Douglas Gould, PhD

Professor
Ophthalmology
[email protected]
+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: 

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

Labelle-Dumais C, Mazur C, Kaya S, Obata Y, Lee B, Acevedo C, Alliston T, Gould DB

Evaluating neural crest cell migration in a Col4a1 mutant mouse model of ocular anterior segment dysgenesis.

Cells & development

Cozzitorto C, Peltz Z, Flores LM, Della Santina L, Mao M, Gould DB

TGFß Signaling Dysregulation May Contribute to COL4A1-Related Glaucomatous Optic Nerve Damage.

Investigative ophthalmology & visual science

Mao M, Kuo YM, Yu AK, Labelle-Dumais C, Ou Y, Gould DB

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

Yin M, Smith JA, Chou M, Chan J, Jittayasothorn Y, Gould DB, Caspi RR, Anderson MS, DeFranco AL

Impaired intracellular Ca2+ signaling contributes to age-related cerebral small vessel disease in Col4a1 mutant mice.

Science signaling

Yamasaki E, Thakore P, Ali S, Sanchez Solano A, Wang X, Gao X, Labelle-Dumais C, Chaumeil MM, Gould DB, Earley S

Local Net Charge State of Collagen Triple Helix Is a Determinant of FKBP22 Binding to Collagen III.

International journal of molecular sciences

Ishikawa Y, Bonna A, Gould DB, Farndale RW

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

Thakore P, Yamasaki E, Ali S, Sanchez Solano A, Labelle-Dumais C, Gao X, Chaumeil MM, Gould DB, Earley S

Deletion of the Unfolded Protein Response Transducer IRE1a Is Detrimental to Aging Photoreceptors and to ER Stress-Mediated Retinal Degeneration.

Investigative ophthalmology & visual science

Massoudi D, Gorman S, Kuo YM, Iwawaki T, Oakes SA, Papa FR, Gould DB

PI3K block restores age-dependent neurovascular coupling defects associated with cerebral small vessel disease.

bioRxiv : the preprint server for biology

Thakore P, Yamasaki E, Ali S, Solano AS, Labelle-Dumais C, Gao X, Chaumeil MM, Gould DB, Earley S

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

Yamasaki E, Ali S, Sanchez Solano A, Thakore P, Smith M, Wang X, Labelle-Dumais C, Gould DB, Earley S

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

Branyan K, Labelle-Dumais C, Wang X, Hayashi G, Lee B, Peltz Z, Gorman S, Li BQ, Mao M, Gould DB

Lysyl hydroxylase 3-mediated post-translational modifications are required for proper biosynthesis of collagen a1a1a2(IV).

The Journal of biological chemistry

Ishikawa Y, Taga Y, Coste T, Tufa SF, Keene DR, Mizuno K, Tournier-Lasserve E, Gould DB

Elevated TGF� signaling contributes to ocular anterior segment dysgenesis in Col4a1 mutant mice.

Matrix biology : journal of the International Society for Matrix Biology

Mao M, Labelle-Dumais C, Tufa SF, Keene DR, Gould DB

Autoantigen specific T-cell receptor induces organ-specific autoimmunity by escaping T cell negative selection.

The Journal of Immunology

Mianmian Yin, Jennifer A Smith, Marissa Chou, Jackie Chan, Yongmei Hu, Clifford A Lowell, Douglas B Gould, Mark S Anderson, Anthony L DeFranco

Development of uveitis in a mouse model of spontaneous autoimmunity correlates with frequency of autoantigen-specific regulatory T cells.

The Journal of Immunology

Mianmian Yin, Kamir J Hiam, Irina Proekt, Jackie Chan, Yongmei Hu, Clifford A Lowell, Douglas B Gould, Matthew Spitzer, Mark S Anderson, Anthony L DeFranco

COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage.

Prenatal diagnosis

Coste T, Vincent-Delorme C, Stichelbout M, Devisme L, Gelot A, Deryabin I, Pelluard F, Aloui C, Leutenegger AL, Jouannic JM, H?ron D, Gould DB, Tournier-Lasserve E

Expanding the horizon of research into the�pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition.

