Michelle Becker-Hapak

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Cellular manipulation by transfection or viral introduction of cDNA expression vectors and microinjection of proteins into cells presents various difficulties, including massive overexpression, broad cell-to-cell intracellular concentration ranges of expressed proteins and low percentage of cells targeted. Moreover, use of antisense approaches to manipulate(More)
Manipulation of mammalian cells has been achieved by the transfection of expression vectors, microinjection, or diffusion of peptidyl mimetics. While these approaches have been somewhat successful, the classic manipulation methods are not easily regulated and can be laborious. One approach to circumvent these problems is the use of HIV TAT-mediated protein(More)
The retinoblastoma tumor suppressor protein (pRB) negatively regulates early-G(1) cell cycle progression, in part, by sequestering E2F transcription factors and repressing E2F-responsive genes. Although pRB is phosphorylated on up to 16 cyclin-dependent kinase (Cdk) sites by multiple G(1) cyclin-Cdk complexes, the active form(s) of pRB in vivo remains(More)
T cell immunity directed against tumor-encoded amino acid substitutions occurs in some melanoma patients. This implicates missense mutations as a source of patient-specific neoantigens. However, a systematic evaluation of these putative neoantigens as targets of antitumor immunity is lacking. Moreover, it remains unknown whether vaccination can augment such(More)
Protein transduction domains (PTDs) offer an exciting therapeutic opportunity for the treatment of many diseases. An 11-amino acid fragment of human immunodeficiency type 1 (HIV-1) TAT-protein can transduce large, biologically active proteins into mammalian cells; recent evidence has shown an in vivo PTD for the 116 kDa beta-galactosidase protein. However,(More)
Hepatocyte growth factor (HGF) signaling via its receptor, the proto-oncogene Met, alters cell proliferation and motility and has been associated with tumor metastasis. HGF treatment of HepG2 human hepatocellular carcinoma cells induces cell migration concomitant with increased levels of the p27(kip1) cyclin-cdk inhibitor. HGF signaling resulted in nuclear(More)
CD40L (CD154) expressed on activated CD4(+) T cells has been shown to provide CD40(+) dendritic cells (DCs), a critical signal for establishing CD8(+) T-cell immunity. CD40L-CD40 interaction leads to DC maturation with IL-12 production and upregulation of various costimulatory molecules. In this study, we show that CD40 engagement provides a unique(More)
RpoS (sigma-38) is the major regulator of genes for survival of Escherichia coli in the stationary phase. OxyR is a transcriptional regulator that responds to H2O2 induced stress in exponential phase. Once considered to act independently of each other, they are now known to be integrally involved in the expression of several oxidative stress genes. While it(More)
Deregulation of the p16INK4a-cyclin D:cyclin-dependent kinases (cdk) 4/6-retinoblastoma (pRB) pathway is a common paradigm in the oncogenic transformation of human cells and suggests that this pathway functions linearly in malignant transformation. However, it is not understood why p16INK4a and cyclin D:cdk4/6 mutations are disproportionately more common(More)
Progression of cells through the G1 phase of the cell cycle requires cyclin D:Cdk4/6 and cyclin E:Cdk2 complexes; however, the duration and ordering of these complexes remain unclear. To address this, we synthesized a peptidyl mimetic of the Cdk4/6 inhibitor, p16INK4a that contained an NH2-terminal TAT protein transduction domain. Transduction of TAT-p16(More)