Research Lab Members:
Lapp, Jacqueline
Lewandowski, Jordan
Li, Qiang
Research Summary:
We are interested in understanding how cells integrate information in a way that directs them to make appropriate decisions. Our research specifically focuses on understanding how cells respond to secreted Hedgehog signaling and how they integrate this response with other signaling pathways. The Hedgehog pathway plays critical roles in literally dozens of distinct developmental systems and accordingly, its activity tightly regulated. Defects in Hedgehog signaling causes a spectrum of human defects. After birth, mutations in cells that cause amplified Hedgehog signaling result in several types of cancer.
The output of Hedgehog signaling is at the DNA level, where it results in the activation of cell-specific effector genes. We seek to define how cells respond to Hedgehog signaling at the transcriptional level and how they integrate this information with other signaling pathways to drive events during development and cancer.
To accomplish our goal, we utilize approaches involving both embryonic development and cancer. Our developmental studies are centered on one of the best model systems for understanding Hedgehog signaling, the embryonic limb bud. Recently, we have also started studying this in Basal Cell Carcinomas, the most common type of cancer. We utilize a combination of genetic, molecular and genomic approaches centered on the mouse as a model system.
Research Images:
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Publications:
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2013
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Liu J, Li Q, Kuehn MR, Litingtung Y, Vokes SA, Chiang C.,
Sonic hedgehog signaling directly targets Hyaluronic Acid Synthase 2, an essential regulator of phalangeal joint patterning,
Dev. Biol.
375:
160-171
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2013
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Momb J, Lewandowski JP, Bryant JD, Fitch R, Surman DR, Vokes SA, Appling DR,
Deletion of Mthfd1l causes embryonic lethality and neural tube and craniofacial defects in mice,
Proc Natl Acad Sci
110:
549-554
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2012
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Rabinowitz, A.H., Vokes, S.A.,
Integration of the transcriptional networks regulating limb morphogenesis,
Dev. Biol.
368:
165-180
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2010
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Lee E.Y., Ji H, Ouyang Z, Zhou B, Ma W, Vokes SA, McMahon AP, Wong WH, Scott MP,
Hedgehog pathway-regulated gene networks in cerebellum development and tumorigenesis.,
Proc Natl Acad Sci USA
107:
9736-9741
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2010
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Niakan, K.K., Ji, H., Maehr, R., Vokes, S.A., Rodolfa, K.T., Sherwood, R.I., Yamaki, M., Dimos, J.T., Chen, A.E., Melton, D.A., McMahon, A.P., Eggan, K. ,
Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal,
Genes & Development
24:
312-326
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2009
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Nishi, Y., Ji, H., Wong, W.H., McMahon, A.P., and Vokes, S.A.,
Modeling the Spatio-Temporal Network that Drives Patterning in the Vertebrate Central Nervous System,
BBA - Gene Regulatory Mechanisms
1789:
299-305
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2008
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Vokes, S.A., Ji, H., Wong, W.H., and McMahon, A.P. ,
Whole Genome Identification and Characterization of Gli Cis-Regulatory Circuitry in Hedgehog-Mediated Mammalian Limb Development.,
Genes & Development
22:
2651-2663
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2007
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Vokes, S.A., Ji, H., McCuine, S., Tenzen, T., Giles, S., Zhong, S., Longabaugh, W.J.R., Davidson, E.H., Wong, W.H., and McMahon, A.P,
Genomic Characterization of Gli-Activator Targets in Sonic Hedgehog-Mediated Neural Patterning,
Development
134:
1977-1989
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