Research Summary

A major goal of our research for many years has been to use mouse genetics to understand the relationships between exposure to environmental carcinogens, including chemicals and radiation, and cancer susceptibility. We have generated mouse models that recapitulate the genetic heterogeneity in human populations, with a view to develop approaches to personalized diagnosis and treatment. The focus of our most recent projects is the development of “Systems Genetics” approaches to analysis of normal tissue biology, and the changes in the genome mutational landscapes and gene expression architecture that are induced by carcinogen exposure. These seek to integrate multidimensional data sets to provide a network view of normal genetic architecture in mouse and human tissues, and the perturbations that take place during development of benign tumors and their progression to metastasis. Studies to date have revealed important roles for genes and pathways linked to stem cell fate decisions, cell cycle control, inflammation, and immune regulation. These integrated systems approaches represent a novel and highly promising route to the identification of the critical interacting components of signaling pathways, and identification of the critical changes in expression networks that are linked to cancer. They will further provide a platform, using chemically induced tumors that have many point mutations, to design and test novel approaches to combinatorial therapy including radiotherapy and immunotherapy, and the development of biomarkers of responsiveness. Finally, analysis of mouse tumors induced by different carcinogens can provide a deeper understanding of the etiology and mutational origins of human cancers.

Research Funding

  • June 1, 2017 - May 31, 2024 - Systems genetics analysis of tumor evolution in the mouse, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R35CA210018
  • August 17, 2017 - July 31, 2022 - Integrating targeted and immunotherapy to treat genetically heterogeneous cancers, Co-Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: U01CA217864
  • May 1, 2015 - April 30, 2020 - The Oncogenic and Tumor Suppressor Functions of the Kras isoform 4A in vivo, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA184089
  • January 1, 2015 - December 31, 2019 - Genetic analysis of ras mutation specificity in skin and lung cancer, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA184510


University of Glasgow, BSc, 1966, Hons. Chemistry
University of Glasgow, Ph.D., 1969, Organic Chemistry
University of Strasbourg, France, Postdoc, 1969-71
German Cancer Research Centre, Heidelberg, West Germany, Postdoc, 1971-72

Honors & Awards

  • Royal Society European Programme Fellowship
  • Alexander Von Humboldt-Stiftung Fellowship
  • 1995
    Elected Fellow of the Royal Society of Edinburgh
  • 1999
    Elected to UICC (International Union Against Cancer) Roll of Honor
  • 2000
    Tom Connors Prize and lecture
  • 2007
    John B. Little Award, Harvard School of Public Health
  • 2011
    American Skin Association Achievement Award
  • 2015
    Elected Fellow of the Royal Society

