David Y. Chen, M.D.,Ph.D.

Assistant Professor
Internal Medicine
Dermatology

Cancer Biology Program
Developmental, Regenerative and Stem Cell Biology Program
Molecular Genetics and Genomics Program

Research Abstract:

The best-defined risk factors for the development of any skin cancer in fair-skinned populations include immune suppression, aging, and sun exposure. Epigenetic changes, including altered DNA methylation and histone modifications, exhibit age and exposure related changes. This interplay between intrinsic and extrinsic factors that modify cancer risk drives the unifying theme of our lab's investigation: defining the genetic and epigenetic drivers of premalignant states in skin cancer. Three lines of inquiry stem from this theme:

-Characterizing aging phenotypes in murine skin.
-Characterizing epigenetic perturbations in mouse models that result in premalignant skin phenotypes.
-Characterizing genetic and functional changes in human premalignant skin.

Selected Publications:

Dnmt3a deficiency in the skin causes focal, canonical DNA hypomethylation and a cellular proliferation phenotype.
Chen DY, Ferguson IM, Braun KA, Sutton LA, Ramakrishnan SM, Helton NM, Smith AM, Miller CA, Ley TJ. Proceedings of the National Academy of Sciences (2021) PMID: 33846253.

Remethylation of Dnmt3a−/− hematopoietic cells is associated with partial correction of gene dysregulation and reduced myeloid skewing.
Ketkar S, Verdoni AM, Smith AM, Bangert CV, Leight E, Chen DY, Brune MK, Helton NM, Hoock M, George DR, Fronick C, Fulton RS, Petti AA, Spencer DH, Miller CA, Ley TJ. Proceedings of the National Academy of Sciences (2020) PMID: 31996479.

A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing.
Petti A, Williams SR, Miller CA, Fiddes IT, Srivatsan SN, Chen DY, Fronick CC, Fulton RS, Church DM, Ley TJ. Nature Communications (2019) PMID: 31413257.

DNMT3AR882-associated hypomethylation is maintained in primary AML xenografts, but not in the DNMT3AR882C OCI-AML3 leukemia cell line.
Chen DY, Christopher M, Helton N, Ferguson I, Ley TJ, Spencer DH. Blood Cancer Journal (2018) PMID: 29618788.

Last Updated: 4/30/2021 10:35:51 AM

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