Guomei Tang, PhD

My laboratory is focused on understanding the cellular and molecular mechanisms of synapse pathology associated with neuropsychiatric disorders, with an emphasis on protein homeostasis (proteostasis), a cellular process that regulate different steps of protein quality control, from protein synthesis to protein degradation. Specifically, we are interested in the mechanistic target of rapamycin (mTOR) and its downstream autophagy-lysosomal degradation pathway.

One major line of research in the laboratory is centered on synaptic and cognitive impairment caused by mutations in the lysosomal gene GBA1, the strongest genetic risk factor for Parkinson’s disease (PD) and Lewy body dementia (LBD). We explore how autophagy-lysosome function is dysregulated by GBA1 mutations, how different brain cells response to GBA1 mutation and how different GBA1 mutant brain cells contribute to synaptic and cognitive impairment associated with PD and LBD.

A second strand of our research investigates the role of mTOR and autophagy signaling in synapse pathology associated with neurodevelopmental conditions, including autism and tuberous sclerosis complex. We aim to understand how mTOR and autophagy pathways are disrupted in different syndromic autism disorders, and to leverage this knowledge to modify the course of disease progression in preclinical mouse models. To support emerging autophagy-lysosomal targeted therapeutics, we are developing autophagy-based peripheral blood biomarker as part of a precision medicine approach.

The methodologies we use in the laboratory involve innovative model systems, including human postmortem brain, genetic mouse models, primary neuronal and astrocyte cultures, patient derived cells (fibroblasts, lymphoblasts and IPSCs), and a multimodal approach that combines mouse genetics, AAV-viral gene delivery or gene editing in vivo, imaging, molecular cell biology, biochemistry, electrophysiology, behavioral phenotyping and molecular systems biology (single cell RNA-seq, translational profiling, lipidomics and proteomics).