Meet the Fall 2024 Seed Funding Awardees
The Dunlevie Maternal-Fetal Medicine Center for Discovery, Innovation and Clinical Impact's mission is to empower an arc of discovery and implementation in maternal-fetal science. Aligned with this mission, the Center continues to provide seed funding for researchers at Stanford working on projects that advance maternal-fetal medicine science. Today, we are excited to announce the recipients of the fall 2024 cycle of funding: Kristy Red-Horse, PhD, and Bo Zhou, PhD.
Director of Research Anna Girsen, MD, PhD, comments, “On behalf of the center, I'm thrilled to see these two basic science projects by the talented Drs. Zhou and Red-Horse were selected for funding. Together, these proposals have the potential to improve the science of maternal-fetal medicine and we can't wait to see the impact of their work.”
Continue reading to learn more about the funded projects.
The proposal “Molecular pathways for uterine artery remodeling by placental trophoblasts” from Professor of Biology Dr. Red Horse was selected due to its ability to increase our understanding of maternal artery remodeling during early pregnancy
During pregnancy, maternal arteries that supply blood to the placenta and developing fetus are remodeled. Artery remodeling involves the invasion of fetal cells from the placenta, invasive trophoblasts, into the wall of arteries, where these trophoblasts displace artery cells and supporting smooth muscle cells surrounding the arteries. This process is necessary for proper pregnancy progression, and improper amounts of remodeling (increased or decreased) are associated with pregnancy complications, notably pre-eclampsia, placenta previa, and placenta accreta. While this transformation of maternal arteries is critical for a successful pregnancy, the molecular drivers used by placental trophoblasts to remodel uterine arteries are poorly understood. This current lack of understanding limits our ability to develop therapeutics and molecular targets for pregnancy complications that result from placental defects.
Trophoblast invasion of maternal arteries is broadly evolutionarily conserved across placental animals that utilize blood-based nutrition to support their developing fetuses. Leveraging this insight, Dr. Red-Horse’s research team will utilize 2D and 3D imaging of the mouse uterus and placenta, along with genetic manipulations, in order to functionally test candidate signaling axes that may affect trophoblast invasion and maternal artery remodeling.
Instructor of Psychiatry and Behavioral Sciences Dr. Zhou’s proposal “Nanopore DNA sequencing for non-invasive prenatal testing of chromosomal microdeletions and microduplications” was selected because of its potential to improve the methodology of non-invasive prenatal testing for fetal chromosomal abnormalities
Non-invasive prenatal testing (NIPT) during pregnancy is now standard for screening to detect abnormal fetal chromosome counts. Chromosomal abnormalities arise from unexpected cellular events and cause birth defects. Inside every cell, the thousands of genes that coordinate human development are coded within 23 pairs of DNA molecules that are each tightly protected by proteins and, under a microscope, show up as 23 pairs of chromosomes. One in the chromosome pair is maternally inherited and one paternally. Twenty-two of the pairs are numbered 1-22, and pair 23 is the sex chromosomes (XX; XY). Variations from this pattern are abnormalities. These can take place with aneuploidy, where an entire chromosome is missing or extra, such an extra chromosome 21 (i.e. Down Syndrome).
NIPT is currently limited to aneuploidy and is achieved by first tracking down pieces of fetal DNA contained within maternal blood that carry sequences marking paternal inheritance and, as a result, make NIPT more accurate and reliable for individuals from populations where DNA sequence markers have been more abundantly cataloged. In other cases of chromosomal abnormalities, only a segment of a chromosome may be missing (i.e. microdeletion) or duplicated (i.e. microduplication). Examples of such include Angelman/Prader-Willi Syndromes and DiGeorge Syndrome. Current NIPT methods cannot screen for the fetal presence of these types of chromosomal abnormalities due to the way the DNA signal must be amplified for detection which blurs the resolution of chromosomal analysis.
Dr. Zhou’s team will develop a NIPT method that leverages a new DNA sequencing technology (nanopore) where DNA is read out with nano-scale pores and does not require signal amplification. This new NIPT method will utilize biomarkers indicative of human biology during pregnancy rather than those genetic markers that are restrictive to ancestry, race, and ethnicity and thus, will make NIPT more accessible to all individuals.
Also supporting Dr. Zhou is his research team which includes Hanlee P. Ji, MD (Medicine - Oncology Division); Alexander E. Urban, PhD (Psychiatry and Behavioral Sciences); Wing H. Wong, PhD (Statistics and Biomedical Data Science).
We extend our congratulations to both researchers and thank the seed grant reviewers for their expertise and time during thorough reviews, and Program Manager Rebecca Mobley for smooth coordination of the grant cycle. We are looking forward to sharing updates about these funded projects and hope that you will keep an eye out for the Center’s future funding opportunities.