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Nikoleta Georgieva Tsvetanova

Assistant Professor of Pharmacology and Cancer Biology
Pharmacology & Cancer Biology

Selected Publications


Chemical biology approaches to resolve the subcellular GPCR signaling landscape.

Journal Article Nat Chem Biol · August 2025 G-protein-coupled receptors (GPCRs) are the largest class of membrane receptors and key drug targets. Over the past decade, extensive evidence has shown that GPCRs signal from various intracellular compartments to generate distinct cellular and physiologic ... Full text Link to item Cite

An engineered trafficking biosensor reveals a role for DNAJC13 in DOR downregulation.

Journal Article Nat Chem Biol · March 2025 Trafficking of G protein-coupled receptors (GPCRs) through the endosomal-lysosomal pathway is critical to homeostatic regulation of GPCRs following activation with agonist. Identifying the genes involved in GPCR trafficking is challenging due to the comple ... Full text Link to item Cite

Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.

Journal Article Proc Natl Acad Sci U S A · February 25, 2025 G protein-coupled receptors (GPCRs) modulate various physiological functions by rewiring cellular gene expression in response to extracellular signals. Control of gene expression by GPCRs has been studied almost exclusively at the transcriptional level, ne ... Full text Link to item Cite

Functional diversification of cell signaling by GPCR localization.

Journal Article J Biol Chem · March 2024 G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and a critical class of regulators of mammalian physiology. Also known as seven transmembrane receptors (7TMs), GPCRs are ubiquitously expressed and versatile, detecting a ... Full text Link to item Cite

Endosome positioning coordinates spatially selective GPCR signaling.

Journal Article Nat Chem Biol · February 2024 G-protein-coupled receptors (GPCRs) can initiate unique functional responses depending on the subcellular site of activation. Efforts to uncover the mechanistic basis of compartmentalized GPCR signaling have concentrated on the biochemical aspect of this r ... Full text Link to item Cite

The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction.

Journal Article J Biol Chem · September 2023 RBM12 is a high-penetrance risk factor for familial schizophrenia and psychosis, yet its precise cellular functions and the pathways to which it belongs are not known. We utilize two complementary models, HEK293 cells and human iPSC-derived neurons, and de ... Full text Link to item Cite

Endosomal cAMP production broadly impacts the cellular phosphoproteome.

Journal Article J Biol Chem · July 2021 Endosomal signaling downstream of G-protein-coupled receptors (GPCRs) has emerged as a novel paradigm with important pharmacological and physiological implications. However, our knowledge of the functional consequences of intracellular signaling is incompl ... Full text Link to item Cite

A high-throughput CRISPR interference screen for dissecting functional regulators of GPCR/cAMP signaling.

Journal Article PLoS genetics · October 2020 G protein-coupled receptors (GPCRs) allow cells to respond to chemical and sensory stimuli through generation of second messengers, such as cyclic AMP (cAMP), which in turn mediate a myriad of processes, including cell survival, proliferation, and differen ... Full text Cite

Chemical Biology Approaches for Genome‐Wide Screening of GPCR Trafficking

Conference The FASEB Journal · April 2020 G protein‐coupled receptor (GPCRs) are the largest family of membrane‐bound signal transduction molecules. Many of these receptors have a complex lifecycle which includes residence at ... Full text Cite

Mechanistic Dissection of Spatially Encoded GPCR Signaling Through High‐throughput CRISPR Screening

Conference The FASEB Journal · April 2020 Our recent work has overturned the prevailing textbook model for GPCR signaling, which held that GPCR activation at the plasma membrane is responsible for all downstream consequences ... Full text Cite

G Protein-Coupled Receptor Endocytosis Confers Uniformity in Responses to Chemically Distinct Ligands.

Journal Article Mol Pharmacol · February 2017 The ability of chemically distinct ligands to produce different effects on the same G protein-coupled receptor (GPCR) has interesting therapeutic implications, but, if excessively propagated downstream, would introduce biologic noise compromising cognate l ... Full text Link to item Cite

The role of GPCR localization in signal transduction

Conference MOLECULAR BIOLOGY OF THE CELL · January 1, 2016 Link to item Cite

Effects of endocytosis on receptor-mediated signaling.

Journal Article Curr Opin Cell Biol · August 2015 Cellular mechanisms of membrane traffic and signal transduction are deeply interconnected. The present review discusses how membrane trafficking in the endocytic pathway impacts receptor-mediated signaling. Examples of recent progress are highlighted, focu ... Full text Link to item Cite

G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins from endosomes.

Journal Article J Biol Chem · March 13, 2015 Some G protein-coupled receptors (GPCRs), in addition to activating heterotrimeric G proteins in the plasma membrane, appear to elicit a "second wave" of G protein activation after ligand-induced internalization. We briefly summarize evidence supporting th ... Full text Link to item Cite

Spatial encoding of cyclic AMP signaling specificity by GPCR endocytosis.

Journal Article Nat Chem Biol · December 2014 G protein-coupled receptors (GPCRs) are well known to signal via cyclic AMP (cAMP) production at the plasma membrane, but it is now clear that various GPCRs also signal after internalization. Apart from its temporal impact through prolonging the cellular r ... Full text Link to item Cite

The secretory pathway in control of endoplasmic reticulum homeostasis.

Journal Article Small GTPases · 2013 In eukaryotic cells, proteins and membranes are transported between successive compartments by vesicle trafficking. Since precise protein localization is crucial for a range of cellular functions, it is not surprising that vesicle trafficking plays a role ... Full text Link to item Cite

The yeast Rab GTPase Ypt1 modulates unfolded protein response dynamics by regulating the stability of HAC1 RNA.

Journal Article PLoS Genet · 2012 The unfolded protein response (UPR) is a conserved mechanism that mitigates accumulation of unfolded proteins in the ER. The yeast UPR is subject to intricate post-transcriptional regulation, involving recruitment of the RNA encoding the Hac1 transcription ... Full text Link to item Cite

Proteome-wide search reveals unexpected RNA-binding proteins in Saccharomyces cerevisiae.

Journal Article PLoS One · September 10, 2010 The vast landscape of RNA-protein interactions at the heart of post-transcriptional regulation remains largely unexplored. Indeed it is likely that, even in yeast, a substantial fraction of the regulatory RNA-binding proteins (RBPs) remain to be discovered ... Full text Link to item Cite