Jen-Sing Liu

Learn More
To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents,(More)
Engineered bispecific antibodies that recruit cytotoxic lymphocytes to kill specific tumor cells have been showing promising clinical results. Here, we describe a bispecific single-chain Fv (scFv) immunofusion or BIf to target CD123(+) leukemia, that contains an anti-CD123 scFv fused at the N-terminus of human IgG1 hinge-C(H)2-C(H)3, and an anti-CD3 scFv(More)
Adozelesin is an alkylating minor groove DNA binder that is capable of rapidly inhibiting DNA replication in treated cells through a trans-acting mechanism and preferentially arrests cells in S phase. It has been shown previously that in cells treated with adozelesin, replication protein A (RPA) activity is deficient, and the middle subunit of RPA is(More)
DT(388)IL3 fusion protein containing the catalytic and translocation domains of diphtheria toxin fused to human interleukin 3 was administered in an inter-patient dose escalation trial by 15 min i.v. infusions every other day for up to 6 doses to patients with chemo-refractory acute myeloid leukemia (AML) and myelodysplasia (MDS). The maximal tolerated dose(More)
Caveolae are critical cell surface structures important in coordinated cell signaling and endocytosis. One of the major proteins of caveolae is caveolin 1 (Cav-1). Cellular levels of Cav-1 are associated with cancer progression. In prostate cancer cells, levels of Cav-1 are positively correlated with tumor progression and metastasis. Cav-1 can be secreted(More)
The bivalent anti-T cell immunotoxin, A-dmDT390-bisFv(UCHT1), was developed for treatment of T-cell leukemia, autoimmune diseases and tolerance induction for transplantation. To obtain clinical grade bivalent anti-T cell immunotoxin for phase I/II clinical trials, a single batch of 120 L bioreactor culture was performed using the Pichia pastoris(More)
The major eukaryotic single-stranded DNA (ssDNA) binding protein, replication protein A (RPA), is a heterotrimer with subunits of 70, 32 and 14 kDa (RPA70, RPA32 and RPA14). RPA-coated ssDNA has been implicated as one of the triggers for intra-S-phase checkpoint activation. Phosphorylation of RPA occurs in cells with damaged DNA or stalled replication(More)
The bivalent anti-human T cell immunotoxin A-dmDT390-bisFv(UCHT1) for treatment of patients with T cell malignancies is a single chain fusion protein composed of the catalytic domain and translocation domains of diphtheria toxin fused to two tandem sFv molecules reactive with human CD3ε. This immunotoxin selectively kills CD3ε positive T cells. To determine(More)
Replication protein A (RPA) is the major eukaryotic single stranded DNA binding protein that plays a central role in DNA replication, repair and recombination. Like many DNA repair proteins RPA is heavily phosphorylated (specifically on its 32 kDa subunit) in response to DNA damage. Phosphorylation of many repair proteins has been shown to be important for(More)
Immunotoxin potency is dependent on cell surface binding specificity as well as internalization efficiency. Current approaches for immunotoxin development are dependent on existing antibodies that were selected for high affinity and/or high production yield. However, these antibodies may demonstrate low internalization efficiency upon cell surface binding(More)