The research program in cellular neuroscience seeks to better understand the fundamental mechanisms used by axons and dendrites to establish connections during development and regeneration of the nervous system. The development and maintenance of the nervous system involves signaling initiated by several families of growth factors, as well as selective pruning of mistargeted axons and the programmed death of particular neurons that are overproduced within the embryo.
There is also strong interest in the cellular mechanisms of neuronal migration, as well as the cytoskeletal pathways the go awry during neurodegenerative disorders such as Alzheimer’s disease, hereditary spastic paraplegia, autism and Gulf War illness. Investigators are using a variety of contemporary biochemical, molecular and computer-assisted imaging techniques to elucidate these developmental and pathological mechanisms.
Research efforts are focused on several key areas. Studies on the cytoskeleton of the neuron are a principal strength of the program (Drs. Baas and Qiang), and are relevant to understanding the mechanisms of neurodegenerative disorders and restoration of function following injury. Neuronal migration and related neurodevelopment orders are another key strength (Dr. Toyooka), as are the cell biology of spinal cord injury (Drs. Fischer, Tom, Qiang and Jin) and traumatic brain injury (Dr. Raghupathi).
All of the research in the program is conducted with the goal of providing a mechanistic understanding of basic cellular processes relevant to nervous system development and maintenance. The ultimate aim of our research is to stimulate the development of new clinical strategies for treating neuropathies and promoting regeneration of the injured nervous system.
The nervous system is composed of a vast number of neurons as well as support cells such as glia. Neurons are amazing cells and, in fact, they are the cell type in all of nature whose morphology and polarity are most intimately related to their functions. Neurons are specialized to transmit and receive information. To accomplish this, they generate two distinct kinds of processes called axons and dendrites, which communicate with one another and with muscle cells via structures known as synapses. Glial cells are important for the appropriate growth and guidance of developing neurons, and for the manufacture of the myelin sheathes that insulate large axons.
Neurons are terminally post-mitotic cells, which means they no longer undergo cell division. Neural progenitors proliferate in certain regions of the developing brain, and recent studies suggest this occurs in the adult brain as well. Having undergone their last mitotic division, newly differentiated neurons migrate through the brain until they reach their destinations, and then cease migration and set forth to develop an axon as well as a complex dendritic arbor. Development and maintenance of the nervous system involves signaling initiated by several families of growth factors, as well as selective pruning of mistargeted axons and the programmed death of particular neurons that are overproduced within the embryo.
Development of the nervous system can sometimes go awry, leading to congenital disorders of the nervous system such as lissencephaly and autism. Neurodegenerative diseases can afflict an individual at any stage of life, and these include Alzheimer's disease, ALS, Hereditary Spastic Paraplegia, and Parkinson's. Injuries can occur to the peripheral nervous system or the central nervous system, and are particularly problematic to the latter because the CNS has very limited regenerative capacity. Traumatic brain injury is becoming more and more common, resulting from traffic and sports accidents and military service. All of these disease and injury conditions have a cellular basis, and presumably have a cellular solution.
The research program in cellular neuroscience at Drexel University College of Medicine seeks to understand the cellular and molecular mechanisms underlying development, maintenance, disease and injury of the nervous system, as well as regeneration and treatment of injury and disease. Investigators are using a variety of contemporary biochemical, molecular and computer-assisted imaging techniques to elucidate these mechanisms. The investigators are highly collaborative with one another, but also reach out to colleagues in other focal groups, such as the Spinal Cord Research Group, which specializes in regeneration after injury. There is also a strong cellular neuroscience group in the Department of Biology at Drexel University, with substantial collaborative ties with the group in the Department of Neurobiology & Anatomy.
There is a strong focus on the cytoskeleton in the group, especially from Drs. Baas, Qiang and Yu, who study several aspects of microtubules in neurons (neuronal development and polarity, diseases including hereditary spastic paraplegia and injury with a focus on microtubule-based therapies), but also including other investigators studying cytoskeletal mechanisms of neuronal migration (Drs. Baas and Toyooka), brain injury (Dr. Raghupathi) and spinal cord injury (Dr. Tom). Drs. Fischer and Jin share a prominent research program in stem cells, with focus on therapy for spinal cord injury. Dr. Raghupathi studies various aspects of traumatic brain injury with a focus on therapy. Dr. Cunningham studies neurodegeneration, with an emphasis on novel neuroprotective peptides as treatment. Drs. Baas and Toyooka are studying various aspects of neuronal migration, with emphases on normal development of the brain as well as congenital disorders arising from flaws in neuronal migration. Dr. Qiang uses human induced pluripotent cells differentiated into neurons to study neurodegenerative diseases.
The group uses a variety of cutting-edge models, including genetically engineered mice, experimentally tractable stem cell lines, cutting-edge live-cell imaging (including confocal, multi-photon, and TIRF), molecular biology, biochemistry, sophisticated primary rodent and human-induced neuronal cell culture, and contemporary drug development approaches. Graduate students provide the centerpiece for the research efforts, and collaborate freely among the various laboratories in an open and welcoming environment.