Reconstructive Biotechnology

Ichiro Nishimura Lab

About

We investigate the pathological mechanism of oral rare diseases and develop new therapeutic modalities. We use small animal models of rare diseases for mechanistic investigations and biotechnology and nanotechnology for therapeutic applications.

Our recent translational research on osteonecrosis of the jaw (ONJ), a rare but severe oral manifestation of anti-resorptive medications, resulted in the successful development of novel compounds to prevent bisphosphonate-related ONJ. The current project is determining the therapeutic effectiveness of our compound therapy in the mouse ONJ model and developing a viable drug formulation for topical application to the oral mucosa and gingiva. After biocomparative studies, we plan to proceed the FDA application for patient treatment.

Separately, we have been investigating the role of circadian rhythm on tissue regeneration, which identified a target clock gene. The knockout mutation of the target clock gene resulted in no significant mutation; but when injured such as tooth extraction, skin punch wounding or calvarial critical bone defect formation, the robust increase of regeneration in respective tissues was observed. Furthermore, High throughput screening of drug compounds has identified a group of small compounds that can modulate the target clock gene. The application of these compounds to the wounded tissues showed promising therapeutic effect of wound healing and tissue regeneration. Our current studies ask the mechanism of circadian rhythm-dependent tissue regeneration.

Current Projects and Grants

R44DE025524 NIH/NIDCR: Competitive equilibrium-based displacement of bisphosphonate as novel therapeutic approach for BRONJ
The major objective of this phase II SBIR study is to develop a new class of chemical compounds suitable for prophylaxis and therapeutic intervention of osteonecrosis of the jaw.

UCLA Innovation Fund: Small molecule inhibitor of Npas2 for surgical wound scar prevention
The objective of this translational research is to develop a therapeutic modality to minimize hypertrophic scarring after surgical wounding in skin, in particular facial scarring.

Publications

  • Ngo JT*, Sasaki H, Nishimura I: Circadian behaviors of oral and skin fibroblasts, J Cal Dent Assoc, 47:12:801-809, 2019. *Dental Student Research
  • Hokugo A, Kanayama K, Sun S, Morinaga K, Sun Y, Wu Q, Sasaki H, Okawa H, Evans C, Ebetino FH, Lundy MW, Sadrerafi K, McKenna CE, Nishimura I: Rescue Bisphosphonate Treatment of Alveolar Bone Improves Extraction Socket Healing and Reduces Osteonecrosis in
  • Sasaki H, Hokugo A, Wang L, Morinaga K, Ngo J, Nishimura I: Neuronal PAS domain 2 (Npas2) Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction, Anat Rec (Special Issue), 2019. PMCID: PMC6733676.
  • Morinaga K, Park S, Hokugo A, Sasaki H, Nishimura I: Osseointegration of rough surface implants requires peripheral clock Npas2. Biomaterials, 192:62-74, 2019. PMCID: PMC6389329.
  • Kaur K, Topchyan P, Kozlowska A, Ohanian N, Chiang J, Maung P, Park S-H, Ko M-W, Fang C, Nishimura I, Jewett A: Super-charged NK cells inhibit growth and progression of stem-like/poorly differentiated oral tumors in vivo in humanized BLT mice; effect on t

Lab Members



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Collaborators

UCLA School of Dentistry:

  • Anahid Jewett
  • Alireza Moshaverinia
  • Igor Spigelman
  • Yi-Ling Lin
  • Mo Kang
  • Renate Lux

UCLA:

  • Akishige Hokugo (Plastic Surgery)
  • Nick Bernthal (Orthopedic Surgery)
  • John Adams (Orthopedic Surgery)
  • Jeff Miller (Molecular Biology)
  • Robert Damoiseaux (CNSI)
  • Andrea Kasko (Bioengineering)
  • Varghese John (Neurology)
  • Christopher Colwell (Psychiatry and Biobehavioral Sciences)
  • Linda Demer (Medicine)

Other:

  • Charles McKenna (USC, Chemistry)
  • F. Hal Ebetino (BioVinc LLC)
  • Giuseppe Pezzotti (Kyoto Institute of Technology)

List of Lab Members:

  • Hiroko Okawa, DDS PhD, Assistant Project Scientist
  • Shuting Sun, PhD, Assistant Project Scientist
  • Kaitlyn Quesada, Bioengineering
  • Daniel Lee, Prosthodontics Resident
  • John Ngo, Dental Student
  • Coutney Evans, Dental Student

Opportunities

Committed students and fellows are welcome to join.