Selected Publications

  1. Fores-Martos J, Cervera-Vidal R, Sierra-Roca J, Lozano-Asencio C, Fedele V, Cornelissen S, Edvarsen H, Tadeo-Cervera I, Eroles P, Lluch A, Tabares-Seisdedos R, Falcó A, Van't Veer LJ, Schmidt M, Quigley DA, Børresen-Dale AL, Kristensen VN, Balmain A, Climent J. Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3VNTR polymorphisms and gene co-expression. NPJ Breast Cancer. 2021 Sep 10; 7(1):118.  View on PubMed
  2. Chen WC, To MD, Westcott PMK, Delrosario R, Kim IJ, Philips M, Tran Q, Bollam SR, Goodarzi H, Bayani N, Mirzoeva O, Balmain A. Targeting KRAS4A splicing through the RBM39/DCAF15 pathway inhibits cancer stem cells. Nat Commun. 2021 07 13; 12(1):4288.  View on PubMed
  3. Balmain A. The critical roles of somatic mutations and environmental tumor-promoting agents in cancer risk. Nat Genet. 2020 11; 52(11):1139-1143.  View on PubMed
  4. Riva L, Pandiri AR, Li YR, Droop A, Hewinson J, Quail MA, Iyer V, Shepherd R, Herbert RA, Campbell PJ, Sills RC, Alexandrov LB, Balmain A, Adams DJ. The mutational signature profile of known and suspected human carcinogens in mice. Nat Genet. 2020 11; 52(11):1189-1197.  View on PubMed
  5. Ku AA, Hu HM, Zhao X, Shah KN, Kongara S, Wu D, McCormick F, Balmain A, Bandyopadhyay S. Integration of multiple biological contexts reveals principles of synthetic lethality that affect reproducibility. Nat Commun. 2020 05 12; 11(1):2375.  View on PubMed
  6. Rose Li Y, Halliwill KD, Adams CJ, Iyer V, Riva L, Mamunur R, Jen KY, Del Rosario R, Fredlund E, Hirst G, Alexandrov LB, Adams D, Balmain A. Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice. Nat Commun. 2020 01 20; 11(1):394.  View on PubMed
  7. Amendola CR, Mahaffey JP, Parker SJ, Ahearn IM, Chen WC, Zhou M, Court H, Shi J, Mendoza SL, Morten MJ, Rothenberg E, Gottlieb E, Wadghiri YZ, Possemato R, Hubbard SR, Balmain A, Kimmelman AC, Philips MR. KRAS4A directly regulates hexokinase 1. Nature. 2019 12; 576(7787):482-486.  View on PubMed
  8. Veniaminova NA, Grachtchouk M, Doane OJ, Peterson JK, Quigley DA, Lull MV, Pyrozhenko DV, Nair RR, Patrick MT, Balmain A, Dlugosz AA, Tsoi LC, Wong SY. Niche-Specific Factors Dynamically Regulate Sebaceous Gland Stem Cells in the Skin. Dev Cell. 2019 11 04; 51(3):326-340.e4.  View on PubMed
  9. Dodagatta-Marri E, Meyer DS, Reeves MQ, Paniagua R, To MD, Binnewies M, Broz ML, Mori H, Wu D, Adoumie M, Del Rosario R, Li O, Buchmann T, Liang B, Malato J, Arce Vargus F, Sheppard D, Hann BC, Mirza A, Quezada SA, Rosenblum MD, Krummel MF, Balmain A, Akhurst RJ. α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas. J Immunother Cancer. 2019 03 04; 7(1):62.  View on PubMed
  10. Li S, Balmain A, Counter CM. A model for RAS mutation patterns in cancers: finding the sweet spot. Nat Rev Cancer. 2018 12; 18(12):767-777.  View on PubMed
  11. Reeves MQ, Kandyba E, Harris S, Del Rosario R, Balmain A. Multicolour lineage tracing reveals clonal dynamics of squamous carcinoma evolution from initiation to metastasis. Nat Cell Biol. 2018 06; 20(6):699-709.  View on PubMed
  12. Huang PY, Kandyba E, Jabouille A, Sjolund J, Kumar A, Halliwill K, McCreery M, DelRosario R, Kang HC, Wong CE, Seibler J, Beuger V, Pellegrino M, Sciambi A, Eastburn DJ, Balmain A. Lgr6 is a stem cell marker in mouse skin squamous cell carcinoma. Nat Genet. 2017 Nov; 49(11):1624-1632.  View on PubMed
  13. Quigley DA, Tahiri A, Lüders T, Riis MH, Balmain A, Børresen-Dale AL, Bukholm I, Kristensen V. Age, estrogen, and immune response in breast adenocarcinoma and adjacent normal tissue. Oncoimmunology. 2017; 6(11):e1356142.  View on PubMed
  14. Halliwill KD, Quigley DA, Kang HC, Del Rosario R, Ginzinger D, Balmain A. Panx3 links body mass index and tumorigenesis in a genetically heterogeneous mouse model of carcinogen-induced cancer. Genome Med. 2016 08 09; 8(1):83.  View on PubMed
  15. Quigley DA, Kandyba E, Huang P, Halliwill KD, Sjölund J, Pelorosso F, Wong CE, Hirst GL, Wu D, Delrosario R, Kumar A, Balmain A. Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer. Cell Rep. 2016 07 26; 16(4):1153-1165.  View on PubMed
  16. Wang MT, Holderfield M, Galeas J, Delrosario R, To MD, Balmain A, McCormick F. K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling. Cell. 2015 Nov 19; 163(5):1237-1251.  View on PubMed
  17. McCreery MQ, Halliwill KD, Chin D, Delrosario R, Hirst G, Vuong P, Jen KY, Hewinson J, Adams DJ, Balmain A. Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers. Nat Med. 2015 Dec; 21(12):1514-20.  View on PubMed
  18. Adams CJ, Yu JS, Mao JH, Jen KY, Costes SV, Wade M, Shoemake J, Aina OH, Del Rosario R, Menchavez PT, Cardiff RD, Wahl GM, Balmain A. The Trp53 delta proline (Trp53ΔP) mouse exhibits increased genome instability and susceptibility to radiation-induced, but not spontaneous, tumor development. Mol Carcinog. 2016 09; 55(9):1387-96.  View on PubMed
  19. Hiraoka K, Inoue T, Taylor RD, Watanabe T, Koshikawa N, Yoda H, Shinohara K, Takatori A, Sugimoto H, Maru Y, Denda T, Fujiwara K, Balmain A, Ozaki T, Bando T, Sugiyama H, Nagase H. Inhibition of KRAS codon 12 mutants using a novel DNA-alkylating pyrrole-imidazole polyamide conjugate. Nat Commun. 2015 Apr 27; 6:6706.  View on PubMed
  20. Letteboer TG, Benzinou M, Merrick CB, Quigley DA, Zhau K, Kim IJ, To MD, Jablons DM, van Amstel JK, Westermann CJ, Giraud S, Dupuis-Girod S, Lesca G, Berg JH, Balmain A, Akhurst RJ. Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14. Front Genet. 2015; 6:67.  View on PubMed

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