Cell Biology and Physiology Center

The investigators in the Cell Biology and Physiology Center are dedicated to understanding the internal workings of cells and how cells interact with their external environment. Research themes in this Center focus on studies on how the molecular machines provide cell structure and oversee cell movement, division, and cargo trafficking, particularly the mechanisms that regulate cell morphology and trafficking of proteins. The goals of these investigations are to identify how these machines and processes shape human health and disease, as abnormal changes in just a single cell can eventually affect the entire body. This basic research helps fuel scientific discovery that may one day help advance research related to heart, lung, blood, and sleep conditions or other fields.

Our Labs

Cell and Tissue Morphodynamics

The process of directed cellular movement is of critical importance to human health, as is observed when immune cells seek out infected tissues or metastatic cancer cells invade new organs. The Laboratory of Cell and Tissue Morphodynamics, led by Dr. Clare Waterman, has made pioneering discoveries into the complex and dynamic mechanical interactions between organelle systems within cells that are required for directed movement. Dr. Waterman’s laboratory established that the two classes of cytoskeletal polymers—microtubules and filamentous actin (f-actin)—exhibit both direct structural interactions and regulatory interactions mediated by Rho GTPases; it also developed specific technologies, including quantitative fluorescent speckle microscopy (qFSM) to systematically dissect the critical features of these interactions.

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Cellular Physiology

The primary research interest of the Laboratory of Cellular Physiology, led by Dr. Lois Greene, is in the formation and breakdown of normal and pathological protein complexes in the cell, with an emphasis on the role of molecular chaperones. Dr. Greene studies the role of molecular chaperones and their co-factors in the formation of vesicular compartments from clathrin-coated pits in the cellular membrane during endocytosis. She has applied her wealth of experience in the cell biology of protein folding and membrane trafficking toward deciphering the mechanisms of prion formation and propagation. However, it is becoming increasingly clear that many neurodegenerative diseases—such as Huntington's disease, amyotrophic lateral sclerosis (ALS), and others that are associated with abnormal protein aggregation initiated through genetic mutations—have a prion-like component to their transmission. Once such proteins are misfolded, they may provide a template for other proteins to misfold. Moreover, these misfolded templates could be transmitted between cells. If correct, such a cumulative model of neurodegenerative transmission could partially account for the relatively late onset of these diseases.

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Developmental Neurobiology

Research in the Developmental Neurobiology Laboratory, led by Dr. Herbert M. Geller, focuses on understanding the mechanisms that control axonal growth and pathfinding during neural development and also the mechanisms that stimulate regeneration after injury to the brain or spinal cord. The development of neurons and the neuronal response to injury are influenced by interactions between neurons and the second major cell type in the nervous system, glia. The predominant glial cells in the central nervous system, astrocytes, normally provide a favorable environment for neurons by promoting neuronal migration and the outgrowth of dendritic and axonal processes during development. However, after injury, astrocytes become reactive and form a major part of the glial scar that forms around the injury site and inhibit regeneration. Dr. Geller is identifying the molecular mechanisms at work under these different conditions. His ultimate goal is to promote neuronal regeneration after injury by preventing these changes in astrocytes, adding permissive molecules to astrocytes, or causing neurons to ignore inhibitory cues.

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Host-Pathogen Dynamics

Viruses are experts at exploiting and manipulating the host in numerous and diverse ways throughout their lifecycle. Elucidating these viral mechanisms provides insight into the viral lifecycle and opportunities for therapeutic intervention. It also can provide insight into the host lifecycle, revealing cellular pathways that we did not know existed until viruses were found taking advantage of it. Using cutting edge imaging and spectroscopic technologies combined with novel lipidomic and proteomic approaches, investigations in the Laboratory of Host-Pathogen Dynamics, led by Dr. Nihal Altan-Bonnet, have been at the forefront of understanding the virus-host interface, revealing novel replication and transmission mechanisms shared by many different human viruses. Their investigations are broadly focused on understanding the role of membranes and specifically lipids, in the viral lifecycle.

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Membrane Biology

To preserve their integrity and function, cells must maintain tight control of their borders. One carefully regulated import mechanism, endocytosis, relies on physical deformation and invagination of the cell membrane to engulf extracellular components and form intracellular vesicles. Endocytosis has been predominantly studied in association with the protein clathrin, which coats the membrane and functions with adaptor proteins to direct incoming vesicular traffic to appropriate intracellular destinations.  While studying one of the molecular components of membrane trafficking—the GTP-binding protein ARF6—Dr. Julie G. Donaldson, who leads the Membrane Biology Laboratory, discovered that cells also operate a distinct endocytic pathway independent of clathrin. Since that discovery, Dr. Donaldson’s laboratory has found that clathrin-independent endocytosis (CIE) occurs in every human cell type they have examined. Currently, researchers there are discovering the protein machinery that is important for CIE.

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