Michael Lampson
University of Pennsylvania, PA·Genetics
Why do so many early embryos stop developing, and why do some chromosomes get passed to offspring more often than chance would predict? Both questions lead to repetitive DNA.
- Fields
Genetics
Biology
Ecology & Evolution
- Topics
centromere drive
repetitive DNA
satellite DNA
- Grants
- 2 known grants, through May 2031
What they work on
- Test whether maternal proteins that activate the paternal genome mismatch with fast-evolving paternal transposons, causing abnormal gene expression in hybrid mouse embryos, using transcriptional and epigenomic profiling of 2-cell embryos.
- Define the chromatin features behind a parent-of-origin effect on embryonic telomere lengthening, using telomere epigenetic editing and parthenogenetic embryos (made from an egg alone) whose telomere lengths vary naturally.
- Apply base editing, a technique that changes single DNA letters, to mouse centromeric satellites to learn how their rapid evolution shapes centromere asymmetry between parental genomes and chromosome transmission.
- Determine how selfish centromeres use the asymmetric egg spindle to bias their segregation, by manipulating microtubule-destabilizing activity at centromeres in live mouse oocytes with chemical optogenetic tools.
- Test whether genetically different centromere DNA recruits rapidly evolving centromere proteins differently, using hybrid mouse zygotes with divergent maternal and paternal satellite DNA.
- Measure reproductive fitness costs of mismatched centromeres in hybrid mice, and test whether recurrent changes in rapidly evolving centromere proteins suppress those costs, guided by molecular evolution analyses of Murinae genomes.
More about the research
These are stretches of sequence repeated many times, such as satellites (short repeats packed at chromosome centers and ends) and transposons ("jumping genes"). Repeats make up more than half of the human genome and are among its fastest-changing parts. Their packaging into chromatin, the DNA–protein complex inside chromosomes, supports chromosome segregation (the sorting of chromosomes into daughter cells) and genome stability. The lab's projects use mice to ask how fast-evolving repeats, and the proteins that bind them, affect egg cell division and the first divisions of the embryo.
Why it matters
More than half of human embryos arrest during the earliest divisions, regardless of the mother's age, and the causes are poorly understood. Errors in egg and sperm formation cause genetic abnormalities, pregnancy loss and developmental defects. By showing how repetitive DNA and centromere conflicts disrupt chromosome inheritance, this work could offer a currently overlooked explanation for early embryonic arrest. It may inform reproductive medicine and fertility care.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Venkatesan Sundaresan
University of California-Davis, CA·Plant Science & Agriculture
Generate diploid, unrecombined gametes in maize by editing multiple genes required for cell division and meiosis, testing whether cis-regulatory elements are conserved between meiosis and mitosis.
Wei Cui
University of Massachusetts, MA·Biology
Define how loss of maternal MCM4, part of the helicase that unwinds DNA for copying, blocks zygotic DNA replication, using oocyte-specific Mcm4 knockout mice and EdU labeling of new DNA.
Fei Li
New York University, NY·Genetics
Define how low-level transcription of centromeres into RNA is regulated in fission yeast and what role it plays in centromere function and chromosome segregation.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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