Overcoming the inherent chemoresistance of pancreatic cancers remains a major goal of therapeutic investigations in this disease. In this study, we discovered a role for the human concentrative nucleoside transporter-1 (hCNT1; SLC28A1), a high-affinity pyrimidine nucleoside transporter, in determining the chemosensitivity of human pancreatic cancer cells to gemcitabine, the drug ... More
A microfluidic processor for gene expression profiling of single human embryonic stem cells.
AuthorsZhong JF, Chen Y, Marcus JS, Scherer A, Quake SR, Taylor CR, Weiner LP,
JournalLab Chip
PubMed ID18094763
'The gene expression of human embryonic stem cells (hESC) is a critical aspect for understanding the normal and pathological development of human cells and tissues. Current bulk gene expression assays rely on RNA extracted from cell and tissue samples with various degree of cellular heterogeneity. These ''cell population averaging'' data ... More
A novel method for long term bone marrow culture and genetic modification of murine neutrophils via retroviral transduction.
AuthorsZemans RL, Briones N, Young SK, Malcolm KC, Refaeli Y, Downey GP, Worthen GS,
JournalJ Immunol Methods
PubMed ID19010330
'Neutrophils are a critical component of the innate immune response to invading microbial pathogens. However, an excessive and/or prolonged neutrophil response can result in tissue injury that is thought to underlie the pathogenesis of various inflammatory diseases. The development of novel therapeutic strategies for inflammatory diseases depends on an improved ... More
Classic
AuthorsHenderson L, Bortone DS, Lim C, Zambon AC,
JournalAm J Physiol Cell Physiol
PubMed ID23392113
'Many common, important diseases are either caused or exacerbated by hyperactivation (e.g., cancer) or inactivation (e.g., heart failure) of the cell division cycle. A better understanding of the cell cycle is critical for interpreting numerous types of physiological changes in cells. Moreover, new insights into how to control it will ... More
Transcription factor BORIS (Brother of the Regulator of Imprinted Sites) directly induces expression of a cancer-testis antigen, TSP50, through regulated binding of BORIS to the promoter.
'Cancer-testis antigens (CTAs) are normally expressed in testis but are aberrantly expressed in a variety of cancers with varying frequency. More than 100 proteins have been identified as CTA including testes-specific protease 50 (TSP50) and the testis-specific paralogue of CCCTC-binding factor, BORIS (brother of the regulator of imprinted sites). Because ... More
MAPK kinase 3 is a tumor suppressor with reduced copy number in breast cancer.
AuthorsMacNeil AJ, Jiao SC, McEachern LA, Yang YJ, Dennis A, Yu H, Xu Z, Marshall JS, Lin TJ,
Journal
PubMed ID24233520
'Cancers are initiated as a result of changes that occur in the genome. Identification of gains and losses in the structure and expression of tumor-suppressor genes and oncogenes lies at the root of the understanding of cancer cell biology. Here, we show that the mitogen-activated protein kinase (MAPK) MKK3 suppresses ... More
Migration of human neural stem cells toward an intracranial glioma.
AuthorsJeon JY, An JH, Kim SU, Park HG, Lee MA,
JournalExp Mol Med
PubMed ID18305401
'Many in vivo and in vitro studies have demonstrated the targeted migration of neural stem cells (NSC) to infiltrating brain tumors, including malignant glioma, highlighting a potential therapeutic approach. However, there is not enough information to apply this approach to clinical therapy. The most important things in stem cell therapy ... More
Activated Ras protein accelerates cell cycle progression to perturb Madin-Darby canine kidney cystogenesis.
AuthorsSakurai A, Matsuda M, Kiyokawa E,
JournalJ Biol Chem
PubMed ID22829590
'In a number of human cancer cells, K-RAS is frequently mutated and activated constitutively, culminating in the induction of continuous cell growth, a hallmark of cancer cells. It is still unclear, however, how the mutated K-RAS induces morphological abnormalities in cancerous tissues. To investigate the mechanism underlying the K-RAS-induced morphological ... More
Adenovirus E4orf4 protein-induced death of p53-/- H1299 human cancer cells follows a G1 arrest of both tetraploid and diploid cells due to a failure to initiate DNA synthesis.
AuthorsCabon L, Sriskandarajah N, Mui MZ, Teodoro JG, Blanchette P, Branton PE,
Journal
PubMed ID24067978
'The adenovirus E4orf4 protein selectively kills human cancer cells independently of p53 and thus represents a potentially promising tool for the development of novel antitumor therapies. Previous studies suggested that E4orf4 induces an arrest or a delay in mitosis and that both this effect and subsequent cell death rely largely ... More
The enrichment of trophoblast giant cells from mid-gestation bovine placentae using fluorescence-activated cell sorting.
