Audrey M Bernstein, PhD
- ASSOCIATE PROFESSOR | Ophthalmology
- ASSOCIATE PROFESSOR (PENDING) | Pharmacological Sciences
Research Topics:Cell Biology, Extracellular Matrix, Fibrosis, Integrins, Lysosomes/endosome, Pathology, Wound Healing
Dr. Bernstein is an Associate Professor at the Icahn School of Medicine at Mount Sinai in the Departments of Ophthalmology and Pharmacology and Systems Therapeutics. She is a full-time researcher working on promoting regenerative healing after wounding in the cornea and other tissues. She is also working to reverse the pathology associated with Exfoliaton Glaucoma in order to prevent glaucoma-induced blindness. See more at http://labs.icahn.mssm.edu/audreybernsteinlab/
Multi-Disciplinary Training AreaDevelopmental and Stem Cell Biology [DSCB]
BS, Lehigh University
PhD, University of Kentucky Medical Center
Post-doctoral Fellow, Icahn School of Medicine at Mount Sinai
Research to Prevent Blindness, Special Scholars Award
The Moise and Chella Safra Award for Exfoliation Syndrome Glaucoma Research
NRSA – Ruth Kirschstein postdoctoral award
The Bright Focus Foundation Glaucoma Awards
The Glaucoma Foundation
Regenerative Healing in the Eye
Our work is focused on two clinically important ocular disorders, scarring and glaucoma.
The involvement of aberrant protein accumulation in these ocular pathologies is the focus of our studies. Specifically, we have elucidated novel intracellular ubiquitin-mediated degradation pathways that control cell-surface integrin expression and subsequent fibrotic growth factor (TGFb) signaling and scarring in the eye. We are using the cornea as a model system because corneal transparency is critical for clear, unobstructed vision, making it an important tissue in which to study fibrotic scarring. The cornea refracts light as it enters the eye so that a properly focused image reaches the retina. When a cornea is wounded by surgery or injury, the wound heals unpredictably, either regeneratively (without scarring) or fibrotically (with scarring). Our goal is to understand the mechanisms that promote regenerative wound healing over fibrotic healing and to apply these finding not only to the cornea, but to other models of fibrotic disease.
In exfoliation glaucoma, the leading identifiable cause of open angle glaucoma, accumulation of protein aggregates in the eye lead to elevated intraocular pressure and subsequent glaucoma. We have discovered that a significant lysosomal/autophagy defect defines primary cells isolated from the eyes of exfoliation patients. Our studies suggest that an age-related autophagy defect may be an underlying cause of this blinding disease. Mechanistic cell biology studies in combination with drug screening to correct the autophagic dysfunction are currently underway. In both studies, the use of patient-derived primary cells and organ culture, quantitative confocal microscopy, histology, flow cytometry, lentivirus technology, and genetic screening are utilized to reveal new therapeutic targets to prevent vision loss.
Want A, Gillespie SR, Wang Z, Gordon R, Iomini C, Ritch R, Wolosin JM, Bernstein AM. Autophagy and Mitochondrial Dysfunction in Tenon Fibroblasts from Exfoliation Glaucoma Patients. PloS one 2016; 11(7).
Inthanon K, Daranarong D, Techaikool P, Punyodom W, Khaniyao V, Bernstein AM, Wongkham W. Biocompatibility Assessment of PLCL-Sericin Copolymer Membranes Using Wharton's Jelly Mesenchymal Stem Cells. Stem cells international 2016; 2016.
Bohnsack RN, Warejcka DJ, Wang L, Gillespie SR, Bernstein AM, Twining SS, Dahms NM. Expression of insulin-like growth factor 2 receptor in corneal keratocytes during differentiation and in response to wound healing. Investigative ophthalmology & visual science 2014 Dec; 55(12).
Yang Y, Wang Z, Yang H, Wang L, Gillespie SR, Wolosin JM, Bernstein AM, Reinach PS. TRPV1 potentiates TGFβ-induction of corneal myofibroblast development through an oxidative stress-mediated p38-SMAD2 signaling loop. PloS ONE 2013; 8(10).
Martignetti JA, Tian L, Li D, Ramirez MC, Camacho-Vanegas O, Camacho SC, Guo Y, Zand DJ, Bernstein AM, Masur SK, Kim CE, Otieno FG, Hou C, Abdel-Magid N, Tweddale B, Metry D, Fournet JC, Papp E, McPherson EW, Zabel C, Vaksmann G, Morisot C, Keating B, Sleiman PM, Cleveland JA, Everman DB, Zackai E, Hakonarson H. Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. American journal of human genetics 2013 Jun; 92(6).
Wang L, Pedroja B, Meyers E, Garcia A, Twining S, Bernstein A. Degradation of internalized αvβ5 integrin is controlled by uPAR bound uPA: Effect on β1 integrin activity and α-SMA stress fiber assembly. PLoS ONE 2012; 7(3).
Wang L, Ly CM, Ko CY, Meyers EE, Lawrence DA, Bernstein AM. uPA binding to PAI-1 induces corneal myofibroblast differentiation on vitronectin. Investigative ophthalmology & visual science 2012; 53(8).
Pedroja BS, Kang LE, Imas AO, Carmeliet P, Bernstein AM. Plasminogen Activator Inhibitor-1 Regulates Integrin αvβ3 Expression and Autocrine TGFβ Signaling. Journal of Biological Chemistry 2009; 284(31): 20708-20717.
Bernstein A, Twining SS, Warejcka DJ, Tall DJ, Masur SK. Urokinase receptor cleavage: a crucial step in fibroblast to myofibroblast differentiation. Molecular Biology of the Cell 2007 Sep; 18(7): 2716-2727.