Collaborative Research Programs
Telethon Institute of Genetics and Medicine (TIGEM)
Telethon Institute of Genetics and Medicine (TIGEM) was founded in 1994 by the Telethon Foundation, one of Italy's leading non-profit organizations, to promote research aimed at diagnosing, preventing and curing human genetic diseases. TIGEM invited world-renowned geneticist Andrea Ballabio, then on faculty at Baylor College of Medicine, to lead the new endeavor. The longstanding relationships between faculty at BCM and TIGEM underpin the new, formal collaboration centered at the NRI. The complementary expertise enjoyed by NRI and TIGEM in lysosomal biology, molecular genetics, cell biology, biochemistry, physiology, bioinformatics, systems biology and viral-mediated gene delivery will allow the collaborators to utilize a variety of animal models (mouse and fruit flies) of human diseases to test discoveries in living organisms before proceeding to clinical trials. Close interactions, the free exchange of data and ideas between researchers, and collaborative funding will accelerate progress in developing innovative therapies. The preliminary results in animal models of lysosomal storage disorders are already proving very promising.
Below are the faculty at TIGEM and NRI who are cooperating in this lysosomal storage research project:
Andrea Ballabio (Director, TIGEM and Investigator, NRI)
Dr. Ballabio is widely acknowledged to be a world leader in the elucidation of the mechanisms of human genetic diseases. Dr. Ballabio's group identified the "master gene," TFEB, which regulates the expression of the CLEAR network in lysosomes. His group has shown that overexpression of TFEB in cultured cells and in murine models enhances lysosomal biogenesis, activates autophagy, and induces lysosomal exocytosis, all of which results in the efficient clearance of glycosaminoglycans, known to accumulate in lysosomal storage diseases, as well as toxic substrates such as the protein responsible for Huntington's disease. The next steps are to develop tools to modulate cellular clearance by acting on the CLEAR network and to use them to treat human diseases. The TIGEM-NRI program will be instrumental in meeting these challenges.
Marco Sardiello (Investigator, NRI)
Dr. Sardiello, one of the NRI's first new hires, is focused on neuronal ceroid lipofuscinoses (NCLs), among the most common neurodegenerative disorders affecting children. In NCLs, the deficiency of proteins participating in lysosomal metabolism leads to the intralysosomal storage of lipofuscin, which ultimately impairs the cell's function and viability. This project sprang from Dr. Sardiello's discovery of TFEB while he was a post-doctoral fellow in Andrea Ballabio's group. A major goal of Dr. Sardiello's project is to modulate TFEB activity in mouse models of NCLs as a therapeutic tool to enhance the clearance of accumulated toxic molecules within the neurons, as seen in certain childhood neurodegenerative diseases like Batten's disease.
Recently, Dr. Sardiello’s team used an Akt inhibitor, MK2206 crosses the blood-brain barrier, to demonstrate that Akt inhibition can indeed activate TFEB and the lysosomal system in the mouse brain. When treated with MK2206 and trehalose, cells derived from patients affected by juvenile Batten disease or other lysosomal storage disorders showed increased clearance of the abnormally accumulated cellular debris. Another exciting possibility that emerges from this study is Akt inhibition could also be explored as a viable therapy for other lysosomal storage diseases and adult-onset neurodegenerative disorders, such as Alzheimer’s and Parkinson’s, which are currently incurable.
Watch this video to learn more about Dr. Sardiello's latest research in Batten's disease.
The Center for Drug Discovery
The mission of the Center for Drug Discovery (CDD) is to develop small molecule probes, preclinical candidates, and drugs for researchers and clinicians in the Texas Medical Center and beyond. It is a resource for investigators in all Baylor College of Medicine departments and will complement efforts in the Department of Pharmacology, the Gulf Coast Consortia, and the Institute for Clinical and Translational Research as well as other departments and centers at Baylor College of Medicine.
Led by Dr. Martin Matzuk and the Assistant Director, Dr. Damian Young, the CDD aims to bridge the gap between academic research and pharmaceutical discovery and provide researchers with an economical path to preclinical drug discovery.