About

Benita Sjogren is an Assistant Professor in the Department of Pharmaceutical Sciences at the University of California, Irvine. She holds a Ph.D. from the Karolinska Institute (2008) in Pharmacology and an M.S. from Stockholm University (2002) in Molecular Biology. Her research focuses on molecular pharmacology, signal transduction, and drug discovery, with particular emphasis on G protein-coupled receptors (GPCRs) and Regulator of G protein Signaling (RGS) proteins. Her work aims to understand the mechanisms regulating RGS protein levels and functions, and how this knowledge can be applied in drug discovery, especially given the role of RGS proteins as drug targets in diseases such as hypertension, cancer, and Parkinson's disease. Sjogren's research investigates the regulation of RGS proteins through transcriptional, epigenetic, and posttranslational mechanisms, including degradation pathways, and explores their potential in therapeutic development.

Research topics

• Computer Science
• Bioinformatics
• Biology
• Information Retrieval
• Biochemistry
• Computational biology
• Pharmacology
• Cell biology
• World Wide Web
• Medicine
• Chemistry
• Immunology

Selected publications

• Regulator of G Protein Signaling 2 (RGS2) Regulates Gs- and Gq-Mediated Endosomal G Protein-Coupled Receptor Signaling (Abstract ID: 225562)

  Journal of Pharmacology and Experimental Therapeutics · 2026-05-01

  articleSenior author
  PublisherDOI

• RGS2 Suppresses Gαq/11 Driven Uveal Melanoma Cell Growth (Abstract ID: 226528)

  Journal of Pharmacology and Experimental Therapeutics · 2026-05-01

  articleSenior author
  PublisherDOI

• Bioinformatic Analysis Reveals a Role for RGS10 in Regulating Microglial Migration (Abstract ID: 229085)

  Journal of Pharmacology and Experimental Therapeutics · 2026-05-01

  articleSenior author
  PublisherDOI

• Discovery of RGS2-FBXO44 interaction inhibitors using a cell-based NanoBit assay

  Molecular Pharmacology · 2025-03-19 · 5 citations

  articleOpen accessSenior author

  Regulators of G protein signaling (RGS) proteins negatively regulate signaling through G protein-coupled receptors, and reduced RGS protein function is involved in numerous pathologies. However, therapeutic intervention is challenging, as RGS proteins lack druggable binding pockets and enzymatic activity. Instead, targeting mechanisms that control RGS protein expression show promise as an alternative. Pharmacological stabilization of RGS2 would be a feasible therapeutic strategy in pathologies associated with reduced RGS2 protein levels, such as hypertension, heart failure, and asthma. RGS2 is rapidly degraded through the ubiquitin-proteasomal system, and we recently identified the E3 ligase that recognizes RGS2. F-box Only Protein 44 (FBXO44) acts as the substrate recognition site for RGS2 in this E3 ligase complex, and we hypothesize that inhibiting the RGS2-FBXO44 interaction will lead to enhanced RGS2 levels. Here, we developed a NanoLuc Binary Technology (NanoBiT) assay that detects the interaction between RGS2 and FBXO44. This assay was used to screen 1600 compounds from the Life Chemicals protein-protein interaction fragment library. We identified a promising hit, denoted compound 10, that inhibits the RGS2-FBXO44 interaction with a potency of 19.6 μM, through direct binding to RGS2. The resulting increase in RGS2 protein levels is dependent on FBXO44, as siRNA-mediated FBXO44 knockdown attenuates the effect of compound 10. Altogether, compound 10 represents the first example of a small-molecule inhibitor of the RGS2-FBXO44 interaction and a first step toward the development of molecular probes with a defined mechanism to stabilize RGS2 protein levels. SIGNIFICANCE STATEMENT: This study provides a strategy to identify molecules that selectively inhibit RGS2 protein degradation as well as the first example of a compound with the ability to inhibit RGS2 interaction with the E3 ligase component FBXO44. This study provides proof of concept that a small-molecule RGS2-FBXO44 interaction inhibitor will increase RGS2 protein levels. Future development of compounds with this mechanism of action would be clinically useful in pathologies associated with low RGS2 protein levels, including hypertension, heart failure, and asthma.

  PublisherOA PDFDOI

• Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2025.3

  IUPHAR/BPS Guide to Pharmacology CITE · 2025-09-10

  articleOpen access

  Regulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [226, 530, 579, 584, 585, 744, 755, 445, 11].

  PublisherOA PDFDOI

• Bioinformatic analysis identifies RGS10 as a modulator of BV-2 microglia migration

  Cellular Signalling · 2025-12-20

  articleOpen accessSenior authorCorresponding

  Regulator of G protein signaling 10 (RGS10) is a GTPase activating protein, selective for Gα i , that has been proposed to play a role in suppressing microglia-driven neuroinflammation. RGS10 expression in microglia is suppressed by inflammatory stimuli and aging, and loss of RGS10 is associated with increased cytokine expression and neurodegeneration. Conversely, RGS10 overexpression provides protection against inflammatory stimuli in rodent models, however the mechanisms by which RGS10 exerts this protective effect are unknown. To understand the neuroprotective functions of RGS10 in microglia, we completed RNA-Seq analysis in the murine microglial cell line BV-2 with intact (BV-2 WT ) and absent (RGS10 −/− ) RGS10 expression, with or without interferon-γ (IFNγ)-stimulation. We identified genes whose expression were altered as a result of RGS10 loss, IFNγ stimulation, or both. As expected, RGS10 loss resulted in changes in processes such as GPCR signaling and synaptic signaling. However, this analysis also revealed that processes such as cell migration and adhesion were altered in RGS10 −/− cells, under both basal and IFNγ-stimulated conditions. Key cell adhesion genes such as Mmp9 and Thbs1 were downregulated in RGS10 −/− cells regardless of stimuli. Experimentally, loss of RGS10 increased BV-2 cell migration, and IFNγ stimulation led to a reduction in migration of both BV-2 WT and RGS10 −/− cells. The effect of RGS10 on migration could only partially be blocked by the Gα i inhibitor Pertussis toxin (PTX), suggesting involvement of both G protein-dependent and -independent mechanisms. Altogether, these results suggest a novel role for RGS10 in reducing microglial migration through regulation of cell adhesion genes. • RGS10 suppresses microglial-driven neuroinflammation through unknown mechanisms. • RNA-Seq analysis revealed that RGS10 suppresses BV-2 cell migration and adhesion. • The effect of RGS10 on migration is both G protein-dependent and -independent. • IFNγ stimulation reduces BV-2 cell migration independent of RGS10.

