John Krais, PhD


Image of John Krais, PhDMy research interests center on the DNA damage response and how to apply new discoveries to the treatment of cancer. I trained in Bioengineering as an undergraduate at the University of Pittsburgh and in graduate school at the University of Oklahoma where I focused on targeted drug delivery strategies. Subsequently, I trained under Neil Johnson at Fox Chase Cancer Center as PARP inhibitors first obtained FDA approval for the targeted treatment of cancers with defects in BRCA1/2-mediated DNA damage response pathways. Here it became clear that targeting the DNA damage response has enormous potential for the treatment of cancers, however much additional work is required to maximize the potential benefit for all patients.

In 2023 I joined the Washington University School of Medicine as an Assistant Professor with the goal of developing a research program aimed at advancing our understanding of the DNA damage response to drive the development of new therapeutics.



DNA damage arises from a multitude of exogenous and endogenous sources. Double-strand breaks in DNA (DSBs) are one of the most consequential forms of DNA damage for the maintenance of genome stability. Several pathways are available to cells for the repair of DSBs, each of which utilize specific substrates and leave unique genomic scars. As a result, repair pathway selection has wide-ranging consequences for cell and organismal biology. We are interested in how the signaling of DSBs regulates pathway selection and how alterations to these mechanisms can be utilized for therapeutic purposes. Our current projects address the following questions about the connections between damage-induced ubiquitin signaling, genetic and epigenetic states, and the competition between repair pathways:

1) How DNA damage signaling processes are regulated2) How they impact tumorigenesis and therapy response, and3) How they can be exploited as drug targets in different genetic backgrounds


Many DNA damage response proteins are essential for normal development of an organism, however are altered in various cancer subsets. This can provide both a source of genome instability and a potential vulnerability that can be exploited by therapeutics. Homologous recombination (HR) pathway deficiencies resulting from BRCA1 and BRCA2 mutations are well studied examples where mutation carriers have elevated risk of cancer development but extreme sensitivity to DNA damaging agents such as PARP inhibitors. Nevertheless, patient responses vary and tumors develop therapy resistance. In prior work, we showed that HR activity varies among subsets of BRCA1 mutant cancers, and that HR-proficiency is impacted by several factors, including mutation-specific hypomorphic BRCA1 activity and alterations in RNF168-pathway signaling. Our studies expanded on the well-established paradigm that RNF168 ubiquitinates histone H2AX to recruit 53BP1 and inhibit the end resection step of HR. We uncovered a role for RNF168-mediated recruitment of RAD18 to H2AX to repair replication-induced breaks and separately established that RNF168 serves an HR-promoting role by recruiting the BRCA1-P complex through its interaction with BARD1. In recent work, we are studying how genetic or pharmacologic inactivation of DNA damage repair pathways can trigger a dependence on alternative repair mechanisms.

Please visit our lab website to learn more:

Recent Publications

Krais JJ, Wang Y, Patel P, Basu J, Bernhardy AJ, Johnson N.  RNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage. Nature Communications. 2021 Aug 18;12(1):5016. doi: 10.1038/s41467-021-25346-4. PubMed PMID: 34408138.

Krais JJ, Johnson N.  BRCA1 Mutations in Cancer: Coordinating Deficiencies in Homologous Recombination with Tumorigenesis. Cancer Research. 2020 Nov 1;80(21):4601-4609. doi: 10.1158/0008-5472.CAN-20-1830. Epub 2020 Aug 3. Review. PubMed PMID: 32747362.

Krais JJ, Wang Y, Bernhardy AJ, Clausen E, Miller JA, Cai KQ, Scott CL, Johnson N.  RNF168-Mediated Ubiquitin Signaling Inhibits the Viability of BRCA1-Null Cancers. Cancer Research. 2020 Jul 1;80(13):2848-2860. doi: 10.1158/0008-5472.CAN-19-3033. Epub 2020 Mar 25. PubMed PMID: 32213544; PubMed Central PMCID: PMC7335334.

Krais JJ, Johnson N.  Ectopic RNF168 expression promotes break-induced replication-like DNA synthesis at stalled replication forks. Nucleic Acids Research. 2020 May 7;48(8):4298-4308. doi: 10.1093/nar/gkaa154. PubMed PMID: 32182354.

Krais JJ, Virani N, McKernan PH, Nguyen Q, Fung KM, Sikavitsas VI, Kurkjian C, Harrison RG.  Antitumor Synergism and Enhanced Survival with a Tumor Vasculature-Targeted Enzyme Prodrug System, Rapamycin, and Cyclophosphamide. Molecular Cancer Therapeutics. 2017 Sep;16(9):1855-1865. doi: 10.1158/1535-7163.MCT-16-0263. Epub 2017 May 18. PubMed PMID: 28522586.