Neuroscience research in the last decade has seen modest gains in learning why and how the brain and spinal cord, and their various trappings and connections, go awry. Alzheimer’s disease and Parkinson’s, multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig’s disease) and other disorders that ravage the brain and spinal cord have so far yielded few secrets to researchers who study the one organ system that most defines a human being.
At New York Medical College, neuroscientists come from many departments, both basic and clinical. A robust culture among members of the neuroscience community thrives in an array of journal clubs, seminar series and collaborative scientific projects. There are many opportunities for training at the Ph. D. and postdoctoral level, and prospective students in the neurosciences can apply to the graduate school or contact faculty members directly.
Basic and Clinical Research
In the Department of Cell Biology and Anatomy, 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, works with 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.
Koko Murakami, Ph.D., research assistant professor, collaborates with Dr. Hannan on the study of NF1, a devastating and complex disorder that may be on the brink of yielding to drug therapy. She proposes to examine how the function of the NF1 protein (neurofibromin) is controlled by the addition of ubiquitin groups. Ubiquitins are small proteins that tag larger proteins for degradation. Just where they attach, and how, is the focus of this study of ubiquitin machinery. Blocking neurofibromin ubiquitination would result in elevated levels of the neurofibromin protein, and may improve tumor suppressor activity, cognitive function and other symptoms caused by defects in signaling pathways that result from reduced levels of neurofibromin. The long term goal is to find a drug that will stop or accelerate the process.
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.
Libor Velisek, MD, PhD, professor, studies the mechanisms of developmental seizures, especially of infantile spasms. Infantile spasms are age-specific seizure syndrome occurring between 3 to 12 months of age with unfavorable prognosis. The laboratory uses animal model of infantile spasms to determine brain structures involved in the origin and control of spasms as well as for testing new mechanistically appropriate treatments. Laboratory uses varierty of techniques from electrophysiological recordings in brain slices in vitro (patch clamp and population responses), histology, immunohistochemistry and molecular biology techniques, as well as EEG and behavioral studies in freely moving rats. The overall goal of this research is to find specific treatments of infantile spasms that would improve neurobehavioral and cognitive outcome in affected children and have minimal side effects compared to current treatments. Additional project in collaboration with Columbia University and Nationwide Children’s Hospital in Columbus, OH, investigates mice haploinsufficient in the Brd2 gene. In humans, this gene has been repeatedly linked and associated with idiopathic generalized epilepsy. Mice heterozygous in Brd2 have increased susceptibility to provoked seizures, develop spontaneous seizures and have region-specific decrease in inhibitory neurotransmitter GABA markers in the brain. Our laboratory determines developmental profile of GABA decrease, seizure susceptibility and behavioral impairment in these mice. An additional project is the assessment of behavioral and cognitive problems after blast-induced brain injury. This research relates to brain injuries occurring in combat areas, as well as during some professional sports and may have significant impact fro preventative measures.
Jana Velíšková, M.D. Ph.D., Professor of Cell Biology & Anatomy, and her team investigate estradiol-induced effects on neuronal excitability and neuroprotection, especially in relation to seizure disorders and epilepsy. Dr. Veliskova’s studies show that estradiol has neuroprotective effects against seizure-induced damage in hippocampal dentate gyrus region and it is associated with modulation of neuropeptide Y and glutamatergic transmission by estradiol. In addition, recent studies from her laboratory show that estradiol modulates long-term plasticity and metaplasticity by regulation of metabotropic glutamate-NMDA receptors interactions, which are lost following ovariectomy. Techniques in the laboratory include seizure induction, long-term EEG/video monitoring, behavioral testing, immunostaining techniques, histological markers for neurodegeneration and in vitro electrophysiology.
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.
In the Department of Physiology, Christopher S. Leonard, Ph.D., professor, is focused on understanding how neurons communicate. Using sophisticated biophysical recording techniques as well as computer modeling, the group examines how neurons in the brain stem and cerebral cortex generate electrical impulses, and how these neurons and their synaptic interactions are modulated by neurotransmitters. Dr. Leonard aims to correlate current cellular studies with the system-level behavior of neurons—processes that regulate how the brain stays awake, sleeps and generates dreams.
William N. Ross, Ph.D., professor, and Nechama Lasser-Ross, Ph.D., research assistant professor, are studying the fundamental aspects of synaptic transmission between central nervous system neurons. (Synaptic transmission relates to how one neuron influences other cells that are connected directly to that neuron.) In this phase of their experiments, which entailed developing and applying high-speed imaging techniques, the Ross lab is exploring how electrical signals in a presynaptic neuron cause changes in calcium concentration in pyramidal neurons. These changes are critical to regulating synaptic plasticity, development and gene expression in neurons.
In the Department of Biochemistry and Molecular Biology, Esther L. Sabban, Ph.D., professor, earned the prestigious Dean’s Distinguished Research Award for her investigations into the biology of the stress response, and her outstanding contributions toward understanding the mechanisms that regulate catecholamine biosynthetic enzymes. Her goal is to develop a better understanding of the molecular changes that distinguish between the beneficial and detrimental effects of stress in order to more easily identify individuals who are susceptible to long-term stress.
Arthur J. L. Cooper, Ph.D., professor, is studying transglutaminases, enzymes that catalyze covalent modifications of protein substrates. Aberrant transglutaminase activity is thought to contribute to neurodegenerative diseases. Selective transglutaminase inhibitors may therefore be clinically useful. Dr. Cooper is also studying the role of cysteine S-conjugate B-lyases, a type of enzyme involved in the bioactivation, or toxification, of endogenous and exogenous electrophiles. Such studies may be useful in devising methods to minimize the harmful effects of certain drugs.
Members of the Department of Otolaryngology are actively collaborating with basic scientists. Steven D. Schaefer, M.D., professor and chairman, professors Christopher J. Lindstrom M.D., and Simon C. Parisier, M.D., assistant professors Ana Kim, M.D., and George Alexiades, M.D., and Joe Arigo, M.D., associate professor of clinical otolaryngology, work with Renato Rozental, M.D., Ph.D., associate professor of cell biology and anatomy, to study how ischemic insults impact the auditory system and balancing ability.
Dr. Rozental collaborates with Raj Murali, M.D., professor and chairman of the Department of Neurosurgery, in examining new models and treatment in ischemic spinal cord injury. Drs. Rozental and Murali also are developing a model to examine the use of stents to deliver drug therapies to the ischemic brain in the treatment of stroke.
Rick M. Roark, Ph.D., associate professor, collaborates with Dr. Schaefer and Michael J. Pitman, Ph.D., assistant professor, in developing a model for regeneration of the larynx. Dr. Schaefer also collaborates with Drs. Hannan and Rozental to study the role of NF2 and other genes in hearing and balance.