Hiroshi Nishimune, PhD

Assistant 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. We are interested in the molecular mechanisms of synapse formation, maintenance, and how it degenerates in Amyotrophic lateral sclerosis (ALS).

Motor neuron degeneration in ALS patients and animal models is preceded by neuromuscular junction (NMJ, the synapse between motor neurons and muscles) denervation, which 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 denervation in ALS to identify new therapeutic targets.

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, a receptor for the organizer (presynaptic voltage dependent calcium channels, VDCC), and active zone proteins (Figure 2). However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies (Figure 3). Currently, we are applying our findings to study the degeneration mechanism of ALS NMJs and seek ways to ameliorate the innervation rate of NMJs in ALS model animals.

Lab Members

Hiroshi Nishimune, PhD Assistant Professor	Lisa Nadeau Research Assistant	Sudheer Tungtur, MS Research Associate

Former Lab Members

• Takafumi Mizushige, PhD: Assistant Professor, Laboratory of Physiological Function of Food, Kyoto University
• Sara Billings, MS: Research Assistant, KU Lawrence
• Jie Chen, MD PhD: Kansas City
• Gwenaelle Clarke, PhD: Private Corporation

Links

• Kansas Intellectual and Developmental Disabilities Research Center
• Institute for Neurological Discoveries