GeroScience

Whitehead SN, Bruno A, Burns JM, Carmichael ST, Csiszar A, Edwards JD, Elahi FM, Faraco G, Gould DB, Gustafson DR, Hachinski V, Rosenberg G, Sorond FA, Shih AY, Tse KH, Ungvari Z, Wilcock DM, Zuloaga KL, Barone FC

Correlation of autoantigen-specific Treg frequency with development of spontaneous organ-specific autoimmunity in a mouse model of uveitis.

The Journal of Immunology

Mianmian Yin, Kamir Hiam, Irina Proekt, Jackie Chan, Yongmei Hu, Clifford A Lowell, Douglas B Gould, Mark S Anderson, Anthony L DeFranco

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

Mianmian Yin, Jennifer A Smith, Marissa Chou, Jackie Chan, Yongmei Hu, Clifford A Lowell, Douglas B Gould, Mark S Anderson, Anthony L DeFranco

Identification of fibronectin 1 as a candidate genetic modifier in a Col4a1 mutant mouse model of Gould syndrome.

Disease models & mechanisms

Mao M, Popli T, Jeanne M, Hoff K, Sen S, Gould DB

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

Ishikawa Y, Taga Y, Zientek K, Mizuno N, Salo AM, Semenova O, Tufa SF, Keene DR, Holden P, Mizuno K, Gould DB, Myllyharju J, B?chinger HP

Aberrant binding of mutant HSP47 affects posttranslational modification of type I collagen and leads to osteogenesis imperfecta.

PLoS genetics

Syx D, Ishikawa Y, Gebauer J, Boudko SP, Guillemyn B, Van Damme T, D'hondt S, Symoens S, Nampoothiri S, Gould DB, Baumann U, B?chinger HP, Malfait F

The novel missense mutation Met48Lys in FKBP22 changes its structure and functions.

Scientific reports

Ishikawa Y, Mizuno N, Holden P, Lim PJ, Gould DB, Rohrbach M, Giunta C, B?chinger HP

COL4A1 Mutations Cause Neuromuscular Disease with Tissue-Specific Mechanistic Heterogeneity.

American journal of human genetics

Labelle-Dumais C, Schuitema V, Hayashi G, Hoff K, Gong W, Dao DQ, Ullian EM, Oishi P, Margeta M, Gould DB

Mutations of conserved non-coding elements of PITX2 in patients with ocular dysgenesis and developmental glaucoma.

Human molecular genetics

Protas ME, Weh E, Footz T, Kasberger J, Baraban SC, Levin AV, Katz LJ, Ritch R, Walter MA, Semina EV, Gould DB

Characterization of a variant of gap junction protein a8 identified in a family with hereditary cataract.

PloS one

Kuo DS, Sokol JT, Minogue PJ, Berthoud VM, Slavotinek AM, Beyer EC, Gould DB

Genetic dissection of anterior segment dysgenesis caused by a Col4a1 mutation in mouse.

Disease models & mechanisms

Mao M, Kiss M, Ou Y, Gould DB

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

Jeanne M, Gould DB

Erratum to: Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation.

BMC biology

Loscertales M, Nicolaou F, Jeanne M, Longoni M, Gould DB, Sun Y, Maalouf FI, Nagy N, Donahoe PK

LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity.

The Journal of clinical investigation

Proekt I, Miller CN, Jeanne M, Fasano KJ, Moon JJ, Lowell CA, Gould DB, Anderson MS, DeFranco AL

Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation.

BMC biology

Loscertales M, Nicolaou F, Jeanne M, Longoni M, Gould DB, Sun Y, Maalouf FI, Nagy N, Donahoe PK

Triggering of organ-specific autoimmunity through synergy of defects in key tolerance checkpoints.

The Journal of Immunology

Irina Proekt, Corey Miller, Marion Jeanne, Kayla Fasano, Clifford A Lowell, Douglas Gould, Mark S Anderson, Anthony L DeFranco

Col4a1 mutations cause progressive retinal neovascular defects and retinopathy.

Scientific reports

Alavi MV, Mao M, Pawlikowski BT, Kvezereli M, Duncan JL, Libby RT, John SW, Gould DB

Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.

