Gender	Female
E-mail	audrey.bernstein@mssm.edu
Education and Training	Ph.D., University of Kentucky Medical Center
	B.S., Lehigh University
	Postdoctoral Training, Mount Sinai School of Medicine
Awards	2006 - 2011 R01 grant (EY017030) NIH National Eye Institute

Dr. Bernstein is an Assistant Professor at Mount Sinai School of Medicine in the Department of Ophthalmology. She is a full-time researcher working on promoting regenerative healing and preventing fibrotic healing after wounding in the cornea and other tissues. 

Education and Training	Ph.D., University of Kentucky Medical Center
	B.S., Lehigh University
	Postdoctoral Training, Mount Sinai School of Medicine

Corneal Wound Healing

Our lab is studying the mechanisms that regulate wound healing in the cornea. The cornea refracts light as it enters the eye so that a properly focused image reaches the retina. Maintaining corneal transparency is critical for clear, unobstructed vision. When a cornea is wounded by surgery or injury, the wound heals unpredictably, either regeneratively (without scarring) or fibrotically (with scarring). Corneal scars may be opaque, and cause severe visual defects. Our goal is to understand the mechanisms that promote regenerative wound healing over fibrotic healing.

Corneal wound healing begins when cells (fibroblasts) migrate into the wound site. Upon reaching the wound, fibroblasts begin producing repair matrix and differentiate into contractile cells (myofibroblasts) that adhere to the surrounding matrix and pull the matrix fibers together, closing the wound. Proper spacing and alignment of fibers is essential for an optically clear tissue. In a regeneratively healed wound, myofibroblasts disappear by apoptosis, whereas the persistence of myofibroblasts results in the overproduction of extracellular matrix and excessive contraction, leading to scarring. Regulation of both fibroblast migration and myofibroblast differentiation are critical for promoting regenerative repair.

To better understand the molecular basis for cell migration and cell differentiation, we have focused on the role of the urokinase (uPA) pathway during wound healing. uPA is an extracellular serine protease that stimulates both a protease cascade at the cell-matrix interface and an intracellular signaling cascade resulting in cytoskeletal reorganization and cell migration. We have found dramatic differences in the uPA pathway between fibroblasts and myofibroblasts leading us to conclude that this pathway is important for both fibroblast migration and regulation of myofibroblast differentiation.

Future work will examine the importance of the extracellular matrix composition after wounding. The matrix appears to change throughout wound healing and understanding the specific, time-dependent changes is critical to fully understand the interactions of cells and matrix and their specific roles in regulating cell migration and differentiation. Furthermore, this is a particularly exciting time in this field as we recognized that multiple pathways are involved in this very important repair process. Consequently, we are beginning to study uPA pathway interactions with growth factors and their downstream targets in order to develop a comprehensive picture of how corneal healing may be controlled to provide a perfect optical surface to maintain clear vision.

Research Topics

• Cell adhesion and extracellular matrix
• Cell migration
• Cell differentiation
• Proteases

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.

Greenberg RS, Bernstein AM, Benezra M, Gelman IH, Taliana L, Masur SK. FAK-dependent regulation of myofibroblast differentiation. FASEB 2006; 20 (7): 1006-8.

Warejcka DJ, Vaughan KA, Bernstein AM, Twining SS. Differential conversion of Plasminogen to Angiostatin by Human Corneal Cell Populations. Molecular Vision 2005; 11: 859-868.

Taliana L, Benezra M, Greenberg RS, Masur SK, Bernstein AM. ZO-1: Lamellipodial Localization in a Corneal Fibroblast Wound Model. Invest Ophthalmol Vis Sci 2005; 46: 96-103.

Bernstein AM, Greenberg RS, Taliana LD, Masur SK. Urokinase Anchors uPAR to the Actin Cytoskeleton. Investigative Ophthalmology and Visual Science 2004; 45(9): 2967-2977.

Turner HC, Alvarez LJ, Candia OA, Bernstein AM. Characterization of Serotonergic Receptors in Rabbit, Porcine and Human Conjunctivae. Current Eye Research 2003; 27(4): 205-215.

Turner HC, Bernstein AM, Candia OA. Presence of CFTR in the Conjunctival Epithelium. Current Eye Research 2002; 24(3): 182-187.