The research program in cellular neuroscience seeks to develop solutions for degenerative diseases and developmental disorders of the nervous system by understanding the underlying cellular mechanisms underlying these conditions. The program consists of a highly collaborative team of scientists with strong credentials in molecular biology, microscopy, computer-assisted imaging, and contemporary techniques in cell biology.
The research utilizes cellular and animal models to study neurodegenerative diseases such as Hereditary Spastic Paraplegia, Gulf War Illness and Frontotemporal Dementia, as well as neurodevelopmental disorders including autism. There is also work on injury scenarios such as Traumatic Brain Injury (TBI) and Spinal Cord Injury (SCI). Experimental models include rats, genetic mice, human induced pluripotent stem cells (differentiated for some experiments into three-dimensional organoids), and primary neuronal cultures from mice and rats. Much of the work focuses on the cytoskeleton of the neuron, which includes studies on axonal transport, tau, and microtubule-based therapies. Other work delves into the mechanisms of neuronal migration, axonal and dendritic differentiation, maintenance of synapses, programmed cell death, and integration of neuronal activity with regeneration and repair.
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.