Research in the Department of Cell Biology and Anatomy
Cells are an intricate system in and of themselves, and when studied in the context of their environment, whether as single cells or multicellular organisms, they present a host of complexities that invite further scientific inquiry. Anatomy is the study of the structure of the body and the relationships among its parts. Areas of special focus include gross anatomy—the structure of the body as seen by the unaided eye—microscopic anatomy (histology), and neuroanatomy, which examines structures of the nervous system such as neurons, the brain and the spinal cord.
Research within the Department addresses the broad areas of neuroscience and cell and developmental biology. Areas within the neurosciences include learning and memory, neurofibromatosis and epilepsy. Neuronal degeneration is studied in diverse conditions such as spinal cord injury, head trauma, stroke, Alzheimer’s disease and glaucoma. Research in cell and developmental biology includes limb development, skeletal muscle atrophy, retinal developmental, platelet activation, proteasome/ubiquitin function, JAK/STAT signaling, vesicular trafficking and pulmonary hypertension.
A diverse range of techniques are employed in service to this research activity, utilizing cell culture, brain slices, drosophila genetics, proteomics, electrophysiology, recombinant DNA, confocal and 2-photon microscopy.
Below is a summary of research currently underway in the department.
Praveen Ballabh, M.D., associate professor of pediatrics and of cell biology and anatomy, is investigating prevention and treatment of brain hemorrhage as well as post-hemorrhagic complications in premature infants. Recently, Dr. Ballabh and his colleagues have shown that rapid formation of new vessels in the brain around the ventricle of premature infants contributes to the fragility of the vasculature. They have also shown that by using celecoxib, an arthritis medication, to suppress neovascularization in the treatment of pregnant rabbits reduces occurrence of brain hemorrhage in premature rabbit pups.
Joseph Etlinger, Ph.D., professor and department chairman, works with Koko Murakami, Ph.D., research assistant professor, and Mutukumara Kumarasiri, Ph.D., assistant professor, in studying the role of the proteasome/ubiquitin system in several pathological conditions. The proteasome is a cellular component that degrades proteins, while ubiquitin serves to “tag” proteins for degradation and/or trafficking to specific intracellular locations. Defects or altered regulation of ubiquitin tagging of proteins appears important in several experimental models studied in our laboratory, and may be a factor in muscle atrophy, pulmonary hypertension, neurofibromatosis and spinal cord injury.
Victor Fried, Ph.D., professor, studies the role of ubiquitin in regulating cellular events. Research in his laboratory employs a multidisciplinary approach using biochemical, recombinant genetics, cellular biology and immunology techniques. Many of the group’s studies apply protein sequencing and mass spectroscopy to identify and characterize specific conjugates of the protein ubiquitin attached to different target proteins."
Frances Hannan, Ph.D., assistant professor, is investigating the cellular basis of learning and memory, employing Drosophila (fruitfly) models of human neurological disorders affecting the Ras/MAPK and mTOR pathways. Among these are neurofibromatosis type 1 (NF1) and tuberous sclerosis. In collaboration with Abraham Grossman, Ph.D., adjunct research assistant professor, her group is also studying cognitive deficits in fly models for autism and schizophrenia, as well as Huntington’s disease. Recently, Dr. Hannan’s group discovered hearing defects and microtubule disorganization in flies with mutations in the NF2 gene, and the team is also screening for novel mutations that affect hearing in flies.
Jian Kang, M.D., Ph.D., associate professor, conducts research using calcium imaging and dual patch-clamp recordings of identified neurons and astrocytes in the hippocampal tissue, the part of the brain that regulates learning and memory. An understanding of the signaling mechanisms, such as astrocytic release of glutamate and ATP involved in astrocyte regulation of synapses, could be useful in treating diseases like brain traumatic injury and epileptic seizures.
Kenneth M. Lerea, Ph.D., associate professor, is researching protein phosphorylation/dephosphorylation, molecular processes that regulate numerous physiological systems. The goal of his laboratory is to understand signaling mechanisms that control platelet activation and generation of prothrombotic platelet-derived microparticles that may participate in increased incidence of thrombotic episodes seen in a variety of malignant and nonmalignant diseases. Their aim is to identify strategies that will dampen the formation/activity of these microparticles in order to restore baseline vascular homeostasis.
Stuart A. Newman, Ph.D., professor, is involved in three major research areas: (1) cellular and molecular mechanisms of vertebrate limb development; (2) the role of physical mechanisms in tissue morphogenesis and cell pattern formation during embryogenesis; (3) the molecular and physical mechanisms that led to the evolutionary origination of organismal form.
Renato Rozental, M.D., Ph.D., associate professor, is investigating nervous system development and diseases mediated by cell-to-cell communication carried out by structures called gap junctions. Specifically, the laboratory is examining the impact of hypoxic-ischemic insults in the brain, spinal cord and retina. Blockers of connexins, the protein components of gap junctions, may have therapeutic applications for various pathological conditions.
Pravin B. Sehgal, M.D., Ph.D., professor, is investigating the cellular physiology of cytokines such as interleukin-6 and interferons, which play a role in the communication between different cells during infection, injury and cancer. Dr. Sehgal and colleagues have discovered that the intracellular factors involved in turning on genes in response to interleukin-6 exist in novel complexes, which may play a role in cytokine functions. In addition, these pathways, as well as defects in intracellular membrane compartment trafficking and signaling, have been implicated in pulmonary hypertension.
Sansar C. Sharma, Ph.D., professor of ophthalmology and of cell biology and anatomy, leads a team of researchers who are engaged in the study of apoptosis, or programmed cell death, in the retina. The group’s long term goal is to understand the specific steps during apoptosis and develop strategies to interfere with the death signals. The team is exploring issues related to the treatment of glaucoma and other eye disorders, including the use of gene therapy.
Alan Springer, Ph.D., professor, is conducting research of the fovea, a depression in the retina that contains only cones and lacks blood vessels, and the underlying mechanisms of cell movement known as foveal morphogenesis. The goal is to develop a biomechanical model of fovea formation by looking at the relationship between eye growth and stretching of the retina, and at variations in the composition of the foveal region compared with the surrounding retina.
Patric K. Stanton, Ph.D., professor, studies the mechanisms of long-term, activity-dependent synaptic plasticity that are thought to underlie learning and memory, as well as how excitatory amino acid receptors contribute to epilepsy and stroke-induced delayed neuronal death. The laboratory uses electrophysiological and fluorescent imaging methods in in vitro brain slices from the hippocampus and neocortex to study both presynaptic and postsynaptic mechanisms of plasticity, including two-photon laser scanning microscopic techniques to measure transmitter release. The overall goal is to better understand the ways that experiences in the external world produce long-lasting footprints in neural connections that we call memories. A natural outgrowth of this fascination is likely to be new treatments for age- and disease-related failures in memory formation, as well as for the neurodegenerative effects of abnormal, pathological activation of the same biochemical cascades.
Richard J. Zeman, Ph.D., associate professor, is investigating mechanisms of recovery from spinal cord injury using radiological, pharmacological and cellular transplantation approaches to promote recovery of motor function. The work centers on understanding molecular mechanisms that can confer neuroprotection and promote axonal regeneration in the injured spinal cord.
Department members who teach gross anatomy also contribute to the development of new surgical techniques and procedures as an extension of the post-graduate courses they teach to residents in sub-surgical specialties. Matthew A. Pravetz, OFM, Ph.D. ’88, assistant professor and gross anatomy program director, applies dissection techniques to the study of functional anatomy and the mechanics of the musculoskeletal system.