Erika L. F. Holzbaur | |
---|---|
Born | 1960 (age 61–62) |
Alma mater | Pennsylvania State University College of William and Mary |
Scientific career | |
Institutions | University of Pennsylvania Worcester Foundation for Biomedical Research Pennsylvania State University |
Thesis | Kinetic and thermodynamic investigations of the microtubule-dynein ATPase pathway (1987) |
Notable students | Chantell Evans |
Website | Holzbaur Lab |
Erika L F. Holzbaur (born 1960) is an American biologist who is the William Maul Measey Professor of Physiology at University of Pennsylvania Perelman School of Medicine. Her research considers the dynamics of organelle motility along cytoskeleton of cells. She is particularly interested in the molecular mechanisms that underpin neurodegenerative diseases.
Holzbaur grew up in Poughkeepsie, New York. [1] She became interested in American history as a teenager, and in particular was inspired by the women's rights advocate Frederick Douglass. [1] As an undergraduate student, Holzbaur majored in history, but became fascinated by the periodic table and chemistry. [1] [2] She eventually graduated from the College of William & Mary with a major in chemistry and history. [1] She completed an undergraduate research project with Melvyn Schiavelli. [2] Holzbaur has said that she became interested in cell biology during her interviews for graduate school. [1] Her doctoral research at the University of Pennsylvania involved studies of the ATPase pathway of axonemal dynein. [3] She worked as a postdoctoral researcher at Pennsylvania State University and the Worcester Foundation for Biomedical Research. During her postdoctoral research, Holzbaur studied cytoplasmic dynein. [3] She was the first person to clone the p150Glued, the largest subunit of the dynactin complex, and went on to show how this subunit binds to microtubules. [1] [4] She recognized that the cytoplasmic dynein-associated proteins closely resembled a Drosophila gene called Glued, which was known to cause neurodegeneration in the fruit-fly. [2]
Holzbaur's research considers the dynamics of organelle motility along cytoskeleton of cells. She was appointed to the faculty at the University of Pennsylvania in 1992. [5] Holzbaur studies various motor proteins, including dyneins, myosins and kinesins. [2] In the axons of neurons, these motor proteins are responsible for the transport of organelles over extraordinarily long distances. [3] She found that targeted disruption of the dynein-dynctin interaction can result in the degeneration of motor neurons. [1] Holzbaur has used her understanding of axonal transport to better understand neurodegenerative disease, including Parkinson's disease and amyotrophic lateral sclerosis. [3] [6] [7]
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components, microfilaments, intermediate filaments and microtubules, and these are all capable of rapid growth or disassembly dependent on the cell's requirements.
Dyneins are a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements important in mitosis, and drives the beat of eukaryotic cilia and flagella. All of these functions rely on dynein's ability to move towards the minus-end of the microtubules, known as retrograde transport; thus, they are called "minus-end directed motors". In contrast, most kinesin motor proteins move toward the microtubules' plus-end, in what is called anterograde transport.
Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytoplasm of its axon called the axoplasm. Since some axons are on the order of meters long, neurons cannot rely on diffusion to carry products of the nucleus and organelles to the end of their axons. Axonal transport is also responsible for moving molecules destined for degradation from the axon back to the cell body, where they are broken down by lysosomes.
Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.
Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).
Huntingtin-associated protein 1 (HAP1) is a protein which in humans is encoded by the HAP1 gene. This protein was found to bind to the mutant huntingtin protein (mHtt) in proportion to the number of glutamines present in the glutamine repeat region.
Tubulin alpha-4A chain is a protein that in humans is encoded by the TUBA4A gene.
Dynactin subunit 2 is a protein that in humans is encoded by the DCTN2 gene
Alpha-centractin (yeast) or ARP1 is a protein that in humans is encoded by the ACTR1A gene.
Cytoplasmic dynein 1 heavy chain 1 is a protein that in humans is encoded by the DYNC1H1 gene.