Current topics in membranes

Mao M, Alavi MV, Labelle-Dumais C, Gould DB

A Transcriptomic Analysis of Cave, Surface, and Hybrid Isopod Crustaceans of the Species Asellus aquaticus.

PloS one

Stahl BA, Gross JB, Speiser DI, Oakley TH, Patel NH, Gould DB, Protas ME

In Vivo Visualization of Endoplasmic Reticulum Stress in the Retina Using the ERAI Reporter Mouse.

Investigative ophthalmology & visual science

Alavi MV, Chiang WC, Kroeger H, Yasumura D, Matthes MT, Iwawaki T, LaVail MM, Gould DB, Lin JH

Strain-Dependent Anterior Segment Dysgenesis and Progression to Glaucoma in Col4a1 Mutant Mice.

Investigative ophthalmology & visual science

Mao M, Smith RS, Alavi MV, Marchant JK, Cosma M, Libby RT, John SW, Gould DB

Allosteric inhibition of the IRE1a RNase preserves cell viability and function during endoplasmic reticulum stress.

Cell

Ghosh R, Wang L, Wang ES, Perera BG, Igbaria A, Morita S, Prado K, Thamsen M, Caswell D, Macias H, Weiberth KF, Gliedt MJ, Alavi MV, Hari SB, Mitra AK, Bhhatarai B, Sch?rer SC, Snapp EL, Gould DB, German MS, Backes BJ, Maly DJ, Oakes SA, Papa FR

Spontaneous development of autoimmune uveitis Is CCR2 dependent.

The American journal of pathology

Chen YF, Zhou D, Metzger T, Gallup M, Jeanne M, Gould DB, Anderson MS, McNamara NA

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

Aikio M, Hurskainen M, Brideau G, H?gg P, Sormunen R, Heljasvaara R, Gould DB, Pihlajaniemi T

Allelic heterogeneity contributes to variability in ocular dysgenesis, myopathy and brain malformations caused by Col4a1 and Col4a2 mutations.

Human molecular genetics

Kuo DS, Labelle-Dumais C, Mao M, Jeanne M, Kauffman WB, Allen J, Favor J, Gould DB

COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage.

Annals of neurology

Weng YC, Sonni A, Labelle-Dumais C, de Leau M, Kauffman WB, Jeanne M, Biffi A, Greenberg SM, Rosand J, Gould DB

COL4A2 mutation associated with familial porencephaly and small-vessel disease.

European journal of human genetics : EJHG

Verbeek E, Meuwissen ME, Verheijen FW, Govaert PP, Licht DJ, Kuo DS, Poulton CJ, Schot R, Lequin MH, Dudink J, Halley DJ, de Coo RI, den Hollander JC, Oegema R, Gould DB, Mancini GM

Abstract 3665: COL4A1 and COL4A2 Mutations cause Genetically Modifiable Cerebrovascular Diseases.

Stroke

Marion Jeanne, Yi-Chinn Weng, Michelle de Leau, Cassandre Labelle-Dumais, Berkeley W Kauffman, Steven M Greenberg, Jonathan Rosand, Douglas B Gould

COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke.

American journal of human genetics

Jeanne M, Labelle-Dumais C, Jorgensen J, Kauffman WB, Mancini GM, Favor J, Valant V, Greenberg SM, Rosand J, Gould DB

COL4A1 mutations cause ocular dysgenesis, neuronal localization defects, and myopathy in mice and Walker-Warburg syndrome in humans.

PLoS genetics

Labelle-Dumais C, Dilworth DJ, Harrington EP, de Leau M, Lyons D, Kabaeva Z, Manzini MC, Dobyns WB, Walsh CA, Michele DE, Gould DB

Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in FREM1.

Journal of medical genetics

Slavotinek AM, Baranzini SE, Schanze D, Labelle-Dumais C, Short KM, Chao R, Yahyavi M, Bijlsma EK, Chu C, Musone S, Wheatley A, Kwok PY, Marles S, Fryns JP, Maga AM, Hassan MG, Gould DB, Madireddy L, Li C, Cox TC, Smyth I, Chudley AE, Zenker M

A male with unilateral microphthalmia reveals a role for TMX3 in eye development.

