PhD by Research Programme (Dermatology and Skin Biology)

Location
Singapore
Posted
Jan 10, 2017
Closes
Jan 30, 2017
Organization Type
University and College
Hours
Full Time
Research Project Title: The Role of Dermal Hedgehog Signaling in Hair Follicle Regeneration and Wound Healing

Principal Investigator:

Assistant Professor WOO Wei-Meng, LKCMedicine

Co-supervisor: 

  • Professor David Becker, LKCMedicine
  • Assistant Professor NG Kee Woei, School Materials Science and Engineering, NTU
  • Professor Artur Schmidtchen, LKCMedicine - Professor Duncan Angus McGrouther, SGH

 

Project Discription:
Our tissue regenerative ability decreases with age, thus adult human usually heal wounds with scars instead of functional tissues. While most wounds heal rapidly without any problem, in the elderly and diabetic populations this process often fails, resulting in chronic wounds in lower limbs that can often lead to amputation. There are currently no effective therapeutic treatments for these chronic wounds and so they represent a significant unmet medical need. Understanding the mechanisms of normal tissue regeneration and the requirements of the normal wound healing process, is central to this project as it can help us understand what has gone wrong when healing stalls and may indicate new therapeutic approaches to treat these hard to heal wounds.

The hair follicle and skin wound models are ideal for investigating the mechanisms of normal tissue regeneration and the normal wound healing process. The mammalian hair follicles regenerate themselves throughout the adulthood, and hair follicle stem cells are capable of regenerating not only the hair follicle during homeostasis, but also the skin epidermis upon wounding. Equally important to stem cells in hair regeneration and wound healing is the tissue microenvironment that surrounds hair follicle stem cells, including dermal cells and other non-stem cell types in the dermis.  Although we know that reciprocal signaling events between stem cell and microenvironment are important in driving and shaping hair follicle regeneration, the underlying mechanism is not fully understood. Similarly, during skin wound healing, it’s not clear how hair follicle stem cells interact with the underlying dermis and other microenvironment cell types to mediate wound healing. 

In this project the PhD student will investigate the role of dermal Hedgehog (Hh) signaling in postnatal hair follicle regeneration and skin wound healing. Using Cre-lox genetic mouse models to knockout Hh signaling in the dermal cells at specific time, the student will characterize hair follicle regeneration during the natural hair cycle. He/she will identify the cellular and molecular changes in the epithelial cells including hair follicle stem/progenitor cells, and in various dermal cell types that interact with the stem/progenitor cells. In parallel, the PhD student will generate skin wounds and examine the wound healing process using the same dermal Hh signaling knockout mouse models. He/she will characterize wound closure in the mutant and the wild-type mice, and identify the cellular and molecular changes in the epithelial cell types and the various cell types in the dermis. Based on the results, the student will isolate specific cell types and perform ex vivo cell biological studies, for example cell migration study of the Hh signaling defective dermal cells using live imaging. In addition, the student will determine the cell fate of Hh signaling knockout dermal cells during the regeneration and healing process, using additional mouse genetic tools to trace the mutant cells in vivo. 

Mini-project:
The rotation student will characterize hair follicle regeneration and wound healing using collected skin samples that we collected from dermal Hh signaling knockout mice and wild-type mice at different hair cycle stages. The student will perform tissue sectioning and immunohistochemistry, to examine cell differentiation, number, survival, migration, as well as signaling molecules, thus determine the cellular and molecular changes of the epithelial, dermal, and other non-dermal cells in the skin.

The student will work closely with both the Woo lab and Becker lab. He/she will master hair follicle biology, skin wound biology, skin dissection, skin cell isolation, minor mouse surgery, immunostaining, confocal imaging and methodologies in molecular biology.

Our previous study has demonstrated a role of dermal Hh signaling in supporting epithelial signaling and growth, in the early developing hair follicle. The requirements of Hh signaling in wound healing have also been reported in several studies, although cell type specific roles are unknown. Understanding the cell type specific requirement and intercellular molecular signaling mechanisms in the physiological regeneration and normal wound healing from the proposed study here could contribute to future therapeutic design for wound healing.

If you have questions regarding this project, please email the Principal Investigator, Assistant Professor Woo Wei-Meng, at woowm@ntu.edu.sg

Please refer to the Lee Kong Chian School of Medicine website http://www.lkcmedicine.ntu.edu.sg/Pages/default.aspx for programme information

If you have questions regarding this project, please email the Principal Investigator, Assistant Professor Woo Wei-Meng, at woowm@ntu.edu.sg