  PublisherDOI

• G protein regulation by RGS proteins in the pathophysiology of dilated cardiomyopathy

  American Journal of Physiology-Heart and Circulatory Physiology · 2025-01-07

  reviewOpen access

  Regulators of G protein signaling (RGS) proteins fine-tune signaling via heterotrimeric G proteins to maintain physiologic homeostasis in various organ systems of the human body including the brain, kidney, heart, and vasculature. Impaired regulation of G protein signaling by RGS proteins is implicated in the pathogenesis of several human diseases including various forms of cardiomyopathy such as hypertrophic cardiomyopathy and dilated cardiomyopathy (DCM). Both genetic and nongenetic changes that impinge on G protein signaling in cardiomyocytes are implicated in the etiology of DCM, and there is accumulating evidence that such genetic and nongenetic changes affecting G protein signaling in cell types other than cardiomyocytes could serve as a DCM trigger in humans. This review discusses and highlights mammalian RGS proteins and their roles in cardiac physiology and disease, with a specific focus on the current understanding of the etiology of DCM and the pathogenic roles of RGS proteins that are prominently expressed in the cardiovascular system. Growing evidence suggests that defects in G protein regulation by RGS proteins in the cardiovascular system likely contribute to cardiomyocyte structural damage and decreased contractile function that hallmark DCM. Further studies that enhance the understanding of the dynamics of G protein regulation by RGS proteins in several cell types in the myocardium and the vasculature are critical to gaining more insight into the etiology of DCM and heart failure, and to the identification of novel therapeutic targets.

  PublisherDOI

• Identification of Small Molecule Modulators of RGS10 in BV-2 Microglial Cells (Abstract ID: 157722)

  Journal of Pharmacology and Experimental Therapeutics · 2025-03-01

  articleSenior author
  PublisherDOI

• Systematic analysis of the RGS2 degron reveals characteristics of substrate recognition by the F-box protein FBXO44

  Journal of Biological Chemistry · 2025-09-23

  articleOpen accessSenior author

  Regulator of G protein signaling 2 (RGS2) negatively modulates signaling downstream of G protein-coupled receptors by accelerating GTP hydrolysis at Gα subunits of heterotrimeric G proteins. Decreased RGS2 levels are implicated in numerous diseases, including cardiovascular disease and asthma. Thus, identifying selective means of enhancing RGS2 protein levels would be a viable therapeutic strategy. RGS2 is rapidly degraded through the ubiquitin-proteasomal pathway, and we previously identified F-box only protein 44 (FBXO44) as the substrate recognition component of the E3 ligase responsible for facilitating RGS2 degradation. As such, the RGS2-FBXO44 interaction is a potential target for pharmacological intervention. Detailed information on the FBXO44 recognition site (degron) in RGS2 will aid in structure-based small-molecule inhibitor design, as well as in identifying additional FBXO44 targets, which would help predict possible side effects of targeting this interaction. Thus, the goal of this study was to dissect the molecular properties for FBXO44 binding of the RGS2 degron. We used a peptide array utilizing systematic residue substitution, combined with AlphaFold modeling and molecular dynamics simulations, to identify several amino acid changes that altered binding both positively and negatively. Finally, we experimentally confirmed our results in cells through coimmunoprecipitation and proteasomal inhibition, using full-length RGS2. Altogether, these results provide structural insights into RGS2-FBXO44 binding, which will aid in structure-guided drug discovery efforts. It also provides a framework for building a consensus recognition motif for FBXO44, which could aid in identifying more substrates for this understudied F-box protein.

  PublisherOA PDFDOI

• Determining molecular characteristics of the RGS2-FBXO44 interaction – A multipronged approach

  Journal of Pharmacology and Experimental Therapeutics · 2024-05-13

  articleSenior author
  PublisherDOI

Frequent coauthors

• Richard R. Neubig

  Michigan State University

  107 shared

• Lauren Aschermann

  The Ohio State University Wexner Medical Center

  85 shared

• Avi Raveh

  Tel Aviv University

  81 shared

• Colleen Carpenter

  Neurological Surgery

  81 shared

• Shugeng Cao

  University of Hawaii at Hilo

  81 shared

• Giselle Tamayo‐Castillo

  Universidad de Costa Rica

  81 shared

• Jon Clardy

  Harvard University

  81 shared

• Pamela J. Schultz

  University of Michigan–Ann Arbor

  81 shared

Labs

• SJOGREN LABPI

  Not provided

Education

• PhD, Physiology & Pharmacology

  Karolinska Institutet

  2008

• MSc, Molecular Biology

  Stockholm University

  2002

Awards & honors

• Postdoctoral Research Fellow, Department of Pharmacology, Un…
• Research Assistant Professor, Department of Pharmacology and…
• Assistant Professor, Department of Medicinal Chemistry and M…
• National Institutes of Health; 01GM143493 “Posttranslational…
• American Heart Association