Tomás L. Falzone, Ph.D.

Research

My lab’s primary focus is to understand the role of axonal transport in neuronal function and how impairments in this process contribute to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Our research delves into the polarity, compartmentalization, and distribution of proteins and organelles within axons, with a particular emphasis on the interplay between cytoskeletal proteins, motor proteins, and their cargo. We study the transport properties of proteins, vesicles, and organelles using fluorescent-tagged cargos combined with high-resolution live-cell imaging, biochemistry, and pathological analysis. By unraveling these mechanisms, we aim to gain a deeper understanding of the transport-related dysfunctions observed in neurodegenerative diseases. To do so, we have developed human-derived neuronal models based on the differentiation of human stem cells to study axonal transport in both healthy and disease states. We expanded our work to include 3D culture technologies, creating human brain organoids as models for studying transport-related pathologies in neural tissues derived from patient-specific induced pluripotent stem cells.

As an Innovation Fund investigator, Tomás Falzone, Ph.D., is teaming up with Jonathon Howard, Ph.D., to uncover how the diameters of both dendrites and axons support the demands of optimal neuronal function. Neurons are key communicators within the body, transmitting electrical signals to and within the brain. Dendrites are branched processes that extend from the cell bodies of neurons and collect inputs from other neurons and the environment. At the same time, axons are long and thin processes that send these signals from the cell body to other neurons. The researchers hypothesize that neuronal diameters are regulated by cytoskeletal structures and intracellular transport. By drawing on Howard’s expertise in dendritic morphology and high-resolution microscopy and on Falzone’s extensive experience in axonal transport and the development of human neuronal models, the team aims to answer this fundamental question regarding neuronal shape. Insights from this collaboration could reveal new knowledge about neuronal development, biology, and function and provide crucial information about how these morphological processes can be disrupted in neurodegenerative disorders associated with branching defects and neurite swelling.