Research

One major limitation in pituitary disease research is the lack of normal human pituitary cell transcriptomic data. The pituitary gland is a heterogeneous tissue, making bulk RNA-sequencing suboptimal for identifying tumor-specific gene expression changes. Recent advances in spatial genomics now allow for transcriptomic analysis using formalin-fixed, paraffin-embedded (FFPE) samples. In our preliminary studies, we utilized the GeoMx Digital Spatial Profiling system, a cutting-edge approach that enables targeted enrichment of specific cell populations within tissue samples. This method provides significant advantages over traditional RNA-sequencing by allowing for the direct comparison of gene expression between CD tumors and normal corticotrophs. Through this technology, we can identify key molecular drivers of pituitary tumor pathogenesis and characterize spatial transcriptomics. In our study, we aim to generate a more comprehensive understanding of pituitary tumors at the cellular level, ultimately facilitating the discovery of novel treatment strategies.

Post COVID sequela of pituitary gland

Pituitary hormone dysregulation has been reported in symptomatic long COVID, but it has not been rigorously studied. To investigate this, we conducted molecular analysis of pituitaries from autopsied COVID subjects. In addition, we performed an observational cross-sectional study to assess pituitary hormone levels in long COVID patients, along with a longitudinal study to follow patients with abnormal results. From these studies, we detected persistently mildly elevated serum prolactin levels among these subjects.
 

Nuclear translocation of E2F1 in Cushing’s Disease

We report that E2F1 expression is specific to the corticotroph lineage in normal human pituitaries and that the E2F1 protein is localized in the cytosol in normal corticotrophs. We demonstrate that pS337-E2F1 is localized in the nucleus specifically in Cushing's tumors, whereas in the normal pituitary, it is found in the perinuclear cytoplasm. This observation demonstrates that pS337 is a marker for Cushing's tumors and suggests that phosphorylation of E2F1 may be a target for developing a novel pharmacological treatment for tumorigenesis and hormone dysregulation of Cushing's disease. Araki, T., Wang, J., Lawrence, R., & Kawakami, Y. (2022). Aberrant Nuclear Translocation of E2F1 and Its Association in Cushing’s Disease. Endocrinology, 163(8).  doi: 10.1210/endocr/bqac086

Mechanism of Sex-Biased Occurrence of Cushing’s Disease

Our lab studies the mechanism of gender-biased occurrences of Cushing’s disease. Cushing's disease is significantly higher in females, with a ratio of 1:4-6. This incidence is more exaggerated with the specific gene mutation of USP8 (1:8-20). This is the highest gender bias in all non-gonadal diseases. Our goal is to discover novel gender-specific, personalized therapies for Cushing's disease tumors and to develop a new mechanism and concept for gender-biased diseases.