TIGEM Lab at NRI
TIGEM has a long-established relationship with the Baylor College of Medicine, one of the world's top research centers. Some of our researchers, including Andrea Ballabio, have worked as professors and researchers at the internationally-renowned Baylor College of Medicine. This tie has opened an opportunity for new research endeavors and scientific collaborations. TIGEM and the Jan and Dan Duncan Neurological Research Institute (NRI) are working together to progress research in lysosomal biology, molecular biology, systems biology and other fields. Close collaborations and data and technique exchange between two leading, complementary institutes make this joint initiative a leading effort in research. TIGEM's research focuses, such as lysosomal storage disorders (LSD's), a group of diseases which causes malfunctioning lysosomes to accumulate substances, have greatly benefited from this project. We have seen promising results in the elucidation of the mechanisms behind genetic diseases and continue to progress in finding translatable data. Currently, TIGEM investigators Andrea Ballabio, Giancarlo Parenti, Nicola Brunetti-Pierri and Alberto Auricchio are active in the NRI-TIGEM collaboration.
TIGEM investigators at TIGEM-NRI
Andrea Ballabio, TIGEM Director and investigator, has been credited for the discovery of TFEB, a master gene which regulates lysosomal function. This has had important implications in the elucidation of the mechanisms causing LSDs. He and his lab group have shown that overexpression of this master gene leads to "revival" of lysosomal function. Lysosomal biogenesis and autophagy, for example, reset lysosomes and allow for substances such as glycosaminoglycans (GAGs) to be expelled from lysosomes. This applies to diseases in which accumulation of toxic substances cause dire symptoms and disorders. The NRI-TIGEM team has proven irreplaceable in the hope for finding a cure for such disorders.
Giancarlo Parenti, a Molecular Therapy TIGEM investigator, is discovering new ways in which to treat genetic diseases. Older techniques such as enzyme replacement therapy, have shown to be useful, but not optimal given some of the side effects. New ways to translate research into treatments has thus become necessary. Giancarlo Parenti works with Pompe Disease, a disorder caused by lack of lysosomal activity. His group has shown that a sort of chaperone therapy using small molecules is a valid corrective measure. Small molecular therapy agents, another potential technique, can also be used to reduce substrates. These two approaches are groundbreaking alternatives to current research hallmarks and are opening new venues in clinical therapy.
Alberto Auricchio, another one of our Molecular Therapy investigators, is a key resource in the NRI-TIGEM project, as his expertise in AAV production and gene therapy are important for translating data into valid clinical approaches. Auricchio's studies include gene studies for the LSD, mucopolysaccharidosis type VI (MPS-VI), which causes organs such as the heart and bone to undergo malfunctions.
Nicola Brunetti's lab makes great use of viral vectors helper-dependent adenoviral (HDAd) for gene therapy studies. HDad have proven safer than traditional first generation adenoviral-based vectors primarily due to their lack of coding sequences. This is crucial, especially for studies at NRI, because they are ideal for brain-involved disorders given their ability to transduce neurons. Brunetti's lab has shown that HDad transduction by injection results in prolonged therapeutic effects, especially in models of mucopolysaccharidoses.