Melinda K. Duncan, Ph.D.

Teaching

• BISC 415/615; ANSC 415/615 - Vertebrate Developmental Biology
• BISC 654* - Biochemical Genetics
• BISC 827* - Graduate Research Seminar

*Course web site available through Sakai
 

Research Interests

The vertebrate lens is a remarkable tissue that has many evolutionary adaptations that allow it to remain transparent throughout life. Further, its cell biology is quite distinct from that of other tissues which results in it being the only epithelial organ which never develops clinically relevant cancers. Aging, ocular injury, genetic alterations or systemic diseases such as diabetes can lead to the loss of lens transparency, or cataract. Cataracts are the predominant cause of blindness worldwide and their incidence is increasing as life expectancies increase. Over the past thirty years, robust techniques to surgically treat cataract have been developed, greatly reducing cataract-related blindness in western countries. In the United States, cataract removal is the most common surgical procedure performed for any reason. While the short term visual outcome for patients undergoing cataract surgery is often excellent, 10-25% of operated eyes subsequently develop posterior capsular opacification (PCO), a condition often referred to as secondary cataract which requires additional treatment and can lead to poor vision in the long term.

My laboratory focuses on understanding the transcriptional control of cell differentiation in the lens and the role of integrins and extracellular matrix proteins in regulating normal lens biology and their alterations in cataracts and PCO.

Current Projects

• Transcriptional control of lens fiber cell differentiation - The differentiation of lens fiber cells is marked by a major reorganization of cell structure and drastic changes in gene expression. βB1-crystallin, one of the genes whose expression is first detected coincident with the morphological differentiation of lens fiber cells, is often used as a molecular marker for this process. We have isolated the complete promoter of this gene and identified some of the cis-elements and transcription factors responsible for its function. We are studying the biochemistry of these transcription factors, particularly how their expression and function is controlled by fiber cell differentiation signals arising outside of the lens. Further, since many of the transcription factors that control βB1-crystallin expression are also expressed in the lens epithelium, we are also studying the influence of other regulators of gene expression, such as chromatin remodeling enzymes, on lens fiber cell differentiation.
• The influence of the lens capsule on lens development and function - The lens is a true epithelium with the basal surface of every transcriptionally active cell attached to a modified basement membrane, the lens capsule. While numerous studies have suggested that extracellular matrix molecules can influence lens cell biology, little is known about either the molecular composition of the capsule or the nature of the receptors present on lens cells that mediate lens cell/lens capsule interactions. We have previously shown that collagen IV is present in the lens capsule and that the molecular composition of the collagen IV network changes during lens development. We are now investigating the functional significance of these changes both in vivo and in vitro as well as the molecular mechanisms by which lens cells could detect a changing collagen IV network.

Research Group

• Bhagwat Alapure, Ph.D. - Postdoctoral Fellow (Ph.D. Manipal University). ECM function in lens and UPR.
• Amal  Aldossary, MS Graduate student. (M.S., King Faisal University)  Role of UPR in lens development
• Yan Wang, M.D. - Laboratory Manager (M.D., China Medical University, China). Mammalian lens regeneration.
• Mallika Pathania Bach.Med. - Graduate Student (Bach.Med., Rajiv Gandhi University of Health Sciences). Function of integrins in early lens development
• Dylan Audette, B.A. - Graduate Student (B.A., University of Delaware). Prox1 function in lens.
• Abby Grabitz, B.S. - Graduate Student (B.S., Alma College). Lens development.
• Fahmy Mamuya, B.S. - Graduate Student (B.S., Grand Valley State University). Integrin functions in the lens.
• David Scheiblin, B.A. - Graduate Student (B.A., University of Delaware). Integrin function in lens fibers.
• Ann Terrell, B.S. - Graduate Student (B.S., Millersville University of Pennsylvania). Integrin function in the lens epithelium.
• Rupa Roy, B.S. - Research Associate (B.S., Viswa Bharati University). DNA binding protein function.
• Victoria Roop - Senior Biological Sciences major. Role of crystallins and integrins in EMT.
• Joceyln Zajac- Junior Biological Sciences major. Transcriptional regulation by Sip1
• Cullen Worsh- Sophomore Biological Sciences major Lens fiber cell structure

