Lanlan Shen
Baylor College of Medicine, TX·Genetics
Genes can be silenced without any change to the DNA sequence itself. One way this happens is DNA methylation, a stable chemical tag that can switch genes off.
- Fields
Genetics
Medicine & Clinical Research
Biology
- Topics
DNA methylation
epigenetics
epimutation
- Grants
- 3 known grants, through Jul 2030
What they work on
- Use inducible dCas9-SunTagTET1 mice, which carry a DNA-targeting CRISPR tool linked to a methylation-removing enzyme, to remove DNA methylation precisely at chosen genes in living animals.
- Develop inducible dCas9-SunTagDNMT3A-3L mice that add DNA methylation at targeted genes, giving researchers a way to switch specific genes off epigenetically in vivo.
- Engineer mice with intact immune systems that combine p16 promoter methylation with activated K-RAS, to model how benign lung tumors progress to malignant adenocarcinoma.
- Test whether drugs that target epigenetic marks and/or anti-PD-L1 immunotherapy suppress p16-epimutant mouse lung tumors during the transition from benign lesions to adenocarcinoma.
- Investigate how combined age-related epimutations change intestinal stem cell function and promote tumors, using intestinal organoids and CRISPR epigenome editing.
- Model advanced and BRAF-mutant colorectal cancer in epigenetically engineered mice, and test combined epigenetic immunotherapy in tumors that carry a driver epimutation.
More about the research
Abnormal methylation shows up in aging and in cancer, but it has been hard to prove that a methylation change at a single gene actually causes disease. Scientists can already test genetic mutations by targeting specific genes in animals. The lab builds a matching approach, "epigenetic gene targeting," in mice and uses it to ask how methylation changes drive lung and colon cancer and whether drugs can reverse them.
Why it matters
The work could help patients with lung and colorectal cancer by providing a mechanistic basis for combining epigenetic drugs with immunotherapy such as anti-PD-L1 treatment, and by guiding how such therapies enter clinical trials. The methylation-editing mice could also give researchers more faithful models for studying epigenetic disorders and testing targeted treatments for them.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
X. Shawn Liu
Columbia University, NY·Neuroscience
Test whether reactivating the healthy MECP2 copy on the silenced X chromosome, by removing promoter methyl tags with dCas9-Tet1, rescues Rett syndrome symptoms in female mouse models.
Yaguang Xi
University of Georgia, GA·Pharmacology
Determine how the oncogenic microRNA miR-10b and its target gene NR4A3 contribute to the experimental compound LG007's activity against triple-negative breast cancer.
Analisa DiFeo
University of Michigan, MI·Medicine & Clinical Research
Determine how loss of the microRNA miR-181a affects immune cell infiltration and interferon signaling in patient-derived ovarian tumor organoids, with and without a STING agonist or anti-PD-L1 immunotherapy.
The school
Baylor College of Medicine: 38 labs on PI Pages, $881M a year on research, 115 research doctorates a year.
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