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职业迁徙
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Summary Statement of Research Interests
A major interest of our lab is the process that produces germline disease mutations each generation at frequencies far above the known normal human mutation rate (100-1,000 times greater). These mutations: 1) are Recurrent and always take place at the same nucleotide site, 2) result in a gain of function so the disease is inherited as an Autosomal dominant, 3) almost always occur in the male germline and 4) are more likely to be transmitted to the man’s children as he ages-the Paternal age effect. We use the acronym RAMP for such mutations. We studied many different RAMP mutations in four different genes. Among these genes are receptor tyrosine kinases and a non-receptor tyrosine phosphatase, all of which are known in the mouse to be important for spermatogonial stem cell (SSC) proliferation and survival. We found that the unusually high RAMP mutation frequency was not because the mutated DNA base was unusually susceptible to the mutation process. Instead, our data suggest that, in a normal man, any SSC that experiences a rare RAMP mutation is also provided with a selective advantage over his un-mutated brother SSC. This results in an ever-increasing proportion of RAMP mutation-carrying sperm as the man ages. We are currently using transgenic mice to compare the proliferation of mutant and non-mutant SSC in the testis. Our goal is to understand the mechanism of SSC selection and why the mutant SSC do not form tumors but continue to make sperm.
Another main interest is developing new technologies that can solve the fundamental conflict between detecting rare mutations in very small samples of DNA and the inherent problem of the artifactual mutations that accompany the standard detection methods.
A major interest of our lab is the process that produces germline disease mutations each generation at frequencies far above the known normal human mutation rate (100-1,000 times greater). These mutations: 1) are Recurrent and always take place at the same nucleotide site, 2) result in a gain of function so the disease is inherited as an Autosomal dominant, 3) almost always occur in the male germline and 4) are more likely to be transmitted to the man’s children as he ages-the Paternal age effect. We use the acronym RAMP for such mutations. We studied many different RAMP mutations in four different genes. Among these genes are receptor tyrosine kinases and a non-receptor tyrosine phosphatase, all of which are known in the mouse to be important for spermatogonial stem cell (SSC) proliferation and survival. We found that the unusually high RAMP mutation frequency was not because the mutated DNA base was unusually susceptible to the mutation process. Instead, our data suggest that, in a normal man, any SSC that experiences a rare RAMP mutation is also provided with a selective advantage over his un-mutated brother SSC. This results in an ever-increasing proportion of RAMP mutation-carrying sperm as the man ages. We are currently using transgenic mice to compare the proliferation of mutant and non-mutant SSC in the testis. Our goal is to understand the mechanism of SSC selection and why the mutant SSC do not form tumors but continue to make sperm.
Another main interest is developing new technologies that can solve the fundamental conflict between detecting rare mutations in very small samples of DNA and the inherent problem of the artifactual mutations that accompany the standard detection methods.
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Peng-Chieh Chen,Sandra Dudley, Wayne Hagen, Diana Dizon, Leslie Paxton, Denise Reichow,Song-Ro Yoon, Kan Yang,Norman Arnheim,R. Michael Liskay,Steven M. Lipkin
crossref(2023)
Peng-Chieh Chen,Sandra Dudley, Wayne Hagen, Diana Dizon, Leslie Paxton, Denise Reichow,Song-Ro Yoon, Kan Yang,Norman Arnheim,R. Michael Liskay,Steven M. Lipkin
crossref(2023)
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The Biology of Mammalian Spermatogoniapp.181-204, (2017)
mag(2015)
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