
Professor
Ophthalmology
+1 415 476-3592
Douglas Gould, PhD studies the extracellular matrix – fundamental non-cellular components of all tissues. Specifically, he studies collagens that are critical components of specialized ECM structures called basement membranes. His lab is working to understand 1) fundamental collagen biosynthesis, 2) how mutations in basement membrane collagens cause a multisystem disorder that includes perinatal stroke and age-related cognitive impairment and dementia, and 3) potential therapeutic interventions including cell-based therapies and gene editing.
Publications
A multifunction murine Col4a1 allele reveals potential gene therapy parameters for Gould syndrome.
The Journal of cell biology
Skeletal pathology in mouse models of Gould syndrome is partially alleviated by genetically reducing TGFβ signaling.
Matrix biology : journal of the International Society for Matrix Biology
Evaluating neural crest cell migration in a Col4a1 mutant mouse model of ocular anterior segment dysgenesis.
Cells & development
TGFß Signaling Dysregulation May Contribute to COL4A1-Related Glaucomatous Optic Nerve Damage.
Investigative ophthalmology & visual science
Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model.
Proceedings of the National Academy of Sciences of the United States of America
Impaired intracellular Ca2+ signaling contributes to age-related cerebral small vessel disease in Col4a1 mutant mice.
Science signaling
Local Net Charge State of Collagen Triple Helix Is a Determinant of FKBP22 Binding to Collagen III.
International journal of molecular sciences
PI3K block restores age-dependent neurovascular coupling defects associated with cerebral small vessel disease.
Proceedings of the National Academy of Sciences of the United States of America
Deletion of the Unfolded Protein Response Transducer IRE1a Is Detrimental to Aging Photoreceptors and to ER Stress-Mediated Retinal Degeneration.
Investigative ophthalmology & visual science
PI3K block restores age-dependent neurovascular coupling defects associated with cerebral small vessel disease.
bioRxiv : the preprint server for biology
Faulty TRPM4 channels underlie age-dependent cerebral vascular dysfunction in Gould syndrome.
Proceedings of the National Academy of Sciences of the United States of America
Elevated TGF� signaling contributes to cerebral small vessel disease in mouse models of Gould syndrome.
Matrix biology : journal of the International Society for Matrix Biology
Lysyl hydroxylase 3-mediated post-translational modifications are required for proper biosynthesis of collagen a1a1a2(IV).
The Journal of biological chemistry
Elevated TGF� signaling contributes to ocular anterior segment dysgenesis in Col4a1 mutant mice.
Matrix biology : journal of the International Society for Matrix Biology
Autoantigen specific T-cell receptor induces organ-specific autoimmunity by escaping T cell negative selection.
The Journal of Immunology
Development of uveitis in a mouse model of spontaneous autoimmunity correlates with frequency of autoantigen-specific regulatory T cells.
The Journal of Immunology
COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage.
Prenatal diagnosis
Epilepsy and related challenges in children with COL4A1 and COL4A2 mutations: A Gould syndrome patient registry.
Epilepsy & behavior : E&B
Correlation of autoantigen-specific Treg frequency with development of spontaneous organ-specific autoimmunity in a mouse model of uveitis.
The Journal of Immunology
T-cell receptor repertoire of mice with organ-specific autoimmunity resulting from a partial defect in T cell negative selection and dendritic cell enhancement.
The Journal of Immunology
Identification of fibronectin 1 as a candidate genetic modifier in a Col4a1 mutant mouse model of Gould syndrome.
Disease models & mechanisms
Type I and type V procollagen triple helix uses different subsets of the molecular ensemble for lysine posttranslational modifications in the rER.
The Journal of biological chemistry
The novel missense mutation Met48Lys in FKBP22 changes its structure and functions.
Scientific reports
COL4A1 Mutations Cause Neuromuscular Disease with Tissue-Specific Mechanistic Heterogeneity.
American journal of human genetics
Use of sodium 4-phenylbutyrate to define therapeutic parameters for reducing intracerebral hemorrhage and myopathy in Col4a1 mutant mice.
