Irina Kufareva

About

Irina Kufareva, Ph.D, is a professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences with a research focus on structural, molecular, and architectural principles of tumor and immune cell responses to stimuli and drugs through computational approaches. Her work primarily centers on GPCRs and G proteins, key classes of cell signaling molecules, where she develops methods for accurate computational prediction of transient interactions of proteins and chemicals with conformationally variable protein interfaces. Her research includes elucidating the structural basis of ligand binding and signaling in chemokine GPCRs such as CXCR4, ACKR3, CCR5, and CCR2, which are involved in cancer progression, metastasis, HIV infection, inflammation, and autoimmunity. Additionally, she has contributed to understanding non-receptor activation of heterotrimeric G proteins and has solved the first structure of a G protein complexed with a non-receptor activator. Her recent work involves network-based modeling and reverse-engineering of cell signaling to decode principles of biological information transfer, aiming to inform therapeutic strategies in cancer and inflammatory diseases. Dr. Kufareva holds a background in mathematics and computer science from Tomsk State University and completed postdoctoral training in Computational Structural Biology at The Scripps Research Institute. She has served as Associate Founding Director of the UC San Diego Center for Network Medicine and has…

Research topics

• Biology
• Cell biology
• Pharmacology
• Neuroscience
• Internal medicine
• Chemistry
• Medicine
• Biochemistry
• Computational biology
• Immunology

Selected publications

• TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin

  Proceedings of the National Academy of Sciences · 2020 · 103 citations

  Sensing of pathogens by Toll-like receptor 4 (TLR4) induces an inflammatory response; controlled responses confer immunity but uncontrolled responses cause harm. Here we define how a multimodular scaffold, GIV (a.k.a. Girdin), titrates such inflammatory response in macrophages. Upon challenge with either live microbes or microbe-derived lipopolysaccharides (a ligand for TLR4), macrophages with GIV mount a more tolerant (hypo-reactive) transcriptional response and suppress proinflammatory cytokin…

  DOI

• Normalization of cholesterol metabolism in spinal microglia alleviates neuropathic pain

  The Journal of Experimental Medicine · 2021 · 101 citations

  Neuroinflammation is a major component in the transition to and perpetuation of neuropathic pain states. Spinal neuroinflammation involves activation of TLR4, localized to enlarged, cholesterol-enriched lipid rafts, designated here as inflammarafts. Conditional deletion of cholesterol transporters ABCA1 and ABCG1 in microglia, leading to inflammaraft formation, induced tactile allodynia in naive mice. The apoA-I binding protein (AIBP) facilitated cholesterol depletion from inflammarafts and reve…

  DOI

• Functional anatomy of the full-length CXCR4-CXCL12 complex systematically dissected by quantitative model-guided mutagenesis

  Science Signaling · 2020-07-14 · 49 citations

  articleOpen accessCorresponding

  Because of their prominent roles in development, cancer, and HIV, the chemokine receptor CXCR4 and its ligand CXCL12 have been the subject of numerous structural and functional studies, but the determinants of ligand binding, selectivity, and signaling are still poorly understood. Here, building on our latest structural model, we used a systematic mutagenesis strategy to dissect the functional anatomy of the CXCR4-CXCL12 complex. Key charge swap mutagenesis experiments provided evidence for pair…

  PublisherOA PDFDOI

• Receptor tyrosine kinases activate heterotrimeric G proteins via phosphorylation within the interdomain cleft of Gαi

  Proceedings of the National Academy of Sciences · 2020 · 36 citations

  The molecular mechanisms by which receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major signaling hubs in eukaryotes, independently relay signals across the plasma membrane have been extensively characterized. How these hubs cross-talk has been a long-standing question, but answers remain elusive. Using linear ion-trap mass spectrometry in combination with biochemical, cellular, and computational approaches, we unravel a mechanism of activation of heterotrimeric G proteins by…

  PublisherOA PDFDOI

• A lymphocyte chemoaffinity axis for lung, non-intestinal mucosae and CNS

  Nature · 2024-09-18 · 29 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM117424

  NIH · $2.2M · 2020

• Computationally informed discovery of scavenging-sparing inhibitors of CC chemokine receptor 2

  NIH · $434k · 2020–2024

• NIH Grant R01AI118985

  NIH · $2.7M · 2021

Frequent coauthors

• Ruben Abagyan

  University of Montana

  155 shared

• Tracy M. Handel

  University of California, San Diego

  74 shared

• Pradipta Ghosh

  University of California, San Diego

  33 shared

• Tony Ngo

  Học viện Tư pháp

  26 shared

• Anne B. Young

  Defence Research and Development Canada

  25 shared

• Mel Β. Feany

  Brigham and Women's Hospital

  25 shared

• Tiago F. Outeiro

  25 shared

• Allison Amore

  Massachusetts General Hospital

  25 shared

Awards & honors

• Invited lectures at the ASCEPT-MPGPCR Joint Scientific Meeti…
• 5th Hawaiian GPCR workshop, Kona, Hawaii (2017)
• 256th ACS National Meeting, Boston, MA (2018)
• Gordon Research Conference on Molecular Pharmacology, Ventur…
• Mail-in reviewer for the NIH NCF study section (2017)

Similar researchers at University of California, San Diego

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• William Gerwickh-114