AuthorsPennington KA, Oliveira LJ, Yang QE, Ealy AD,
JournalPlacenta
PubMed ID20646758
The objective of this work was to determine if fluorescence-activated cell sorting (FACS) can be used to isolate trophoblast giant cells (TGCs) from bovine placentae. Cotyledons were harvested, minced and digested with dispase/pancreatin. Tissue homogenates were incubated with Vybrant Dye Cycle-Green. FACS was completed, and cells with DNA content 2- ... More
Pharmacological brake-release of mRNA translation enhances cognitive memory.
AuthorsSidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, Gamache K, Gallagher CM, Ang KK, Wilson C, Okreglak V, Ashkenazi A, Hann B, Nader K, Arkin MR, Renslo AR, Sonenberg N, Walter P,
Journal
PubMed ID23741617
Phosphorylation of the a-subunit of initiation factor 2 (eIF2) controls protein synthesis by a conserved mechanism. In metazoa, distinct stress conditions activate different eIF2a kinases (PERK, PKR, GCN2, and HRI) that converge on phosphorylating a unique serine in eIF2a. This collection of signaling pathways is termed the 'integrated stress response' ... More
Apoptotic programs are determined during lineage commitment of CD4+ T effectors: selective regulation of T effector-memory apoptosis by inducible nitric oxide synthase.
AuthorsPurushothaman D, Marcel N, Garg M, Venkataraman R, Sarin A,
JournalJ Immunol
PubMed ID23225886
Lineage-committed T effectors generated in response to Ag during the inflammatory phase are destined to die during termination of the immune response. We present evidence to suggest that molecular signatures of lineage commitment are reflected in apoptotic cascades activated in CD4(+) T effectors. Exemplifying this, ablation of inducible NO synthase ... More
Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases.
AuthorsHarbut MB, Velmourougane G, Dalal S, Reiss G, Whisstock JC, Onder O, Brisson D, McGowan S, Klemba M, Greenbaum DC,
JournalProc Natl Acad Sci U S A
PubMed ID21844374
Malaria causes worldwide morbidity and mortality, and while chemotherapy remains an excellent means of malaria control, drug-resistant parasites necessitate the discovery of new antimalarials. Peptidases are a promising class of drug targets and perform several important roles during the Plasmodium falciparum erythrocytic life cycle. Herein, we report a multidisciplinary effort ... More
Mitotic progression becomes irreversible in prometaphase and collapses when Wee1 and Cdc25 are inhibited.
AuthorsPotapova TA, Sivakumar S, Flynn JN, Li R, Gorbsky GJ,
JournalMol Biol Cell
PubMed ID21325631
Mitosis requires precise coordination of multiple global reorganizations of the nucleus and cytoplasm. Cyclin-dependent kinase 1 (Cdk1) is the primary upstream kinase that directs mitotic progression by phosphorylation of a large number of substrate proteins. Cdk1 activation reaches the peak level due to positive feedback mechanisms. By inhibiting Cdk chemically, ... More
In vitro generation of Plasmodium falciparum ookinetes.
AuthorsBounkeua V, Li F, Vinetz JM,
JournalAm J Trop Med Hyg
PubMed ID21118920
Plasmodium transmission from the human host to the mosquito depends on the ability of gametocytes to differentiate into ookinetes, the invasive form of the parasite that invades and establishes infection in the mosquito midgut. The biology of P. falciparum ookinetes is poorly understood, because sufficient quantities of this stage of ... More
Expression of a testis-specific form of Gal3st1 (CST), a gene essential for spermatogenesis, is regulated by the CTCF paralogous gene BORIS.
AuthorsSuzuki T, Kosaka-Suzuki N, Pack S, Shin DM, Yoon J, Abdullaev Z, Pugacheva E, Morse HC, Loukinov D, Lobanenkov V,
JournalMol Cell Biol
PubMed ID20231363
Previously, it was shown that the CTCF paralogous gene, BORIS (brother of the regulator of imprinted sites) is expressed in male germ cells, but its function in spermatogenesis has not been defined. To develop an understanding of the functional activities of BORIS, we generated BORIS knockout (KO) mice. Mice homozygous ... More
A screen for modifiers of notch signaling uncovers Amun, a protein with a critical role in sensory organ development.
AuthorsShalaby NA, Parks AL, Morreale EJ, Osswalt MC, Pfau KM, Pierce EL, Muskavitch MA,
JournalGenetics
PubMed ID19448274
Notch signaling is an evolutionarily conserved pathway essential for many cell fate specification events during metazoan development. We conducted a large-scale transposon-based screen in the developing Drosophila eye to identify genes involved in Notch signaling. We screened 10,447 transposon lines from the Exelixis collection for modifiers of cell fate alterations ... More