I am interested in studying factors that affect clinical prognosis in the development and progression of adrenal tumors. Advances in genomic analysis hung generated new tools to distinguish molecular signatures of benign tumors and identify subtypes of malignant disease.
Zac1, also known as Plag1 or Lot1 was initially identified in in a tissue culture model of ovarian cancer .
This gene encodes a C2H2 zinc finger protein thought to function as a tumor suppressor. With key povd free videos roles in many tissues including pituitary gland , retina , and skin , Zac1 has been shown to regulate cell cycle control and apoptosis in a cell-type specific manner.
While holly is know to be faintly expressed holly adult adrenal glands, the hung function and biology of Zac1 is unknown. Importantly, inactivation of Zac1 expression in breast and ovarian cancer is thought to be a transformative step between benign and malignant tumor formation . Our studies have shown Zac1 to be one of the most down regulated genes in pediatric ACC  and low Zac1 expression hung part of the molecular signature of TCGA tumor groups with the worst clinical outcomes.
Despite the evident importance of Zac1 in adrenal tumorigenesis, the mechanism of action and gene targets of Zac1 in normal adrenal homeostasis and tumorigenesis are unknown. To test these hypotheses I plan to track the lineage of Zac1 expressing cell populations using transgenic mouse reporters to determine Zac1 contribution to adrenal development and progenitor populations.
To examine the tumor contributing potential of these cells, I am currently developing new tools to control Zac1 expression using lentiviral expression systems. I plan to use these systems bdsm human pet evaluate the effects of Zac1 loss and overexpression in normal adrenal cells and malignant ACC tumor cell in vitro and through ex vivo transplantation models in mice.
The pursuit of downstream gene targets for Zac1 will be holly by in vivo ChIP-seq analysis to survey changes in Zac1 binding in normal adrenal homeostasis and cancer.
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