Lia Baki

Lia Baki
Rutgers New Jersey Medical School | UMDNJ · Department of Microbiology and Molecular Genetics (RWJ Medical School)

PhD

About

48
Publications
4,656
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,313
Citations
Citations since 2017
4 Research Items
670 Citations
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
Introduction
• Mechanisms underlying CNS diseases. • Various forms of signal transduction. • Development and optimization of cell-based assays for high throughput screening. • GPCR pharmacology – GPCR heteromerization – GPCR signaling. • Project management. • Training/mentoring/supervising junior scientists.
Additional affiliations
July 2019 - present
Rutgers New Jersey Medical School
Position
  • Research Associate
February 2016 - May 2019
Northeastern University
Position
  • Professor (Assistant)
September 2008 - January 2016
Virginia Commonwealth University
Position
  • Professor (Assistant)

Publications

Publications (48)
Article
Full-text available
We previously reported that co-expression of the Gi-coupled metabotropic glutamate receptor 2 (mGlu2R) and the Gq-coupled serotonin (5-HT) 2A receptor (2AR) in Xenopus oocytes (Fribourg et al. Cell 147:1011–1023, 2011) results in inverse cross-signaling, where for either receptor, strong agonists suppress and inverse agonists potentiate the signali...
Article
Full-text available
Atypical antipsychotic drugs, such as clozapine and risperidone, have a high affinity for the serotonin 5-HT(2A) G protein-coupled receptor (GPCR), the 2AR, which signals via a G(q) heterotrimeric G protein. The closely related non-antipsychotic drugs, such as ritanserin and methysergide, also block 2AR function, but they lack comparable neuropsych...
Article
Full-text available
Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2) or PIP(2)] is a direct modulator of a diverse array of proteins in eukaryotic cells. The functional integrity of transmembrane proteins, such as ion channels and transporters, is critically dependent on specific interactions with PIP(2) and other phosphoinositides. Here, we report a novel requireme...
Article
Full-text available
Phosphatidylinositol 3-kinase (PI3K) promotes cell survival and communication by activating its downstream effector Akt kinase. Here we show that PS1, a protein involved in familial Alzheimer's disease (FAD), promotes cell survival by activating the PI3K/Akt cell survival signaling. This function of PS1 is unaffected by gamma-secretase inhibitors....
Article
Full-text available
The role of presenilin-1 (PS1) in neuronal phosphatidylinositol 3-kinase (PI3K)/Akt signaling was investigated in primary neuronal cultures from wild-type (WT) and PS1 null (PS1-/-) embryonic mouse brains. Here we show that in PS1-/- cultures, the onset of neuronal maturation coincides with a decrease in the PI3K-dependent phosphorylation-activatio...
Article
Full-text available
Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain and other peripheral tissues. Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. The gasotransmitter carbon monoxide has been shown to regulate Kir cha...
Article
Full-text available
Several pharmacophore models have been proposed for 5-HT2A serotonin receptor antagonists. These typically consist of two aromatic/hydrophobic moieties separated by a given distance from each other, and from a basic amine. Although specified distances might vary, the models are relatively similar in their general construction. Because our prelimina...
Article
G protein-coupled Receptors (GPCRs) transduce various extracellular stimuli to intracellular signaling across the plasma membrane. Ligand binding causes a conformational change of the GPCR, resulting in interaction with the GDP-bound G alpha, which forms a heterotrimer with G beta-gamma. Nucleotide exchange of GDP for GTP follows causing the GTP-bo...
Article
G protein-coupled receptors (GPCRs) play critical roles in signal transduction and represent around half of drug targets. Accumulating evidence supports that GPCRs form both homomers and heteromers. Utilizing electron microscopic immunocytochemistry, cannabinoid 1 (CB1) receptors were found to co-localize with dopamine 2 (D2) receptors in the somat...
Article
Full-text available
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can form multiprotein complexes (heteromers), which can alter the pharmacology and functions of the constituent receptors. Previous findings demonstrated that the Gq/11-coupled serotonin 5-HT2A receptor and the Gi/o-coupled metabotropic glutamate 2 (mGlu2) recep...
Article
Full-text available
Cholesterol is one of the major lipid components of membranes in mammalian cells. In recent years, cholesterol has emerged as a major regulator of ion channel function. The most common effect of cholesterol on ion channels in general and on inwardly rectifying potassium (Kir) channels in particular is a decrease in activity. In contrast, we have re...
Article
Atypical antipsychotic drugs targeting the Gq-coupled serotonin 5-HT2A receptor (2AR) are widely used in the treatment of schizophrenia, whereas recent studies point to a new class of potential antipsychotic drugs targeting the Gi-coupled metabotropic glutamate 2 receptor (mGluR2). A physical and functional interaction between the two receptors in...
Article
Full-text available
Anionic phospholipids are critical constituents of the inner leaflet of the plasma membrane, ensuring appropriate membrane topology of transmembrane proteins. Additionally, in eukaryotes, the negatively charged phosphoinositides serve as key signals not only through their hydrolysis products but also through direct control of transmembrane protein...
Article
Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We recorded channel traces and current histograms in patch-experiments on synthetic lipid membranes. We show that these events are voltage-gated with voltage dependence as expected from electrostatic theory of capacitors. The voltage-dependence...
Article
We recently reported that a heteromeric complex formed between the Gi-coupled metabotropic glutamate 2 receptor (mGluR2) and the Gq-coupled serotonin 5-HT2A receptor (2AR) integrates the actions of serotonergic and glutamatergic drugs, modulating the balance between Gi and Gq signaling in a way that can be used to predict the psychoactive propertie...
