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Keith J. Holyoak, Ph.D

Keith Holyoak, Ph.D.

Biography

Combining behavioral studies of normal cognition, computational modeling, and neuropsychological and neuroimaging studies, to understand the role of the prefrontal cortex in human thinking Keith J. Holyoak conducts research in human reasoning and problem solving. Much of his work is concerned with the role of analogy in thinking. One of the major themes of this work is the way in which analogy serves as a psychological mechanism for learning and transfer of knowledge. In his book Mental Leaps with Paul Thagard, he presents a general theory of analogical thinking that includes analysis of how the capacity to use analogy evolved in primates, how it develops in children, and how it is used to reason in domains ranging from law and politics to science. Other related reserach, in collaboration with Dan Simon, deals with complex decision-making in fields such as the law. Holyoaks research combines studies of thinking in normal adults with neuropsychological studies of how thinking in brain-damaged individuals. This work, in collaboration with Barbara Knowlton and others, is investigating the role of prefrontal cortex in complex human reasoning. In addition to experimental work, Holyoak works with John Hummel to develop computational models of human thinking based on neural-network models. These models use neural synchrony to preform dynamic variable binding, and thereby represent and maniputlate symbolic knowledge. The overall goal is to understand the neural basis for human thought.

Volker Hartenstein, M.D., Ph.D.

Volker Hartenstein, M.D., Ph.D.

Biography

Research Interest: Neuronal development in Drosophila Areas of Research A. Neural development in Drosophila melanogaster. 1. We are focussing on the function of the adhesion molecules Drosophila E-cadherin homolog (DE-cad) and Fas (an Ig-like protein) during neuroblast formation, axonogensis and synapse formation in the embryonic and larval brain. Following the cloning of DE-cad, its phenotypic and expression analysis, we have generated constructs that allow us to overexpress normal and mutant DE-cad forms at specific times and locations during nervous system development. Tepass, U., Gruszynski-de Feo, E., Haag, T.A., Omatyar, L., Török, T., and Hartenstein, V. (1996). shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neuroectoderm and other morphogenetically active epithelia. Genes & Dev. 10, 672-685 Lekven, A., Tepass, U., Keshmeshian, M., Hartenstein, V. (1998) faint sausage encodes a novel member of the Ig superfamily required for cell movement and axonal pathfinding in the Drosophila nervous system. Development 125, 2747-2758 Haag, T., Prtina, N., Lekven, A.C., Hartenstein, V. (1999). Discrete steps in the morphogenesis of the Drosophila heart require faint sausage, shotgun/ DE-cadherin, and laminin A. Dev. Biol. 208, 56-69 2. Of special interest is the question of the dynamic regulation of DE-cad. Based on genetic evidence we hypothesize that the Drosophila EGF-receptor is crucially involved in this regulation. We use a genetic and biochemical approach to investigate this hypothesis Dumstrei, K., Nassif, C., Abboud, G., Aryai, A., Aryai, AR, Hartenstein, V. (1998) EGFR signaling is required for the differentation and maintenance of neural progenitors along the dorsal midline of the Drosophila embryonic head. Development 125, 3417- 3426 3. Using specific markers, we have initiated a “Drosophila brain mapping” project. The markers are expressed from embryonic stages onward in specif ventral gradient that specifies the different domains within the eye field. Hh is secreted at the lateral boundary of the eye field and may form a gradient that antagonizes the early Dpp gradient. We are reconstructing the details of the fate map of the Drosophila head, and study experimentally the function of the Hh and Dpp gradients in patterning the fatemap. Rudolph, K., Liaw, G., Daniel, A., Green, P.J., Courey, A.J., Hartenstein, V., Lengyel, J. (1997). Complex regulatory region mediating tailless expression in early embryonic patterning and brain development. Development 124, 4297-4308 Nassif, C., Daniel, A., Lengyel, J.A., and Hartenstein, V. (1998) The role of morphogenetic cell death during embryonic head development of Drosophila Dev. Biol. 197, 170-186 Daniel, A., Dumstrei, K., Lengyel, J., Hartenstein, V. (1999) tailless and atonal control cell fate in the embryonic visual system. Development 126, 2945-2954 Lebestky, T., Chang, T., Hartenstein, V., Banerjee, U. (2000) Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science 288, 146-149 C. Neural development in primitive invertebrates: platyhelminthes One of the most astounding realizations of modern developmental biology is the high degree to which genes or even complete gene networks are conserved among all animal groups. Examples can be cited for virtually all fundamental developmental steps (e.g., establishment of body axes, gastrulation) and organ systems. In light of these findings the interest in comparative embryology as a basis for discussion of homologies between cells, tissues and organs has increased over the recent years. The fact that animals as divergent as flies and humans express regulatory genes such as eyeless , orthodenticle or the Hox genes implies that the common ancestor had these genes in its genetic repertoire; but what biological function did they serve? It is generally believed that the common ancestor of gastroneuralians (“protostomes”) was a simple bilaterian organism with features such as a small acoelomate body, ciliated epidermis with underlying muscle layer, and a single gut opening. Many of these primitive features are conserved among the present day platyhelminths, a taxon that on the basis of morphological evidence has split early from the gastroneuralian (protostomian) line. We have studied the normal development of representative of several flatworm taxa and are now focussing on two species that can be raised in the lab. PCR based cloning of homologs of genes involved in neural development of both Drosophila and vertebrates is under way. Younossi-Hartenstein, A., Ehlers, U., Hartenstein, V. (2000) Embryonic development of the nervous system of the rhabdocoel flatworm Mesostoma lingua (Abildgaard, 1789). J. Comp. Neur. 416, 461-476 Hartenstein, V., Dwine, K. (2000). A new freshwater dalyellid flatworm, Gieysztoria superba sp. nov. (Dalyellidae: Rhabdocoela) from Southeast Queensland, Australia. Memoirs of the Queensland Museum 45, 381-383 Younossi-Hartenstein, A., Hartenstein, V. (2000a) The embryonic development of the dalyellid flatworm Gieysztoria superba .Int.J.Dev.Biol. (in press) Younossi-Hartenstein, A., Hartenstein, V. (2000b) The embryonic development of the polyclad flatworm Imgogine mcgrathi Dev. Genes Evol. 210, 383-398 Hartenstein, V., Ehlers, U. (2000) The embryonic development of the rhabdocoel flatworm Mesostoma lingua. Dev. Genes Evol. 210, 399-415 Ramachandra, N.B., Ladurner, P., Jacobs, D. and Hartenstein, V. Neurogenesis in the primitive bilaterian NeochildiaI. Normal development and isolation of genes controlling neural fate. In prep.

