Publications by authors named "Janine Steiger"

Death Receptor 5 (DR5) agonists demonstrate anti-tumor activity in preclinical models but have yet to demonstrate robust clinical responses. A key limitation may be the lack of patient selection strategies to identify those most likely to respond to treatment. To overcome this limitation, we screened a DR5 agonist Nanobody across >600 cell lines representing 21 tumor lineages and assessed molecular features associated with response.

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Tankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis, and mitosis, offering attractive targets for anticancer treatment. Using unbiased combination screening in a large panel of cancer cell lines, we have identified a strong synergy between TNKS and MEK inhibitors (MEKi) in KRAS-mutant cancer cells. Our study uncovers a novel function of TNKS in the relief of a feedback loop induced by MEK inhibition on FGFR2 signaling pathway.

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Expression of metabotropic GABA(B) receptors is essential for slow inhibitory synaptic transmission in the CNS, and disruption of GABA(B) receptor-mediated responses has been associated with several disorders, including neuropathic pain and epilepsy. The location of GABA(B) receptors in neurons determines their specific role in synaptic transmission, and it is believed that sorting of subunit isoforms, GABA(B)R1a and GABA(B)R1b, to presynaptic or postsynaptic membranes helps to determine this role. GABA(B)R1a and GABA(B)R1b are thought to arise by alternative splicing of heteronuclear RNA.

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gamma-Aminobutyric acid type B receptors (GABA(B)Rs) mediate both slow inhibitory synaptic activity in the adult nervous system and motility signals for migrating embryonic cortical cells. Previous papers have described the expression of GABA(B)Rs in the adult brain, but the expression and functional significance of these gene products in the embryo are largely unknown. Here we examine GABA(B)R expression from rat embryonic day 10 (E10) to E18 compared with adult and ask whether embryonic cortical neurons contain functional GABA(B)R.

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The type A gamma-aminobutyric acid (GABA(A)) receptors mediate the majority of fast inhibitory neurotransmission in the CNS, and alterations in GABA(A) receptor function is believed to be involved in the pathology of several neurological and psychiatric illnesses, such as epilepsy, anxiety, Alzheimer's disease, and schizophrenia. GABA(A) receptors can be assembled from eight distinct subunit families defined by sequence similarity: alpha(1-6), beta(1-3), gamma(1-3), delta, pi, theta, and rho(1-3). The regulation of GABA(A) receptor function in the brain is a highly compensating system, influencing both the number and the composition of receptors at the cell surface.

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Exposure of pregnant rats to protein malnutrition throughout pregnancy alters the developing hippocampus, leading to increased inhibition and selective changes in hippocampal-mediated behaviors. Given that GABA mediates most inhibitory neurotransmission, we asked whether selective changes in the levels of GABA receptor subunit mRNAs might result. Quantitative RNase protection profiling of 12 GABAA and GABAB receptor subunit mRNAs show that alpha1 and beta2 decrease in the adult (P90) hippocampal formation of prenatally malnourished rats, while the levels of alpha3 are increased.

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Rats exposed to prenatal protein malnutrition are less sensitive to the amnestic effects of chlordiazepoxide when administered directly into the medial septum. Here we report that prenatal malnutrition selectively decreases gamma-aminobutyric acid A (GABA(A)) receptor gamma(2L) mRNA levels in the medial septum, consistent with malnutrition-induced decreases in the amnestic effects of chlordiazepoxide infusion. In the lateral septum, beta(2) and beta(3) mRNA levels are also decreased, suggesting that prenatal malnutrition alters GABA(A) receptor gene expression in the septal complex.

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