BBS Faculty Member - Joseph Arboleda-Velasquez

Joseph Arboleda-Velasquez

Department of Ophthalmology

The Schepens Eye Research Institute
20 Staniford Street
Boston, MA 02115
Tel: 617-842-4954
Fax: 617-912-0128
Email: joseph_arboleda@meei.harvard.edu
Visit my lab page here.



There is now overwhelming evidence indicating that VEGF, TGFβ, PDGF, and Notch among others, the molecules that are essential for vascular formation, are also part of the cell signaling circuitry contributing to vessel maintenance and the cellular response to injury and metabolic change. However, very little is known about how different signaling pathways are integrated in the microvasculature cell program and even less is understood about how these cell communication mechanisms are challenged in diabetes.

Do these signaling molecules operate through the same molecular targets during development and in the adult? Which molecules predominate? In what order do they function in the process of vascular remodeling in response to diabetes or other metabolic conditions? How can one devise therapeutic approaches through manipulation of a signaling pathway without interfering with the function of other interconnected signaling mechanisms?

My laboratory uses cutting edge cell culture and molecular methodologies to study cell–cell interactions between endothelial cells and pericytes/vascular smooth muscle cells and examine how a diabetic environment affects these interactions. Cellular behavior is tracked using molecular imaging approaches that harness the power of enzymes and fluorescent proteins to track molecular interactions across cellular boundaries. Next Generation RNA-seq and DNA-seq approaches are used to identify candidate genes at the crossroads of cell signaling crosstalk between major signaling pathways. Lastly, novel mouse models targeting our candidate genes are generated to establish causality in relevant experimental models for diabetes and vascular dementia, two prevalent conditions associated with microvascular degeneration.

My research program is based on novel transgenic tools and experimental platforms that allow for a “multisystem” approach combining cellular, molecular and animal models, which in my view provides an exceptionally conducive environment for graduate student’s training and scientific growth.



Last Update: 8/6/2015



Publications

For a complete listing of publications click here.

 


 

Kim LA, Wong LL, Amarnani DS, Bigger-Allen AA, Hu Y, Marko CK, Eliott D, Shah VA, McGuone D, Stemmer-Rachamimov AO, Gai X, D’Amore PA*, Arboleda-Velasquez JF*. Characterization of cells from patient-derived fibrovascular membranes in proliferative. Mol Vis. 2015 Jun 12:21:673-687. (*co-corresponding authors)

Valdez CN*,
Arboleda-Velasquez JF*, Amarnani DS, Kim LA, D'Amore PA. Retinal microangiopathy in a mouse model of inducible mural cell loss. Am J Pathol. 2014 Oct;184(10):2618-26. (*contributed equally to this manuscript)

Arboleda-Velasquez JF*, Primo V*, Graham M, James A, Manent J, D'Amore PA. Notch signaling functions in retinal pericyte survival. Invest Ophthalmol & Vis Sci. 2014 Jul 11;55(8):5191-9. (*contributed equally to this manuscript)

Arboleda-Velasquez JF, Manent J, Lee JH, Tikka S, Ospina C, Vanderburg CR, Frosch MP, Rodríguez-Falcón M, Villen J, Gygi S, Lopera F, Kalimo H, Moskowitz MA, Ayata C, Louvi A, Artavanis-Tsakonas S. Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease. Proc Natl Acad Sci U S A. 2011 May 24;108(21):E128-35.

Arboleda-Velasquez JF*, Zhou Z*, Shin HK, Louvi A, Kim H-H, Savitz S, Liao J, Salomone S, Ayata C, Moskowitz MA. Artavanis-Tsakonas S. Linking notch signaling to ischemic stroke. Proc Natl Acad Sci U S A. 2008 March 25; 105 (12):4856-61. (*contributed equally to this manuscript)



© 2016 President and Fellows
of Harvard College