Nima Mosammaparast, MD, PhD


N MosammaparastI am an Iranian-American physician-scientist, with an interest in genomic stability, cell signaling, and how we can apply our understanding of these cellular mechanisms to improve cancer therapy responses. As an undergraduate at the University of Rochester, I initially thought I would become an engineer, but a class in biochemistry fascinated me and changed my career trajectory. Studying under David Goldfarb and David Hinkle, I became enthralled with using genetically tractable systems to study nuclear processes, particularly DNA repair. Thereafter, I obtained my MD and PhD degrees from the University of Virginia, where I studied the mechanisms of histone nuclear import and chromatin assembly with Lucy Pemberton. In 2006, I moved to Boston for residency training in pathology at Brigham & Women’s Hospital, where I also did a post-doc in Yang Shi’s lab at Boston Children’s Hospital, Harvard Medical School. I focused on chromatin associated factors in the DNA damage response, and also moonlighted as an attending physician in the Infectious Disease Diagnostics Laboratory at Boston Children’s Hospital.

I moved to Washington University in 2012 to set up my own lab in the department of Pathology and Immunology. When not thinking about science, I enjoy cooking, biking, running, and spending time with my wife, Sara, and my daughter, Ida.


 The focus of genomic integrity has naturally been on how DNA is replicated and repaired. While most of the machinery that performs these functions are well-understood, how the cell “knows” which repair pathway to activate when it encounters a specific form of DNA damage is quite unexplored. This was highlighted with our group’s discovery of the first signaling pathway that is activated in human cells specifically with base alkylating agents (Brickner et al., Nature, 2017; see Figure 1). Since this discovery, our primary focus has been to understand how this pathway integrates with other cellular processes, such as inflammatory signaling (Zhao et al., Molecular Cell, 2018). It has become clear that this pathway sits at the interface between DNA and RNA damage, highlighting the role that RNA damage during transcription may play in signaling DNA repair (Soll et al., J. Biol. Chem., 2018; Brickner & Tsao et al., Molecular Cell, under revision; see Figure 1). This has led us to propose that RNA, being much more abundant that DNA, may serve as the “canary in the coal mine” to promote genomic maintenance (see Figure 2).

Beyond this major focus of the lab, we are involved in a number of projects with other groups at the Center for Genomic Integrity. For example, we have a long-standing collaboration with the Vindigni lab focusing on uncovering novel factors that regulate DNA replication and repair (Byrum and Carvajal et al., J Cell Biol., 2019; Byrum et al., Trends Cell Biol., 2019). We are also actively developing novel technologies to detect and quantify various DNA lesions and other markers of genomic damage, using ultra-high sensitive mass spectrometry and other cutting-edge methods.

Figure 1 (cgi Website)a
Figure 1. Model for the recruitment of the ASCC-ALKBH3 DNA repair complex. Our work suggests that the signal for its activation and recruitment, which relies on the E3 ligase RNF113A, is damage to newly transcribed RNA.
Figure 2 (cgi Website)
Figure 2. Our work suggests that RNA damage may have a signaling function in the cell, acting as the “canary in the coal mine” to activate DNA repair.


Lab website:

Recent publications

Zhao Y, Majid MC, Soll JM, Brickner JB, Dango S, Mosammaparast N. Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase.

EMBO Journal. 2015;1687-703.

Brickner JB, Soll JM, Lombardi PM, Vagbo CB, Mudge MC, Oyeniran C, Rabe R, Jackson J, Sullender ME, Blazosky E, Byrum AK, Zhao Y, Corbett MA, Gecz J, Field M, Vindigni A, Slupphaug G, Wolberger C, Mosammaparast N. A ubiquitin-dependent signaling axis specific for ALKBH-mediated DNA dealkylation repair.

Nature. 2017; 551:389-393.

Soll JM, Brickner JB, Mudge MC, Mosammaparast N. Regulation of the ALKBH3-ASCC alkylation repair complex by the accessory subunit ASCC1.

J. Biol Chem. 2018; 293:13524-13533.

Byrum AK, Carvajal DC, Mudge MC, Patel R, Sowa ME, Gygi S, Harper JW, Shi Y, Vindigni A, Mosammaparast N. TPX2/Aurora-A promote replication fork stability and DNA end resection via negative regulation of 53BP1. (*co-corresponding authors)

J Cell Biol. – 2019; 218:422-432.

Byrum AK, Vindigni A, Mosammaparast N. Defining and modulating ‘BRCAness’.

Trends Cell Biol. 2019; 29:740-751.

Tsao N, Brickner JR, Rodell R, Ganguly A, Wood M, Oyeniran C, Ahmad T, Sun H, Bacolla A, Zhang L, Lukinovic V, Soll JM, Casanova AG, Tainer JA, Vindigni A, He C, Reynoird N, Mosammaparast N. Aberrant RNA methylation triggers recruitment of an alkylation repair complex.

Molecular Cell. 2021; 81:4228-4242.

Ashour ME, Mosammaparast N. Mechanisms of damage tolerance and repair during DNA replication.

Nucleic Acids Res. 2021; 49:3033-3047.

Lukinovic V, Tsao N, Oyeniran C, Brickner JR, Roth GS, Casanova AG, Vayr J, Couté Y, Jansen P, Vermeulen M, Hainaut P, Mazur PK*, Mosammaparast N*, Reynoird N*. SMYD3 regulates a methylation-phosphorylation switch on the RNF113A E3 ligase to promote alkylation damage resistance.
(*co-corresponding authors)

Cancer Discovery. 2022; 12:2158-2179.

Townley BA, Beurer JL, Tsao N, Bacolla A, Rusanov T, Schmidt N, Srivatsan S, Clark N, Brickner JR, Tsai MS, Walter M, Holehouse A, Tainer JA, Fairbrother W, Mosammaparast N. A functional link between lariat debranching enzyme and the intron binding complex is defective in non-photosensitive trichothiodystrophy.

Molecular Cell. 2023; doi: 10.1016/j.molcel.2023.06.011.

Buerer L, Duan D, Clark NE, Rong S, Welch A, Townley BA, Taggart AJ, Wang J, Soemedi R, Lin CL, Zeng Y, Katolik A, Staley JP, Damha MJ, Mosammaparast N, Fairbrother WG. The RNA debranching enzyme Dbr1 regulates lariat turnover and intron splicing.

Nature Communications. 2023; (in revision)