Graduate School at The University of Cincinnati - Innovation Incentive Initiative - Neuroscience
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Innovation Incentive Initiative - Neuroscience

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Doctoral Program in Biological Sciences
Number of Participating Faculty = 5
Number of Related Peer-Reviewed Journal Papers 2003-05 = 21
Total Current Related External Funding = $1,107,010

The Department of Biological Sciences has an emerging group of junior and senior faculty in Neuroscience and Behavior. Some of these faculty members are active participants in the Doctoral Program in Neuroscience based in the College of Medicine, and several collaborate with faculty in other departments (Mathematics, Psychology, Philosophy) and colleges (Engineering, Medicine) whose work relates to Neuroscience. Moreover, this group has ties to researchers in the Computational Sciences group, as well as interdisciplinary programs such as Bio-Medical Engineering, the Center for Surgical Innovation, the Brain and Mind Studies program, and the center for Cognition Action and Perception. Strengthening the doctoral program in this area will have positive impact on the newly-developed collaborative interdisciplinary undergraduate major in Neuroscience (A & S, Medicine), which will increase undergraduate research and recruitment of doctoral students.

The 5 neuroscience-oriented faculty in Biological Sciences (Elke Buschbeck, John Layne, Bruce Jayne, Edwin Griff, George Uetz) conduct research on diverse topics in basic neuroscience (molecular biology, cell physiology, animal behavior, sensory-motor control, sensory neurophysiology, computational neuroscience, evolution of sensory systems and behavior). Current funding of the neuroscience faculty members in Biological Sciences is over $1 million. With the addition of a new faculty member in Biological Sciences next year (Dr. Stephanie Rollmann - genomics of sensory-guided behavior), we expect an increase in funding and capacity for research collaboration across campus.

List of Participating Faculty
Dr. Elke Buschbeck Neuroethology; Evolution of the insect visual and other sensory systems: insect neurobiology, anatomy, physiology, optics, behavior, invertebrate systematics and evolution.

Dr. Edwin Griff Neurobiology and electrophysiology of the vertebrate olfactory bulb; analysis of mitral cell responses; electrophysiology of the vertebrate retina; interactions between photoreceptors and the retinal pigment epithelium

Dr. Bruce Jayne- Functional morphology; evolution of behavior, structure and function; neuromuscular basis of locomotion in ectothermic vertebrates.

Dr. John Layne Behavioral neurobiology and sensory ecology; computational neurobiology; vision in natural habitats, control systems in visual guidance; animal orientation and navigation.

Dr. Stephanie Rollmann (new Assistant Professor Winter 2007) Functional genomics of chemosensory behavior.

Dr. George Uetz Sensory basis of animal communication; digital motion capture and video playback studies of visual signaling; environmental substrates and seismic (vibration) signals; multimodal communication.

Doctoral Program in Biomedical Engineering
Number of Participating Faculty = 3
Number of Related Peer-Reviewed Journal Papers 2003-05 = 26
Total Current Related External Funding = $2,500,000

Dr. Johnson is developing a rat model of the cognitive deficits that arise in early-stage Parkinson’s disease. Their work is based on the hypothesis that specific learning deficits will arise years before the occurrence of the hallmark motor symptoms and that these deficits are distinguishable from those that arise during normal aging or Alzheimer’s disease. This research is designed to test a hypothesis developed during our computational modeling of the role of dopamine in Parkinson’s disease.

Dr. Lee, in collaboration with the CIR, is interested in developing MRI and MRS methodology for neuroscience research. Using imaging tissue segmentation approach, his group is studying the brain sub-cortical tissue structures variations with normal aging and pathological brain. Using fMRI and (H-1 and P-31) MRS, they are investigating the possibility of mitochondrial impairment in bipolar disorder and Parkinson’s patients.

The medical and therapeutic ultrasound research lab led by Dr. Holland is working on developing ultrasound-assisted thrombolysis for stroke therapy and ultrasound-mediated drug delivery using nanoparticles. Ultrasound is being used to promote cavitation in the clot in situ by speeding thrombolysis. In addition, liposomal encapsulation of tPA can be used to promote clot lysis. Ultrasound can assess both liposomal arrival at the clot site as well as lyse the liposomal membrane to release tPA in situ.

List of Participating Faculty
Jeffrey Johnson Neuroinformatics, Computational modeling in neuroscience, Parkinson’s Disease.
Jing-Huei Lee, Ph.D. MR biomarkers of cellular function, targeted contrast agents for cellular and molecular imaging.
Christy Holland, Ph.D Ultrasound-assisted thrombolysis and ultrasound-mediated drug delivery.

