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JOURNAL ARTICLE
Agata Gruszczynska, Abhishek Maiti, Christopher A Miller, Sai Mukund Ramakrishnan, Daniel C Link, Geoffrey L Uy, Allegra A Petti, Kala Hayes, Courtney D DiNardo, Farhad Ravandi, Timothy J Ley, David H Spencer, Feng Gao, Marina Y Konopleva, John S Welch
Not available.
April 11, 2024: Haematologica
#2
JOURNAL ARTICLE
Yang Li, Haley J Abel, Michelle Cai, Taylor A LaValle, Tiankai Yin, Nichole M Helton, Amanda M Smith, Christopher A Miller, Timothy J Ley
Here, we characterize the DNA methylation phenotypes of bone marrow cells from mice with hematopoietic deficiency of Dnmt3a or Dnmt3b (or both enzymes) or expressing the dominant-negative Dnmt3a R878H mutation [R882H in humans; the most common DNMT3A mutation found in acute myeloid leukemia (AML)]. Using these cells as substrates, we defined DNA remethylation after overexpressing wild-type (WT) DNMT3A1, DNMT3B1, DNMT3B3 (an inactive splice isoform of DNMT3B), or DNMT3L (a catalytically inactive "chaperone" for DNMT3A and DNMT3B in early embryogenesis)...
February 2, 2024: Science Advances
#3
JOURNAL ARTICLE
Robert W Sprung, Qiang Zhang, Michael H Kramer, Matthew C Christopher, Petra Erdmann-Gilmore, Yiling Mi, James P Malone, Timothy J Ley, R Reid Townsend
Previous work has shown that inhibition of abundant myeloid azurophil granule-associated serine proteases (ELANE, PRTN3, CTSG, and NSP4) is required to stabilize some proteins in myeloid cells. We therefore hypothesized that effective inhibition of these proteases may be necessary for mass-spectrometry based proteomics of samples containing myeloid cells. To test this hypothesis, we thawed viably preserved acute myeloid leukemia (AML) cells from cryovials in the presence or absence of diisopropyl flurophosphate (DFP), a cell-permeable, irreversible serine protease inhibitor...
January 12, 2024: Molecular & Cellular Proteomics: MCP
#4
JOURNAL ARTICLE
Ryan B Day, Julia A Hickman, Ziheng Xu, Casey Ds Katerndahl, Francesca Ferraro, Sai Mukund Ramakrishnan, Petra Erdmann-Gilmore, Robert W Sprung, Yiling Mi, R Reid Townsend, Christopher A Miller, Timothy J Ley
Several canonical translocations produce oncofusion genes that can initiate Acute Myeloid Leukemia (AML). Although each translocation is associated with unique features, the mechanisms responsible remain unclear. While proteins interacting with each oncofusion are known to be relevant for how they act, these interactions have not yet been systematically defined. To address this issue in an unbiased fashion, we fused a promiscuous biotin ligase ("TurboID") in-frame with three favorable-risk acute myeloid leukemia (AML) oncofusion cDNAs (PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11), and identified their interacting proteins in primary murine hematopoietic cells...
December 7, 2023: Journal of Clinical Investigation
#5
REVIEW
Aránzazu Manzano, Silvio Weging, Daniela Bezdan, Joseph Borg, Thomas Cahill, Eugénie Carnero-Diaz, Henry Cope, Colleen S Deane, Timothy Etheridge, Stefania Giacomello, Gary Hardiman, Natalie Leys, Pedro Madrigal, Felice Mastroleo, F Javier Medina, Jakub Mieczkowski, Manuel A Fernandez-Rojo, Keith Siew, Nathaniel J Szewczyk, Stephen B Walsh, Willian A da Silveira, Raúl Herranz
Following on from the NASA twins' study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA's GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research...
September 15, 2023: IScience
#6
JOURNAL ARTICLE
Haley J Abel, Karolyn A Oetjen, Christopher A Miller, Sai M Ramakrishnan, Ryan B Day, Nichole M Helton, Catrina C Fronick, Robert S Fulton, Sharon E Heath, Stefan P Tarnawsky, Sridhar Nonavinkere Srivatsan, Eric J Duncavage, Molly C Schroeder, Jacqueline E Payton, David H Spencer, Matthew J Walter, Peter Westervelt, John F DiPersio, Timothy J Ley, Daniel C Link
TP53-mutated myeloid malignancies are associated with complex cytogenetics and extensive structural variants, which complicates detailed genomic analysis by conventional clinical techniques. We performed whole genome sequencing (WGS) of 42 AML/MDS cases with paired normal tissue to better characterize the genomic landscape of TP53-mutated AML/MDS. WGS accurately determines TP53 allele status, a key prognostic factor, resulting in the reclassification of 12% of cases from mono-allelic to multi-hit. Although aneuploidy and chromothripsis are shared with most TP53-mutated cancers, the specific chromosome abnormalities are distinct to each cancer type, suggesting a dependence on the tissue of origin...
