Department of Biological Sciences: Leading the way to Prominence
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Melinda K. Duncan, Ph.D.

Professor

Graduate Program Director

Melinda K. Duncan, Ph.D.

Duncan

Phone: (302) 831-0533
Fax: (302) 831-2281
Email: duncanm@udel.edu
Office: 327 Wolf Hall
Lab: 266 Wolf Hall

Address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

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Education

  • 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

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
**Course web site available through MyCourses

Research Interests

Lens isolated from an adult cow
Lens isolated from an adult cow

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, representing over 2.5% of the total Medicare budge. 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

  • Rebecca Helton, Ph.D. - Postdoctoral Fellow (Ph.D., University of Delaware). Development of conditional null mice.
  • Vladimir Simirskii, Ph.D. - Postdoctoral Fellow (Ph.D., Russian Academy of Science, Russia). The lens capsule and lens development.
  • Yan Wang, M.D. - Laboratory Researcher (M.D., China Medical University, China). Mammalian lens regeneration.
  • Dylan Audette, B.A. - Graduate Student (B.A., University of Delaware). Prox1 function in lens.
  • Brian Danysh, B.A. - Graduate Student (B.A., University of Delaware). Role of the lens capsule in lens biology.
  • Zeynep Firtina, B.S. - Graduate Student (B.S., Sabanci University, Turkey). Unfolded protein response in cataract development.
  • 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.
  • Matthew King - Junior Biology major. Fibronectin in lens.
  • Robert Sheehan - Junior Quantitative Biology major. Histone dynamics during fiber cell differentiation.
  • Jamie Stull - Junior Cellular and Molecular Biology major. Unfolded protein response induced by mutations in ECM genes.

Selected Publications

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