Associated Centre/s: Clinical and Diagnostic Oral Sciences
Associated Research: Oral Cancer
- Dr. Ahmad Waseem is interested in keratin filaments and their role(s) in oral keratinocyte function. Keratins are expressed in all epithelia in a tissue specific fashion; for example, the keratins that are expressed in undifferentiated keratinocytes are different from those expressed in differentiated cells. The molecular mechanism that induces these genes in this way is largely unknown. Waseem is using keratin K15 as an example to define the tissue-specific expression of these proteins. K15 is normally expressed in undifferentiated basal keratinocytes of stratified epithelia; however, Waseem has found that this protein can be induced in differentiating keratinocytes as well. The mechanism of K15 expression in progenitor cells of stratified epithelia is different from the one involved in K15 expression in differentiated cells. The functions of this protein in basal keratinocytes are not known and Waseem is working in defining the role(s) of K15 in keratinocytes.
- Dr Hong Wan has identified new markers for the differentiation of stem cells from transit-amplifying cells that include the down regulation of the desmosomal protein desmoglein 3 (see also above). Dr Wan has cloned the human desmonglein 3 (DSG3) cDNA for the first time and is focusing on investigating the novel cellular and molecular functions of this gene product. The knockdown of DSG3 could block the transition of keratinocyte stem cells into transit cells for example and this will need to be investigated. Such experiments will be highly relevant to the goal of enriching stem cells for tissue engineering purposes. However, it is also clear that DSG3 may have non-junctional functions that involve in the regulation of actin cytoskeleton organization and membrane morphology. This finding will advance our knowledge on desmosomal cadherins in cell biology but the relationship of this function to normal oral keratinocyte biology has yet to be explored.
- Professor Parkinson is interested in the ageing of keratinocyte stem cells and how this can be antagonized to increase either their numbers or fitness to treat age-related diseases. His current interests surround the ability of the protein component of the telomerase enzyme to promote stem cell self-renewal without engaging the cancer-promoting functions of the enzyme (see also the programme in oral oncology. Professor Parkinson’s group have identfied three genes that are transcribed following telomere uncapping and are repressed by telomerase. One of these (HOPx) is a candidate tumour suppressor gene and is being investigated for its effects on keratinocyte senescence in vitro and ageing in vivo.
Professor Ian MacKenzie
+44 20 7882 7159 (Tel)
Fax: +44 20 7882 7172 (Fax)
Centre for Cutaneous Research
Blizard Institute of Cell and Molecular Science
4 Newark Street