Key publications

Mullighan CG, Zhang J, Kasper LH, Lerach S, Payne-Turner D, Phillips LA, Heatley SL, Holmfeldt L, Collins-Underwood JR, Ma J, Buetow KH, Pui C-H, Baker SD, Brindle PK, and Downing JR. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature. 471(7337):235-9 (2011).

Wang J, Mullighan CG, Easton J, Roberts S, Ma J, Rusch MC, Chen K, Harris CC, Ding L, Heatley SL, Holmfeldt L, Payne-Turner D, Fan X, Wei L, Zhao D, Obenauer JC, Naeve C, Mardis ER, Wilson RK, Downing JR, and Zhang J. CREST: an algorithm that directly maps structural variations for next-generation sequencing data. Nature Methods. 8(8):652-4 (2011).

Zhang J*, Ding L*, Holmfeldt L*, Wu G, Heatley SL, Payne-Turner D, Easton, J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, and Mullighan CG. The genetic basis of early T-cell precursor acute lymphoblastic leukemia. Nature. 481(7380):157-63 (2012). * Equal contribution

Holmfeldt L*, Wei L*, Diaz-Flores E, Zhang J, Walsh M, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen SC, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Phillips LA, Song G, Easton J, Parker M, Chen X, Rusch M, Boggs K, Vadodaria B, Hedlund E, Drenberg C, Baker S, Pei D, Cheng C, Huether R, Lu C, Fulton RS, Fulton LL, Tabib Y, Dooling DJ, Ochoa K, Minden M, Lewis ID, To LB, Marlton P, Roberts AW, Raca G, Stock W, Neale G, Drexler HG, Dickins RA, Ellison DW, Shurtleff SA, Pui CH, Ribeiro RC, Devidas M, Carroll AJ, Heerema NA, Wood B, Borowitz MJ, Gastier-Foster JM, Raimondi SC, Mardis ER, Wilson RK, Downing JR, Hunger SP, Loh ML, Mullighan CG. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet. 45(3):242-52 (2013). *Equal contribution

Ntziachristos P, Tsirigos A, Welstead GG, Trimarchi T, Bakogianni S, Xu L, Loizou E, Holmfeldt L, Strikoudis A, King B, Mullenders J, Becksfort J, Nedjic J, Paietta E, Tallman MS, Rowe JM, Tonon G, Satoh T, Kruidenier L, Prinjha R, Akira S, Van Vlierberghe P, Ferrando AA, Jaenisch R, Mullighan CG, and Aifantis I. Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukemia. Nature. 514(7523):513-7 (2014).

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

linda.holmfeldt@igp.uu.se

Contact page at Uppsala University

Last updated: 2022-11-30

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