Jörg Heierhorst
University of Melbourne
GeneInternal medicineDNA repairMutantDNA damageMolecular biologyKinaseChemistrySaccharomyces cerevisiaeCheckpoint Kinase 2Cell cycleG2-M DNA damage checkpointGeneticsDNABiochemistryTranscription factorBiologyCell biologyProtein kinase A
108Publications
29H-index
3,220Citations
Publications 80
Newest
#1Rui Liu (St. Vincent's Institute of Medical Research)H-Index: 14
#2Ashleigh King (St. Vincent's Institute of Medical Research)H-Index: 5
Last. Jörg Heierhorst (St. Vincent's Institute of Medical Research)H-Index: 29
view all 4 authors...
Toll-like receptors (TLRs) and IL-1 receptors regulate immune and inflammatory responses by activating the nuclear factor (NF)-κB pathway. Here we report that B cell-specific loss of Dynein light chain-1 (DYNLL1, LC8) or its designated transcription factor ASCIZ (ATMIN) leads to severely reduced in vivo antibody responses to TLR4-dependent but not T cell-dependent antigens in mice. This defect was independent of DYNLL1's established roles in modulating BIM-dependent apoptosis and 53BP1-dependent...
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#1Diannita Kwang (St. Vincent's Institute of Medical Research)H-Index: 1
Last. Louise E. PurtonH-Index: 29
view all 7 authors...
We have previously shown that mice null for the vitamin A receptor, retinoic acid receptor gamma (Rarg-/- mice) developed a myeloproliferative-like syndrome, accompanied by bone marrow (BM) B lymphopenia and reduced BM erythrocytes, and we have shown that all of these phenotypes were microenvironment-induced. Here, we deleted Rarg in tamoxifen-inducible Cdh5(PAC)CreERT2 (VE-Cadherin)-expressing endothelial cells (ECs) in 3-week old mice and investigated their haematopoiesis and BM niche paramete...
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#1Ashleigh King (St. Vincent's Institute of Medical Research)H-Index: 5
#2Nicolas C. Hoch (St. Vincent's Institute of Medical Research)H-Index: 9
Last. Jörg Heierhorst (St. Vincent's Institute of Medical Research)H-Index: 29
view all 6 authors...
: Mutations in subunits of the cilia-specific cytoplasmic Dynein-2 (CD2) complex cause short-rib thoracic dystrophy syndromes (SRTDs), characterized by impaired bone growth and life-threatening perinatal respiratory complications. Different SRTD mutations result in varying disease severities. It remains unresolved whether this reflects the extent of retained hypomorphic protein functions or relative importance of the affected subunits for the activity of the CD2 holoenzyme. To define the contrib...
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#1Jordan R. Becker (University of Oxford)H-Index: 10
#2Raquel Cuella-Martin (University of Oxford)H-Index: 2
Last. J. Ross Chapman (University of Oxford)H-Index: 21
view all 13 authors...
53BP1 controls a specialized non-homologous end joining (NHEJ) pathway that is essential for adaptive immunity, yet oncogenic in BRCA1 mutant cancers. Intra-chromosomal DNA double-strand break (DSB) joining events during immunoglobulin class switch recombination (CSR) require 53BP1. However, in BRCA1 mutant cells, 53BP1 blocks homologous recombination (HR) and promotes toxic NHEJ, resulting in genomic instability. Here, we identify the protein dimerization hub—DYNLL1—as an organizer of multimeri...
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#1Sarah A. Clark (OSU: Oregon State University)H-Index: 5
#2Janette B. Myers (PSU: Portland State University)H-Index: 6
Last. Elisar Barbar (OSU: Oregon State University)H-Index: 28
view all 9 authors...
Proteins help to regulate almost every process in the body, and come in various forms, sizes and purposes. Cells contain thousands of different proteins, but not every protein is needed at all times. To create new proteins, the information on a gene first needs to be transcribed into RNA (template molecules of the DNA) in a process known as transcription. A complex machinery inside the cell then uses the copy as a template to assemble the protein. So-called transcription factors (also proteins) ...
Source
#1Sarah A. Clark (OSU: Oregon State University)H-Index: 5
#2Janette B. Myers (PSU: Portland State University)H-Index: 6
Last. Elisar Barbar (OSU: Oregon State University)H-Index: 28
view all 9 authors...
Source
#1Rui Liu (St. Vincent's Institute of Medical Research)H-Index: 14
#2Ashleigh King (St. Vincent's Institute of Medical Research)H-Index: 5
Last. Jörg Heierhorst (St. Vincent's Institute of Medical Research)H-Index: 29
view all 6 authors...
The pro-apoptotic BH3-only protein BIM (Bcl2l11) plays key roles in the maintenance of multiple hematopoietic cell types. In mice, germline knockout or conditional pan-hematopoietic deletion of Bim results in marked splenomegaly and significantly increased numbers of B cells. However, it has remained unclear whether these abnormalities reflect the loss of cell-intrinsic functions of BIM within the B lymphoid lineage and, if so, which stages in the lifecycle of B cells are most impacted by the lo...
Source
#1Ashleigh King (St. Vincent's Institute of Medical Research)H-Index: 5
#2Lingli Li (St. Vincent's Institute of Medical Research)H-Index: 2
Last. Jörg Heierhorst (St. Vincent's Institute of Medical Research)H-Index: 29
view all 8 authors...
Mechanistic differences in the development and function of adaptive, high-affinity antibody-producing B-2 cells and innate-like, “natural” antibody-producing B-1a cells remain poorly understood. Here we show that the multi-functional dynein light chain (DYNLL1/LC8) plays important roles in the establishment of B-1a cells in the peritoneal cavity and in the ongoing development of B-2 lymphoid cells in the bone marrow of mice. Epistasis analyses indicate that Dynll1 regulates B-1a and early B-2 ce...
Source
#1Rui Liu (St. Vincent's Institute of Medical Research)H-Index: 14
#2Ashleigh King (St. Vincent's Institute of Medical Research)H-Index: 5
Last. Jörg Heierhorst (St. Vincent's Institute of Medical Research)H-Index: 29
view all 7 authors...
Abstract The ATM kinase plays critical roles in the response to DNA double-strand breaks, and can also be activated by prolonged DNA replication blocks. It has recently been proposed that replication stress-dependent ATM activation is mediated by ASCIZ (also known as ATMIN, ZNF822), an essential developmental transcription factor. In contrast, we show here that ATM activation, and phosphorylation of its substrates KAP1, p53 and H2AX in response to the replication blocking agent aphidicolin was u...
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#1Sylvie van Twest (St. Vincent's Institute of Medical Research)H-Index: 5
#2Vincent J. Murphy (St. Vincent's Institute of Medical Research)H-Index: 7
Last. Andrew J. Deans (St. Vincent's Institute of Medical Research)H-Index: 21
view all 9 authors...
Summary Monoubiquitination and deubiquitination of FANCD2:FANCI heterodimer is central to DNA repair in a pathway that is defective in the cancer predisposition syndrome Fanconi anemia (FA). The "FA core complex" contains the RING-E3 ligase FANCL and seven other essential proteins that are mutated in various FA subtypes. Here, we purified recombinant FA core complex to reveal the function of these other proteins. The complex contains two spatially separate FANCL molecules that are dimerized by F...
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