Publications

A selected list of publications:

Younossi-Hartenstein, A Hartenstein, V   The embryonic development of the polyclad flatworm Imogine mcgrathi Development genes and evolution. , 2000; 210(8-9): 383-98.
Hartenstein, V Ehlers, U   The embryonic development of the rhabdocoel flatworm Mesostoma lingua (Abildgaard, 1789) Development genes and evolution. , 2000; 210(8-9): 399-415.
Noveen, A., Daniel, A., Hartenstein, V.   The role of eyeless in the embryonic development of the Drosophila mushroom body, Development, 2000; 127: 3475-3488.
Lebestky, T Chang, T Hartenstein, V Banerjee, U   Specification of Drosophila hematopoietic lineage by conserved transcription factors Science. , 2000; 288(5463): 146-9.
Younossi-Hartenstein, A Ehlers, U Hartenstein, V   Embryonic development of the nervous system of the rhabdocoel flatworm Mesostoma lingua (Abilgaard, 1789) The Journal of comparative neurology. , 2000; 416(4): 461-74.
Daniel, A Dumstrei, K Lengyel, JA Hartenstein, V   The control of cell fate in the embryonic visual system by atonal, tailless and EGFR signaling Development (Cambridge, England) , 1999; 126(13): 2945-54.
Haag, T., Prtina, N., Lekven, A.C., Hartenstein, V.   Discrete steps in the morphogenesis of the Drosophila heart require faint sausage, shotgun/ DE-cadherin, and laminin A, Developmental Biology, 1999; 208: 56-69.
Nassif, C Noveen, A Hartenstein, V   Embryonic development of the Drosophila brain. I. Pattern of pioneer tracts The Journal of comparative neurology. , 1998; 402(1): 10-31.
Hartenstein, V Nassif, C Lekven, A   Embryonic development of the Drosophila brain. II. Pattern of glial cells The Journal of comparative neurology. , 1998; 402(1): 32-47.
Dumstrei, K., Nassif, C., Abboud, G., Aryai, A., Aryai, AR, Hartenstein, V.   EGFR signaling is required for the differentation and maintenance of neural progenitors along the dorsal midline of the Drosophila embryonic head, Development, 1998; 125: 3417- 3426.
Lekven, A., Tepass, U., Keshmeshian, M., Hartenstein, V   faint sausage encodes a novel member of the Ig superfamily required for cell movement and axonal pathfinding in the Drosophila nervous system, Development, 1998; 125: 2747- 2758.
Nassif, C Daniel, A Lengyel, JA Hartenstein, V   The role of morphogenetic cell death during Drosophila embryonic head development Developmental biology. , 1998; 197(2): 170-86.
Campos-Ortega, J.A., Hartenstein, V.   The Embryonic Development of Drosophila melanogaster, , 1997; .
Younossi-Hartenstein, A., Nassif, C. and Hartenstein, V.   Early neurogenesis of the Drosophila brain, J. Comp. Neur, 1996; 370: 313-329.
Tepass, U., Gruszynski-de Feo, E., Haag, T.A., Omaryar, L., Torok, T., and Hartenstein, V.   Shotgun encodes Drosophilia E-Cadherin and is preferentially required during cell rearrangement in the neuroectoderm and other morphogenetically active epithelia, Genes & Dev, 1996; 10: 672-685.
Hartenstein, V., Lee, A., and Toga, A.W.   Graphic digital database of Drosophila embryogenesis, Trends in Genetics, 1995; 11: 51-58.
Carolyn R. Houser, Ph.D.

