A5025654622- Mitochondrial Function and Pathology
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Metabolism and Genetic Disorders
- Advanced biosensing and bioanalysis techniques
- Breast Cancer Treatment Studies
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Advanced Breast Cancer Therapies
- Autophagy in Disease and Therapy
- HER2/EGFR in Cancer Research
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- DNA and Nucleic Acid Chemistry
- Genetics, Aging, and Longevity in Model Organisms
- Fungal and yeast genetics research
- Genetics and Neurodevelopmental Disorders
- Neurogenetic and Muscular Disorders Research
- Cardiac Ischemia and Reperfusion
University of Alberta
2019-2024
University of Bristol
2017-2022
Vanderbilt University Medical Center
2022
Comprehensive Blood & Cancer Center
2014-2021
University of Washington
2015-2018
Fred Hutch Cancer Center
2015-2018
Bloomberg (United States)
2017
Johns Hopkins Children's Center
2017
Children's Hospital of Philadelphia
2017
Johns Hopkins University
2017
Abstract Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast NANOG , SNAIL NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), translation subset these stimulated under hypoxia. The accumulation the corresponding proteins induces plasticity “fate-switching” toward stem cell-like phenotypes....
The purpose of the NBRST study is to compare a multigene classifier conventional immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) subtyping predict chemosensitivity as defined by pathological complete response (pCR) or endocrine sensitivity partial response.The includes women with histologically proven breast cancer, who will receive neoadjuvant chemotherapy (NCT) therapy. BluePrint combination MammaPrint classifies patients into four molecular subgroups: Luminal A, B,...
Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas12a is widely used for genome editing and diagnostics, so it important to understand how RNA-guided DNA recognition activates the cleavage of target strand (TS) following non-target-strand (NTS) cleavage. Here we single-molecule magnetic tweezers, gel-based assays nanopore sequencing explore unwinding In addition dynamic heterogenous R-loop formation, also directly observed transient double-stranded downstream...
Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of (origins). Prior to S phase, are poised initiate by recruitment pre-replicative complex (pre-RC). For proper occur, origin activation must be tightly regulated. At population level, each has a distinct firing time and frequency within phase. Many studies have shown that chromatin can strongly influence initiation replication. However, parameters affect properties not been thoroughly...
Abstract In the budding yeast Saccharomyces cerevisiae, ribosomal RNA genes are encoded in a highly repetitive tandem array referred to as DNA (rDNA) locus. The rDNA is site of diverse set DNA-dependent processes, including transcription RNAs by polymerases I and III, noncoding polymerase II, replication initiation, fork blocking, recombination-mediated regulation repeat copy number. All this takes place context chromatin, but little known about roles played ATP-dependent chromatin...
Interruption of blood supply to the heart is a leading cause death and disability. However, molecular events that occur during ischemia, how these changes prime consequent cell upon reperfusion, are poorly understood. Protein SUMOylation post-translational modification has been strongly implicated in protection cells against variety stressors, including ischemia-reperfusion. In particular, SUMO2/3-specific protease SENP3 emerged as an important determinant survival after ischemic infarct....
Abstract When cells undergo replication stress, proper checkpoint activation and deactivation are critical for genomic stability cell survival therefore must be highly regulated. Although mechanisms of well studied, far less understood. Previously, we reported that chromatin remodeling factors Isw2 Ino80 attenuate the S-phase activity in Saccharomyces cerevisiae, especially during recovery from hydroxyurea. In this study, found have a more pronounced role attenuating late S phase presence...
Increased post-translational modification of proteins by SUMO-2/3 is a cytoprotective response against cell stress induced ischaemia and reperfusion. However, it still unclear what other stressors trigger protein SUMOylation, mechanisms enhance maintain the enhanced if general protective mediator cytotoxic stresses. Here, we show increased levels SUMOylation decreased SUMO deconjugating enzyme SENP3 in PC12 cells treated with toxic heavy metal cadmium. In addition, knockdown reduced...
The mitochondrial outer membrane protein Mitochondrial Fission Factor (Mff) plays a key role in both physiological and pathological fission. It is well established that at stressed or functionally impaired mitochondria, PINK1 recruits the ubiquitin ligase Parkin which ubiquitinates Mff other proteins to facilitate removal of defective mitochondria maintain integrity network. Here we show that, addition this clearance pathway, also PINK1-dependent manner under non-stressed conditions regulate...
