Kian Peng Koh, Ph.D.
Associate Professor
Positions
- Associate Professor
-
Molecular and Cellular Biology
Ctr for Precision Environmental Health
Baylor College of Medicine
Education
- BA from Williams College
- 06/1999 - Williamstown, Massachusetts, United States
- Biology, Chemistry
- PhD from Yale University
- 12/2004 - New Haven, Connecticut, United States
- Pharmacology
- Postdoctoral Training at Harvard Medical School
- 08/2011 - Boston, Massachusetts, United States
Professional Statement
Early life exposures to environmental insults have a profound impact on health across the course of life, ranging from birth defects to increased susceptibility to diseases such as cancer, cardiovascular and metabolic disease in adulthood. The epigenome is an important target of these exposures, as it functions as a highly dynamic interface between the genome and the environment. However, the epigenome-genome-environment (ExGxE) interactions that together determine how environmental exposures impact the developing epigenome to adversely affect health remain largely uncharted.
The Jumonji family of DNA and histone demethylases, as iron (II)- and alpha-ketoglutarate-dependent dioxygenases, are potentially epigenetic rheostats that integrate environmental inputs with the genome and epigenome to regulate pre-natal development. In particular, the Tet-Eleven-Translocation (TET) DNA dioxygenases erase DNA methylation by reiterative oxidation of 5-methylcytosine via 5-hydroxymethylcytosine. Our current studies examine the nuanced and long-term developmental impact of DNA demethylation mediated by TET1, as well as its non-catalytic functions, during early embryonic differentiation using mouse models. We also leverage on complementary genomic and epigenomic approaches to elucidate how genetic variants and nutritional stressors interact with TET1 and other dioxygenases in the etiologies of congenital malformations including neural tube defects.
The Jumonji family of DNA and histone demethylases, as iron (II)- and alpha-ketoglutarate-dependent dioxygenases, are potentially epigenetic rheostats that integrate environmental inputs with the genome and epigenome to regulate pre-natal development. In particular, the Tet-Eleven-Translocation (TET) DNA dioxygenases erase DNA methylation by reiterative oxidation of 5-methylcytosine via 5-hydroxymethylcytosine. Our current studies examine the nuanced and long-term developmental impact of DNA demethylation mediated by TET1, as well as its non-catalytic functions, during early embryonic differentiation using mouse models. We also leverage on complementary genomic and epigenomic approaches to elucidate how genetic variants and nutritional stressors interact with TET1 and other dioxygenases in the etiologies of congenital malformations including neural tube defects.
Selected Publications
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Chen L, van der Veer BK, Chen Q, Champeris Tsaniras S, Brangers W, Kwak HHM, Khoueiry R, Lei Y, Cabrera R, Gross SS, Finnell RH, Koh KP.. " The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development. " EMBO Rep.. 2024 Nov 22;
Pubmed PMID: 39578553. -
van der Veer BK, Chen L, Custers C, Athanasouli P, Schroiff M, Cornelis R, Chui JS, Finnell RH, Lluis F, Koh KP.. " Dual functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation. " Nucleic Acids Res .. 2023 Apr 6;
Pubmed PMID: 37021585. -
Luo X, van der Veer BK, Sun L, Bartoccetti M, Boretto M, Vankelecom H, Khoueiry R. Koh, KP. " Coordination of germ-layer lineage choice by TET1 during primed pluripotency. " Genes & Dev. 2020 ; 34 (7-8) : 598-618.
Pubmed PMID: 32115407. -
Bartoccetti M, van der Veer BK, Luo X, Khoueiry R, She P, Bajaj M, Xu J, Janiszewski A, Thienpont B, Pasque V and Koh KP. " Regulatory dynamics of Tet1 and Oct4 resolve stages of global DNA demethylation and transcriptomic changes in pluripotency. " Cell Rep. 2020 ; 30 (7) : 2150-2169.
Pubmed PMID: 32075734.
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