Doctoral Program in Epidemiology and Industrial Hygiene
Number of Participating Faculty = 2
Number of Related Peer-Reviewed Journal Papers 2003-05 = 29
Total Current Related External Funding = $3,122,000

Dr. Dietrich studies children's environmental health, which is the study and prevention of disease resulting from exposure to chemical, biologic, physical and social agents. The Cincinnati Children's Environmental Health Center (CCEHC) is a joint venture between the University of Cincinnati Department of Environmental Health and the Children's Hopsital Medical Center.

The research and intervention efforts are focused on the effects of prevalent neurodevelopmental toxicants on the motor, cognitive and behavioral development of children as well as utlizing controlled animal model studies to further understand the mechanisms whereby environmental chemicals compromise learning and behavior. The objectives of the CCEHC are to identify environmental antecedents for neurodevelopmental morbidities originating from exposures to multiple environmental contaminants during pregnancy and childhood in a large birth cohort; to conduct interventions to reduce exposures to prevalent neurotoxicants such as lead (Pb) and pesticides; to assesss the long-term morbidities associated with exposure to Pb, pesticides and manganese (Mn) in a longstanding cohort study; to assess the modifying effects of genetic polymorphisms related to neurotransmitter function and to conduct conduct controlled experiments utilizing a rodent model to assess the impact of Pb, Mn and stress on different aspects of animal learning.

Dr. Bhattacharya has developed a non-invasive tool for the early monitoring of neuromotor effects of toxicants such as lead, jet fuel, solvents, volatile organic compounds and organophosphates. This non-invasive tool can quickly (about 30 seconds) quantify objectively a common body function known as postural sway as a “signature” of sub-clinical neurotoxicity effects among humans. This technique also provides relative contributions of various physiological pathways critical for the maintenance of upright postural balance.

List of Participating Faculty
Amit Bhattacharya Stress physiology and biomedical engineering Kim Dietrich Developmental effects of prenatal and early postnatal exposure to lead in infants, toddlers, school-age children, adolescents and adults

Doctoral Program in Molecular, Cellular and Biochemical Pharmacology
Number of Participating Faculty = 2
Number of Related Peer-Reviewed Journal Papers 2003-05 = 13
Total Current Related External Funding = $2,530,352

Dr. Scott Belcher’s laboratory research is focused on understanding fundamental molecular mechanisms that regulate development and survival of neurons and glia in the mammalian nervous system. One of their major research efforts is aimed at fully understanding the role played by the endogenous steroid hormone estrogen during development and aging of the central nervous system (CNS). They are employing neuroanatomical, molecular biological, as well as genomic and proteomic approaches to elucidate the signaling pathways that are modulated by endogenous and environmental estrogens in different brain regions. Recent results from our laboratory have shown that estrogen and certain environmental estrogens can regulate both mitogenesis and viability of developing non-endocrine neurons through novel mechanisms that are mediate through a membrane associated estrogen receptor.

Dr. John Maggio’s laboratory investigates the process of amyloid formation in Alzheimer's disease (AD) and other amyloidoses. The characteristic lesion of AD is brain senile plaques formed mainly of the human amyloid peptide Ab, a *40-mer which occurs naturally in normal as well as AD brain. By reconstituting plaque growth (deposition of Ab at physiological concentrations onto authentic plaques) in vitro, we can characterize the process and identify conditions and components which enhance or inhibit its kinetics. Structure/activity studies have identified amino acids critical for amyloid deposition and active peptide analogues suitable for high resolution structure determination by nuclear magnetic resonance spectroscopy. The latter studies have further identified conformational elements essential to plaque deposition.

List of Participating Faculty
Scott Belcher understanding fundamental molecular mechanisms that regulate development and survival of neurons and glia in the mammalian nervous system.
John Maggio Understanding bioactive peptides and their receptors, in the nervous system and elsewhere.

Doctoral Program in Molecular & Developmental Biology
Number of Participating Faculty = 11
Number of Related Peer-Reviewed Journal Papers 2003-05 = 58
Total Current Related External Funding = $12,389,761

Research in this area focuses on the development of the peripheral and central nervous systems and how intrinsic and extrinsic factors cause disease and influence human behavior. Our neurobiological research is leading to a better understanding of diseases affecting these systems. Current initiatives are aimed at harnessing the developmental potential of stem cells in the treatment of neural degeneration and disease.

