Hiroshi Nishimune, PhD

Associate Professor
Anatomy and Cell Biology

Ph.D., 1997 Osaka University, Japan
Postdoctoral, IBDM, INSERM U.382, France, C.E. Henderson lab
Postdoctoral, Washington Univ. Sch. of Med., St. Louis, J.R. Sanes lab
Postdoctoral, Harvard Univ. Dept. MCB, Cambridge, J.R. Sanes lab

Publications: Click here for PubMed, Click here for Google Scholar

The nervous system plays essential roles for our daily life, for example, movement, communicating, sensing, learning, and memory. All these functions of the nervous system depend on cell-cell communication at synapses. The synapses between motor neurons and skeletal muscles are called neuromuscular junctions (NMJs). We are interested in the molecular mechanisms of synapse formation, maintenance, and degeneration in Amyotrophic Lateral Sclerosis (ALS) and aging.

In ALS patients and animal models, degeneration of NMJs precedes that of the motor neuron cell bodies. This degeneration of NMJs (denervation) suggests that ALS is a dying-back neuropathy. The mechanisms of NMJ denervation and the reasons for the preferential death of motor neurons in ALS remain unknown; therefore, effective treatments for ALS are lacking. Thus, our long-term goal is to elucidate the molecular mechanisms underlying NMJ denervation in ALS and to identify new therapeutic targets.

Aged rodents also show NMJ denervation similar to ALS model rodents. We have identified that physical exercise ameliorates NMJ denervation and degeneration of synaptic proteins in NMJs of aged rats. We seek molecular mechanisms that are activated by exercise and have beneficial role for the maintenance of NMJs in aged animals. We are applying these findings to ALS model rodents as well.

Presynaptic active zones are synaptic vesicle release sites that play essential roles for synaptic transmission and pathology of NMJs (Figure 1). Our studies show that NMJ active zones are organized via interactions between an active zone-organizer (laminin beta2), a receptor for the organizer (presynaptic voltage gated calcium channels, VGCC), and active zone proteins (Figure 2).

However, active zones become impaired during aging and ALS. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies (Figure 3).

Recently, we have analyzed the active zone specific proteins at the NMJ using a super resolution microscopy (STED microscope), which gives resolution beyond conventional confocal microscopes (Figure 4). We revealed the protein distribution patter at much higher resolution (PQ-VGCC) and an unexpected sandwich pattern (Bassoon-Piccolo-Bassoon).

Currently, we are applying our findings to study the degeneration mechanism of ALS and aging NMJs, and seek ways to ameliorate NMJ denervation in ALS model animals and aged rodents using exercise intervention and adult stem cells.

figure 1

figure 2

figure 3

figure 4

Lab Members

Hiroshi Nishimune
S Tungtur
N Nishimune
Hiroshi Nishimune, PhD
Associate Professor
Sudheer Tungtur, MS
Research Associate
 Natsuko Nishimune
Research Assistant
Y Badawi
Robert Rogers Phd  
 Yomna Badawi, PhD
Postdoctoral Fellow
 Robert Rogers, PhD
Postdoctoral Fellow

Former Lab Members

  • Takafumi Mizushige, PhD: Associate Professor Department of Applied Biological Chemistry, Faculty of Agriculture, Utsunomiya University
  • Sara Billings, MS: Research Assistant, Stanford School of Medicine
  • Jie Chen, MD PhD: Kansas City
  • Gwenaelle Clarke, PhD: Private Corporation
  • Lisa Nadeau: Kirksville College of Osteopathic Medicine (2013)
  • Tomohiro Tanaka, PhD: Postdoctoral fellow, Scripps Research Institute


Last modified: Aug 08, 2016

Hiroshi Nishimune


Hiroshi Nishimune, PhD
Associate Professor

3901 Rainbow Blvd.,
MS 3051, HLSIC Rm. 2073
Kansas City, KS 66160, USA

P: 913-588-4146
F: 913-588-5677