Ludmil Alexandrov

About

Ludmil B. Alexandrov is a Professor in the Department of Cellular and Molecular Medicine and the Department of Bioengineering at the University of California San Diego. His research is focused on disentangling the enigmatic secrets hidden in large omics datasets by developing novel machine-learning approaches. He leverages these approaches to elucidate the basic molecular mechanisms underlying cancer development and progression, with the aim of improving cancer treatment and prevention.

Research topics

• Biology
• Genetics
• Computational biology
• Evolutionary biology
• Mathematics
• Internal medicine
• Cancer research
• Oncology
• Statistics
• Virology

Selected publications

• The repertoire of mutational signatures in human cancer

  Nature · 2020 · 3673 citations

  1st authorCorresponding

  , enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unk…

  DOI

• The evolutionary history of 2,658 cancers

  Nature · 2020 · 1112 citations

  , we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are…

  DOI

• Patterns of somatic structural variation in human cancer genomes

  Nature · 2020 · 976 citations

  . Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions-as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inve…

  DOI

• Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

  Nature Genetics · 2020 · 763 citations

  Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothrips…

  DOI

• Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

  Nature · 2020 · 655 citations

  , raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.

  DOI

Recent grants

• Comprehensive identification of germline-somatic interactions

  NIH · $1.8M · 2022–2027

• Detecting Mutational Signatures of Environmental Mutagens in Heathy Individuals for Personalized Cancer Prevention

  NIH · $3.4M · 2021–2025

Frequent coauthors

• David C. Wedge

  Cancer Research UK Manchester Institute

  176 shared

• Erik N. Bergstrom

  University of California, San Diego

  141 shared

• Michael R. Stratton

  Wellcome Sanger Institute

  133 shared

• Peter Van Loo

  The University of Texas MD Anderson Cancer Center

  121 shared

• Nischalan Pillay

  University College London

  112 shared

• Peter J. Campbell

  University of Cambridge

  109 shared

• Serena Nik‐Zainal

  108 shared

• Keiran Raine

  Wellcome Sanger Institute

  104 shared

Labs

• The Alexandrov LabPI

Awards & honors

• NIEHS 2020 Outstanding New Environmental Scientist Award
• David and Lucile Packard Foundation 2019 Packard Fellowship…
• V Foundation for Cancer Research 2019 Abeloff V Scholar
• The International Academy for Medical and Biological Enginee…
• Genetics Society 2018 The Balfour Prize Lecture

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