and progression, we combine enzymatic in vitro assays, and studies of the downstream effects of these mutations using cell lines as well as mice, and analyze the mutated cells by ChIP-seq for trimethylated H3K27, as well as by RNA-sequencing.
Group members
Ren Sun, Post doc
Svea Stratmann, PhD student
Aron Skaftason, Bioinformatician
Key publications
External homepage
http://www.igp.uu.se/forskning/experimentell-klinisk-onkologi/linda-holmfeldt/
Contact
Contact page at Uppsala University