Disease models & mechanisms
Mutations of conserved non-coding elements of PITX2 in patients with ocular dysgenesis and developmental glaucoma.
Human molecular genetics
Genetic dissection of anterior segment dysgenesis caused by a Col4a1 mutation in mouse.
Disease models & mechanisms
Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations.
Matrix biology : journal of the International Society for Matrix Biology
LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity.
The Journal of clinical investigation
Triggering of organ-specific autoimmunity through synergy of defects in key tolerance checkpoints.
The Journal of Immunology
Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.
Current topics in membranes
In Vivo Visualization of Endoplasmic Reticulum Stress in the Retina Using the ERAI Reporter Mouse.
Investigative ophthalmology & visual science
Strain-Dependent Anterior Segment Dysgenesis and Progression to Glaucoma in Col4a1 Mutant Mice.
Investigative ophthalmology & visual science
Spontaneous development of autoimmune uveitis Is CCR2 dependent.
The American journal of pathology
Collagen XVIII short isoform is critical for retinal vascularization, and overexpression of the Tsp-1 domain affects eye growth and cataract formation.
Investigative ophthalmology & visual science
Allelic heterogeneity contributes to variability in ocular dysgenesis, myopathy and brain malformations caused by Col4a1 and Col4a2 mutations.
Human molecular genetics
COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets.
Human molecular genetics
COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage.
Annals of neurology
COL4A2 mutation associated with familial porencephaly and small-vessel disease.
European journal of human genetics : EJHG
Abstract 3665: COL4A1 and COL4A2 Mutations cause Genetically Modifiable Cerebrovascular Diseases.
Stroke
COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke.
American journal of human genetics
Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in FREM1.
Journal of medical genetics
Endoplasmic reticulum stress as a primary pathogenic mechanism leading to age-related macular degeneration.
Advances in experimental medicine and biology
Abnormal expression of collagen IV in lens activates unfolded protein response resulting in cataract.
The Journal of biological chemistry
Developmental distribution of collagen IV isoforms and relevance to ocular diseases.
Matrix biology : journal of the International Society for Matrix Biology
Absence of PITX2, BARX1, and FOXC1 mutations in De Hauwere syndrome (Axenfeld-Rieger anomaly, hydrocephaly, hearing loss): a 25-year follow up.
American journal of medical genetics. Part A
Col4a1 mutation causes endoplasmic reticulum stress and genetically modifiable ocular dysgenesis.
Human molecular genetics
Mutant myocilin nonsecretion in vivo is not sufficient to cause glaucoma.
Molecular and cellular biology
Role of COL4A1 in small-vessel disease and hemorrhagic stroke.
The New England journal of medicine
Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly.
Journal of medical genetics
Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly.
Science (New York, N.Y.)
High-dose radiation with bone marrow transfer prevents neurodegeneration in an inherited glaucoma.
Proceedings of the National Academy of Sciences of the United States of America
Complex genetics of glaucoma susceptibility.
Annual review of genomics and human genetics
Mutational analysis of BARHL1 and BARX1 in three new patients with Joubert syndrome.
American journal of medical genetics. Part A
Genetically increasing Myoc expression supports a necessary pathologic role of abnormal proteins in glaucoma.
Molecular and cellular biology
Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: relevance to ocular dysgenesis and hearing impairment.
BMC medical genetics
Anterior segment development relevant to glaucoma.
The International journal of developmental biology
Anterior segment dysgenesis and the developmental glaucomas are complex traits.
Human molecular genetics
Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25.
European journal of human genetics : EJHG
Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly.
American journal of human genetics
Autosomal Dominant Axenfeld-Rieger Anomaly Maps to 6p25.
The American Journal of Human Genetics
Autosomal dominant Axenfeld-Rieger anomaly maps to 6p25.
American journal of human genetics
Autosomal dominant iridogoniodysgenesis anomaly maps to 6p25.
American journal of human genetics