Boston University School of Medicine
School of Medicine Instructional Building, L903
715 Albany Street
Boston, MA 02118
Lab Phone: 617-638-4536
Joint Appointment: Professor of Ophthalmology
AB, Kenyon College, Gambier, OH
PhD, University of Wisconsin, Madison, WI
MAMS Student/Confocal specialist
Our laboratory is mainly interested in the response to injury. Corneal disease and injury remain a major cause of blindness according to the W.H.O. and affect over 10 million people worldwide. This tissue is avascular under normal conditions but vessels are quickly recruited to the site of injury and it is highly innervated by sensory neurons. We demonstrated that both the corneal epithelium and neurons express a number of purinoreceptors that respond quickly to soluble factors that are released with injury. The signaling events that occur between these 2 cell types is critical and we have begun to identify the role of specific purinoreceptors that mediate the phosphorylation of a number of downstream signaling proteins. These studies and others will facilitate our understanding of why cell migration and wound healing is impaired under environmental stress or pathologies such as diabetes. In fact we have found that P2X7 is present at significantly higher levels in diabetic epithelium and appears to be regulated differently than in normal cells. Moreover, as cells deposit proteins on their basal lamina or underlying matrix depending on their environment, it is important to understood how cells sense their substrate and respond as they migrate. Lastly we have begun collaborations to ask how scar formation can be prevented in the corneal stroma. These require an understanding of the dynamics between matrix molecules (proteoglycans) and growth factors in the corneal stroma and how they are released from various depots. To ask these questions we have developed an organ culture model where we can induce injuries and examine the response using imaging along with biochemical, cell and molecular technologies. In addition as rodent models have limitations we have collaborations with investigators who developed a human corneal construct.
We are also involved in the Amyloidosis Center and collaborate on AL Amyloid. The center is a large multidisciplinary group that examines the diseases from a basic science and translational view. Our lab has played a role in the understanding of long sugar chains or glycosaminoglycans on the formation of oligomers and fibrils in light chain amyloid disease using atomic force microscopy, negative staining and biochemical technologies.
Minns MS, Teicher G, Rich CB, Trinkaus-Randall V. Purinoreceptor P2X7 Regulation of Ca(2+) Mobilization and Cytoskeletal Rearrangement Is Required for Corneal Reepithelialization after Injury. Am J Pathol. 2016 Feb; 186(2):285-96. PubMed
Derricks KE, Trinkaus-Randall V, Nugent MA. Extracellular matrix stiffness modulates VEGF calcium signaling in endothelial cells: individual cell and population analysis. Integr Biol (Camb). 2015 Sep 1; 7(9):1011-25. PubMed
Sanderson J, Dartt DA, Trinkaus-Randall V, Pintor J, Civan MM, Delamere NA, Fletcher EL, Salt TE, Grosche A, Mitchell CH. Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland. Exp Eye Res. 2014 Oct; 127:270-9. PubMed
In vitro model suggests oxidative stress involved in keratoconus disease. Karamichos D, Hutcheon AE, Rich CB, Trinkaus-Randall V, Asara JM, Zieske JD. Sci Rep. 2014 Apr 9;4:4608.
- Hypoxia-induced changes in Ca(2+) mobilization and protein phosphorylation implicated in impaired wound healing. Lee A, Derricks K, Minns M, Ji S, Chi C, Nugent MA, Trinkaus-Randall V. Am J Physiol Cell Physiol. 2014 May 15;306(10):C972-85.
- Wounding the cornea to learn how it heals. Stepp MA, Zieske JD, Trinkaus-Randall V, Kyne BM, Pal-Ghosh S, Tadvalkar G, Pajoohesh-Ganji A. Exp Eye Res. 2014 Apr;121:178-93.
- Epithelial wounds induce differential phosphorylation changes in response to purinergic and EGF receptor activation. Kehasse A, Rich CB, Lee A, McComb ME, Costello CE, Trinkaus-Randall V. Am J Pathol. 2013 Dec;183(6):1841-52.
- TGF-β3 Stimulates Stromal Matrix Assembly by Human Corneal Keratocyte-Like Cells. Karamichos D, Rich CB, Zareian R, Hutcheon AE, Ruberti JW, Trinkaus-Randall V, Zieske JD. Invest Ophthalmol Vis Sci. 2013 Oct 9;54(10):6612-9. doi: 10.1167/iovs.13-12861.
- New insights in wound response and repair of epithelium. Chi C, Trinkaus-Randall V. J Cell Physiol. 2013 May;228(5):925-9. doi: 10.1002/jcp.24268.
- Communication between corneal epithelial cells and trigeminal neurons is facilitated by purinergic (P2) and glutamatergic receptors. Oswald DJ, Lee A, Trinidad M, Chi C, Ren R, Rich CB, Trinkaus-Randall V. PLoS One. 2012;7(9):e44574. doi: 10.1371/journal.pone.0044574. Epub 2012 Sep 7.