June 20, 2023: Blood Advances
#7
JOURNAL ARTICLE
David Y Chen, Leslie A Sutton, Sai Mukund Ramakrishnan, Eric J Duncavage, Sharon E Heath, Leigh A Compton, Christopher A Miller, Timothy J Ley
Alterations in epigenetic regulators are increasingly recognized as early events in tumorigenesis; thus, patients with acquired or inherited variants in epigenetic regulators may be at increased risk for developing multiple types of cancer. DNMT3A overgrowth syndrome (DOS), caused by germline pathogenic variants in the DNA methyltransferase gene DNMT3A , has been associated with a predisposition toward development of hematopoietic and neuronal malignancies. DNMT3A deficiency has been described to promote keratinocyte proliferation in mice...
April 2023: Cold Spring Harbor Molecular Case Studies
#8
JOURNAL ARTICLE
Michael J Slade, Reza Ghasemi, Michelle O'Laughlin, Tasha Burton, Robert S Fulton, Haley J Abel, Eric J Duncavage, Timothy J Ley, Meagan A Jacoby, David H Spencer
PURPOSE: Persistent molecular disease (PMD) after induction chemotherapy predicts relapse in AML. In this study, we used whole-exome sequencing (WES) and targeted error-corrected sequencing to assess the frequency and mutational patterns of PMD in 30 patients with AML. MATERIALS AND METHODS: The study cohort included 30 patients with adult AML younger than 65 years who were uniformly treated with standard induction chemotherapy. Tumor/normal WES was performed for all patients at presentation...
April 2023: JCO Precision Oncology
#9
JOURNAL ARTICLE
Lyn Ley Lam, Nick Pavlakis, Kohei Shitara, Katrin M Sjoquist, Andrew J Martin, Sonia Yip, Yoon-Koo Kang, Yung-Jue Bang, Li-Tzong Chen, Markus Moehler, Tanios Bekaii-Saab, Thierry Alcindor, Christopher J O'Callaghan, Niall C Tebbutt, Wendy Hague, Howard Chan, Sun Young Rha, Keun-Wook Lee, Val Gebski, Anthony Jaworski, John Zalcberg, Timothy Price, John Simes, David Goldstein
BACKGROUND: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases. Regorafenib 160 mg daily prolonged progression free survival compared to placebo (INTEGRATE, phase 2). Regorafenib 80 mg daily in combination with nivolumab 3 mg/kg showed promising objective response rates (REGONIVO)...
February 22, 2023: BMC Cancer
#10
Haley J Abel, Karolyn A Oetjen, Christopher A Miller, Sai M Ramakrishnan, Ryan B Day, Nichole M Helton, Catrina C Fronick, Robert S Fulton, Sharon E Heath, Stefan P Tarnawsky, Sridhar Nonavinkere Srivatsan, Eric J Duncavage, Molly C Schroeder, Jacqueline E Payton, David H Spencer, Matthew J Walter, Peter Westervelt, John F DiPersio, Timothy J Ley, Daniel C Link
UNLABELLED: TP53 -mutated myeloid malignancies are most frequently associated with complex cytogenetics. The presence of complex and extensive structural variants complicates detailed genomic analysis by conventional clinical techniques. We performed whole genome sequencing of 42 AML/MDS cases with paired normal tissue to characterize the genomic landscape of TP53 -mutated myeloid malignancies. The vast majority of cases had multi-hit involvement at the TP53 genetic locus (94%), as well as aneuploidy and chromothripsis...