Although neocortical neuronal morphology has been documented in the adult giraffe (Giraffa camelopardalis tippelskirchi) and African elephant (Loxodonta africana), no research explored cortical architecture newborns of these species. To this end, current study examined neurons from several areas newborn elephant. After were stained with a modified Golgi technique (N = 153), dendritic branching spine distributions analyzed by using computer-assisted morphometry. The results showed that...
We previously demonstrated that hexokinase II (HK2) dissociation from mitochondria during cardiac ischemia correlates with cytochrome c (cyt-c) loss, oxidative stress and subsequent reperfusion injury. However, whether HK2 release is the primary signal mediating this ischemia-induced mitochondrial dysfunction was not established. To investigate this, we studied effects of dissociating isolated heart mitochondria. Mitochondria Langendorff-perfused rat hearts before after 30 min global ±...
Abstract Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast NANOG , SNAIL NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), translation subset these stimulated under hypoxia. This leads to accumulation corresponding proteins which induce plasticity “fate-switching” toward stem-cell like phenotypes....
Abstract Background: MammaPrint (MP) is used to identify breast cancer (BC) patients who can safely forego adjuvant chemotherapy. MP combined with the BluePrint (BP) molecular subtyping signature identifies BC subtypes distinct therapeutic response rates and survival outcomes. In Neoadjuvant Breast Symphony Trial (NBRST), BP (MP/BP) predicted of pathologic complete neoadjuvant chemotherapy (NCT) partial endocrine therapy (NET). Here, we report 5-year overall (OS) distant metastasis-free...
TNF-alpha is a physiological regulator of mammary gland development that stimulates the growth both normal and malignant epithelial cells in primary culture inhibits functional differentiation. To understand how TNF exerts its effects, current study examined mechanism by which down-regulates expression beta-casein whey acidic protein (WAP) genes. treatment markedly decreased activity WAP promoters transiently transfected HC11 cells. Overexpression nuclear factor-kappaB (NFkappaB) p50 and/or...
Abstract Mapping the precise position of DNA cleavage events plays a key role in determining mechanism and function endonucleases. ENDO-Pore is high-throughput nanopore-based method that allows time resolved mapping single molecule vitro. Following linearisation circular substrate by endonuclease, resistance cassette ligated recording event. A library constructed subjected to rolling circle amplification generate concatemers. These are sequenced used produce accurate consensus sequences. To...
Abstract Adaptation to hypoxia enhances cancer cell malignancy and negatively impacts patient outcomes. Reprogramming of mRNA translation is an essential component the hypoxia-adaptive response. During hypoxia, cells undergo a global decrease in protein synthesis. However, subsets transcripts encoding stress-response, survival stemness factors increased. This selective regulation thought be governed largely via interactions between specific features remodeling translational apparatus. our...
Abstract Interruption of blood supply to the heart is a leading cause death and disability. However, molecular events that occur during ischaemia, how these changes prime consequent cell upon reperfusion, are poorly understood. Protein SUMOylation post-translational modification has been strongly implicated in protection cells against variety stressors, including ischaemia-reperfusion. In particular, SUMO2/3-specific protease SENP3 emerged as an important determinant survival after ischaemic...
SUMMARY Adaptation to stresses entails coordination of transcriptional and post-transcriptional gene regulation, but the mechanisms remain largely unknown. We interrogated effects hypoxia on transcriptomes, epigenomes translatomes T47D breast cancer cells H9 human embryonic stem cells. This revealed hypoxia-induced alterations in H3K4me3 associating with pervasive changes transcription start site (TSS) selection, leading 5’UTR remodeling a concomitant reshaping translational landscapes....
Woods-Hill, Charlotte; Fackler, James; Lee, Laura; Smith, Michelle; Xie, Anping; King, Anne; Colantuoni, Elizabeth; Voskertchian, Annie; Milstone, Aaron Author Information
Abstract The mitochondrial outer membrane protein Mitochondrial Fission Factor (Mff) plays a key role in both physiological and pathological fission. It is well established that stressed or functionally impaired mitochondria the PINK1 recruits ubiquitin ligase Parkin which ubiquitinates Mff to facilitate removal of defective maintain integrity network. Here we show that, addition this clearance pathway, also PINK1-dependent manner under basal, non-stressed conditions regulate constitutive...