- Disorganized collagen scaffold interferes with fibroblast mediated deposition of organized extracellular matrix in vitro. Saeidi N, Guo X, Hutcheon AE, Sander EA, Bale SS, Melotti SA, Zieske JD, Trinkaus-Randall V, Ruberti JW. Biotechnol Bioeng. 2012 Oct;109(10):2683-98. doi: 10.1002/bit.24533. Epub 2012 May 4.
- Mankus C, Chic C, Ren R, Rich CB and Trinkaus-Randall V. The P2X7 Receptor Regulates Proteoglycan Expression in the Corneal Stroma. Molecular Vision. 2012; 18:128-138.
- Mankus C, Rich CB, Minns M, Trinkaus-Randall V. Corneal Epithelium Expresses a Variant of P2X(7) Recetpor in Health and Disease. PLoS One. 2011; 6(12):e28541. Epub 2011, Dec. 6.
- Ward JE, Ren R, Toraldo G, Soohoo P, Guan J, O’Hara C, Jasuja R, Trinkaus-Randall V, Liao R, Connors LH, Seldin DC. Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis. Blood. 2011. Dec 15; 118(25):6610-7. Epub 2011, Oct. 12.
- Karamichos D, Rich C, Hutcheon A, Ren R, Saitta B, Trinkaus-Randall V, Zieske J. Self-Assembled Matrix by Umbilical Cord Stem Cells. J. Functional Biomaterials (Biomaterials in Wound Healing) 2011, 2(3), 213-229; doi:10.3390/jfb20302013.
- Boucher I, Kehasse A, Marcincin M, Rich C, Rahimi N, Trinkaus-Randall V. Distinct Activation of Edpidermal Growth Factor Receptor by UTP Contributes to Epithelial Cell Wound Repair. Am J. Pathol. 2011 Mar;178(3):1092-105. PMID: 21356361 [PubMed – in process].
- Karamichos D, Rich C, Hutcheon A, Ren R, Saitta B, Trinkaus-Randall V, Zieske J. Self-Assembled Matrix by Umbilical Cord Stem Cells. J. Functional Biomaterials. 2011. 2:213-229.
- Ren R, Hong Z, Gong H, Laporte K, Skinner M, Seldin DC, Costello CE, Connors LH, Trinkaus-Randall V. The role of glycosaminoglycan sulfation in the formation of immunoglobulin light chain amyloid oligomers and fibrils. J Biol Chem. 2010 [Epub ahead of print] PMID: 20870723 [PubMed – as supplied by publisher]Free Article
- Boucher I, Rich C, Lee A, Marcincin M, Trinkaus-Randall V. The P2Y2 receptor mediates the epithelial injury response and cell migration. Am J Physiol Cell Physiol. 2010 Aug;299(2):C411-21. Epub 2010 Apr 28.PMID: 20427708 [ PubMed – indexed for MEDLINE]
- Wang X, Belguise K, O’Neill CF, Sánchez-Morgan N, Romagnoli M, Eddy SF, Mineva ND, Yu Z, Min C, Trinkaus-Randall V, Chalbos D, Sonenshein GE. RelB NF-kappaB represses estrogen receptor alpha expression via induction of the zinc finger protein Blimp1. Mol Cell Biol. 2009 Jul;29(14):3832-44. Epub 2009 May 11. PMID: 19433448 [PubMed – indexed for MEDLINE]
- Mayo C, Ren R, Rich C, Stepp MA and Trinkaus-Randall V, Regulation by P2X7: Epithelial migration and stromal organization in the cornea. Inv Ophthal Vis Sci. 49: 4384-4391. 2008.
- Ren R, Hutcheon AEK, Guo XQ, Melotti S, Ruberti JW, Zieske JD and Trinkaus-Randall V. Human primary corneal fibroblasts synthesize and deposit proteoglycans in longterm 3_D cultures. Dev Dyn. 237L2705-2715. 2008.
- Guo X, Hutcheon A, Melotti S, Zieske JD, Trinkaus-Randall V, Ruberti JW. Morphological Characterization of Organized Extracellular Matrix Deposition by Ascorbic Acid-Stimulated Human Corneal Fibroblasts. IOVS. 48:4050-60.2007
- Boucher I, Yang LL, Mayo C, Klepeis V and Trinkaus-Randall V. Injury and nucleotides induce phosphorylation of Epidermal Growth Factor Receptor:MMP and HB-EGF Dependent Pathway. Experimental Eye Res. 85:130-41E pub ahead of print. 2007.
- 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
Selected Invited Chapters
- Cornell-Bell A, Jung P, Trinkaus-Randall V. 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.
- Jung, P., Cornell-Bell A.H., Dreher M., deGrauw A., Strawsburg R., Trinkaus-Randall V.: Statistical analysis and modeling in calcium waves in healthy and pathological astrocyte syncytia. In Stochastic Processes in Physics, Chemistry and Biology. Springer Verlag, 2001.
- 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.