Adult stem cells maintain proliferating cellular systems for life. They do this by generating not only cells primed to enter differentiation pathways, but also cells that instead retain the undifferentiated stem cell characteristics of the parent - a process called "self-renewal".
We are interested in the genes that come into play when stem cells undergo self-renewal divisions, and in the means by which some initially renewing daughter cells lose self-renewal capacity while others continue to retain it through multiple cell divisions. Our findings in the hemopoietic system have led us to focus increasingly on particular homeobox genes as central effectors of self-renewal divisions, and on the genes that control their expression as specifiers of stable stem cell identity in this system. The emergence of leukemia subsequent to retrovirally enforced expression of HOXB4, and the dependence of continued propagation of the leukemia on the HOXB4 transgene, illustrates the therapeutic potential of targeting self-renewal mechanisms. The findings lend urgency to working out the mechanisms that underlie the connection between HOXB4 and self-renewal.
Identifying genes and pathways that differ between normal self-renewing hemopoietic stem cells and more advanced cells that do not sustain self-renewal. This work aims toward understanding how differentiating cells lose the immortality uniquely characteristic of the stem cells.
Identifying genes and pathways that differ between normal hemopoietic precursor cells that do not self-renew and similar cells that do self-renew by virtue of expression of a HOXB4 transgene. These experiments are directed at identifying pathways, circuits and proteins essential to self-renewal and immortalization.
Identifying, purifying and characterizing the biology of HOXB4-dependent leukemia stem cells. This work targets the molecular basis of the sustained self-renewal of the leukemia stem cells, and aims at developing strategies to interfere with the critical elements driven by the HOXB4 transgene.
More detailed description can be found at our laboratory homepage.