Mentors

Hong Wu, Ph.D.

Research Interests:

My current research interest lies in defining the molecular mechanisms responsible for the development of the acute and chronic leukemias. Leukemogenesis is a poorly understood process in spite of recent advances in defining many of the cellular signaling pathways that are involved. The acute leukemias are the most common childhood malignancy with an incidence of about 4 cases per 100,000 children per year. Cure rates for acute lymphocytic leukemia (ALL) are now 75 to 80%. However, for acute myeloid leukemias (AML), cure rates still only range from 40 to 50%.

I am currently looking at the role of the tumor suppressor PTEN in this process. We have generated a transgenic mouse in which PTEN is deleted from a primitive hematopoietic and endothelial precursor termed the hemangioblast. These mice, early on, develop a myeloproliferative disorder which then progresses to an aggressive leukemia and death of the animal.

Recent studies have established that maintenance of effective hematopoiesis is dependant upon a functional bone marrow "niche" or microenvironment. There are likely multiple mechanisms at work which play a part in mediating HSC-vascular niche interactions and maintaining both the quantity and quality of hematopoietic stem cells. Dysregulation of the bone marrow niche has been shown to play a role in hematopoietic malignancies. I am interested in looking at the role of the hematopoietic microenvironment in both normal and malignant hematopoiesis using in vivo imaging techniques such as bioluminescence. Using these techniques, homing and the kinetics of engraftment (both normal and leukemic) can be monitored in "real time". The PTEN mouse model along with in vivo imaging could be useful tools with which to study these factors and test potential therapeutics that may modify disease progression.

Assistant Professor
Division of Pediatric Hematology/Oncology
Clinical Director, UCLA Pediatric Neuro-oncology

Lasky JL, Wu H. Notch signaling, brain development, and human disease. Pediatr Res. 2005 May;57(5 Pt 2):104R-109R.

Ching N, Lasky J, Lazareff J, Moore TB, Nielsen K. Enlarging parietal mass with lytic skull lesion. Pediatr Infect Dis J 2004;23(6):589, 595-6.