Biography
Dr. Baas earned his PhD from Michigan State University, and then trained as a Postdoctoral Fellow at Temple University. From there, he was on the faculty of the University of Wisconsin for ten years before joining the faculty of Drexel University in 2000. Baas is interested in all aspects of the neuronal cytoskeleton, with a particular emphasis on the regulation of microtubules in developing neurons. In recent years, his interests have expanded to include the underlying mechanisms by which flaws in microtubule-related proteins contribute to neurodegenerative diseases. Baas is frequently invited to present his work at national and international symposia, and has been consistently funded for over two decades by federal agencies (NIH, NSF, DOD) as well as private foundations with missions related to treating neurodegenerative diseases and nerve injury. Baas is currently the Director of the Graduate Program in Neuroscience, and the Director of an NIH-funded Postdoctoral Training Program in the Neurosciences at Drexel University.
Research Interests
The mission of the Baas Laboratory is to elucidate the cellular and molecular mechanisms by which the microtubule arrays of the neuron are established and regulated during development, health, and disease. Toward this end, the laboratory uses a variety of techniques including microscopic, biochemical, and molecular assays.
 Microtubules form the infrastructure of eucaryotic cells, acting as both architectural elements and as railways for the transport of cytoplasmic constituents. To serve these functions, microtubules must be organized into a wide variety of configurations, ranging from the bipolar conformation of the mitotic spindle to the dense paraxial arrays that occupy elongated cellular processes. Thus an important question in cell biology is how different cell types organize their microtubules into these various configurations. Neurons are terminally postmitotic cells that no longer organize their microtubules into mitotic spindles. Instead, the microtubules of the neuron are utilized for the formation of elongated processes termed axons and dendrites. These two types of processes contain dense arrays of paraxially-oriented microtubules, none of which are attached to the centrosome or any comparable structure. Despite this, the microtubules within these processes are highly organized with respect to their intrinsic polarity. In the axon, the microtubules are uniformly oriented with their plus-ends distal to the cell body of the neuron. In the dendrite, the microtubules are nonuniformly oriented with roughly similar numbers of microtubules of each orientation. These distinct microtubule patterns are essential for defining the cytoplasmic composition of each type of process, as well as for regulating morphological characteristics such as their relative lengths. For almost twenty years, the central issue addressed by the Baas Laboratory has been to elucidate the molecules and mechanisms by which the microtubule arrays of the neuron are established during development.
.jpg) One of the major conceptual breakthroughs came when it was established by the Baas Laboratory that neurons do not abandon the fundamental mechanisms that organize microtubules during mitosis. In the mitotic spindle, microtubule organization is orchestrated by a combination of the assembly properties of the microtubules together with forces generated on the microtubules by molecular motor proteins. The Baas Laboratory has established that this same general theme is true in neurons, and many of the very same proteins that organize microtubules in the mitotic spindle also do so in axons and dendrites. In particular, many of the molecular motor proteins that had been assumed to be mitosis-specific continue to be expressed in neurons, where they play critical roles in orchestrating microtubules in axons, dendrites, axonal branches, and growth cones.
Most recently, the laboratory has put forward a model called “cut and run” in which the molecular motors can only transport microtubules if they are very short. If the microtubules are longer than just a few microns, then forces imposed upon them by the molecular motors do not transport the microtubules but instead enable the microtubules to participate in events such as growth cone turning or axonal retraction. In order for microtubules to be mobile, they must be cut into short pieces by enzymes called microtubule-severing proteins. Thus, the behavior and configuration of the microtubules and the roles they perform are dependent upon the forces generated by molecular motor proteins as well as the activity of microtubule-severing proteins that determine the consequences of these motor-driven forces on the microtubules.
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There are two major projects currently underway in the Baas Laboratory. The first is a direct continuation of the studies on the cellular and molecular mechanisms that orchestrate microtubules during development. These studies include live-cell imaging of microtubules in neurons, together with manipulations of the relevant molecular motor proteins such as cytoplasmic dynein and kinesin-5. These studies also include a strong focus on the microtubule-severing proteins, namely katanin and spastin. The studies are aimed at understanding how axons grow, how dendrites are differentiated, how axonal branches are formed, and how growth cones navigate to find their targets.
