New Faculty Spotlight

Hao Chen, Ph.D.
Hao Chen, Ph.D.
Assistant Professor - Department of Pharmacology

My long-term interest is to elucidate the complex interaction between social, genetic, and sensory factors in regulating drug abuse behavior, particularly cigarette smoking and alcohol drinking, by using rodent models. Read more about Dr. Chen...

Victor Chizhikov, Ph.D.
Victor Chizhikov, Ph.D.
Assistant Professor - Anatomy and Neurobiology

Our laboratory has two goals: (1) to identify the molecular mechanisms that regulate the development of the mammalian brain and (2) to define the pathogenic mechanisms that underlie human developmental brain disorders. Read more about Dr. Chizhikov...


Hao Chen, Ph.D.
Assistant Professor - Department of Pharmacology

Research Highlights

  1. The role of social learning in nicotine self-administration
    Cigarette smoking is a social behavior. We established a novel rodent model of socially-acquired intravenous nicotine self-administration, where nicotine is delivered concurrently with olfactory and gustatory cues. We found that rats self-administering nicotine alone under this condition developed strong conditioned aversion to nicotine. However, when a demonstrator rat that consumes the same olfactory and gustatory cue was placed in the operant chamber, stable self-administration of nicotine was established. Our data indicated that social learning reversed the aversive response and enabled stable voluntary nicotine intake. We are studying the role of social learning using behavioral, pharmacological, genetic, and functional genomic methods.

  2. Menthol as a conditioned cue for nicotine reward
    Menthol is the most widely used additive for tobacco products. It is also one of the most preferred flavors of electronic cigarettes. We are studing the effect of a contingent oral menthol cue on intravenous nicotine self-administration. Our data support the hypothesis that the cooling sensation of menthol, rather than its odor or taste, is critical for its effect on nicotine intake.

  3. Laser capture microdissection (LCM) and Next-Gen sequencing
    LCM allows the precise dissection of thin (10 micron) tissue under a microscope. DNA and RNA can then be extracted. Working with the Molecular Resource Center, we have developed a workflow that allows the extracted RNA to be analyzed using next-gen sequencing methods.

  4. Genomic and bibliomic data analysis
    Using the various computer clusters provided by the Center for Integrative and Translational Genomics, we have analyzed large amount of RNA-seq and genomic sequences. Our PubMed text-mining application automatically extracts relationships from multiple genes or keywords and presents the results as an interactive graph. It not only is widely used but also inspired many research projects.
  5. 3D printing
    3D printing is a fun way to manufacture small to medium sized parts. We have designed many parts that fit our needs in the lab, such as this surgical implant for rat jugular catheters.

Victor Chizhikov, Ph.D.
Assistant Professor - Anatomy and Neurobiology

Research Highlights

Our laboratory has two goals: (1) to identify the molecular mechanisms that regulate the development of the mammalian brain and (2) to define the pathogenic mechanisms that underlie human developmental brain disorders. We primarily focus on the developing cerebellum, which is a major center of motor-coordination, and on the cerebral cortex, which mediates sensorimotor skills and higher cognitive functions.

One project in the laboratory focuses on the LIM-homeodomain transcription factor Lmx1a. Lmx1a mutant mice are ataxic, hyperactive and have a malformation of the cerebellum (Fig. 1A, B), which mimics the cerebellar phenotype in human Dandy-Walker patients.


(A, B) Midsagittal sections of adult cerebellum of wild type (A) and Lmx1a-/- (B) mice stained with hematoxylin and eosin. Lmx1a-/- cerebellum is small and misfolded. (C, D) Cerebellar rhombic lip of wild type (C) and Lmx1a-/- (D) embryos at embryonic day 18 (e18) stained with hematoxylin and eosin. In e18 wild type embryos, rhombic lip (RL, arrow) is located between the choroid plexus (CP) and external granule cells layer (EGL). By e18, rhombic lip precociously regresses in Lmx1a-/- embryos and the choroid plexus becomes connected with the external granule cell layer.

Recently we showed that during development Lmx1a controls maintenance of the cerebellar rhombic lip, a major embryonic germinal zone that gives rise to multiple classes of cerebellar neurons, neurons of the precerebellar system and contributes cells to the developing choroid plexus. Our analysis revealed that in Lmx1a-/- mice, the rhombic lip is initially formed normally but precociously regresses as development proceeds (Fig. 1C, D). It is believed that abnormal regression of the rhombic lip underlies cerebellar hypoplasia in adult Lmx1a mutant mice. To understand how Lmx1a regulates rhombic lip development, we performed microarray expression experiments using rhombic lip isolated from wild type and Lmx1a mutant embryos by laser capture microdissection, just before rhombic lip regression begins in Lmx1a-/- embryos. This analysis identified approximately 40 genes misexpressed in Lmx1a-/- rhombic lip. Currently we are performing analysis of these candidate Lmx1a downstream genes to identify which of them are critical mediators of Lmx1a function. This analysis will identify the genetic network regulating rhombic lip development.

Several other mouse mutants with developmental abnormalities of the cerebellum and cerebral cortex are currently under investigation in the laboratory.

Our studies will identify new mechanisms regulating brain development and will contribute to understanding the etiology of human brain developmental disorders affecting cerebellum and cerebral cortex.

Recent Publications

  1. Millen KJ, Steshina EY, Iskusnykh IY and Chizhikov VV (2014). Transformation of the cerebellum into more ventral brain stem fates causes cerebellar agenesis in the absence of Ptf1a function. Proc Natl Acad Sci U S A (in press).
  2. Curry CJ, Rosenfeld JA, Grant E, Gripp KW, Anderson C, Aylsworth AS, Saad TB, Chizhikov VV, Dybose G, Fagerberg C, Falco M, Fels C, Fichera M, Graakjaer J, Greco D, Hair J, Hopkins E, Huggins M, Ladda R, Li C, Moeschler J, Nowaczyk MJ, Ozmore JR, Reitano S, Romano C, Roos L, Schnur RE, Sell S, Suwannarat P, Svaneby D, Szybowska M, Tarnopolsky M, Tervo R, Tsai AC, Tucker M, Vallee S, Wheeler FC, Zand DJ, Barkovich AJ, Aradhya S, Shaffer LG and Dobyns WB (2013). The duplication 17p13.3 phenotype: analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes. Am J Med Genet A. 161A:1833-52.
  3. Blank MC, Grinberg I, Aryee E, Laliberte C, Chizhikov VV, Henkelman RM and Millen KJ (2011). Multiple developmental programs are altered by loss of Zic1 and Zic4 to cause Dandy-Walker malformation cerebellar pathogenesis. Development 138:1207-16.
  4. Chizhikov VV, Lindgren AG, Mishima Y, Roberts RW, Aldinger KA, Miesegaes GR, Currle DS, Monuki ES and Millen KJ (2010). Lmx1a regulates fates and location of cells originating from the cerebellar rhombic lip and telencephalic cortical hem. Proc Natl Acad Sci U S A. 107:10725-30.
  5. Swanson DJ, Steshina EY, Wakenight P, Aldinger KA, Goldowitz D, Millen KJ and Chizhikov VV (2010). Phenotypic and genetic analysis of the cerebellar mutant tmgc26, a new ENU-induced ROR-alpha allele. Eur J Neurosci. 32:707-16.
  6. Aldinger KA, Lehmann OJ, Hudgins L, Chizhikov VV, Bassuk AG, Ades LC, Krantz ID, Dobyns WB, Millen KJ (2009). FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet. 41:1037-42.

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William E. Armstrong, Ph.D.

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Anton J. Reiner, Ph.D.

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Shannon Guyot

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