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  • Glioblastoma Multiforme (GBM) accounts for about 15% of all intracranial tumors and about 60% of astrocytic tumors, it often occurs between the age of 45 and 70. Although it is rare, with the incidence of 2-3 new cases per 100,000 people in the United States and Europe, patients with GBM have a dismal prognosis, usually survive less than 15 months with standard-of-care therapy, and survival without treatment (at least surgery) is only 4-6 months. Previous work mainly focused on the role of genes on GBM survival or on the maintenance of glioblastoma stem cells (GSCs).
  • Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. The levels in the genomic sequence, gene expression, pre-mRNA splicing have been extensively studied between human and nonhuman primates. However, the chromatin structure---- this higher order of genome interaction map is less well known, especially across different primates’ species.
  • The major challenge of third-generation sequencing (i.e. PacBio and Nanopore sequencing) is the high sequencing error rate, PacBio has 10-15% while Nanopore is 5-20%. Although Illumina allows rapid, cheap, and accurate sequencing, its short reads (usually < 300 bp) doesn’t enable complete genome assembly or intact full-length mRNA transcriptome analysis. Scientists have developed hybrid assembly pipelines by combing long-reads for contig formation and short-reads for nucleotide accuracy to improve de novo genome assembly.
  • Early detection of causative microorganisms in patients with severe infection is critical to informing clinical interventions and the administration of appropriately targeted antibiotics. The traditional culture-based method is time-consuming (taking days or even weeks), especially some microorganisms are unculturable in a lab setting. PCR tests using conserved 16S ribosomal RNA gene and 28S-ITS PCR regions of bacteria and fungi, respectively have low sensitivity of genus/species level. Specifical clinical tests only focusing on certain pathogens makes it impossible for discovering unknown pathogens as most infectious syndromes present with indistinguishable clinical manifestations.
  • Cancer immunotherapy like chimeric antigen receptor (CAR) T cells has been approved and used in blood and bone marrow cancer. Although CAR-T therapy is much more powerful and promising in these types of cancers, long-term remissions are still observed in < 50% of patients.
  • In 2020, The Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry 2020 to Emmanuelle Charpentier and Jennifer A. Doudna, who have discovered CRISPR/Cas9 system, a genetic scissor for rewriting the code of life. David Liu’s lab at the Broad Institute of MIT & Harvard has been inventing new CRISPR gene-editing systems without double-strand DNA break in CRISPR/Cas9 system. In 2016, they invented “base editing”, which seamlessly does four transition editing (C to T, G to A, A to G, and T to C). In 2019, they gave the world “prime editing”, which is devised to achieve all 12 base-to-based conversions, in addition, it can mediate targeted insertions and deletions.
  • Chronic lymphocytic leukemia (CLL) is a disease that remains incurable by conventional chemotherapy. SF3B1 is a splicing factor, a core component of the U2 snRNP of the spliceosome, and associates with the U2 snRNA and branch point adenosine of the pre-mRNA. Recurrent somatic mutations in SF3B1 have been linked to CLL. In CLL, mutations in the heat-repeat domain of SF3B1 is shown to associate with poor clinical outcome. Previous whole transcript profiling mainly focused on exon level using Illumina short reads NGS platform. The extent to which full-length isoforms contribute to such disease due to splicing regulator SF3B1 mutations are not well characterized.
  • Stem cell therapy or regenerative medicine promotes the repair response of diseased, injured, or dysfunctional tissues using stem cells. The important biosafety for the use of human pluripotent stem cells is to make sure there are not any mutations, especially in genes associated with cancer that occurred during stem cell in vitro propagation.
  • Human cancer cell lines have been a driving force in cancer research. The NCI-60 Human Tumor Cell Lines cover 60 different human tumor cell lines, representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney cancers (ref1). The Cancer Cell Line Encyclopedia (CCLE) project started in 2008 as a collaboration between the Broad Institute, and the Novartis Institutes for Biomedical Research, and its Genomics Institute of the Novartis Research Foundation (ref2).
  • Autism is a serious developmental disorder that impairs the ability to communicate and interact. According to the Centers for Disease Control, autism affects an estimated 1 in 54 children in the United States today. It is a genetic disorder in multiple genes.

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