Research Fellow, Cancer Science Institute
A postdoctoral position is available immediately in Prof. Yoshiaki Ito’s lab. The successful candidate will study one of the following on-going projects.
Characterization of two types of stem cells in stomach.
It is widely accepted that cancer originates from aberrant regulation of tissue stem cells. However, studies of tissue stem cells in many organs are still at early stages. There are two types of stem cells in stomach: rapidly proliferating stem cells (Isthmus stem cells) and dormant stem cells, a subpopulation of terminally differentiated chief cells at the gland base. Isthmus stem cells are responsible for generating all cell types in the stomach under the homeostatic conditions. We recently identified cytoskeletal scaffold protein, IQGAP3, as a highly specific isthmus stem cell factor during homeostasis (GUT, 2020). We further found that upon tissue damage, IQGAP3 was robustly induced in dormant stem cells, which acquired proliferating capacity to engage in tissue repair. The objective is detailed molecular characterization of these two types of stem cells.
IQGAP3 is also widely expressed in rapidly proliferating areas of gastric cancer. We call IQGAP3 the “common denominator of homeostasis, tissue repair and cancer”. Tumors have been described as “wounds that do not heal (Dvorak, 1986)”. We will investigate the possibility that elevated IQGAP3 expression during chronic tissue damage induces cell plasticity and redirects cell fate to drive malignant transformation.
We have identified transcription factors responsible for the exclusive expression of IQGAP3 in stem cells. We have also found the proteins that interact with and stabilize the IQGAP3 mRNA in stem cells. We will study the role of IQGAP3 in the formation of stomach epithelial stem cells during development. Conversely, we found that depletion of these transcription factors in undifferentiated cancer cells induced differentiation as well as reduced cancer cell properties. Understanding how these factors regulate IQGAP3 will lead to novel insights on induction of terminal differentiation as cancer therapy for aggressive tumor types.
The fact that IQGAP3 is expressed not only in gastric but virtually all other types of cancer cells indicates a fundamental role for IQGAP3 in cancer growth. Developing drugs to inhibit IQGAP3 activity will be important
We seek a highly motivated and innovative postdoctoral fellow with the ability to work independently and as part of a team. Candidates should have PhD and/or MD degree with a strong background in molecular biology, biochemistry and cell biology. Prior experience with using mouse models to study cancer and 1-2 years of postdoctoral experience in these areas are preferred.
Applications should include cover letter, curriculum vitae, publication list, information on years of experience in research and laboratory work, and names and contact information of 2 referees (email and telephone numbers). Please also include a summary of your research experience.
Kindly send your application to:
April Chan ( firstname.lastname@example.org )
Cancer Science Institute, National University of Singapore