About

Paul Khavari is the principal investigator of the Khavari lab at Stanford University, affiliated with the Stanford School of Medicine in the Department of Dermatology and the Program in Epithelial Biology. His research focuses on understanding the molecular mechanisms underlying epithelial biology, cancer, and skin diseases. As a professor, he contributes to advancing knowledge in these areas through his leadership of the lab and collaboration with a team of research scientists, graduate students, and postdoctoral fellows. The lab's work involves exploring the genetic and biochemical pathways that regulate epithelial cell function and transformation, aiming to develop targeted therapies for skin-related conditions and cancers. Paul Khavari's role encompasses guiding research efforts, mentoring students and scientists, and fostering innovative approaches to biomedical research in epithelial biology and oncology.

Research topics

• Genetics
• Biology
• Computational biology
• Medicine
• Pathology
• Cancer research
• Immunology
• Cell biology

Selected publications

• Characterizations of G-Quadruplex RNA-Protein Interactions in Living Cells

  Analytical Chemistry · 2026-04-17

  article

  RNA guanine quadruplexes (rG4s) are noncanonical nucleic acid structures that contribute to diverse cellular functions and disease mechanisms. Defining the proteins that interact with rG4s (rG4IPs) is essential for elucidating their biological roles. Here, we build on the RNA–protein interaction detection (RaPID) platform to develop G4-RaPID, a tailored chemoproteomic strategy for the unbiased profiling of rG4IPs in living cells. Using G4-RaPID, we identified 105 candidate rG4IPs that were commonly enriched across three distinct rG4 sequences. Biochemical analyses confirmed that recombinant hnRNPA0, CHD4, and IGF2BP1 proteins directly bind rG4 structures in vitro. In addition, CLIP-seq experiments revealed significant enrichment of hnRNPA0 binding at endogenous rG4 loci. Luciferase reporter assays further demonstrated that hnRNPA0 engages the rG4 in the 5′ UTR of NRAS mRNA to negatively regulate its translation. Together, these results establish G4-RaPID as a robust approach for mapping rG4–protein interactions in living cells and document hnRNPA0–rG4 recognition as a regulatory mechanism controlling NRAS mRNA translation.

  PublisherDOI

• Bridging technical innovation and computational advances in studies of RNA–protein assemblies

  Nature Reviews Genetics · 2026-02-16

  articleSenior author
  PublisherDOI

• irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein assemblies on RNA

  Nature · 2025-03-26 · 14 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• In Vivo CRISPR Interference Screen Reveals Long Noncoding RNA Portfolio Crucial for Cutaneous Squamous Cell Carcinoma Tumor Growth

  Journal of Investigative Dermatology · 2025-05-27 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• 0914 Glucose binds and modulates the function of RNA helicases in epidermal differentiation

  Journal of Investigative Dermatology · 2025-07-21

  articleSenior author
  PublisherDOI

• The adhesion GPCR ADGRL2 engages Gα13 to enable epidermal differentiation

  Proceedings of the National Academy of Sciences · 2025-11-18 · 1 citations

  articleOpen accessSenior authorCorresponding

  Homeostasis relies on signaling networks controlled by cell membrane receptors. Although G-protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors, their specific roles in the epidermis are not fully understood. Dual CRISPR-Flow and single cell Perturb RNA-sequencing knockout screens of all epidermal GPCRs were thus performed, uncovering an essential requirement for adhesion GPCR ADGRL2 (latrophilin 2) in epidermal differentiation. Among potential downstream guanine nucleotide-binding G proteins, ADGRL2 selectively activated Gα13. Follow-up tissue knockouts verified that Gα13 is also required for epidermal differentiation. A cryoelectron microscopy structure in lipid nanodiscs showed that ADGRL2 engages with Gα13 at multiple interfaces, including via an interaction between ADGRL2 intracellular loop 3 and a Gα13-specific QQQ glutamine triplet sequence in its GTPase domain. In situ gene mutation of this interface sequence impaired epidermal differentiation, highlighting an essential new role for an ADGRL2-Gα13 axis in epidermal differentiation.

