Thorold Theunissen
Washington University in St Louis, MO·Genetics
The earliest days of human development are almost impossible to study directly. This is especially true of the placenta, which forms inside the womb and differs from animal placentas.
- Fields
Genetics
Biology
Medicine & Clinical Research
- Topics
naive pluripotency
human pluripotent stem cells
hPSC
- Grants
- 2 known grants, through May 2030
What they work on
- Map the signaling cascade during early primed-to-naïve conversion of human pluripotent stem cells using quantitative phosphoproteomics, to find ways to activate naïve genes without causing instability.
- Preserve parent-specific imprinting and promote normal random X-chromosome inactivation in naïve hPSCs, using fluorescent reporter cell lines with chemical and genetic approaches.
- Improve naïve hPSCs' ability to form endoderm, mesoderm and ectoderm through targeted epigenome editing of cis-regulatory elements that open during the naïve-to-primed transition.
- Build an epigenome roadmap of naïve hPSCs becoming trophoblast stem cells and specialized trophoblasts, testing whether specification relies on unmarked regulatory elements becoming active.
- Define the core transcription factor circuitry of trophoblast specification, starting from a genome-wide CRISPR/Cas9 knockout screen in human trophoblast stem cells.
- Test whether the receptor CCR7 and the transcription factor TEAD1 are needed for invasive extravillous trophoblast formation, using organoids from knockout stem cell lines, and identify regulators of syncytiotrophoblast formation.
More about the research
Human pluripotent stem cells (hPSCs), cells that can become any cell type, offer a window into these stages. Most lab-grown hPSCs, however, are in a "primed" state that resembles a later embryo. "Naïve" hPSCs better match the cells of the pre-implantation embryo and can also form placental cells. The lab studies how genes and epigenetics guide these early cell fates. Epigenetics means chemical marks that change gene activity without changing the DNA sequence. One project improves naïve stem cells themselves, and the other uses them to model the placenta.
Why it matters
Placental problems underlie implantation failure, preeclampsia and preterm birth. Defining the genes that build the human placenta could improve how these complications are understood and eventually diagnosed or treated. More faithful naïve stem cells could provide a reliable platform for modeling early human development and X-linked disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Stefan Pinter
University of Connecticut, CT·Genetics
Link specific X/Y gene pairs and downstream pathways to impaired placental gene expression in monosomy-X, using trophoblast models derived from matched monosomy-X and normal human induced pluripotent stem cells.
Mana M Parast
University of California-San Diego, CA·Medicine & Clinical Research
Test whether villitis of unknown etiology (VUE) linked to fetal growth restriction has a distinct cellular profile of chronic immune responses and trophoblast or endothelial damage, using mass cytometry on banked placental tissue.
Mariko Horii
University of California-San Diego, CA·Medicine & Clinical Research
Identify which stem cell-based culture method best reproduces the abnormal trophoblast differentiation seen in preeclamptic placentas, comparing approaches for modeling syncytiotrophoblast and extravillous trophoblast development.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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