Shown in this figure is a recent experiment in which the distribution of kinesin-5 was determined during the turning of a growth cone, leading to a mechanistic model whereby kinesin-5 cooperates with other motors to regulate the polarized distribution of microtubules that is essential for a growth cone to make a turn.
The second major project focuses on how these microtubule-based mechanisms go awry during neurodegenerative diseases as well as nerve injury, and how the growing body of knowledge about neuronal microtubules can be used to develop new therapeutic strategies for treating injured or diseased axons. For example, mutations of the spastin gene are the most common cause of Hereditary Spastic Paraplegia, and the Baas Laboratory is actively seeking to understand how the mutant forms of spastin cause the corticospinal tracts to degenerate. Other studies in the laboratory include testing the hypothesis that axons may degenerate during Alzheimer’s disease because of too much microtubule-severing when the tau protein dissociates from the microtubules. In addition, there are ongoing projects on how manipulation of certain molecular motors and severing proteins might provide avenues for clinical strategies to augment regeneration of damaged nerves after injury.
Lab Members
Senior Scientists:
Dr. Wenqian Yu
Dr. Joanna Solowska
Postdoctoral Fellows:
Dr. Mei Liu
Dr. Haruka Sudo
Dr. Shen Lin
Dr. Irina Tint
Graduate Students:
Vidya Nadar
Daphney Jean
Aditi Falnikar
Liang (Oscar) Qiang
Technician:
Herbert Francisco
Selected Publications
Baas, P.W., and L. Qiang. 2005. Neuronal microtubules: when the MAP is the roadblock. Trends in Cell Biology 15:183-187.
He, Y., F. Frances, K.A. Myers, W. Yu, M. Black, and P.W. Baas. 2005. Role of cytoplasmic dynein in the axonal transport of microtubules and neurofilaments. J. Cell Biol. 168: 697-703.
Yu, W., J.M. Solowska, L. Qiang, A. Karabay, D. Baird, and P.W. Baas. 2005. Regulation of microtubule severing by katanin subunits during neuronal development. J. Neurosci. 25: 5573-5583.
Baas, P.W., A. Karabay, and L. Qiang. 2005. Microtubules cut and run. Trends in Cell Biology 15: 518-524.
Qiang, L., W. Yu, A. Andreadis, M. Luo, and P.W. Baas. 2006. Tau protects microtubules in the axon from severing by katanin. J. Neurosci. 26: 3120-3129.
Baas, P.W., V.C. Nadar, and K.A. Myers. 2006. Axonal microtubule transport: the long and short of it. Traffic 7: 490-498.
Myers, K.A., I. Tint, C.V. Nadar, Y. He, M.M. Black, and P.W. Baas. 2006. Antagonistic forces generated by cytoplasmic dynein and myosin-II during growth cone turning and axonal retractions. Traffic 7: 1333-1351.
King, M.E., H.-M. Kan, P.W. Baas, A. Erisir, C.G. Glabe, and G.S. Bloom. 2006. Tau-dependent microtubule disassembly initiated by pre-fibrillar -amyloid. J. Cell Biol. 175: 541-546.
Myers, K.A., and P.W. Baas. 2007. Kinesin-5 regulates the growth of the axon by acting as a break on its microtubule array. J. Cell Biol. 178: 1081-1091.
Yu, W., Qiang, L., and P.W. Baas. 2007. Microtubule-severing in the axon: implications for development, disease, and regeneration after injury. J. Environ. Biomed. 1: 1-7.
Solowska, J.M, G. Morfini, A. Falnikar., B.T. Himes, S.T. Brady, D. Huang, and P.W. Baas.. 2008. Quantitative and functional analyses of spastin in the nervous system: implications for hereditary spastic paraplegia. Journal of Neuroscience 28: 2147-2157.
Yu, W., L. Qiang, J.M. Solowska, A. Karabay, S. Korulu, and P.W. Baas. 2008. Spastin is more specialized than P60-katanin to participate in the formation of axonal branches. Molecular Biology of the Cell 19: 1081-1098.
Nadar, V.C., A. Ketschek, K.A. Myers, G. Gallo, and P.W. Baas. 2008. Kinesin-5 is essential for growth cone turning. 2008. Current Biology 18: 1972-1977. |