  PublisherDOI

• Functional analysis of cancer-associated germline risk variants

  Nature Genetics · 2025-02-17 · 10 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Thermal proteome profiling identifies glucose binding proteins involved in metabolic disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-07 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Recent work has shown that glucose can directly bind non-enzymatic proteins to modulate their function. We sought to build on this work by adapting thermal proteome profiling screens to uncover novel glucose interactors involved in metabolism. Proteome integral solubility alternation (PISA) profiling nominated 23 proteins with glucose-induced thermal solubility, including two proteins strongly implicated in metabolic disease, TSC22D4 and IGF2BP2. First, we characterized glucose binding of TSC22D4, an intrinsically disordered leucine zipper protein strongly implicated in hepatic steatosis. MST confirmed direct glucose-protein interaction of TSC22D4. UV-crosslinking mass spectrometry identified putative glucose binding at the C-terminal leucine zipper. Mutating isoleucine 322 to tryptophan (I322W) abolishes glucose binding. Crosslinking-MS and chemo-proteomic experiments suggest that glucose increases accessibility of the leucine zipper region, resulting in intra-protein contacts between C-terminal zipper domain and N-terminal intrinsically-disordered domain. TSC22D4 associates with fatty acid metabolism machinery proteins in response to high glucose conditions, suggesting a possible role for TSC22D4 in altering fatty acid metabolism. Next, we characterized glucose-binding in IGF2BP2, an RNA-binding protein essential for beta cell insulin secretion. We first confirmed direct IGF2BP2-glucose interaction and created glucose-binding mutant Y40A based on computational docking predictions. IGF2BP2 Y40A exhibited a dominant negative impact on proliferation and insulin secretion in MIN6-6 beta cells. Glucose increased IGF2BP2 binding to client mRNAs Igf2 and Pdx1, which has previously been demonstrated to mediate its impact on insulin secretion. Thus, our data suggests that IGF2BP2 directly binds glucose to enhance insulin secretion.

  PublisherOA PDFDOI

• 0522 Sumoylation and neddylation are opposing forces in stratified epithelial homeostasis

  Journal of Investigative Dermatology · 2025-07-21

  articleSenior author
  PublisherDOI

• Disease-linked regulatory DNA variants and homeostatic transcription factors in epidermis

  Nature Communications · 2025-09-25 · 2 citations

  articleOpen accessSenior authorCorresponding

  Identifying noncoding single nucleotide variants (SNVs) in regulatory DNA linked to polygenic disease risk, the transcription factors (TFs) they bind, and the genes they dysregulate is a goal in polygenic disease research. Here, we use massively parallel reporter analysis of 3451 SNVs linked to risk for polygenic skin diseases with disrupted epidermal homeostasis to identify 355 differentially active SNVs (daSNVs). daSNV target gene analysis, combined with daSNV editing, underscored dysregulated epidermal differentiation as a shared pathomechanism. CRISPR knockout screens of 1772 human TFs revealed 123 TFs essential for epidermal homeostasis, highlighting ZNF217 and CXXC1. Population sampling CUT&RUN of 27 homeostatic TFs identified allele-specific DNA binding (ASB) differences at daSNVs enriched near epidermal homeostasis and monogenic skin disease genes, with notable representation of SP/KLF and AP-1/2 TFs. High TF-occupancy promoters were "buffered" against ASB. This resource implicates dysregulated binding of specific homeostatic TF families in risk for diverse polygenic skin diseases.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R29AR043799

  NIH · $338k · 2001

• Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa

  NIH · $3.5M · 2009–2015

• Regulators of Tumorigenesis

  NIH · $3.5M · 2010–2022

• NIH Grant P01AR044012

  NIH · $21.7M · 2008

• NIH Grant R55AR043371

  NIH · $41k · 1996

Frequent coauthors

• Zurab Siprashvili

  Stanford University

  66 shared

• Howard Y. Chang

  Stanford University

  64 shared

• Qun Lin

  Wenzhou Central Hospital

  62 shared

• M. Peter Marinkovich

  49 shared

• Adam J. Rubin

  Harvard University Press

  42 shared

• Shiying Tao

  Stanford University

  39 shared

• John W. Tamkun

  University of California, Santa Cruz

  38 shared

• Brian Zarnegar

  38 shared

Labs

• The Khavari LaboratoryPI