Benjamin Braun, MD, PhD
Now Accepting Post-Doc Applications!
Background: Cancer arises when mutations subvert the mechanisms used by cells to control proliferation, differentiation and survival. Curing cancer with signal transduction inhibitors is possible if, and only if, a specific catalytic activity is essential for survival of cancer cells but non-essential for the rest of the organism. Our knowledge of biochemistry in primary cancer cells is too limited at present for this strategy to work well. Furthermore, it is particularly important to understand the biochemistry of long-lived tumor cells, even when such “cancer stem cells” make up a small fraction of the overall tumor bulk.
The Ras signaling network is activated by nearly all growth stimuli, and it is a frequent target of oncogenic mutations that lead to its inappropriate activation. About one-third of human cancers have mutations in one of the three RAS genes, KRAS, NRAS, or HRAS. We primarily study myeloid leukemia because there is a high incidence of KRAS and NRAS mutations and the hematopoietic system is uniquely accessible for studying both cell fates and biochemistry. We have used a conditional knock-in Kras allele to produce a model of human leukemia that is highly accurate at both genetic and phenotypic levels.
Our Major Goals are to: (i) to define the influence of Ras signaling on the fate of normal and malignant hematopoietic stem cells; (ii) to discover biochemical mechanisms underlying the effects of Ras signaling in hematopoiesis; (iii) to find new opportunities for treating Ras-related cancers based on their unique biochemical regulation of cell survival and proliferation.