Vickery Trinkaus-Randall, PhD, FARVO
PROFESSOR OF BIOCHEMISTRY AND OPHTHALMOLOGY
DIRECTOR, CELL AND MOLECULAR BIOLOGY GRADUATE PROGRAM
A.B., Kenyon College, Gambier, OH
Ph.D., University of Wisconsin, Madison, WI
Schepens Eye Research Institute Boston, MA
Boston University School of Medicine Boston, MA
We are interested in the signals that corneal epithelial cells utilize to migrate after injury or environmental changes. ATP is released at the site of tissue damage and rapidly activates purinergic receptors, which mediate cell communication and wound repair. Students are examining differences between EGF and nucleotide induced migration and recruitment of docking proteins to the EGFR. Previously we had shown that the activation of the purinergic receptors results in phosphorylation of a subset of tyrosine residues. Recently we have shown that two residues play an active role in the ability of a cell to migrate to a specific cue. Cells lacking certain residues maintain the ability to move but lack directionality and the ability to close a wound. Our results provide evidence that while phosphorylation of EGFR may be critical for wound closure it can be achieved by either direct ligand stimulation or through other signaling pathways. When the latter occurs we hypothesize that recruitment of signaling molecules is modified.
Purinergic receptors are also involved in the development of the corneal stroma and we are examining changes in collagen and proteoglycan expression. The P2X7 null mouse results in a lack of organization of the stromal matrix. Since the P2X7 receptor is a ligand gating channel and controls the flow of ions into the cell it was thought to play an important role in apoptosis and inflammation. However epithlelial cells rarely apoptose and we found that while the cells demonstrate certain canonical P2X7 responses, others that are more typical of cell death such as blebbing and pore formation did not occur. We then demonstrated that the epithelial cells express C-terminal truncated P2X7 splice variants that respond to the agonist.
These questions are addressed using a number of molecular and cell biological technologies including transfection, site directed mutagenesis, mass spectrometry, migration assays, confocal imaging (live cell imaging and evaluation of expression).
We are studying a disease called Primary (AL) amyloidosis. Amyloid deposition is hypothesized to play a role in many diseases including rheumatoid arthritis, diabetes, as well as the amyloidoses themselves. The amyloidoses exhibit depostion of insoluble fibrillar proteins in organs and tissues and AL amyloidosis results from a plasma cell dyscrasia. Glycosaminoglycans (GAGs) are one of the major extracellular matrix components and the in vivo relationship between GAGs and amyloid deposits has been shown. Furthermore, the presence of MMPs has been shown to be correlated with the diseases. Methods that are used include live cell confocal microscopy and trafficking, atomic force microscopy, and electron microscopy.
We are collaborating with faculty at two other universities in Boston to use a tissue engineering approach to produce 3-dimensional organ corneal constructs.
Dr. Trinkaus-Randall has 2 confocal laser scanning microscopes located on the ninth floor that she has brought to BUSM by NCRR grants. They are available for usage by members of the BUSM community.
Some of her current service commitments include the MDPhD and SMED admission committees, the Biochemistry Qualifying Examination Committee, the Committee on Faculty Affairs and the APC.
Trinkaus-Randall,V., Walsh,M.T., Steeves,S., Monis ,G., Connors,L., and Skinner,M. Cellular response of cardiac fibroblasts to amyloidogenic light chains. American J Pathol. 166:197-208, 2005.
Kaczmarek E., Erb L., Koziak K., Jaryna R., Wink M.R., Guckelberger O., Blusztajn JK. Trinkaus-Randall V., Weisman GA., Robson SC. Modulation of endothelial cell migration by extracellular nucleotides involvement of focal adhesion kinase and phosphatidylinositol 3-kinase-mediated pathways. Thrombosis and Homeostasis. 93: 735-742, 2005.
Weinger I, Klepeis V and Trinkaus-Randall,V. Trinucleotide receptors play a critical role in epithelial wound repair. Purinergic Signaling, 1: 281-292, 2005.
Monis, G, Schultz C, Ren R, Eberhard J, Costello E.C, Connors L, Skinner,M and Trinkaus-Randall,V. Role of endocytic inhibitory drugs on internalization of amyloidogenic light chains by cardiac fibroblasts. Amer J Pathol. 169 (6) 1939-52, 2006
Boucher I, Yang LL, Mayo C, Klepeis V and V. Trinkaus-Randall. Injury and nucleotides induce phosphorylation of Epidermal Growth Factor Receptor:MMP and HB-EGF Dependent Pathway. Experimental Eye Res. 85:130-141. 2007.
Guo X, Hutcheon Audrey, Melotti Suzanna, Zieske James D, Trinkaus-Randall Vickery, Ruberti Jeffrey W. Morphological Characterization of Organized Extracellular Matrix Deposition by Ascorbic Acid-Stimulated Human Corneal Fibroblasts. IOVS. 48:4050-60.2007
Ren R, Hutcheon AEK, Guo XQ, Melotti S, Ruberti JW, Zieske JD and V. Trinkaus-Randall. Human primary corneal fibroblasts synthesize and deposit proteoglycans in longterm 3-D cultures. Dev Dyn. 237L2705-2715. 2008.
Mayo C, Ren R, Rich C, Stepp MA and V. Trinkaus-Randall, Regulation by P2X7: Epithelial migration and stromal organization in the cornea. Inv Ophthal Vis Sci. 49: 4384-4391. 2008.
Wang X., Belguise K., O’Neill F., Sanchez-Morgan N., Romagnoli M., Eddy S., Mineva N., Yu Z., Min C., Trinkaus-Randall V., Chalbos D., and G. Sonenshein. RelB NF-B represses estrogen receptor expression via induction of the zinc finger protein Blimp1. Mol Cell Biol. 2009.
Selected Invited Chapters:
Trinkaus-Randall,V.: Cornea: Biological Responses. Ch. 35 pp 471-491 In: Principles of Tissue Engineering (second edition). eds. R. Lanza and R. Langer and E. Chick . Academic Press,Calif. 2000.
Jung, P., A.H. Cornell-Bell, M. Dreher, A. deGrauw, R. Strawsburg, V. Trinkaus-Randall: Statistical analysis and modeling in calcium waves in healthy and pathological astrocyte syncytia. In Stochastic Processes in Physics, Chemistry and Biology. Springer Verlag, 2001.
Cornell-Bell A, Jung P, V. Trinkaus-Randall. Decoding Calcium Wave Signaling. Vol 31. pp. 661-689. In Advances in Molecular and Cell Biology. Elsevier Science, 2003
Ruberti J., Zieske JD., and V. Trinkaus-Randall.: Corneal Tissue Replacement in: The Principles of Tissue Engineering. Ch. 68. ed. Lanza, langer and Vacanti. Elsevier. 2007.