January 11, 2023: medRxiv
#11
JOURNAL ARTICLE
Hidayat Trimarsanto, Roberto Amato, Richard D Pearson, Edwin Sutanto, Rintis Noviyanti, Leily Trianty, Jutta Marfurt, Zuleima Pava, Diego F Echeverry, Tatiana M Lopera-Mesa, Lidia M Montenegro, Alberto Tobón-Castaño, Matthew J Grigg, Bridget Barber, Timothy William, Nicholas M Anstey, Sisay Getachew, Beyene Petros, Abraham Aseffa, Ashenafi Assefa, Awab G Rahim, Nguyen H Chau, Tran T Hien, Mohammad S Alam, Wasif A Khan, Benedikt Ley, Kamala Thriemer, Sonam Wangchuck, Yaghoob Hamedi, Ishag Adam, Yaobao Liu, Qi Gao, Kanlaya Sriprawat, Marcelo U Ferreira, Moses Laman, Alyssa Barry, Ivo Mueller, Marcus V G Lacerda, Alejandro Llanos-Cuentas, Srivicha Krudsood, Chanthap Lon, Rezika Mohammed, Daniel Yilma, Dhelio B Pereira, Fe E J Espino, Cindy S Chu, Iván D Vélez, Chayadol Namaik-Larp, Maria F Villegas, Justin A Green, Gavin Koh, Julian C Rayner, Eleanor Drury, Sónia Gonçalves, Victoria Simpson, Olivo Miotto, Alistair Miles, Nicholas J White, Francois Nosten, Dominic P Kwiatkowski, Ric N Price, Sarah Auburn
Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection's country of origin...
December 23, 2022: Communications Biology
#12
JOURNAL ARTICLE
Ian J Saldanha, Gaelen P Adam, Lionel L Bañez, Eric B Bass, Elise Berliner, Beth Devine, Noah Hammarlund, Anjali Jain, Susan L Norris, Andrea C Skelly, Kelly Vander Ley, Zhen Wang, Timothy J Wilt, Meera Viswanathan
OBJECTIVES: We developed guidance to inform decisions regarding the inclusion of nonrandomized studies of interventions (NRSIs) in systematic reviews (SRs) of the effects of interventions. STUDY DESIGN AND SETTING: The guidance workgroup comprised SR experts and used an informal consensus generation method. RESULTS: Instead of recommending NRSI inclusion only if randomized controlled trials (RCTs) are insufficient to address the SR key question, different topics may require different decisions regarding NRSI inclusion...
September 19, 2022: Journal of Clinical Epidemiology
#13
JOURNAL ARTICLE
Georgina Ryland, Masayuki Umeda, Linda Holmfeldt, Sören Lehmann, Morten Krogh Herlin, Jing J Ma, Mahsa Khanlari, Jeffrey E Rubnitz, Rhonda E Ries, Hansen J Kosasih, Paul G Ekert, Hwee Ngee Goh, Ing Soo Tiong, Sean M Grimmond, Claudia Haferlach, Ryan B Day, Timothy J Ley, Soheil Meshinchi, Xiaotu Ma, Piers Blombery, Jeffery M Klco
No abstract text is available yet for this article.
September 30, 2022: Blood
#14
JOURNAL ARTICLE
Taichi A Suzuki, J Liam Fitzstevens, Victor T Schmidt, Hagay Enav, Kelsey E Huus, Mirabeau Mbong Ngwese, Anne Grießhammer, Anne Pfleiderer, Bayode R Adegbite, Jeannot F Zinsou, Meral Esen, Thirumalaisamy P Velavan, Ayola A Adegnika, Le Huu Song, Timothy D Spector, Amanda L Muehlbauer, Nina Marchi, Hyena Kang, Lisa Maier, Ran Blekhman, Laure Ségurel, GwangPyo Ko, Nicholas D Youngblut, Peter Kremsner, Ruth E Ley
The gut microbiomes of human populations worldwide have many core microbial species in common. However, within a species, some strains can show remarkable population specificity. The question is whether such specificity arises from a shared evolutionary history (codiversification) between humans and their microbes. To test for codiversification of host and microbiota, we analyzed paired gut metagenomes and human genomes for 1225 individuals in Europe, Asia, and Africa, including mothers and their children. Between and within countries, a parallel evolutionary history was evident for humans and their gut microbes...
