Understanding how evolutionary forces shape genomic imprinting and affect healthy development

Columbia University received a $158,264 Project Grant from the National Institute of General Medical Sciences under the Biomedical Research and Research Training program (CFDA 93.859), effective January 20, 2026 through September 15, 2028. The award supports fundamental research investigating the evolutionary forces that shape genomic imprinting and its effects on healthy development. The research addresses a critical gap in understanding parent-of-origin-specific gene expression, which is essential for embryonic and placental development and directly relevant to improving assisted reproductive technologies and treating imprinting-related genetic diseases affecting approximately one in ten thousand live births.

The project employs two complementary research approaches to advance the field's understanding of imprinting evolution at the molecular level. The first approach leverages population genetic tools and publicly available sequencing data to empirically characterize how evolutionary forces drive imprinting changes across populations. The second approach involves experimental investigation of disrupted imprinting in deer mouse hybrids to elucidate underlying mechanisms. The anticipated outcomes will provide novel molecular insights into gene regulation across generations and within individuals, with potential applications to human disease prevention and assisted reproductive technology optimization.

Abstract

Genomic imprinting, the parent-of-origin-specific monoallelic expression of a subset of genes, is critically important to human gene regulation and the healthy development of the embryo and placenta. Proper regulation of imprinted gene dosage is a key challenge for assisted reproductive technologies. Moreover, several human diseases that affect as many as one in ten thousand live births result from genetic alterations that change the dosage of imprinted genes. Although essential for development, imprinting is thought to evolve rapidly, raising the possibility that the evolution of imprinting affects mammalian development and human disease. Despite a rich body of theory on the evolutionary forces that shape genomic imprinting, almost nothing is known empirically, especially at the molecular level. My overarching goal is to uncover the forces, mechanisms, and molecules underpinning the evolution of imprinting, which will provide novel insights into how this important process works. I will take two approaches to this question. First, i will leverage population genetic tools and publicly available sequencing data to empirically characterize how these evolutionary forces drive the evolution of genomic imprinting. Second, i will perform a focused experimental dissection of disrupted imprinting in deer mouse hybrids. This work will be crucial for understanding gene regulation across generations and within individuals.