Positions

Assistant Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US

Education

BS from Universita Bari
PhD from Universita Bari
Post-Doctoral Fellowship at Telethon Institute Of Genetics And Medicine

Professional Interests

  • Regulatory networks of cell metabolism and neurological disorders

Professional Statement

My laboratory uses genetics, cell biology and systems biology approaches to study how the cell regulates its metabolic programs and how dysfunctions in these programs lead to neurological disease. Our ultimate goal is to translate our knowledge of these regulatory networks into therapeutic approaches for neurodegenerative disorders.

Using systems biology approaches, we discovered and characterized a gene network regulating lysosomal biogenesis and function. Lysosomes are cellular organelles central to degradation and recycling processes. Defects in genes participating in lysosomal function lead to the accumulation of toxic substances into the cell, which ultimately results in diseases collectively known as lysosomal storage disorders (LSDs). We discovered that the transcription factor EB (TFEB) is a master regulator of the biogenesis and activity of lysosomes. Under aberrant lysosomal storage conditions, TFEB translocates from the cytoplasm to the nucleus, resulting in the activation of genes with lysosomal function. TFEB overexpression induces lysosomal biogenesis and increases the clearance of ceroid lipopigment, glycosaminoglycans and mutant huntingtin, which are pathologically accumulated in Batten disease, mucopolysaccharidoses and Huntington’s disease, respectively. We are now using genetic and chemical tools to modulate TFEB activity in mouse models of neurodegenerative diseases to enhance the clearance of stored molecules and determine the effects on disease symptoms.

My laboratory is also investigating other regulatory networks. We have discovered a mitochondrial gene network that regulates energy metabolism in Drosophila. Nuclear and mitochondrial genes involved in oxidative phosphorylation are connected in a common regulatory circuit, for which we have now identified a candidate master regulator. Drosophila mutants for this gene display severe impairment of energy metabolism and die at the larval stage. Surprisingly, this gene network is analogous, but non homologous, to the mammalian mitochondrial network, being based on different molecules and regulatory signals.

Additional metabolic gene networks regulated by transcription factors or microRNAs are currently under study. These studies aim at dissecting the regulatory circuitry that controls the basal metabolism of the cell.

Selected Publications