Aneta Mikulasova Research Group

(Epi)genomic Instability in Multiple Myeloma

Dr Aneta Mikulasova

Research Fellow

Contact details

Research in a Nutshell

Explain your research in lay terms. Possible to copy/paste from PURE/ Research Explorer, current website – edit as required 200 words maximum.

Our research focuses on how the structure and regulation of the genome go wrong in multiple myeloma, a type of blood cancer affecting plasma cells in the bone marrow. We are particularly interested in large-scale changes in DNA, called structural variants, which can disrupt multiple genes and regulatory regions at once. These changes often occur in parts of the genome that are usually inactive or “silent”, such as near centromeres, and are difficult to study due to their complex structure.

To uncover these hidden abnormalities, we use advanced genome sequencing technologies alongside data on how DNA is packaged and regulated, known as the epigenome. We also develop computational methods to detect these complex changes and to integrate different layers of genomic and epigenomic data. This multi-omics approach helps us understand how structural variants affect gene activity and contribute to disease progression or treatment resistance.

By analysing data from hundreds of patients with multiple myeloma, we aim to identify genomic patterns that explain why the disease behaves differently between individuals and how this can be predicted. In the long term, our goal is to use this detailed genomic knowledge to support the development of more personalised and effective treatments.

We gratefully welcome donations to support our research and engagement activities:

Key Publications

  1. Mikulasova A, Kent D, Trevisan-Herraz M, Karataraki N, Fung KTM, Ashby C, Cieslak A, Yaccoby S, van Rhee F, Zangari M, Thanendrarajan S, Schinke C, Morgan GJ, Asnafi V, Spicuglia S, Brackley CA, Corcoran AE, Hambleton S, Walker BA, Rico D, Russell LJ. Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers. 2022. Genome Res. 32(7):1343–1354. https://doi.org/10.1101/gr.276042.121
  2. Mikulasova A, Morgan GJ, Walker BA. Chromosomal abnormalities in multiple myeloma. 2022. Nat. Rev. Dis. Primers. 8(1):42. https://doi.org/10.1038/s41572-022-00374-6
  3. Mikulasova A, Ashby C, Tytarenko RG, Qu P, Rosenthal A, Dent JA, Ryan KR, Bauer MA, Wardell CP, Hoering A, Mavrommatis K, Trotter M, Deshpande S, Yaccoby S, Tian E, Keats J, Auclair D, Jackson GH, Davies FE, Thakurta A, Morgan GJ, Walker BA. Microhomology-mediated end joining drives complex rearrangements and overexpression of MYC and PVT1 in multiple myeloma. 2020. Haematologica 105(4):1055–1066. https://doi.org/10.3324/haematol.2019.217927
  4. Mikulasova A, Wardell CP, Murison A, Boyle EM, Jackson GH, Smetana J, Kufova Z, Pour L, Sandecka V, Almasi M, Vsianska P, Gregora E, Kuglik P, Hajek R, Davies FE, Morgan GJ, Walker BA. The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma. 2017. Haematologica 102(9):1617–1625. https://doi.org/10.3324/haematol.2017.163766
  5. Mikulasova A, Smetana J, Wayhelova M, Janyskova H, Sandecka V, Kufova Z, Almasi M, Jarkovsky J, Gregora E, Kessler P, Wrobel M, Walker BA, Wardell CP, Morgan GJ, Hajek R, Kuglik P. Genomewide profiling of copy-number alteration in monoclonal gammopathy of undetermined significance. 2016. Eur. J. Haematol. 97(6):568–575. https://doi.org/10.1111/ejh.12774

Collaborations

  • Dr Victoria L. Campbell, Western General Hospital, NHS Lothian, Edinburgh, UK
  • Prof Brian A. Walker, University of Miami, Miami, FL, USA
  • Prof Gareth J. Morgan, NYU Langone Health, New York, NY, USA
  • Dr Daniel Rico, Andalusian Molecular Biology and Regenerative Medicine Centre, Seville, Spain
  • Dr Linda B. Baughn, Mayo Clinic, Rochester, MN, USA

Partners and Funders

  • Medical Research Council
  • Peter McCleave & Gob for Good campaign (https://gobforgood.com/), major donors: DKMS, Love Hope Strength, Adlard Foundation

 

Scientific Themes

genomic instability, structural variation, chromatin architecture, 3D genome organisation, epigenomic regulation, B-cell biology, heterochromatin rearrangements, cancer progression and resistance mechanisms

Disease Areas

multiple myeloma, smouldering myeloma, MGUS and other monoclonal gammopathies, B-cell and plasma cell disorders, haematological malignancies

Technology Expertise

whole-genome sequencing (short- and long-read), RNA sequencing, ChIP-seq, DNA methylation profiling, Micro-C / 3D genome mapping, computational genomics, structural variant detection, multi-omics data integration