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Melinda K. Duncan, Ph.D., FARVO
- BISC 415/615; ANSC 415/615 - Vertebrate Developmental Biology
- BISC 654* - Biochemical Genetics
- BISC 827* - Graduate Research Seminar
*Course web site available through Sakai
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, a large proportion 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 pathogenesis of cataracts, the molecular mechanisms responsible for the side effects of cataract and other ocular surgeries, as well as the regulation of lens development and cellular differentiation.
- The mechanisms controlling posterior capsular opacification - Cataract surgery is a true marvel of modern medicine which has greatly reduced the burden of blindness, particularly in developed countries. However, like all surgeries, cataract surgery is not without its side effects. Posterior capsular opacification (PCO) results when lens cells remaining behind after surgery proliferate, migrate into the visual axis, and produce scar tissue which distorts the patient's vision. While this, the most common negative outcome of cataract surgery, can be treated as well, each further intervention reduces final visual outcome, and can cause or exacerbate other blinding ocular conditions such as retinal detachments and glaucoma. We have discovered that some integrins and extracellular matrix molecules are critical for PCO development. We are investigating the molecular mechanisms by which these molecules drive PCO in the hopes of identifying clinical interventions to block this potentially blinding condition. This work is supported by the National Eye Institute
- The regulation 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. While we have developed a good understanding of the growth and transcription factors that drive these changes in gene expression, we know very little about how this regulates the morphological changes necessary to form a transparent lens. We have performed RNAseq (next generation sequencing) to analyze the transcriptome of a mouse mutant which fails to undergo these morphological changes to discover genes likely to regulate this process. We are using a combination of mouse and chicken models to study the mechanisms controling lens morphogenesis using this set of candidate genes as a starting point.
- Aniridia fibrosis syndrome- Aniridia is a genetic condition characterized by numerous ocular abnormalities including the lack of an iris and abnormalities of the retina that are apparent at birth. Later, Aniridia patients develop numerous other ocular complications including glaucoma, corneal scarring and cataracts and these patients usually require multiple surgeries to manage these conditions. However, aniridia patients often have poorer visual outcomes from these interventions than expected due to their tendency to develop massive ocular fibrosis (scarring) in response to these surgeries. We have evidence that the disruption of the Pax6 gene that causes Aniridia negatively impacts the normal wound healing response to ocular surgery and we are investigating the molecular mechanisms of this observation . The overall goal of this research is to identify interventions that can be used in the clinic to prevent aniridia fibrosis syndrome, thus improving the long term vision of anridia patients. This work is supported by Aniridia Foundation International.
- Yan Wang, M.D. - Laboratory Manager (M.D., China Medical University, China). Posterior capsular opacification
- Yichen Wang, Bach. Med. - Graduate Student (Bach. Med., Masters of Med. Capital Medical University, China). Aniridia fibrosis syndrome
- Ramachandran Balasubramanian, B.Tech. Graduate Student (B. Tech, Anna University, India) Fibronectin function in lens development
- Mahbubul Shihan, MPharm. Graduate Student (Bachelors and Masters of Pharmacy, University of Dhaka, Bangladesh) Posterior capsular opacification
- Priyha Mahesh,- Undergraduate BA biology major (University of Delaware, USA), hyaluronan function in lens
- Troy Rubenstein,- Undergraduate BA biology major (University of Delaware, USA), lens fiber cell elongation
Dylan S. Audette, Deepti Anand, Tammy So, Troy B. Rubenstein, Salil A. Lachke, Frank J. Lovicu and Melinda K. Duncan (2015) Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression Development in press.
- Lei Lyu, Shuhong Jiang, Min-Lee Chang, Yumei Gu, Melinda K. Duncan, Ales Cvekl, Wei-Lin Wang, Saima Limi, Lixing W. Reneker, Linfang Du, Fu Shang, Elizabeth A. Whitcomb, Allen Taylor (2015) p27 stabilization due to an unfolded protein response interferes with lens fiber denucleation and causes cataract Faseb J. in press.
- Abby L. Manthey, Anne M. Terrell, Salil A. Lachke, Shawn W. Polson, and Melinda K. Duncan (2014) Development of novel filtering criteria to analyze RNA-sequencing data obtained from the murine ocular lens during embryogenesis Genomics Data; Data in Brief 2, 369-374.
- Abby L. Manthey, Anne Terrell, Yan Wang, Jennifer R. Taube, Alisha R. Yallowitz, and Melinda K. Duncan (2014) The Zeb proteins, deltaEF1 and Sip1, may have distinct functions in lens cells following cataract surgery Investigative Ophthalmology and Visual Sciences, 55, 5445-5455..
- David A. Scheiblin, Junyuan Gao, Jeffrey L. Caplan, Vladimir N. Simirskii, Kirk J. Czymmek, Richard T. Mathias and Melinda K. Duncan (2014) Beta-1 integrin is important for the structural maintenance and homeostasis of differentiating fiber cells International Journal of Biochemistry and Cell Biology, 50, 132-145
- Mallika Pathania, Elena V. Semina, and Melinda K. Duncan (2014) Lens extrusion from Laminin alpha 1 mutant zebrafish The Scientific World Journal-Developmental Biology, 524929. doi: 10.1155/2014/524929. eCollection
- Fahmy A. Mamuya, Yan Wang, Victoria H. Roop, David A. Scheiblin, Jocelyn C. Zajac and Melinda K. Duncan (2014) The Roles of αV Integrin in Lens EMT and Posterior Capsular Opacification Journal of Cellular and Molecular Medicine, 18, 656-670.
- Abby L. Manthey, Salil A. Lachke, Paul G. FitzGerald, Robert W. Mason, David A. Scheiblin, John H. McDonald, and Melinda K. Duncan (2014) Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development Mechanisms of Development, 131, 86-110.
- Robb U. de Iongh and Melinda K. Duncan (2014) Growth factor signaling in lens fiber differentiation in Lens Epithelium and Posterior Capsular Opacification, Shizuya Saika, Liliana Werner and Frank J. Lovicu, editors. Springer Japan KK (Tokyo)
- Sharmila Chatterjee, Yan Wang, Melinda K. Duncan and Ulhas P. Naik (2013) Junctional adhesion molecule-A regulates vascular endothelial growth factor receptor-2 signaling-dependent mouse corneal wound healing. PLOS one 8(5):e63674. doi: 10.1371/journal.pone.0063674
- Bhagwat V. Alapure*, Jaime K. Stull*, Zeynep Firtina and Melinda K. Duncan (2012) The Unfolded Protein Response is activated in Connexin50 mutant mouse lenses Experimental Eye Research 102, 28-37
- 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 16, 445-455
- Abby L. Grabitz-Manthey and Melinda K. Duncan (2012) Focus on molecules: Smad Interacting Protein 1 (Sip1, ZEB2, ZFHX1B). Experimental Eye Research. 101,105-106.
- 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.
Graduate Program Director
Phone: (302) 831-0533
Fax: (302) 831-2281
Office: 327 Wolf Hall
Lab: 266 Wolf Hall
Department of Biological Sciences
University of Delaware
Newark, DE 19716
- B.S. - Lafayette College
- Ph.D. - The University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School and Rutgers the State University of New Jersey
- Postdoctoral - The National Eye Institute, The National Institutes of Health