Funding

Ongoing Grant Support

Evaluation of PLK1 inhibitors in a pre-clinical LAM animal model

Funded by the University of Pennsylvania Orphan Disease Center (2015) / Million Dollar Bike Ride 2014
We demonstrated that PLK1 inhibitors can decrease the survival and induce cell death of TSC1 and TSC2 negative cells
This project will evaluate the efficacy of PLK1 inhibitors, alone or in combination with rapamycin, in a LAM mouse model to inhibit tumor growth and lung metastases, and prevent tumor regrowth and lung metastases after discontinuation of treatment.
PI: Astrinidis, co-PIs: Magdalena Karbowniczek (TTUHSC), Jane J. Yu (University of Cincinnati College of Medicine)

Completed Grant Support

Screen of FDA-approved drugs as a therapeutic approach for Tuberous Sclerosis Complex

Funded by the Tuberous Sclerosis Alliance (2010-2012).
Current treatments for TSC are mostly symptomatic. Rapamycin provides significant imrpovement of quality of life, however it is not clear that rapamycin will be sufficient to provide a permament cure for TSC.
Our goal is to identify new drugs that could be used as therapeutics for TSC. We are currently screening a library of FDA-approved drugs for their potential to inhibit the growth of TSC-related cells. After the initial screens, a number of targets will be further validated, interactions with other drugs will be investigated, and their effects on cell death and mTOR signaling will be studied.
Future studies in TSC animal models will be required to test the efficacy of these drugs.
PI: Astrinidis

Role of the PLK1-Hamartin interaction in the pathogenesis of Tuberous Sclerosis Complex

Funded by the Department of Defense (2009-2012).
We demonstrated that TSC1 interacts with the mitotic kinase PLK1. Furthermore, this interaction seems to render the TSC1/TSC2 complex inactive.
This project focuses in three areas: (a) to investigate the mechanism of PLK1-dependent mTOR signaling, (b) to study the role of PLK1, TSC1/TSC2, and mTOR in mitotic progression, and (c) to determine whether PLK1 can be use as a therapeutic target for TSC.
PI: Astrinidis

Role of the hamartin-Plk1 interaction in the pathogenesis of pulmonary lymphangioleio-myomatosis