September 16, 2022: Science
#15
JOURNAL ARTICLE
Michael H Kramer, Qiang Zhang, Robert Sprung, Ryan B Day, Petra Erdmann-Gilmore, Yang Li, Ziheng Xu, Nichole M Helton, Daniel R George, Yiling Mi, Peter Westervelt, Jacqueline E Payton, Sai M Ramakrishnan, Christoper A Miller, Daniel C Link, John F DiPersio, Matthew J Walter, R Reid Townsend, Timothy J Ley
We have developed a deep-scale proteome and phosphoproteome database from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls. After confirming data quality, we orthogonally validated several previously undescribed features of AML revealed by the proteomic data. We identified examples of post-transcriptionally regulated proteins both globally (i.e. in all AML samples), and also, in patients with recurrent AML driver mutations. For example, samples with IDH1/2 mutations displayed elevated levels of the 2‑oxoglutarate-dependent histone demethylases KDM4A/B/C, despite no changes in mRNA levels for these genes; we confirmed this finding in vitro...
July 27, 2022: Blood
#16
JOURNAL ARTICLE
Cheng Hu, Timothy J Griffis, Lingjun Xia, Wei Xiao, Cheng Liu, Qitao Xiao, Xin Huang, Yanrong Yang, Leying Zhang, Bo Hou
China is the largest CO2 emitting country on Earth. During the COVID-19 pandemic, China implemented strict government control measures on both outdoor activity and industrial production. These control measures, therefore, were expected to significantly reduce anthropogenic CO2 emissions. However, large discrepancies still exist in the estimated anthropogenic CO2 emission reduction rate caused by COVID-19 restrictions, with values ranging from 10% to 40% among different approaches. Here, we selected Nanchang city, located in eastern China, to examine the impact of COVID-19 on CO2 emissions...
July 20, 2022: Environmental Pollution
#17
Allegra A Petti, Stephen R Williams, Christopher A Miller, Ian T Fiddes, Sridhar N Srivatsan, David Y Chen, Catrina C Fronick, Robert S Fulton, Deanna M Church, Timothy J Ley
No abstract text is available yet for this article.
July 21, 2022: Nature Communications
#18
EDITORIAL
Andrew J Menssen, Ajay Khanna, Christopher A Miller, Sridhar Nonavinkere Srivatsan, Gue Su Chang, Jin Shao, Joshua Robinson, Michele O'Laughlin, Catrina C Fronick, Robert S Fulton, Kimberly Brendel, Sharon E Heath, Raya Saba, John S Welch, David H Spencer, Jacqueline E Payton, Peter Westervelt, John F DiPersio, Daniel C Link, Matthew J Schuelke, Meagan A Jacoby, Eric J Duncavage, Timothy J Ley, Matthew J Walter
Progression from myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (AML) is associated with the acquisition and expansion of subclones. Our understanding of subclone evolution during progression, including the frequency and preferred order of gene mutation acquisition, remains incomplete. Sequencing of 43 paired MDS and secondary AML samples identified at least one signaling gene mutation in 44% of MDS and 60% of secondary AML samples, often below the level of standard sequencing detection...
July 6, 2022: Blood cancer discovery
#19
REVIEW
Current Reality of Beef Cattle Veterinary Practice in North America: A Systems Thinking Perspective.
Dale M Grotelueschen, Rebecca A Funk, John T Groves, Timothy J Goldsmith, Brian Vander Ley
Beef cattle veterinarians provide services to the increasingly complex beef industry system. Systems thinking offers pathways to better understand and communicate ranges of issues such as prevailing mental models, importance of match quality relative to clientele needs, and identification of leverage to better adapt and continually improve. Thinking in systems identifies and helps us to understand patterns or structures that are organized and interconnected that result in the outcomes observed and experienced in the practice of beef cattle veterinary medicine...
July 2022: Veterinary Clinics of North America. Food Animal Practice
#20
JOURNAL ARTICLE
Sidan Li, Juo-Chin Yao, Karolyn A Oetjen, Joseph Ryan Krambs, Jun Xia, Jingzhu Zhang, Amy P Schmidt, Nichole M Helton, Robert S Fulton, Sharon E Heath, Isaiah R Turnbull, Gabriel Mbalaviele, Timothy J Ley, Matthew J Walter, Daniel C Link
Hematopoietic stem/progenitor cells (HSPCs) reside in localized microenvironments, or niches, in the bone marrow that provide key signals regulating their activity. A fundamental property of hematopoiesis is the ability to respond to environmental cues, such as inflammation. How these cues are transmitted to HSPCs within hematopoietic niches is not well established. Here, we show that perivascular bone marrow dendritic cells (DCs) express a high basal level of toll-like receptor-1 (TLR1) and TLR2. Systemic treatment with a TLR1/2 agonist induces HSPC expansion and mobilization...
June 8, 2022: Blood
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