Current projects include but not limited to:
1) Effect of thyroid hormones on pituitary stem cells. Pituitary stem cells (PSCs), which express SOX2, line the pituitary cleft and can proliferate and differentiate into every pituitary hormone cell-type. What extracellular factors might regulate PSCs? We detect expression of thyroid hormone (TH) transporters such as SLC16A2 in PSCs, suggesting that TH regulates PSC function. Iodine deficiency causes hypothyroidism in humans and mice, and we have used single-cell RNA sequencing (scRNAseq) to identify expression changes occurring specifically in hypothyroid stem cells. This project asks how TH affects PSCs, and how might impaired TH signaling such as hypothyroidism impact PSC function?
2) Etiology of growth hormone defects in patients with CCDC186 mutations. CCDC186 is a Golgi trafficking protein that regulates dense-core vesicles such as those in pituitary and hypothalamic (neuro)endocrine cells that produce hormones. Human genetic variants in CCDC186 can cause endocrine and central nervous system defects potentially including pituitary hormone deficiency. Ccdc186-null mice have pituitary hypoplasia. This collaborative project with Prof. Ken-Ichi Takemaru and Prof. Feng-Qian Li asks how does the loss of function of Ccdc186 impact hypothalamic-pituitary neuroendocrine axes?
3) Spatial gene expression in human pituitary tumors. Human pituitary neuroendocrine tumors (PitNETs) have varied presentation even within the same broad class of classification, for example cabergoline responsive and non-responsive prolactin-producing prolactinomas. However, molecular mechanisms causing this difference in patient outcomes are poorly understood. We are collaborating with colleagues in Argentina to perform spatial transcriptomics using the 10X Genomics Visium HD platform. This project asks what regionalization and cell clusters may be conferring selective advantages to tumor cells leading to differential responses in pitNETs?