Heather Broihier, Ph.D.

Heather Broihier, Ph.D.
Assistant Professor
Department of Neurosciences
Case Western Reserve University


School of Medicine
10900 Euclid Ave
Cleveland OH, 44106-4975

Phone : (216) 368-4326
Fax : (216) 368-4650
Email : heather.broihier@case.edu
Website : http://www.broihierlab.com/
 
 

RESEARCH INTERESTS

Our laboratory investigates the development of neural circuits. In particular, we study molecular mechanisms controlling neuronal communication in Drosophila. We combine genetic, cellular, and electrophysiological approaches in this powerful model system to analyze the interaction of neurons with their environment during development. Extracellular signaling pathways regulate core attributes of neuronal identity—from neuronal survival to process outgrowth and synaptic function. Furthermore, aberrant intercellular signaling is a common feature of neurodevelopmental disorders. Thus, it is important to map the underlying molecular pathways. We focus on two major questions:

1. How are morphogenetic signaling pathways specialized for nervous system function? The same extracellular signaling pathways that play widespread roles throughout the body also regulate neuronal development. Neurons present a unique set of challenges for these pathways, as they are electrically active and have elaborate polarized morphologies. We are interested in the molecular mechanisms that customize TGFβ/BMP signaling for the nervous system.

We have identified the evolutionarily conserved transmembrane protein Crimpy as a novel regulator of BMP signaling in neurons. Our work demonstrates that Crimpy is required for both presynaptic localization and activity-dependent release of presynaptic BMP at the neuromuscular junction. We are currently analyzing the molecular mechanism by which Crimpy controls presynaptic BMP activity. BMPs are neuromodulators in the mammalian brain, and dysregulated BMP signaling is linked to major psychiatric disorders—making molecular characterization of this pathway significant.

2. How is the activity of individual transcription factors shaped by extracellular signals? Transcription factors establish and maintain neuronal cell fates in development and adulthood. Some are expressed only transiently, as they function exclusively to initiate comprehensive gene expression programs. Others, however, have sustained expression profiles, pointing to ongoing requirements in modulating neuronal characteristics.

We study the role of the FOXO transcription factor in neuronal survival, morphology, and plasticity. FOXO proteins integrate developmental and environmental cues in many cell types, and are important emerging regulators of neuronal development. We have found that FOXO is expressed in developing and adult Drosophila neurons and that FOXO activity is profoundly influenced by neurotrophic signaling pathways. We are currently dissecting the signal transduction pathways that couple FOXO activity to extracellular signals in both motor and sensory neurons. Neurotrophic signaling networks are key to neuronal survival and function, making elucidation of the downstream molecular cascades important.

Dr. Broihier, a Cleveland native, received her Ph.D. from M.I.T. in 1998 and was a postdoctoral fellow at Washington University in St. Louis.

SELECTED PUBLICATIONS

  1. Nechipurenko, IV, Broihier HT. (2012)
    FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption. Journal of Cell Biology. 2012 Feb; 196(3):345-362.
  2. James RE, Broihier HT. (2011)
    Crimpy inhibits the BMP homolog Gbb in motoneurons to enable proper growth control at the Drosophila neuromuscular junction. Development. 2011 July; 138(15):3273-3286.
  3. Miller CM, Liu N, Page-McCaw A, Broihier HT. (2011)
    Drosophila Mmp2 regulates the matrix molecule faulty attraction (Frac) to promote motor axon targeting in Drosophila. Journal of Neuroscience. 2011 April; 31(14):5335-5347.
  4. Weng YL, Liu N, DiAntonio, A, Broihier HT. (2011)
    The cytoplasmic adaptor protein Caskin mediates Lar signal transduction during Drosophila motor axon guidance. Journal of Neuroscience. 2011 March; 23(31):4421-4133.
 
faculty/broihier/index.txt · Last modified: 2013/11/25 17:40 by htb
 
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