Research Summary:
In the process of development, a single egg cell develops into a complex organism. Understanding how that first cell generates such astonishing complexity is one of biology's great tasks. Not only is this task fundamental to our understanding of ourselves, but it is also critical to understanding the causes of birth defects and other diseases. Many of the mechanisms underlying development depend on intercellular communication, the ability of cells to send and receive information. Secreted signaling proteins can communicate many different types of information, from what type of cell a cell should become to whether a cell should live or die. We are studying the mechanisms by which a cellular organelle, the primary cilium, receives and interprets these signals during development. We are also studying how mistakes in these signals contribute to diseases such as cancer.
Publications
A stem cell-based platform for functional analysis of genetic variants in lung disease.
Primary cilia and BBS4 are required for postnatal pituitary development.
The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture.
Smoothened inhibition of PKA at cilia transduces Hedgehog signals.
Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions.
Multicilia dynamically transduce Shh signaling to regulate choroid plexus functions.
ADPKD-Causing Missense Variants in Polycystin-1 Disrupt Cell Surface Localization or Polycystin Channel Function.
The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture.
Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.
Cilia-enriched oxysterol 7β,27-DHC is required for polycystin ion channel activation.
Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.
Rab35 Is Required for Embryonic Development and Kidney and Ureter Homeostasis through Regulation of Epithelial Cell Junctions.
Emerging mechanistic understanding of cilia function in cellular signalling.
GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway.
Polycystin-2-dependent transcriptome reveals early response of autosomal dominant polycystic kidney disease.
Rab35 is required for embryonic development and kidney and ureter homeostasis through regulation of epithelial cell junctions.
An RFX transcription factor regulates ciliogenesis in the closest living relatives of animals.
Hedgehog target genes regulate lipid metabolism to drive basal cell carcinoma and medulloblastoma.
Seriously cilia: A tiny organelle illuminates evolution, disease, and intercellular communication.
GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway.
A kinesin mimics DNA.
The Intimate Connection Between Lipids and Hedgehog Signaling.
The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans.
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity.
ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas.
Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation.
A ciliopathy complex builds distal appendages to initiate ciliogenesis.
Label-retention expansion microscopy.
Melanocortin 4 receptor signals at the neuronal primary cilium to control food intake and body weight.
Smoothened-activating lipids drive resistance to CDK4/6 inhibition in Hedgehog-associated medulloblastoma cells and preclinical models.
Sterol and oxysterol synthases near the ciliary base activate the Hedgehog pathway.
How the centriole builds its cilium: of mothers, daughters, and the acquisition of appendages.
SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL.
Hedgehog Pathway Activation Alters Ciliary Signaling in Primary Hypothalamic Cultures.
Misactivation of Hedgehog signaling causes inherited and sporadic cancers.
Cilia-Associated Oxysterols Activate Smoothened.
How the Ciliary Membrane Is Organized Inside-Out to Communicate Outside-In.
Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.
Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.
Hedgehog signaling drives medulloblastoma growth via CDK6.
Erratum: Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome.
Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome.
Genes and molecular pathways underpinning ciliopathies.
Cilia and Obesity.
Open Sesame: How Transition Fibers and the Transition Zone Control Ciliary Composition.
Endothelial primary cilia inhibit atherosclerosis.
Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling.
Phosphoinositides Regulate Ciliary Protein Trafficking to Modulate Hedgehog Signaling.
TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone.
Ciliary vesicle formation: a prelude to ciliogenesis.
Hair follicle and interfollicular epidermal stem cells make varying contributions to wound regeneration.
C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals.
A central region of Gli2 regulates its localization to the primary cilium and transcriptional activity.
Hedgehog signaling controls T cell killing at the immunological synapse.
Keratin 79 identifies a novel population of migratory epithelial cells that initiates hair canal morphogenesis and regeneration.
Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism.
Kif3a interacts with Dynactin subunit p150 Glued to organize centriole subdistal appendages.
Trask loss enhances tumorigenic growth by liberating integrin signaling and growth factor receptor cross-talk in unanchored cells.
Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis.
Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access.
A high-fat diet regulates gastrin and acid secretion through primary cilia.
Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal.
Disruption of a ciliary B9 protein complex causes Meckel syndrome.
A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.
Role of epidermal primary cilia in the homeostasis of skin and hair follicles.
Wounding mobilizes hair follicle stem cells to form tumors.
Crippling SWI-SNF makes tumors GLI-ful.
The ciliogenic protein Oral-Facial-Digital 1 regulates the neuronal differentiation of embryonic stem cells.
Tilting at nodal windmills: planar cell polarity positions cilia to tell left from right.
Vive la science! Vive le hérisson!
Ofd1, a human disease gene, regulates the length and distal structure of centrioles.
Floxin, a resource for genetically engineering mouse ESCs.
Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis.
The extracellular domain of Smoothened regulates ciliary localization and is required for high-level Hh signaling.
Building it up and taking it down: the regulation of vertebrate ciliogenesis.
A cilium is not a cilium is not a cilium: signaling contributes to ciliary morphological diversity.
Neur-ons and neur-offs: regulators of neural induction in vertebrate embryos and embryonic stem cells.
The primary cilium at the crossroads of mammalian hedgehog signaling.
Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms.
Vesicle transport, cilium formation, and membrane specialization: the origins of a sensory organelle.
The primary cilium as the cell's antenna: signaling at a sensory organelle.
Tectonic, a novel regulator of the Hedgehog pathway required for both activation and inhibition.
Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli.
Notch signaling can regulate endoderm formation in zebrafish.
Bmp2b and Oep promote early myocardial differentiation through their regulation of gata5.
Multiple roles for Gata5 in zebrafish endoderm formation.
The zebrafish bonnie and clyde gene encodes a Mix family homeodomain protein that regulates the generation of endodermal precursors.
Gata5 is required for the development of the heart and endoderm in zebrafish.
Extracellular signal regulated kinases. Localization of protein and mRNA in the human hippocampal formation in Alzheimer's disease.
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