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Paul G. Richardson

Bio: Paul G. Richardson is an academic researcher from Harvard University. The author has contributed to research in topics: Multiple myeloma & Bortezomib. The author has an hindex of 183, co-authored 1533 publications receiving 155912 citations. Previous affiliations of Paul G. Richardson include Broomfield Hospital & Dartmouth College.


Papers
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Book ChapterDOI
01 Jan 2013
TL;DR: This chapter focuses on new therapeutic targets which have shown promising preclinical results and early evidence of anti-MM activity in clinical studies.
Abstract: The past decade has witnessed a dramatic increase in the therapeutic options for the treatment of multiple myeloma (MM) with the introduction of novel biologically targeted agents which in turn have resulted in significantly improved outcomes. However, myeloma remains incurable, and ongoing efforts to identify novel therapeutic approaches remain an urgent priority. Newer agents that target tumour and stromal compartments can be categorized as those that target protein dynamics (such as ubiquitin–proteasome system and heat-shock protein 90), drugs modulating anti-MM immune response (IMiDs), antibodies targeting membrane-bound receptors (including CS1, CD38, CD138), epigenetic modulators (DNA methyltransferase and histone deacetylase inhibitors), intracellular-signalling kinase inhibitors (PI3k/Akt/mTOR, MAPK pathways) and compounds disrupting the cell-cycle molecular machinery (such as CDKIs and Aurora kinase inhibitors). This chapter focuses on new therapeutic targets which have shown promising preclinical results and early evidence of anti-MM activity in clinical studies.

1 citations

Journal ArticleDOI
TL;DR: In this paper, the authors measured soluble biomarkers of endothelial injury in the peri-transplant period to determine if they correlated with the occurrence of VOD, and found that patients with VOD had significantly elevated levels of Von Willebrand Factor (vWF) and thrombomodulin.

1 citations

Book ChapterDOI
01 Jan 2018
TL;DR: This chapter provides a succinct overview of the issues affecting the treatment of RRMM patients, including a summary of important recent data and recommendations for treatment approaches in different patient subgroups and in different disease settings.
Abstract: Despite remarkable improvements in outcome for patients with multiple myeloma (MM) and frontline therapy becoming increasingly effective, with prolonged disease control, MM remains incurable and relapse remains an inevitability for the majority of patients. The past two decades have witnessed an unprecedented increase in the number and variety of therapeutic options for MM, including the emergence of four novel classes of agents with distinct mechanisms of action and the approval of ten new individual agents. Treatment selection and sequencing are emerging as important new issues for consideration by clinicians when planning for the longer-term management of their MM patients. Additionally, the emerging treatment paradigms of triplet versus doublet therapy and the use of treat-to-progression and/or maintenance approaches are influencing the treatment of relapsed/refractory MM (RRMM). With the wealth of therapeutic options becoming available to us, it is important to try to establish recommended treatment options for RRMM patients to guide selection of subsequent therapies based on key factors of importance. Furthermore, the development of new agents with unique mechanisms of anti-myeloma activity remains a very high priority in the field. This chapter provides a succinct overview of the issues affecting the treatment of RRMM patients, including a summary of important recent data and recommendations for treatment approaches in different patient subgroups and in different disease settings. It also provides a longer-term perspective, examining how treatment of RRMM patients may evolve in parallel with the evolution of frontline therapy and with the emergence of next-generation novel agents in the future.

1 citations

Journal ArticleDOI
TL;DR: This work presents the unique co-occurrence of IgA kappa multiple myeloma (MM) and pemphigus foliaceus (PF), an IgGmediated subtype of pemPHigus.
Abstract: While the link between paraneoplastic pemphigus (PNP) and malignancy is well documented, reports of other pemphigus variants in association with neoplasms are scarcer. Reports have linked either IgA pemphigus with IgA monoclonal gammopathy or IgG-mediated pemphigus with IgG monoclonal gammopathy. We present the unique co-occurrence of IgA kappa multiple myeloma (MM) and pemphigus foliaceus (PF), an IgGmediated subtype of pemphigus.

1 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: The definition and use of family-specific, manually curated gathering thresholds are explained and some of the features of domains of unknown function (also known as DUFs) are discussed, which constitute a rapidly growing class of families within Pfam.
Abstract: Pfam is a widely used database of protein families and domains. This article describes a set of major updates that we have implemented in the latest release (version 24.0). The most important change is that we now use HMMER3, the latest version of the popular profile hidden Markov model package. This software is approximately 100 times faster than HMMER2 and is more sensitive due to the routine use of the forward algorithm. The move to HMMER3 has necessitated numerous changes to Pfam that are described in detail. Pfam release 24.0 contains 11,912 families, of which a large number have been significantly updated during the past two years. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/).

14,075 citations

Journal ArticleDOI
J. Craig Venter1, Mark Raymond Adams1, Eugene W. Myers1, Peter W. Li1  +269 moreInstitutions (12)
16 Feb 2001-Science
TL;DR: Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems are indicated.
Abstract: A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

12,098 citations

Journal ArticleDOI
14 Jan 2005-Cell
TL;DR: In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of the gene set.

11,624 citations

Journal ArticleDOI
TL;DR: A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided at http://genome.ucsc.edu.
Abstract: As vertebrate genome sequences near completion and research refocuses to their analysis, the issue of effective genome annotation display becomes critical. A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided at http://genome.ucsc.edu. This browser displays assembly contigs and gaps, mRNA and expressed sequence tag alignments, multiple gene predictions, cross-species homologies, single nucleotide polymorphisms, sequence-tagged sites, radiation hybrid data, transposon repeats, and more as a stack of coregistered tracks. Text and sequence-based searches provide quick and precise access to any region of specific interest. Secondary links from individual features lead to sequence details and supplementary off-site databases. One-half of the annotation tracks are computed at the University of California, Santa Cruz from publicly available sequence data; collaborators worldwide provide the rest. Users can stably add their own custom tracks to the browser for educational or research purposes. The conceptual and technical framework of the browser, its underlying MYSQL database, and overall use are described. The web site currently serves over 50,000 pages per day to over 3000 different users.

9,605 citations