Professor of Physiology and Biophysics, and Ophthalmology
USC Keck School of Medicine
Sarah F. Hamm-Alvarez, Ph.D.
University of Southern California
School of Pharmacy
1985 Zonal Ave.
Los Angeles, CA 90033
Office phone: 323-442-1445
Office fax: 323-442-1390
Our principal area of study is the investigation of the role of
the cytoskeleton, molecular motor proteins and other trafficking effectors
such as rabs, SNARES, and signaling molecules in the events involved in the regulated secretory
traffic to and from the apical membrane of lacrimal acinar cells,
specialized secretory epithelial cells found in the lacrimal gland. These
acinar cells exocytose tear proteins and fluid necessary for maintenance of
the health of the cornea and ocular surface. Changes in this regulated secretory process are
associated with development of several ocular surface diseases. We study the basic cellular and molecular mechanisms underlying the exocytosis of tear proteins in in vitro (cell culture) and in vivo systems. We also investigate the changes in these processes that contribute to defective tear protein secretion, and that contribute to the development of severe dry eye and the autoimmune disease, Sjogren's syndrome. Several of our projects endeavor to treat diseases of the lacrimal gland by introducing therapeutic factors using novel drug targeting and delivery approaches, and we also aim to treat ocular diseases by engineering the lacrimal gland to produce therapeutic factors using similar approaches. A major strategy to achieve targeted drug delivery is the use of different capsid proteins of adenovirus serotype 5 to facilitate the selective uptake of proteins, peptide and DNA- based drugs into the lacrimal gland. Other projects investigate the cellular and molecular mechanisms of production of secretory IgA and secretory component by the lacrimal gland. These projects also investigate in vivo the role of secretory component and secretory IgA in the protection of the ocular surface from bacterial infection. Finally, new laboratory projects focus on the use of imaging techniques to investigate changes in extracellular matrix organization in the tissues of the ocular surface that may contribute to disease development, and investigate the mechanisms of endocytic trafficking that may be exploited for targeted drug delivery. Major tools in the laboratory include the application of high resolution microscopy approaches for analysis of fixed and live cells utilizing confocal and multiphoton fluorescence microscopy, real-time and time-lapse imaging and other dynamic microscopy applications such as fluorescence recovery after photobleaching. We also extensively utilize biochemical and molecular biological strategies to analyze trafficking effectors. With our model systems ranging from primary cell cultures to knockout mouse models, we have the unique capability of combining detailed and mechanistic cell biological investigations of molecular targets with functional analysis of different parameters of ocular surface function.
Below are microtubules (green) and actin filaments (red) in rabbit lacrimal
gland acinar cells. This site was last updated on July 23, 2009 (RMA
Below are microtubules (green) and actin filaments (red) in rabbit lacrimal gland acinar cells.
This site was last updated on July 23, 2009 (RMA