From decades of genetically-based studies in metazoan animals, a handful of intercellular signaling molecules that control adult stem cell self-renewal have been identified. These include the Hedgehog (Hh) and Wnt family of secreted proteins that play critical roles in cell fate decision-making during embryogenesis and post-embryonic tissue homeostasis. Misregulation in the activity of these signaling molecules frequently results in malformations or cancer. Our research program incorporates functional and chemical genomics approaches to understand how these signaling molecules coordinately control stem cell behavior in tissue development and regeneration, and disease. We use this newfound knowledge to establish novel therapeutic strategies for attacking cancerous cells and improving regeneration of tissue in post-trauma and degenerative disease contexts.
RESEARCH INTERESTS
signal transduction
signaling networks
Hedgehog and Wnt
RECENT PUBLICATIONS
Yao S, Lum L, and Beachy PA, "The ihog cell-surface proteins bind Hedgehog and mediate pathway activation" Cell, 125(2):343-57, April 2006
Echeverri CJ, Beachy PA, Baum B, Boutros M, Buchholz F, Chanda SK, Downward J, Ellenberg J, Fraser AG, Hacohen N, Hahn WC, Jackson AL, Kiger A, Linsley PS, Lum L, Ma Y, Mathey-Prevot B, Root DE, Sabatini DM, Taipale J, Perrimon N, Bernards R, "Minimizing the risk of reporting false positives in large-scale RNAi screens" Nat Methods, 3(10):777-9, October 2006
Jacob L and Lum L, "Deconstructing the Hedgehog pathway in development and disease" Science, 318:66-8, October 2007
SIGNIFICANT PUBLICATIONS
Lum L, Yao S, Mozer B, Rovescalli A, Von Kessler D, Nirenberg M, Beachy PA, "Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells" Science, 299 (5615):2039-45, March 2003
Lum L, Zhang C, Oh S, Mann R, Von Kessler DP, Taipale J, Weis-Garcia F, Gong R, Wang B, Beachy PA, "Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2" Mol Cell, 12:1261-1274, November 2003
Ma Y, Creanga A, Lum L, and Beachy PA, "Prevalence of off-target effects in Drosophila RNAi screens" Nature, 443(7109):359-63, September 2006
Tang W, Dodge M, Gundapaneni D, Michnoff C, Roth M, Lum L, "A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer" PNAS, 105(28):9697-9702, July 2008
Chen B, Dodge M, Tang W, Lu J, Ma Z, Fan C-W, Wei S, Hao W, Kilgore J, Williams N, Roth M, Amatruda J, Chen C, and Lum L., "Small molecule-mediated disruption of Wnt-dependent signal transduction in tissue regeneration and cancer" Nature Chemical Biology, January 2008
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