List of Participating Faculty
Nadean Brown Transcription factors required for specification of retinal progenitor cells into neurons
Kenneth Campbell Cellular and molecular control of vertebrate forebrain development
Tiffany Cook Molecular basis of eye development
Steve Danzer Elucidating the role of neurogenesis in the development of epilepsy.
Brian Gebelein Patterning of the nervous and digestive systems during development
Chia-Yi (Alex) Kuan Understanding the regulation of neuronal cell death and neurogenesis during development and in ischemic brain injury
Masato Nakafuku Molecular control of neural stem cells in development and regeneration of mammalian central nervous system
Nancy Ratner The peripheral nerve in development and disease
David Repaske Molecular basis of endocrine disorders; control of signal transduction
Charles Vorhees Mechanism of action of substituted amphetamines on brain development; Use of gene targeting to determine how deletion of specific brain proteins affect learning and memory
Michael Williams Interaction of stress-induced hormones and drugs of abuse on adult learning and memory abilities; physiological responses to later stressors; behavioral and physiological consequences of drug reexposure.

Doctoral Program in Molecular Genetics, Biochemistry & Microbiology
Number of Participating Faculty = 1
Number of Related Peer-Reviewed Journal Papers 2003-05 = 3
Total Current Related External Funding = $1,093,000

Dr. Richard Thompson’s major thrust is to understand the critical genes of Herpes Simplex virus that are involved with the establishment of, and reactivation from the latent state in neurons.

List of Participating Faculty
Richard Thompson Herpes Simplex virus

Doctoral Program in Neuroscience
Number of Participating Faculty = 39
Number of Related Peer-Reviewed Journal Papers 2003-05 = 567
Total Current Related External Funding = $85,020,449

