Dr. Xiyu Ge is a postdoctoral fellow working with Dr. Joy Y. Wu at Stanford University School of Medicine, Division of Endocrinology, Gerontology and Metabolism. Dr. Ge obtained her Ph.D. degree from University of Illinois Urbana-Champaign, mentored by Dr. Lori T. Raetzman. At Stanford, Dr. Ge's research interests focus on single cell profiling and multomics analysis of bone marrow microenvironment under regulation of parathyroid hormone receptor signaling.
Honors & Awards
MCB Outstanding TA Award, University of Illinois Urbana-Champaign (2022)
Early Career Forum Award, Endocrine Society (2021)
First Place- Oral Presentation, Illinois Symposium on Reproductive Sciences (2021)
Graduate Student Travel Award, University of Illinois Urbana-Champaign (2021)
Early Career Investigator in Precision Medicine Scholarship, Mayo Clinic (2018)
Ullyot Fellowship, University of Illinois Urbana-Champaign (2017)
National Collage English Speaking Competition, 3rd prize, Shanghai Division, “21st Century Cup” National English Speaking Competition (2015)
East China Normal University Scholarship, East China Normal University (2014-2016)
Joy Wu, Postdoctoral Faculty Sponsor
Characterization of Somatotrope Cell Expansion in Response to GHRH in the Neonatal Mouse Pituitary.
In humans and mice, loss of function mutations in growth hormone releasing hormone receptor (GHRHR) cause isolated growth hormone deficiency. The mutant GHRHR mouse model, GhrhrLit/Lit (LIT) exhibits loss of serum growth hormone, but also fewer somatotropes. However, how loss of growth hormone releasing hormone signaling affects expansion of stem and progenitor cells giving rise to growth hormone producing cells is unknown. LIT mice and wildtype littermates were examined for differences in proliferation and gene expression of pituitary lineage markers by quantitative real-time PCR and immunohistochemistry at postnatal day 5 (p5) and 5 weeks. At p5, the LIT mouse shows a global decrease in pituitary proliferation measured by proliferation markers Ki67, and Phospho-Histone H3 (pH3). This proliferative defect is seen in a pituitary cell expressing POU1F1 with or without growth hormone (GH). SOX9 positive progenitors show no changes in proliferation in p5 LIT mice. Additionally, the other POU1F1 lineage cells are not decreased in number, rather we observe an increase in lactotrope cell population as well as mRNA for Tshb and Prl. In the 5 week LIT pituitary, the proliferative deficit in POU1F1 expressing cells observed neonatally persists, while the number and proliferative proportion of SOX9 cells does not appear changed. Treatment of cultured pituitary explants with GHRH promotes proliferation of POU1F1 expressing cells, but not GH positive cells, in a MAPK dependent manner. These findings indicate that hypothalamic GHRH targets proliferation of a POU1F1 positive cell, targeted to the somatotrope lineage, to fine tune their numbers.
View details for DOI 10.1210/endocr/bqad131
View details for PubMedID 37616545
Improving adenine and dual base editors through introduction of TadA-8e and Rad51DBD.
2023; 14 (1): 1224
Base editors, including dual base editors, are innovative techniques for efficient base conversions in genomic DNA. However, the low efficiency of A-to-G base conversion at positions proximal to the protospacer adjacent motif (PAM) and the A/C simultaneous conversion of the dual base editor hinder their broad applications. In this study, through fusion of ABE8e with Rad51 DNA-binding domain, we generate a hyperactive ABE (hyABE) which offers improved A-to-G editing efficiency at the region (A10-A15) proximal to the PAM, with 1.2- to 7-fold improvement compared to ABE8e. Similarly, we develop optimized dual base editors (eA&C-BEmax and hyA&C-BEmax) with markedly improved simultaneous A/C conversion efficiency (1.2-fold and 1.5-fold improvement, respectively) compared to A&C-BEmax in human cells. Moreover, these optimized base editors catalyze efficiently nucleotide conversions in zebrafish embryos to mirror human syndrome or in human cells to potentially treat genetic diseases, indicating their great potential in broad applications for disease modeling and gene therapy.
View details for DOI 10.1038/s41467-023-36887-1
View details for PubMedID 36869044
Phenotypic differences based on lateralization of intrahippocampal kainic acid injection in female mice.
