Miri VanHoven, Ph. D.

Assistant Professor

Department of Biological Sciences

San José State University
Department of Biological Sciences
One Washington Square
San José, CA 95192-0100
Duncan Hall, Room 447

Telephone: (408) 924-4845
FAX: (408) 924-4840

E-mail: Miri.VanHoven@sjsu.edu
VanHoven Lab Website




FALL COURSE

  • Genetics (Biol 115)

Education

Professional Experience

  • Adjunct Professor, Dominican University of California, Cell Biology Lecture and Laboratory, and Organismal Biology Laboratory, 2005
  • Biological Research Associate, Protein Design Labs, Dr. Chung Nan Chang’s lab, 1998

Research:

The focus of my research is to understand the molecular and genetic mechanisms by which neurons identify the correct partners and form appropriate synaptic connections during the development of the nervous system.Understanding how neurons choose the correct synaptic partner is at the heart of understanding the organization and function of the nervous system, yet very little is known about how it is accomplished.

The nervous system is composed of an immensely complex network of neural circuits that govern perception, thought and behavior.For instance, for an organism to sense its environment, sensory neurons must make synaptic connections onto interneurons that convey input to the correct region of the brain for processing. At each step of this sensory circuit, neurons must identify appropriate synaptic targets among the many neurites they contact before forming synaptic connections – a process known as synaptic partner choice. Altered synaptogenesis is thought to play a role in disorders such as schizophrenia and autism, underscoring the importance of this process in neural development. However, despite its central role in circuit formation, the mechanisms neurons employ to choose the correct synaptic partner are poorly understood.

I chose to study this question in the microscopic nematode (roundworm) C. elegans because it is an ideal model organism for genetic studies due to the extensive genetic and molecular tools available (Figure 1).  Cell specific promoters have been characterized which allow the study of interactions between individual neurons.  In addition, previous work indicates that molecules regulating synapse formation and synaptic transmission in C. elegans are conserved in humans.  Most importantly, it is the only organism for which a complete map of synaptic connections has been generated through decades of study making it ideal for the study of synaptic partner choice.

My goal is to discover new genes and molecular mechanisms governing synaptic partner choice in complex nerve bundles, where parallel neural processes must distinguish among multiple potential targets to form appropriate connections. The majority of the nervous system is composed of such bundles, yet little is known about how synaptic partner choice is mediated in these environments. However, a forward genetic screen to isolate new genes was not possible, due to the lack of a method to rapidly identify inappropriate connections. Visualizing alignment of existing pre- and postsynaptic markers was not possible in such a complex environment due to the resolution limit of conventional light microscopy. Reconstruction of synaptic connections using electron microscopy would take months to years for each animal, making it impractical for this purpose. Therefore, I developed a novel trans-synaptic marker called NLG-1 GRASP that allows visualization of changes in synaptic connectivity in live animals with conventional fluorescence microscopy (Figure 2 and Feinberg, et al, 2008). I fused complementary fragments of a split GFP (Green Fluorescent Protein) to pre- and postsynaptically localized proteins (Figure 1). This system offers a simple and rapid means to query synaptic specificity: the presence (or absence) of GFP fluorescence indicates the formation (or lack) of the appropriate
synapse.  I discovered that the C. elegans Neuroligin protein was localized to both pre- and postsynaptic terminals, and therefore was able to use this protein for both pre- and postsynaptic markers.  I then expressed each marker under cell-specific promoters that drive expression in either pre- or postsynaptic neurons of interest.  Using NLG-1 GRASP, I have successfully visualized changes in connectivity in three characterized circuits using known synaptic specificity mutants in live animals.  I am now taking genetic approaches to discover novel molecular mechanisms guiding synaptic partner choice in complex nerve bundles, utilizing NLG-1 GRASP to detect defects in connectivity.  This marker will allow us to rapidly identify synaptic partner choice mutants that would not be isolated with conventional methods, allowing the identification of new pathways mediating this fundamental process.

I hope that insights gained from these studies will aid in understanding circuit formation in the complex environments of the vertebrate nervous system.  Understanding the mechanisms that regulate circuit formation will bring us closer to understanding and treating neurological diseases.

Publications:

·         Feinberg E.H., VanHoven M.K., Bendesky A., Wang G., Fetter R.D., Shen K., Bargmann C.I. (2008).  GFP Reconstitution Across Synaptic Partners (GRASP) defines cell contacts and synapses in living nervous systems.  Neuron. 57, 353-63.

 

·         Bauer Huang S.L., Saheki Y., VanHoven M.K., Torayama I., Katsura I., van der Linden A., Sengupta P., Bargmann C.I. (2007).  Antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 determine asymmetric olfactory receptor choice in C. elegans.  Neural Development 2, 24.

 

·         Chuang C.F., VanHoven M.K., Fetter R.D., Verselis V.K., Bargmann C.I. (2007).  An innexin-dependent cell network establishes left-right neuronal asymmetry in C. elegans.  Cell 129, 787-99.

 

·         VanHoven M.K., Bauer Huang S.L., Albin S.D., Bargmann C.I. (2006).  The claudin superfamily protein NSY-4 biases lateral signaling to generate left-right asymmetry in C. elegans olfactory neurons.  Neuron 51, 291-302.

 

·         Lanjuin A., VanHoven M.K., Bargmann C.I., Thompson J.K., Sengupta P. (2003).  Otx/otd homeobox genes specify distinct sensory neuron identities in C. elegans.  Developmental Cell 5, 621-33.

 

·         Davies A.G., Pierce-Shimomura J.T., Kim H., VanHoven M.K., Thiele T.R., Bonci A., Bargmann C.I., McIntire S.L. (2003).  A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans.  Cell 115, 655-66.

 

Oral and Poster Presentations at Scientific Meetings:

 

  • A Novel Trans-synaptic Marker to Visualize Changes in Synaptic Target Choice (2008).  Bay Area C. elegans Meeting.  Oral presentation.

  • Pre- and postsynaptic localization of the Neuroligin ortholog NLG-1 in C. elegans (2007).  Synapses: From Molecules to Circuits & Behavior, Cold Spring Harbor.  Poster presentation.

  • Pre- and postsynaptic localization of the Neuroligin ortholog NLG-1 (2007).  San Francisco Bay Area C. elegans Meeting.  Poster presentation.
     
  • Contact-mediated regulation of odorant receptor expression (2005).  International C. elegans Meeting.  Poster presentation.

  • Sensory neuron cell fate determination (2004).  West Coast C. elegans Meeting.  Poster presentation.

  • Sensory neuron cell fate determination in C. elegans (2003).  International C. elegans Meeting.  Poster presentation.

  • Cell fate determination of asymmetric olfactory neurons (2002).  San Francisco Bay Area C. elegans Meeting.  Oral presentation.

  • Sensory neuron cell fate determination (2002).  West Coast C. elegans Meeting.  Poster presentation.

  • Identification and Characterization of Genes Required in a Cell-Cell Signaling Event that Results in Asymmetric Odorant Receptor Expression in C. elegans (2001).  International C. elegans Meeting.  Poster presentation.
 
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