List of Participating Faculty
Anthenelli, Robert clinical research in alcoholism and related disorders (e.g., smoking, mood disorders, antisocial personality disorder).
Belcher, Scott understanding fundamental molecular mechanisms that regulate development and survival of neurons and glia in the mammalian nervous system.
Ben-Jonathan, Nira hypothalamo-pituitary axis at the whole animal, cellular and molecular levels. The major effort is to isolate and sequence a novel peptide, prolactin regulating factor, from the posterior pituitary. A second project is investigating the distribution and regulation of estrogen receptors in the pituitary and the effects of environmental estrogens on the reproductive system. A third project focuses on the role of prolactin and prolactin isoforms in breast cancer, especially as related to angiogenesis.
Benoit, Stephen neurobiological controls over behavior with emphases on food intake and learning.
Bickle, John combines information gathered using a variety of neuroscientific techniques, including neurocomputational modeling (and computer simulation), functional neuroimaging, and electrophysiology to investigate the cellular and molecular mechanisms of cognition and consciousness, specifically (recently) memory.
Broderick, Joseph The development of acute treatments for stroke and clinical research into the environmental and genetic causes of stroke.
Buschbeck, Elke how other organisms perceive the world, and how their sensory systems have evolved to adjust to specific needs. More specifically my lab is interested in the eyes of three different insects: the stalk-eyed fly Cyrtodiopsis whitei, the twisted-wing insect Xenos peckii, and recently also the larvae of the diving beetle Thermonectus marmoratus.
Chiu, Peter Cognitive and neural basis of auditory memory, functional neuroimaging, cochlear implant and development of speech recognition.
Clark, Joesph The study of vascular function and dysfunction during disease.
Clegg, Deborah Nutrition, Sex Hormones, Hypothalamic Control of Food Intake, and Body Fat Distribution
Collier, Tim uses cell culture and animal models to address features of neuronal vulnerability to degeneration and novel therapies for Parkinson's disease.
Eliassen, Jim examine the neural basis of learning in order to better understand mechanisms of plasticity in the human brain.
Gregerson, Karen Prolactin (PRL)
Gudelsky, Gary focus 1) on the mechanisms and consequences of MDMA (Ecstasy)-induced serotonin neurotoxicity and 2) the actions of atypical antipsychotic agents.
Herman, James examining the relationship between the physiological actions of central nervous system stress circuits and their place in the central nervous system.
Holland, Scott functional MR imaging of the brain (fMRI) using dynamic perfusion imaging, diffusion imaging and BOLD activation imaging; in vivo 31P and 1H NMR spectroscopy (MRS) of brain metabolism using localized single voxel techniques and chemical shift imaging; microscopic MRI of transgenic mice; MR perfusion imaging (pMRI) for studies of cerebral vascular perfusion anomalies, and image processing of MR images.
Horseman, Nelson prolactin regulation and molecular actions from the organismal level to the gene.
Ip, Wallace S. focus on a disease called neurofibromatosis type 2 (NF2), whose clinical manifestation is nervous system tumors called schwannomas and meningiomas.
Kao, Winston understanding of diseases which cause blindness, so that we can develop better treatment. We study the structure-function relationships of eye-specific genes which are vital for the maintenance of vision. Two research projects which are mutually supportive are: 1). Regulation of Cornea-specific K12 keratin gene expression, and 2). Corneal wound-healing. K12 keratin, exclusively expressed by corneal epithelial cells, is vital for normal corneal functions, and also plays an important role in corneal wound-healing. We are using the transgenic approach to examine the role of cytokines, receptors and/or other gene products in corneal wound-healing and development.
Keck, Paul treatments for people with bipolar disorder.
Khan, Sohaib mechanism involved in estrogen-induced cell differentiation and apoptosis of normal and malignant target tissues such as breast and uterus.
Kleene, Steve studies olfaction, the sense of smell. Our goal is to describe how an external chemical stimulus (an odorant) is transduced into the electrical signal that ultimately reaches the brain.
Kuan, Chia-Yi Egulation of programmed cell death during the development of the vertebrate nervous system and signal transduction mechanism leading to apoptosis in ischemic stroke.
Lipton, Jack understanding the mechanisms of growth, differentiation, damage and degeneration of monoamine transmitter systems in the brain.
Maggio, John Understanding bioactive peptides and their receptors, in the nervous system and elsewhere, Nakafuku, Masato development and regeneration of the central nervous system (CNS).
Ratner, Nancy confluence of Developmental, Molecular and Cellular Neuroscience with Cancer Biology. Mutations in genes (NF1, NF2) lead to peripheral nerve Schwann cell tumors.
Richards, David behavior of glutamatergic synapses in the central nervous system, at the level of individual synapses.
Richtand, Neil study of mechanisms underlying behavioral plasticity. Our goal is to understand behavioral plasticity of neuronal systems directly relevant to psychiatric disorders, and to then apply this knowledge to prevention and treatment of psychiatric conditions.
Sakai, Randall Role of the renin angiotensin system and adrenal steroids in mediating thirst and sodium appetite.
Seeley, Randy neuroendocrine regulation of food intake and body weight.
Seroogy, Kim biochemical events underlying Parkinson's disease, schizophrenia and depression.
Sortwell, Caryl cellular and trophic factor replacement approaches for the treatment of Parkinson's disease.
Stern, Javier elucidating cellular mechanisms underlying neuronal excitability, synaptic connectivity, and plasticity of central neuronal circuits involved in autonomic and neuroendocrine control.
Steece-Collier, Kathy and understanding pathological changes in the brain as it relates to Parkinsons disease and associated therapies.
Strakowski, Stephen outcome studies with magnetic resonance imaging studies of brain function, structure and chemistry in patients with bipolar and related disorders.
Tschoep, Matthias study of neuroendocrine and dietary aspects of obesity and diabetes research. Our scientific endeavors focus on the (patho-) physiology of energy homeostasis, including the detailed characterization of rodent models for genetically or environmentally induced obesity; gut hormone-brain interactions as drug targets for "diabesity"; and the differentiation between essential and redundant pathways regulating energy balance in the central nervous system.
Vorhees, Charles effects of drugs of abuse on the the developing brain. Principle areas of investigation are the substituted amphetamines, especially methamphetamine, methyeledioxymethamphetamine (MDMA or ecstasy), and fenfluramine.
Woods, Stephen examines the role of gastrointestinal hormones in influencing food intake and body weight.

Doctoral Program in Systems Biology & Physiology
Number of Participating Faculty = 7
Number of Related Peer-Reviewed Journal Papers 2003-05 =141
Total Current Related External Funding =$21,114,206

The neuroscience related faculty in the program focus on two areas, metabolism (see Metabolic Disease section) and the neuroendocrinology of reproduction and parenting. Studies relate to the interactions between the brain and the reproductive axis during pregnancy, lactation and adaptations to pregnancy and the postpartum. Studies involve the role of the brain in directing the activity of the pituitary and reproductive glands, and the role of lactation physiology in postpartum mood regulation and postpartum depression.