2022; 355: 114118
Clinical evidence indicates that patients with temporal lobe epilepsy (TLE) often show differential outcomes of comorbid conditions in relation to the lateralization of the seizure focus. A particularly strong relationship exists between the side of seizure focus and the propensity for distinct reproductive endocrine comorbidities in women with TLE. Therefore, here we evaluated whether targeting of left or right dorsal hippocampus for intrahippocampal kainic acid (IHKA) injection, a model of TLE, produces different outcomes in hippocampal granule cell dispersion, body weight gain, and multiple measures of reproductive endocrine dysfunction in female mice. One, two, and four months after IHKA or saline injection, in vivo measurements of estrous cycles and weight were followed by ex vivo examination of hippocampal dentate granule cell dispersion, circulating ovarian hormone and corticosterone levels, ovarian morphology, and pituitary gene expression. IHKA mice with right-targeted injection (IHKA-R) showed greater granule cell dispersion and pituitary Fshb expression compared to mice with left-targeted injection (IHKA-L). By contrast, pituitary expression of Lhb and Gnrhr were higher in IHKA-L mice compared to IHKA-R, but these values were not different from respective saline-injected controls. IHKA-L mice also showed an increased rate of weight gain compared to IHKA-R mice. Increases in estrous cycle length, however, were similar in both IHKA-L and IHKA-R mice. These findings indicate that although major reproductive endocrine dysfunction phenotypes present similarly after targeting left or right dorsal hippocampus for IHKA injection, distinct underlying mechanisms based on lateralization of epileptogenic insult may contribute to produce similar emergent reproductive endocrine outcomes.
View details for DOI 10.1016/j.expneurol.2022.114118
View details for PubMedID 35597270
Prenatal exposure to the phthalate DEHP impacts reproduction-related gene expression in the pituitary.
Reproductive toxicology (Elmsford, N.Y.)
2022; 108: 18-27
Phthalates are chemicals used in products including plastics, personal care products, and building materials, leading to widespread contact. Previous studies on prenatal exposure to Di-(2-ethylhexyl) phthalate (DEHP) in mice and humans demonstrated pubertal timing and reproductive performance could be affected in exposed offspring. However, the impacts at the pituitary, specifically regarding signaling pathways engaged and direct effects on the gonadotropins LH and FSH, are unknown. We hypothesized prenatal exposure to DEHP during a critical period of embryonic development (e15.5 to e18.5) will cause sex-specific disruptions in reproduction-related mRNA expression in offspring's pituitary due to interference with androgen and aryl hydrocarbon receptor (AhR) signaling. We found that prenatal DEHP exposure in vivo caused a significant increase in Fshb specifically in males, while the anti-androgen flutamide caused significant increases in both Lhb and Fshb in males. AhR target gene Cyp1b1 was increased in both sexes in DEHP-exposed offspring. In embryonic pituitary cultures, the DEHP metabolite MEHP increased Cyp1a1 and Cyp1b1 mRNA in both sexes and Cyp1b1 induction was reduced by co-treatment with AhR antagonist. AhR reporter assay in GHFT1 cells confirmed MEHP can activate AhR signaling. Lhb, Fshb and Gnrhr mRNA were significantly decreased in both sexes by MEHP, but co-treatment with AhR antagonist did not restore mRNA levels in pituitary culture. In summary, our data suggest phthalates can directly affect the function of the pituitary by activating AhR signaling and altering gonadotropin expression. This indicates DEHP's impacts on the pituitary could contribute to reproductive dysfunctions observed in exposed mice and humans.
View details for DOI 10.1016/j.reprotox.2021.12.008
View details for PubMedID 34954075
View details for PubMedCentralID PMC8882145
VarSAn: associating pathways with a set of genomic variants using network analysis.
Nucleic acids research
2021; 49 (15): 8471-8487
There is a pressing need today to mechanistically interpret sets of genomic variants associated with diseases. Here we present a tool called 'VarSAn' that uses a network analysis algorithm to identify pathways relevant to a given set of variants. VarSAn analyzes a configurable network whose nodes represent variants, genes and pathways, using a Random Walk with Restarts algorithm to rank pathways for relevance to the given variants, and reports P-values for pathway relevance. It treats non-coding and coding variants differently, properly accounts for the number of pathways impacted by each variant and identifies relevant pathways even if many variants do not directly impact genes of the pathway. We use VarSAn to identify pathways relevant to variants related to cancer and several other diseases, as well as drug response variation. We find VarSAn's pathway ranking to be complementary to the standard approach of enrichment tests on genes related to the query set. We adopt a novel benchmarking strategy to quantify its advantage over this baseline approach. Finally, we use VarSAn to discover key pathways, including the VEGFA-VEGFR2 pathway, related to de novo variants in patients of Hypoplastic Left Heart Syndrome, a rare and severe congenital heart defect.
View details for DOI 10.1093/nar/gkab624
View details for PubMedID 34313777
View details for PubMedCentralID PMC8421213