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.

MM-219: Pivotal DREAMM-2 Study: Single-Agent Belantamab Mafodotin (Belamaf; GSK2857916) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Refractory to Proteasome Inhibitors and Immunomodulatory Agents, and Refractory and/or Intolerant to Anti-CD38 Monoclonal Antibodies (mAbs), Including Subgroups with Renal Impairment (RI) and High-Risk (HR) Cytogenetics

Abstract: Context: Belamaf showed deep and durable single-agent activity in the pivotal DREAMM-2 study primary analysis ( NCT03525678 ) (1–7) in a patient population that historically has a poor prognosis (overall survival [OS] 6–9 months). Objective: To present longer-term efficacy/safety outcomes (13-month follow-up) with single-agent belamaf in DREAMM-2 in the overall patient population and patients with HR cytogenetics and RI, subgroups with poor outcomes. Methods: DREAMM-2 is an ongoing study of belamaf 2.5 mg/kg (n=97) or 3.4 mg/kg (n=99). Primary outcome: overall response rate (ORR; ≥partial response). In post-hoc analyses, HR-cytogenetics included t(4;14), t(14;16), 17p13del, or 1q21 + . RI was based on eGFR (mild: ≥60– Results: Overall population ORRs in the 2.5 mg/kg and 3.4 mg/kg groups were 32% (97.5% CI: 21.7–43.6) and 35% (97.5% CI: 24.8–47.0); 19% and 23% of patients (58% and 66% of responders) achieved very good partial response or better. Median duration of response was 11.0 (95% CI: 4.2–not reached [NR]) and 6.2 months (95% CI: 4.8–NR). Median progression-free survival was 2.8 (95% CI: 1.6–3.6) and 3.9 months (95% CI: 2.0–5.8); median estimated OS was 13.7 (95% CI: 9.9–NR) and 13.8 months (95% CI: 10.0–NR). Most common Grade ≥3 adverse events (AEs) were keratopathy (microcyst-like epithelial changes [MECs] observed on eye examination; 2.5 mg/kg: 46%; 3.4 mg/kg: 42%), thrombocytopenia (2.5 mg/kg: 22%; 3.4 mg/kg: 32%), and anemia (2.5 mg/kg: 21%; 3.4 mg/kg: 27%). AE-related permanent discontinuation occurred in 9% and 12%; discontinuation due to MECs was rare (2.5 mg/kg: 1%; 3.4 mg/kg: 3%). HR cytogenetics and RI subgroup analyses will be presented at the conference. Conclusions: Deep and durable responses to single-agent belamaf were sustained and no new safety signals identified with longer follow-up in this heavily pretreated RRMM population. Funding: GSK (205678). Drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. References: [1] Lonial et al. Lancet Oncol. 2020. [2] Lonial et al. ASCO 2020. EP436. [3] Lonial et al. EHA 2020. EP970. [4] Cohen et al. ASCO 2020. EP441. [5] Trudel et al. EHA 2020. EP1037. [6] Lee et al. ASCO 2020. EP419. [7] Lee et al. EHA 2020. EP1006.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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。

The Pfam protein families database

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/).

The sequence of the human genome.

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.

The Human Genome Browser at UCSC

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.