Cell and Developmental Biology Center

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.

Selfish genetic elements distort their own transmission ratio by preferentially segregating to the egg during female meiosis. The Laboratory of Chromosome Dynamics and Evolution, led by Dr. Takashi Akera investigates this non-Mendelian transmission of selfish elements called meiotic drive. Meiotic drive has significant impacts on genetics, evolution, and reproduction, as selfish elements distort transmission ratios and allele frequencies in populations and manipulate gamete production. Dr. Akera’s lab uses the mouse oocyte model to reveal both the cell biological basis and evolutionary consequences of meiotic drive.

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.

The primary research interests of the Molecular Cell Biology Laboratory, led by Dr. John A. Hammer, revolve around the roles played by motor proteins and cytoskeletal protein dynamics in driving the motility of organelles and cells. The inside of a living cell is not a still place. From the motor protein-dependent transport of organelles inside the cell, to the changes in overall cell shape driven by cytoskeletal dynamics, normal cell function is highly dependent on movement. Dr. Hammer’s lab uses cell biological, genetic, biochemical, and biophysical approaches, coupled with advanced imaging techniques, to study the molecular interactions that give rise to cellular and intracellular movements, and to define the functional significance of these movements in the context of whole organisms. Recently, Dr. Hammer has focused more efforts on understanding the role played by cytoskeletal protein dynamics in driving the proper function of certain white blood cells called T lymphocytes.

The Laboratory of Molecular Machines and Tissue Architecture, led by Dr. Nasser M. Rusan, studies the role of centrosomes during animal development. The centrosome is a non-membrane bound organelle that serves as the main microtubule (MT) organizing center of most animal cells. Centrosomes function to initiate and maintain cell polarity, guide cell migration, direct intracellular cargos, and properly distribute other organelles. In mitosis, or cell division, centrosomes are critical for accurate construction of the mitotic spindle to ensure faithful chromosome separation to the two daughter cells. Thus, it is not a surprise that defects in centrosome function lead to a wide range of failures at the cellular level, which in turn, leads to tissue defects and many human diseases. The lab aims to determine how centrosomes are properly constructed from their individual parts and how centrosomes function in a wide range of cell types to avoid human diseases such as polycystic kidney disease, microcephaly, and cancer.

Early work in the Laboratory of Molecular Physiology, led by Dr. James R. Sellers, focused on the regulation of the myosin II isoforms found in smooth muscle and non-muscle cells. Myosins are cellular motor proteins. As new myosin isoforms were discovered, his interests shifted to also include studies of these “unconventional” myosins. Dr. Sellers has focused on studying myosin diversity as a means of understanding meaningful molecular differences that give rise to disparate functions. His interdisciplinary laboratory brings together a breadth of experience in fields such as developmental biology, biochemistry, cell biology, biophysics, and engineering and encompasses studies of systems ranging from single molecules to fruit fly models (Drosophila melanogaster).

The selective recycling of lipids and proteins is critical to healthy cellular function. Many genes associated with human diseases encode components of the cellular machinery that sorts lipids and proteins for selective trafficking along endocytic pathways leading to lysosomal degradation. The Laboratory of Protein Trafficking and Organelle Biology, led by Dr. Rosa Puertollano, seeks to understand precisely how defects in intracellular trafficking—specifically, in endosomal and lysosomal pathways—contribute to human diseases.

The overarching goal of the Laboratory of Stem Cell and Neurovascular Research, led by Dr. Yoh-suke Mukouyama, is to uncover the molecular control of the morphologic processes underlying the branching morphogenesis and patterning of the vascular and nervous systems. These systems share several anatomic and functional characteristics and are often patterned similarly in peripheral tissues. These characteristics suggest that there is interdependence between these two networks during tissue development and homeostasis. Thus, Dr. Mukouyama is studying neuronal influences on vascular branching patterns and vascular influences on both neuronal guidance and neural stem cell maintenance. He has recently extended the lab’s research to the unanticipated roles of tissue macrophages and microglia in neuronal and vascular development. His laboratory approaches these problems using a combination of high-resolution whole-mount imaging, advanced genetic perturbations, and in vitro organ culture techniques.

The laboratory of Structural Cell Biology aims to understand the molecular mechanisms governing specialized cell shapes, such as those of neurons, activated immune cells or platelets and certain cancer cells. We visualize the key factors determining different cell morphologies using in situ cellular cryo-electron tomography in combination with interdisciplinary techniques such as single-particle cryo-EM, X-ray crystallography, in vitro reconstitution and light microscopy.