Baojie Li received his BSc in Biology from Beijing Normal University in 1988 and his PhD from Albert Einstein College of Medicine of Yeshiva University in 1997. He pursued postdoctoral training in Howard Hughes Medical Institute at Columbia University, where he studied a non-receptor tyrosine kinase, c-Abl and its role in bone development. Baojie Li was a Cancer Research Institute fellow at Columbia University. He joined IMCB in 2001. Presently, he is an associate professor.

The laboratory uses biochemical and genetic approaches to study the physiological function of ABL kinases and the signaling pathways that involve ABL kinases. The oncogenic form, BCR-ABL is responsible for the pathogenesis of chronic myeloid leukemia. The proto-oncogene, c-Abl, is known to be involved in the regulation of genotoxic stress response and many aspects of mouse development. Our main focuses are DNA damage activated Atm-c-Abl-p53 pathway, BMP-BMPR-Smad pathway, and BMP-BMPR-Tak1-MAPK pathways. We study how ABL kinases regulate these pathways and the roles of these pathways in development and tumorigenesis.

Bone development and osteoporosis.
The integrity of the skeleton relies on complex interactions between osteoclasts and osteoblasts. Osteoclasts tear down bone, whereas osteoblasts work to rebuild it. When the balance is disrupted, diseases such as osteoporosis result. Mice deficient for c-Abl or Atm are osteoporotic. Osteoblasts isolated from these two knockout mice show defects in differentiation/maturation, and expansion. p53 knockout mice show osteosclerosis, accompanied by increased bone formation and enhanced osteoblast differentiation. We are currently studying the molecular mechanisms by which c-Abl, Atm and p53 modulate osteoblast differentiation and bone remodeling. Fig. A shows a longitudinal section of a long bone from c-Abl knockout mouse.

DNA damage/oxidative stress response and tumorigenesis. 
c-Abl is activated by genotoxic stress in an Atm dependent manner and modulates DNA damage induced cell cycle arrest and programmed cell death.  Our current focus is on the molecular mechanisms by which c-Abl acts in DNA damage response.  c-Abl is also activated by oxidative stress.  Osteoblasts deficient for c-Abl are hypersensitive to oxidative stress and some of these effects of c-Abl are mediated by PKC d.  Accumulating evidence support a link between DNA damage and oxidative stress to cell senescence, tumorigenesis, and aging.  Mice deficient for c-Abl, Atm, or p53 might present useful models to study these complex interactions.  Fig. B shows that c-Abl affects the formation of DNA damage induced nuclear foci, centers of DNA damage and repair.

Heart development.
Several c-Abl interacting proteins have been identified by yeast two-hybrid and GST pull-down experiments.  These proteins have been biochemically characterized and mice deficient for them are being generated.  One such knockout mice show defects in myoblast differentiation and congenital cardiomyopathy.  These mouse models are used to elucidate the physiological roles of c-Abl and its interacting proteins.  Figure below shows H&E staining of skeletal muscle from a knockout mouse.