Year 2

Stem cells are endowed with the ability to self-renew, that means to give rise to other cells with the same potential to regenerate a tissue. Recently, we found a gene that also regulates this mechanism. In addition, expression of high levels of this gene can reduce the number of stem cells in the bone marrow, breast and the brain. This gene is expressed in the Chromosome 21 and hence can potentially contribute to the pathology of people with Down Syndrome (people with Down Syndrome has three copies of Chromosome 21). In line with that, we now observe that mouse models for Down Syndrome have fewer stem cells in their bone marrow, breast and brain.
Outcomes from this study have begun to shed more light in understanding not only the normal process of stem cell maintenance, but also in deciphering the complex biology underlying Down Syndrome. In particular, our second year results appear to suggest why Down Syndrome patients have a defect in learning. If our results continue to confirm our hypothesis, then pharmacologic agents that inhibit the function of this gene might ameliorate the pathology of Down Syndrome.
Another important aspect of our research on this pertains to cancer development: indeed cancer initiating cells take advantage of the normal self-renewal machinery to proliferate without restraint. Data generated in the second year of funding suggest that high levels of this gene counteract some solid tissue tumors, putting a brake on cancer cells proliferation. Interestingly, people with Down Syndrome have a much lower risk of developing solid tumors than the general population. Using human breast cancer samples, in particular breast and colon tumors that we received directly from Stanford Hospital, we find this single gene inhibits cancer. These studies will give hint to alternative strategies for cancer treatment.