Melinda K. Duncan, Ph.D., FARVO

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

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 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.

Current Projects

  • 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.

Research Group

  • Yan Wang, M.D. - Laboratory Manager (M.D., China Medical University, China). Posterior capsular opacification
  • Mallika Pathania Bach.Med. - Graduate Student (Bach.Med., Rajiv Gandhi University of Health Sciences, India). Function of integrins in early lens development
  • Dylan Audette, B.A. - Graduate Student (B.A., University of Delaware, USA). Prox1 function in lens.
  • 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

Selected Publications

Professor
Graduate Program Director

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

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