Carolyn Houser, Ph.D.

Biography

Research Interest: Neurochemical anatomy, neuronal plasticity and development of the CNS

The broad research interests of the laboratory are the neurochemical anatomy and morphological plasticity of the mammalian central nervous system. Research is focused on the gamma-aminobutyric acid (GABA) system. GABA is an extremely important neurotransmitter in many brain regions and may also have trophic roles during development of the nervous system. Both the presynaptic neurons that use GABA as a neurotransmitter and the postsynaptic sites at which these neurons exert their influence are being studied. Immunohistochemical and in situ hybridization methods are used to study the localization and regulation of the proteins and mRNAs of two forms of the synthesizing enzyme for GABA, glutamic acid decarboxylase (GAD) and multiple subtypes of the GABA-A receptor. Interrelationships between the GABA neurons and their receptors are being studied in the normal brain, during development and in experimental conditions in which the GABA system is altered. The brain region of major interest in these studies is the hippocampus.

The goals of a second but related group of studies are to identify the morphological and neurochemical changes that occur in epilepsy. Such changes are being studied in human tissue and in animal models of seizures. These models allow us to identify the changes that occur following an initial insult to the nervous system and then to determine the progression of morphological and neurochemical changes that may lead to the development of increased excitability and spontaneous seizures.

Larry F. Hoffman, Ph.D.

Larry Hoffman, Ph.D.

Biography

Clinical Interests: Clinical Neurophysiology Research Interests: Vestibular Neuroscience Dr. Hoffman’s research is conducted under the auspice of the National Multipurpose Research and Training Center for vestibular neuroscience from the National Institute on Deafness and Other Communication Disorders (NIDCD). It is devoted to improving the understanding of how information regarding head movements, resulting from transduction mechanisms of the vestibular receptors within the inner ear, is encoded, distributed, and utilized within the central nervous system (CNS). Currently, these investigations are focused upon the neurophysiologic and neuroanatomic organization of vestibular primary afferent neurons, the cells providing the communication between the peripheral vestibular receptors and the CNS. Considerable effort is also devoted to the pathophysiology of these neurons in models of nerve regeneration, ototoxicity, and regeneration of the sensory epithelium. Additionally, current research includes investigations of the anatomy and cell biology of efferent vestibular neurons (cells that provide communication from the CNS back to the peripheral vestibular receptors). Dr. Hoffman is very active in teaching and supervising projects of research trainees at various levels including undergraduate, graduate, medical, postdoctoral, and resident students. His administrative activities include the organization of the Division’s Basic Science curriculum, and assisting in the administration of the Division’s institutional training grant from the NIDCD.

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