Christopher Bakkenist, PhD

  • Associate Professor, Radiation Oncology
  • Associate Professor, Pharmacology and Chemical Biology
  • Julius Paul and Freeda Greenberger Chair in Radiation Oncology Research
  • Vice Chair for Basic Science
  • Member, Graduate Program in Microbiology and Immunology (PMI)

Education & Training

  • Postdoctoral Fellow, St. Jude Children's Research Hospital
  • PhD, Imperial College, University of London, UK
  • BSc (Hons) in Biochemistry/Chemistry, University of Liverpool, UK

Research Interests

Higher eukaryotes evolved with mechanisms that initiate DNA replication at multiple origins on multiple chromosomes in a pattern that is broadly conserved from one cell division to the next.  Multiple origins are needed as the replication of human chromosome 1 from a single origin would take 50 days.  The number of origins that can fire at a given time is limited, however, as cellular dNTP concentrations are 50-fold lower than that needed to replicate the genome. The mechanisms that determine when and where origins fire are not known.     

Activation of the replicative helicase is the first step in origin firing in eukaryotes.  Activation of the replicative helicase at a single origin in each of ~50,000 replicons is sufficient to replicate the human genome in the absence of stress.  These ~50,000 origins are selected from a tenfold excess of licensed origins.  Activation of additional replicative helicases at origins that would otherwise be passively replicated is observed after stress.  This plasticity in origin use is a simple mechanism to recover DNA replication between stalled replication forks.  The mechanisms that limit origin firing to one per replicon in the absence of stress are not known.

CD8 T cells divide 15 to 20 times in 7 days and a T cell can replicate its genome in less than 4 hours.  We are interested in the fundamental mechanisms that limit origin firing, how these mechanisms are alleviated to allow accelerated replication, and the impact of unrestricted DNA replication on genome stability and immune cell function. 


Vendetti FP, Lau A, Schamus S, Conrads TP, O’Connor MJ, Bakkenist CJ. 2015. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo. Oncotarget. 6: 44289-44305.

Moiseeva TN, Gamper AM, Hood BL, Conrads TP, Bakkenist CJ. 2016. Human DNA polymerase e is phosphorylated at serine-1940 after DNA damage and interacts with the iron-sulphur complex chaperones CIAO1 and MMS19. DNA Repair. 43: 9-17. 

Vendetti FP, Leibowitz BJ, Barnes J, Schamus S,  Kiesel BF, Abberbock S, Conrads T, Clump DA, Cadogan E, O’Connor MJ, Yu J, Beumer JH, Bakkenist CJ. 2017. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation. Scientific Reports. 7: 41892. 

Moiseeva T, Hood B, Schamus S, O’Connor MJ, Conrads TP, Bakkenist CJ. 2017. ATR kinase inhibition induces unscheduled origin firing through a Cdc7-dependent association between GINS and And-1. Nature Communications. 8: 1392.

Vendetti FP, Karukonda P, Clump DA, Teo T, Lalonde R, Nugent K, Ballew M, Kiesel BF, Beumer JH, Sarkar SN, Conrads TP, O’Connor MJ, Ferris RL, Tran PT, Delgoffe GM, Bakkenist CJ. 2018. ATR kinase inhibitor AZD6738 potentiates CD8+ T cell activity in the tumor microenvironment following radiation. Journal of Clinical Investigation, AOP.

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