List of Participating Faculty
Nira Ben-Johnathan hypothalamo-pituitary axis at the whole animal, cellular and molecular levels. The major effort is to isolate and sequence a novel peptide, prolactin regulating factor, from the posterior pituitary. A second project is investigating the distribution and regulation of estrogen receptors in the pituitary and the effects of environmental estrogens on the reproductive system. A third project focuses on the role of prolactin and prolactin isoforms in breast cancer, especially as related to angiogenesis.
Karen Gregerson Prolactin (PRL)
James Herman examining the relationship between the physiological actions of central nervous system stress circuits and their place in the central nervous system.
Nelson Horseman prolactin regulation and molecular actions from the organismal level to the gene.
Randall Sakai Role of the renin angiotensin system and adrenal steroids in mediating thirst and sodium appetite.
Randy Seeley neuroendocrine regulation of food intake and body weight.
Steven Woods examines the role of gastrointestinal hormones in influencing food intake and body weight.

Infrastructure for Neuroscience

UC Mass Spectrometry Facility and Proteomics Research & Development Center
Nano and Microfabrication Facility
Biomedical Informatics/Center for Computational Medicine
The Mouse Physiology Core Facility
Transgenic Gene Targeting Core Facility
DNA Core
Live Microscopy Core
Neuroscience Laboratories
Multiple laboratory facilities and animal colonies dedicated to aspects of neuroscience research in sensory structures, bio-mechanics of locomotor performance and behavior of vertebrate and invertebrate species are located throughout UC. These labs are equipped with high-speed video and digital capture cameras, laser Doppler vibrometry, bioacoustic recording, computer-assisted behavioral activity recording, a variety of histological techniques (including fluorescent fills, whole tissue stains, and immunohistochemistry) to investigate the shape and size of individual neurons. Advanced software allows for behavioral tests of the spatial resolution of animal vision and motion computation systems, structural dynamics of animal locomotion, visual and seismic communication, and 3-D reconstruction of microscopic aspects of animal optical systems..

Laboratories in Molecular Genetics, Biochemistry & Microbiology Biology
The department houses five state-of-the-art spectrometers in the NMR facility. These range from 400 to 800 MHz and include full computational support for high resolution structures and molecular modeling.

The X-ray crystallography program is relatively new and resources are comprised of a RigakuMSC MicroMax-007 microfocus X-ray generator with Osmic VariMax HR highresolution optics, an R-axis-IV++ image plate detector and an X-stream cryosystem. Crystallization robots for high-throughput screening will facilitate the growth of macromolecular crystals.

The department also houses an analytical ultracentrifuge with absorbance and interference optics, an isothermal titration calorimeter, circular dichroism/fluorescence and EPR spectrophotometers and a dynamic light scattering instrument for biophysical analysis of macromolecules in solution.

Laboratories in Environmental Health
The Affymetrix GeneChip® System provides a systems biology perspective to study the complex mechanisms and networks involved in biological processes and diseases in response to various kinds of environmental exposure. Applications including studying gene expression profiling, whole-genome mapping, cancer genetics research, pathogen subtyping and pharmacogenetics can be performed in this state-of-the-art instrument. This integrated system includes a GeneChip® Scanner 3000 7G System and Fluidics Station 450 with a complete workstation for data and bioinfomatics analyses.

LTQ-Orbitrap (Thermo Electron), a newly commercialized mass spectrometer, enables proteomics and metabolomics analysis to be performed with high sensitivity and fast analysis time. The combination of the large ion capacity of the linear ion trap (LTQ) and the novel detection in the OrbiTrap, the LTQ-Orbitrap offers high mass accuracy and resolution in peptide/ metabolite measurements of wide dynamic range. It is especially suited for shot-gun proteomics applications using various peptide labeling reagents, such as iCAT, iTRAQ and metabolic labeling, or even for label-free profiling, where high resolution is required. Thousand of proteins in two samples can be identified and their relative levels accurately quantitated in a single experiment, which is superior to traditional two-dimensional gel electrophoresis in terms of throughput and reproducibility. The LTQ-OrbiTrap also finds great utilities in metabolomics studies due to its ability of discerning the elemental composition of compounds and performing MSn (tandem mass spectrometry). With the softwares commercially or academically available, metabolites and their fragmentation patterns can be compared between samples.

The IVIS Lumina Imaging System (Xenogen) in the Department enables non-invasive, highly sensitive and accurate detection of in vivo bioluminescence/fluorescence in animal models of oncology/angiogenesis, inflammation, drug metabolism/toxicology and metabolic diseases. The system includes a highly sensitive CCD camera, a light-tight imaging chamber with complete computer automation, and the Living Image® software package for image acquisition and analysis.

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