Joshua Heyza
Assistant Professor of Environmental Health Sciences and of Pharmacology
Joshua Heyza
Biography
The Heyza lab uses innovative genome-editing and live-cell imaging techniques to study the molecular mechanisms responsible to maintain genome stability in human cells.
The genomes of all organisms are constantly damaged as result of exposure to endogenous and exogenous chemicals and as part of critical cellular and organismal processes (e.g. DNA replication, meiotic recombination, somatic hypermutation, class-switch recombination, etc.). DNA double-strand breaks (DSBs) are lesions that physically disrupt the continuity of the DNA double helix and are widely considered to be the most toxic form of DNA damage occurring in cells.
DSBs pose dangerous threats to genomic integrity because they can lead to loss of genetic information if unrepaired or repaired improperly. For this reason, eukaryotic cells evolved a set of complex and tightly regulated pathways to repair these DNA lesions. Highlighting the importance of these pathways for human health, a diverse set of pathologies are linked to mutations in genes encoding DSB repair proteins, including immunodeficiencies, neurological diseases, and cancers.
Therefore, uncovering the mechanisms by which cells maintain their genomic integrity is critically important to understand how defects in DNA repair contribute to the etiology of disease. In addition, advancing our understanding of mechanisms of DSB repair will guide current and future development and implementation of therapeutics that depend upon particular DSB repair pathways for efficacy.
For more information, visit: www.jheyzalab.com
Training
Postdoc, Jens Schmidt lab, Michigan State University, 2019-2025
Education
B.S. Biology, University of Michigan-Flint, 2014
Ph.D. Cancer Biology, Wayne State University School of Medicine, 2019
Areas of Expertise
DNA double-strand break repair, Mitotic DNA repair mechanisms, Genome-editing, Genome-wide CRISPR Screens, Fluorescence microscopy, Live-cell single-molecule imaging
Publications
Joshua R Heyza, Mariia Mikhova, Gloria I Perez, David G Broadbent, Jens Christopher Schmidt. The PST repeat region of MDC1 is a tunable multivalent chromatin tethering domain. bioRxiv 2025.01.10.632395
Mashayekhi F, Ganje C, Caron MC, Heyza JR, Gao Y, Zeinali E, Fanta M, Li L, Ali J, Mersaoui SY, Schmidt JC, Godbout R, Masson JY, Weinfeld M, Ismail IH. PNKP safeguards stalled replication forks from nuclease-dependent degradation during replication stress. Cell Rep. 2024 Dec 24;43(12):115066.
Mikhova M, Goff NJ, Janovič T, Heyza JR, Meek K, Schmidt JC. Single-molecule imaging reveals the kinetics of non-homologous end-joining in living cells. Nat Commun. 2024 Nov 23;15(1):10159.
Heyza JR*, Mikhova M*, Schmidt JC. Live cell single-molecule imaging to study DNA repair in human cells. DNA Repair (Amst). 2023 Sep;129:103540. *Denotes co-first authors
Brambati A, Sacco O, Porcella S, Heyza J, Kareh M, Schmidt JC, Sfeir A. RHINO directs MMEJ to repair DNA breaks in mitosis. Science. 2023 Aug 11;381(6658):653-660.
Heyza JR, Mikhova M, Bahl A, Broadbent DG, Schmidt JC. Systematic analysis of the molecular and biophysical properties of key DNA damage response factors. Elife. 2023 Jun 21;12:e87086.
Heyza JR, Ekinci E, Lindquist J, Lei W, Yunker C, Vinothkumar V, Rowbotham R, Polin L, Snider NG, Van Buren E, Watza D, Back JB, Chen W, Mamdani H, Schwartz AG, Turchi JJ, Bepler G, Patrick SM. ATR inhibition overcomes platinum tolerance associated with ERCC1- and p53-deficiency by inducing replication catastrophe. NAR Cancer. 2023 Jan 11;5(1):zcac045.
Hu C, Zhang M, Moses N, Hu CL, Polin L, Chen W, Jang H, Heyza J, Malysa A, Caruso JA, Xiang S, Patrick S, Stemmer P, Lou Z, Bai W, Wang C, Bepler G, Zhang XM. The USP10-HDAC6 axis confers cisplatin resistance in non-small cell lung cancer lacking wild-type p53. Cell Death Dis. 2020 May 7;11(5):328.
Heyza JR, Lei W, Watza D, Zhang H, Chen W, Back JB, Schwartz AG, Bepler G, Patrick SM. Identification and Characterization of Synthetic Viability with ERCC1 Deficiency in Response to Interstrand Crosslinks in Lung Cancer. Clin Cancer Res. 2019 Apr 15;25(8):2523-2536.
For a full list of publications, visit Pubmed