Genome Stability Lab (GSL)
Research in the group aims to better understand how cells maintain stable genomes and how genomically instable cancers can be detected and targeted in novel ways. Specifically, we are working on the following topics that in the longer term have potential to lead to improved strategies of preventing and treating diseases of unmet need.
1. How do ubiquitylation pathways regulate the DNA damage response and associated processes? To address this question we are integrating cell biology, biochemistry, bioinformatics and high through-put/high-content quantitative microscopy/microarray techniques. The importance of ubiquitylation and DNA damage response pathways is illustrated by the fact that a declining ubiquitin system and accumulating DNA damage can give rise to various human disorders such as cancer and neurodegenerative diseases.
2. Ovarian cancer displays rampant genomic instability and has low long-term survival rates with less than 30 percent of women outliving the disease for more than ten years. This is mainly due to a lack of early detection methods. We are integrating cutting-edge nanotechnology, cell biology, molecular biology, biochemistry and advanced microscopy methods to develop innovative bio-hybrid drug-delivery vehicles to detect and target the disease earlier.
Xu H, Medina-Sanchez M$, Brison DR, Edmondson RJ, Taylor SS, Nelson L, Zeng K, Bagley S, Ribeiro C, Restrepo LP, Lucena E, Schmidt CK$, Schmidt OG$. Human spermbots for cancer-relevant drug delivery. arXiv (2019) 1904.12684. http://arxiv.org/abs/1904.12684. $Co-corresponding authors
van den Tempel N, Zelensky AN, Odijk H, Laffeber C, Schmidt CK, Brandsma I, Demmers J, Krawczyk PM, Kanaar R. On the mechanism of hyperthermia-induced BRCA2 protein degradation. Cancers (2019)
11: 97 (doi: 10.3390/cancers11010097).
Cabello-Lobato MJ, Wang S, Schmidt CK. SAMHD1 sheds moonlight on DNA double-strand break repair. Trends Genetics (2017) 12: 895-897.
Xi W$, Schmidt CK$, Sanchez S, Gracias DH, Carazo-Salas RE, Butler R, Lawrence N, Jackson SP, and Schmidt OG. Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes. ACS Nano (2016) 10: 5835–5846. $Co-corresponding authors; highlighted in acs.org (ACS, June 2016) and sciencenews.org (Sciencenews, June 2016).
Schmidt CK$, Galanty Y$, Sczaniecka-Clift M, Coates J, Jhujh S, Demir M, Jackson SP. Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair. Nature Cell Biology (2015) 17: 1458-1470. $Co-first authors
Aymard F, Bugler B, Schmidt CK, Guillou E, Caron P, Briois S, Iacovoni JS, Daburon V, Miller KM, Jackson SP et al. Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks. Nat Struct Mol Biol (2014) 21: 366–374.
Knobel PA, Belotserkovskaya R, Galanty Y, Schmidt CK, Jackson SP, Stracker TH. USP28 is recruited to sites of DNA damage by the tandem BRCT domains of 53BP1 but plays a minor role in double-strand break metabolism. Mol Cell Biol (2014) 34: 2062–2074.
Xi W, Schmidt CK$, Sanchez S$, Gracias DH, Carazo-Salas RE, Jackson SP, Schmidt OG. Rolled-up Functionalized Nanomembranes as Three-Dimensional Cavities for Single Cell Studies. Nano Letters (2014) 14: 4197–4204. $Co-corresponding authors (Impact Factor: 13; Top 4 Nanoscience & Nanotechnology Journal by Impact Factor); featured as front cover image (Cover Art).
Koch B, Sanchez S$, Schmidt CK$, Swiersy A, Jackson SP, Schmidt OG. Confinement and Deformation of Single Cells and Their Nuclei Inside Size-Adapted Microtubes. Adv Healthc Mater (2014) 3: 1753–1758. $Co-corresponding authors; featured as back cover image.
Roukos V, Voss TC, Schmidt CK, Lee S, Wangsa D, Misteli T. Spatial dynamics of chromosome translocations in living cells. Science (2013) 341: 660–664.
Schmidt CK and Jackson SP. On your MARK, get SET(D2), go! H3K36me3 primes DNA mismatch repair. Cell (2013) 153: 513-515.
Smith EJ, Xi W, Makarov D, Monch I, Harazim S, Quinones VAB, Schmidt CK, Mei YF, Sanchez S, Schmidt OG. Lab-in-a-tube: ultracompact components for on-chip capture and detection of individual micro-/nanoorganisms. Lab Chip (2012) 12: 1917-1931.
Harazim SM, Xi W, Schmidt CK, Sanchez S, Schmidt OG. Fabrication and applications of large arrays of multifunctional rolled-up SiO/SiO2 microtubes. J Mater Chem (2012) 22: 2878-2884.
Schneede A, Schmidt CK, Holtta-Vuori M, Heeren J, Willenborg M, Blanz J, Domanskyy M, Breiden B, Brodesser S, Landgrebe J et al. Role for LAMP-2 in endosomal cholesterol transport. J Cell Mol Med (2011) 15: 280-295.
Roukos V, Misteli T, Schmidt CK. Descriptive no more: the dawn of high-throughput microscopy. Trends Cell Biol (2010) 20: 503-506.
Schulze S, Huang GS, Krause M, Aubyn D, Quinones VAB, Schmidt CK$, Mei YF$, Schmidt OG. Morphological Differentiation of Neurons on Microtopographic Substrates Fabricated by Rolled-Up Nanotechnology. Adv Eng Mater (2010) 12: B558-B564. $Co-corresponding authors
Schmidt CK, Brookes N, Uhlmann F. Conserved features of cohesin binding along fission yeast chromosomes. Genome Biol (2009) 10: R52.
Bernard P$, Schmidt CK$, Vaur S$, Dheur S, Drogat J, Genier S, Ekwall K, Uhlmann F, Javerzat JP. Cell-cycle regulation of cohesin stability along fission yeast chromosomes. Embo J (2008) 27: 111-121 $Co-first authors
D'Ambrosio C, Schmidt CK, Katou Y, Kelly G, Itoh T, Shirahige K, Uhlmann F. Identification of cis-acting sites for condensin loading onto budding yeast chromosomes. Genes Dev (2008) 22: 2215-2227.
Willenborg M, Schmidt CK, Braun P, Landgrebe J, von Figura K, Saftig P, Eskelinen, E-L. Mannose 6-phosphate receptors, Niemann-Pick C2 protein, and lysosomal cholesterol accumulation. J Lipid Res (2005) 46: 2559–2569.
Eskelinen E$, Schmidt CK$, Neu S, Willenborg M, Fuertes G, Salvador N, Tanaka Y, Lüllmann-Rauch R, Hartmann D, Heeren J et al. Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts. Mol Biol Cell (2004) 15: 3132–3145. $Co-first authors