PloS one

Chao R, Nevin L, Agarwal P, Riemer J, Bai X, Delaney A, Akana M, JimenezLopez N, Bardakjian T, Schneider A, Chassaing N, Schorderet DF, FitzPatrick D, Kwok PY, Ellgaard L, Gould DB, Zhang Y, Malicki J, Baier H, Slavotinek A

Abnormal expression of collagen IV in lens activates unfolded protein response resulting in cataract.

The Journal of biological chemistry

Firtina Z, Danysh BP, Bai X, Gould DB, Kobayashi T, Duncan MK

Developmental distribution of collagen IV isoforms and relevance to ocular diseases.

Matrix biology : journal of the International Society for Matrix Biology

Bai X, Dilworth DJ, Weng YC, Gould DB

Mutant COL4A1 triggers oxidative stress in a genetic model of AMD.

Matrix Biology

Yi-Chinn Weng, David J. Dilworth, Richard T. Libby, Simon W.M. John, Douglas B. Gould

Clinical and brain MRI follow-up study of a family with COL4A1 mutation.

Neurology

Vahedi K, Boukobza M, Massin P, Gould DB, Tournier-Lasserve E, Bousser MG

Col4a1 mutation causes endoplasmic reticulum stress and genetically modifiable ocular dysgenesis.

Human molecular genetics

Gould DB, Marchant JK, Savinova OV, Smith RS, John SW

Mutant myocilin nonsecretion in vivo is not sufficient to cause glaucoma.

Molecular and cellular biology

Gould DB, Reedy M, Wilson LA, Smith RS, Johnson RL, John SW

Role of COL4A1 in small-vessel disease and hemorrhagic stroke.

The New England journal of medicine

Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, Bousser MG, Heutink P, Miner JH, Tournier-Lasserve E, John SW

Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly.

Journal of medical genetics

Breedveld G, de Coo IF, Lequin MH, Arts WF, Heutink P, Gould DB, John SW, Oostra B, Mancini GM

Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly.

Science (New York, N.Y.)

Gould DB, Phalan FC, Breedveld GJ, van Mil SE, Smith RS, Schimenti JC, Aguglia U, van der Knaap MS, Heutink P, John SW

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

Anderson MG, Libby RT, Gould DB, Smith RS, John SW

Complex genetics of glaucoma susceptibility.

Annual review of genomics and human genetics

Libby RT, Gould DB, Anderson MG, John SW

Mutational analysis of BARHL1 and BARX1 in three new patients with Joubert syndrome.

American journal of medical genetics. Part A

Gould DB, Walter MA

Genetically increasing Myoc expression supports a necessary pathologic role of abnormal proteins in glaucoma.

Molecular and cellular biology

Gould DB, Miceli-Libby L, Savinova OV, Torrado M, Tomarev SI, Smith RS, John SW

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: relevance to ocular dysgenesis and hearing impairment.

BMC medical genetics

Gould DB, Jaafar MS, Addison MK, Munier F, Ritch R, MacDonald IM, Walter MA

Anterior segment development relevant to glaucoma.

The International journal of developmental biology

Gould DB, Smith RS, John SW

Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25.

European journal of human genetics : EJHG

Mirzayans F, Gould DB, Héon E, Billingsley GD, Cheung JC, Mears AJ, Walter MA

Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly.

American journal of human genetics

Mears AJ, Jordan T, Mirzayans F, Dubois S, Kume T, Parlee M, Ritch R, Koop B, Kuo WL, Collins C, Marshall J, Gould DB, Pearce W, Carlsson P, Enerbäck S, Morissette J, Bhattacharya S, Hogan B, Raymond V, Walter MA

Autosomal Dominant Axenfeld-Rieger Anomaly Maps to 6p25.

The American Journal of Human Genetics

DOUGLAS B. GOULD, WILLIAM G. PEARCE, MICHAEL A. WALTER

Autosomal dominant Axenfeld-Rieger anomaly maps to 6p25.

American journal of human genetics

Gould DB, Mears AJ, Pearce WG, Walter MA

Autosomal dominant iridogoniodysgenesis anomaly maps to 6p25.

American journal of human genetics

Mears AJ, Mirzayans F, Gould DB, Pearce WG, Walter MA