Article
The hallmark functional property of K ATP (ATP-sensitive potassium) channels is inhibition by intracellular ATP, which binds to a well-defined binding site on Kir6.x subunits and stabilizes the closed conformation of a gate in the channel pore. Numerous inwardly-rectifying potassium (Kir) channels possess an aromatic residue in the 'helix bundle cr...
Article
Full-text available
HIV protease inhibitors (HIV PI) reduce morbidity and mortality of HIV infection but cause multiple untoward effects. Because certain HIV PI evoke production of reactive oxygen species (ROS) and volume-sensitive Cl(-) current (I(Cl,swell)) is activated by ROS, we tested whether HIV PI stimulate I(Cl,swell) in ventricular myocytes. Ritonavir and lop...
Article
Full-text available
Kir3 channels control heart rate and neuronal excitability through GTP-binding (G) protein and phosphoinositide signaling pathways. These channels were the first characterized effectors of the βγ subunits of G proteins. Because we currently lack structures of complexes between G proteins and Kir3 channels, their interactions leading to modulation o...
Article
Full-text available
We assessed regulation of volume-sensitive Cl(-) current (I(Cl,swell)) by endothelin-1 (ET-1) and characterized the signalling pathway responsible for its activation in rabbit atrial and ventricular myocytes. ET-1 elicited I(Cl,swell) under isosmotic conditions. Outwardly rectified Cl(-) current was blocked by the I(Cl,swell)-selective inhibitor DC...
Article
HL-1 cells derived from mouse atrial myocytes retain many features of differentiated adult cardiomyocytes, continuously divide, and are emerging as a useful experimental tool. Features of several HL-1 cation channels have been described, but the characteristics of its Cl− channels are unknown. We studied regulation of volume-sensitive Cl− current,...
Article
The KAch channel slows the heart rate it in response to acetylcholine (ACh). Binding of ACh to the M2 Muscarinic receptor triggers Gβγ-mediated activation of the cardiac GIRK1/GIRK4 inwardly rectifying K channel, which is a heterotetrameric complex of the Kir3.1 and Kir3.4 subunits. Several reports, including work from our laboratory, suggest that...
Article
Full-text available
Strong support for a primary causative role of the Abeta peptides in the development of Alzheimer's disease (AD) neurodegeneration derives from reports that presenilin familial AD (FAD) mutants alter amyloid precursor protein processing, thus increasing production of neurotoxic Abeta 1-42 (Abeta 42). This effect of FAD mutants is also reflected in...
Article
Full-text available
Article
Full-text available
Bidirectional signaling triggered by interacting ephrinB receptors (EphB) and ephrinB ligands is crucial for development and function of the vascular and nervous systems. A signaling cascade triggered by this interaction involves activation of Src kinase and phosphorylation of ephrinB. The mechanism, however, by which EphB activates Src in the ephr...
Article
Full-text available
Presenilin1 (PS1), a protein involved in cellular development, forms functional complexes with β-catenin, a regulator of Wnt signaling and cell-cell adhesion. In addition, both proteins have been shown to play important roles in disease including cancer and Alzheimer disease. Although PS1 and β-catenin are found in the same complexes, it is not cle...
Article
Full-text available
We have previously reported that severe heat shock of HeLa cells stably transfected with a chloramphenicol acetyltransferase (CAT) gene, transcription of which is controlled by two glucocorticoid-responsive elements and a minimal promoter, pronouncedly enhanced glucocorticoid-induced CAT expression compared to that of non-heated cells, in spite of...
Article
Full-text available
E-cadherin controls a wide array of cellular behaviors including cell-cell adhesion, differentiation and tissue development. Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease, controls a gamma-secretase-like cleavage of E-cadherin. This cleavage is stimulated by apoptosis or calcium influx and occurs between human E-ca...
Article
Full-text available
Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease, binds directly to epithelial cadherin (E-cadherin). This binding is mediated by the large cytoplasmic loop of PS1 and requires the membrane-proximal cytoplasmic sequence 604-615 of mature E-cadherin. This sequence is also required for E-cadherin binding of protein p120...
Article
Full-text available
Presenilin-1 is polytopic transmembrane protein expressed in many tissues, including embryonic and adult brain, where it is enriched in neurons. PS1 mutations are responsible for most cases of early-onset autosomal dominant familial Alzheimer's disease. Recently we showed that PS1 concentrates at synaptic and epithelial cell-cell contact sites, whe...
Article
Full-text available
Following 70% hepatectomy, the induction of tyrosine amino-transferase mRNA by glucocorticoids was marginal at 1.5 h, significantly impaired between 3 and 8 h and, at 16 h post-hepatectomy, reached a value approx. 5-fold the basal level, similar to the level observed in quiescent liver. The fold induction of the mRNA was accounted for by a similar...
Article
Full-text available
Following a two-thirds partial hepatectomy, an approximately fivefold increase in the levels of nuclear and total mRNA for tyrosine aminotransferase was observed at 1 h and 1.5 h, respectively, and a return to the levels of the quiescent state, i.e. the levels found in non-operated livers from adrenalectomized rats, was established 16 h post-hepate...
Article
Full-text available
Transformation of the glucocorticoid-receptor complex by heating the cytosol in the presence of calcium is accompanied by formation of a series of truncated complexes, of which DI and DIIc are the major members. Formation of DIIc (but not of DI) is inhibited by leupeptin, and the intact transformed complex DIIa appears instead. Estimation of the mo...

Network

Cited By

Projects

Project (1)
Project
Study of GPCR biased agonism Development of cell based assays to monitor GPCR/β-Arrestin signaling