Selected Publications

• Fahmy A. Mamuya and Melinda K. Duncan (2012) αV-β integrins and TGF-β induced EMT; a circle of regulation.  Journal of Cellular and Molecular Medicine in press
• Abby L. Grabitz-Manthey and Melinda K. Duncan Focus on molecules: Smad Interacting Protein 1 (Sip1, ZEB2, ZFHX1B). Experimental Eye Research. 2012;in press.
• Melinda K. Duncan (2011) Development. A new focus on RNA in the lens.  Science 331, 1523-1524.
• Zeynep Firtina and Melinda K. Duncan. Unfolded Protein Response (UPR) is activated during normal lens development Mechanisms of Development. Gene Expression Patterns. 2011;11, 135-143.
• Geetha Parthasarathy, Bo Ma, Cheng Zhang, Celine Gongora, Samuel Zigler Jr, Melinda K Duncan, and Debasish Sinha Expression of βA3/A1-crystallin in the developing and adult rat eye. Journal of Molecular Histology. 2011; 42, 59-69.
• Brian P. Danysh, Tapan P. Patel, Kirk J. Czymmek, David A. Edwards, Liyun Wang, Jayanti Pande, and Melinda K. Duncan. Characterizing molecular diffusion in the lens capsule. Matrix Biology. 2010;29:228–236.
• Vivek D. Desai, Yan Wang, Vladimir N. Simirskii and Melinda K. Duncan. CD44 expression is developmentally regulated in the mouse lens and increases in the lens epithelium after injury. Differentiation. 2010;79(2):111–119.
• Brian P. Danysh and Melinda K. Duncan. The lens capsule. Exp Eye Res. 2009;88(2):151–164.
• Zeynep Firtina, Brian P. Danysh, Xiaoyang Bai, Douglas B. Gould, Takehiro Kobayashi, and Melinda K. Duncan. Abnormal Expression of Collagen IV in Lens Activates Unfolded Protein Response Resulting in Cataract. J Biol Chem. 2009;284(51):35872–35884.
• Xiaoren Chen, Tapan P. Patel, Vladimir I. Simirskii and Melinda K. Duncan. PCNA interacts with Prox1 and represses its transcriptional activity. Mol Vis. 2008;14:2076–2086.
• Xiaoren Chen, Jennifer R. Taube, Vladimir I. Simirskii, Tapan P. Patel and Melinda K. Duncan . Dual roles for Prox1 in the regulation of the chicken betaB1-crystallin promoter. Invest Ophthalmol Vis Sci. 2008;49(4):1542–1552.
• Brian P. Danysh, Kirk J. Czymmek, Pecos T. Olurin and Melinda K. Duncan . Contributions of mouse genetic background and age on anterior lens capsule thickness. Anat Rec (Hoboken). 2008;291(12):1619–1627.
• Michelle M. Lucey, Yan Wang, Michael Bustin and Melinda K. Duncan. Differential expression of the HMGN family of chromatin proteins during ocular development. Gene Expr Patterns. 2008;8(6):433–437.
• Meghna U. Naik, Tejal U. Naik, Arthur T. Suckow, Melinda K. Duncan^, and Ulhas P. Naik. Attenuation of junctional adhesion molecule-A is a contributing factor for breast cancer cell invasion. Cancer Res. 2008;68(7):2194–2203.
• Arivudainambi Ramalingam, James B. Duhadaway, Erika Sutanto-Ward, Yan Wang, Joseph Dinchuk, Minzhou Huang, P. Scott Donover, Janette Boulden, Lois M. McNally, Alejandro P. Soler, Alexander J. Muller, Melinda K. Duncan, and George C. Prendergast . Bin3 deletion causes cataracts and increased susceptibility to lymphoma during aging. Cancer Res. 2008;68(6):1683–1690.
• Ales Cvekl and Melinda K. Duncan. Genetic and epigenetic mechanisms of gene regulation during lens development. Prog Retin Eye Res. 2007;26(6):555–597.
• Kevin M. DuPrey, Kimberly M. Robinson, Yan Wang, Jennifer R. Taube and Melinda K. Duncan. Subfertility in mice harboring a mutation in betaB2-crystallin. Mol Vis. 2007;13:366–373.
• Liang I. Kang, Yan Wang, Arthur T. Suckow, Kirk J. Czymmek, Vesselina G. Cooke, Ulhas P. Naik and Melinda K. Duncan Deletion of JAM-A causes morphological defects in the corneal epithelium. Int J Biochem Cell Biol. 2007;39(3):576–585.
• Simirskii VN, Wang Y, Duncan MK. Conditional deletion of beta1-integrin from the developing lens leads to loss of the lens epithelial phenotype. Dev Biol. 2007;306(2):658–668.
• Xiaoren Chen, Tapan P. Patel, William Cain and Melinda K. Duncan. Production of monoclonal antibodies against Prox1. Hybridoma (Larchmt). 2006;25(1):27–33.
• Kristen M. Huang, Junhua Wu, Melinda K. Duncan, Chris Moy, Amalia Dutra, Jack Favor, T. Da and Dwight Stambolian. Xcat, a novel mouse model for Nance-Horan syndrome inhibits expression of the cytoplasmic-targeted Nhs1 isoform. Hum Mol Genet. 2006;15(2):319–327.
• Vladimir I. Simirskii, Robert S. Lee, Eric F. Wawrousek and Melinda K. Duncan. Inbred FVB/N mice are mutant at the cp49/Bfsp2 locus and lack beaded filament proteins in the lens. Invest Ophthalmol Vis Sci. 2006;47(11):4931–4934.