Dynactin subunit 3 is a protein that in humans is encoded by the DCTN3 gene.
John Quinn Trojanowski was an American academic research neuroscientist specializing in neurodegeneration. He and his partner, Virginia Man-Yee Lee, MBA, Ph.D., are noted for identifying the roles of three proteins in neurodegenerative diseases: tau in Alzheimer's disease, alpha-synuclein in Parkinson's disease, and TDP-43 in Amyotrophic Lateral Sclerosis (ALS) and frontotemporal degeneration.
Ronald David Vale is a biochemist and cell biologist. He is a professor at the Department of Cellular and Molecular Pharmacology, University of California, San Francisco. His research is focused on motor proteins, particularly kinesin and dynein. He was awarded the Canada Gairdner International Award for Biomedical Research in 2019, the Shaw Prize in Life Science and Medicine in 2017 together with Ian Gibbons, and the Albert Lasker Award for Basic Medical Research in 2012 alongside Michael Sheetz and James Spudich. He is a fellow of the American Academy of Arts and Sciences and a member of the National Academy of Sciences. He was the president of the American Society for Cell Biology in 2012. He has also been an investigator at the Howard Hughes Medical Institute since 1995. In 2019, Vale was named executive director of the Janelia Research Campus and a vice president of HHMI, his appointment began in early 2020.
Intracellular transport is the movement of vesicles and substances within a cell. Intracellular transport is required for maintaining homeostasis within the cell by responding to physiological signals. Proteins synthesized in the cytosol are distributed to their respective organelles, according to their specific amino acid’s sorting sequence. Eukaryotic cells transport packets of components to particular intracellular locations by attaching them to molecular motors that haul them along microtubules and actin filaments. Since intracellular transport heavily relies on microtubules for movement, the components of the cytoskeleton play a vital role in trafficking vesicles between organelles and the plasma membrane by providing mechanical support. Through this pathway, it is possible to facilitate the movement of essential molecules such as membrane‐bounded vesicles and organelles, mRNA, and chromosomes.
Samara Reck-Peterson is an American cell biologist and biophysicist. She is a Professor of Cellular and Molecular Medicine and Cell and Developmental Biology at the University of California, San Diego and an Investigator of the Howard Hughes Medical Institute. She is known for her contributions to our understanding of how dynein, an exceptionally large motor protein that moves many intracellular cargos, works and is regulated. She developed one of the first systems to produce recombinant dynein and discovered that, unlike other cytoskeletal motors, dynein can take a wide variety of step sizes, forward and back and even sideways. She lives in San Diego, California.
Susan R. Weiss is an American microbiologist who is a Professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania. She holds vice chair positions for the Department of Microbiology and for Faculty Development. Her research considers the biology of coronaviruses, including SARS, MERS and SARS-CoV-2. As of March 2020, Weiss serves as Co-Director of the University of Pennsylvania/Penn Medicine Center for Research on Coronavirus and Other Emerging Pathogens.
Sara R. Cherry is an American microbiologist who is a Professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania. Her research involves genetic and mechanistic studies of virus–host interactions. During the COVID-19 pandemic, Cherry looked to identify novel therapeutic strategies.
Jennifer L. Ross is an American physicist who is Professor and Chair of the Department of Physics at Syracuse University. Her research considers active biological condensed matter physics. She was elected Fellow of the American Physical Society in 2018.
Marisa Bartolomei is an American cell biologist, the Perelman Professor of Cell and Developmental Biology and Co-Director of the Epigenetics Institute at the Perelman School of Medicine at the University of Pennsylvania. Her research considers epigenetic processes including genomic imprinting. She was elected to the National Academy of Sciences in 2021.
Chantell Skye Evans is an American cell biologist who is a professor at Duke University. Her research looks to understand the dynamical processes of mitochondria and their role in neurodegenerative disease. In 2022, Popular Science named her as one of their "Brilliant 10" US scientists and engineers.