Neurosciences

JOSHUA PARK, Ph.D.

park

Professor
Office: Block Health Science Building, Room 184
Tel: 419-383-4085
Lab: 419-383-4376
Email:  joshua.park2@utoledo.edu

EDUCATION:
1991: B.A., Korea University
1998: MS, Medical University of South Carolina
2003: Ph.D., Johns Hopkins University

 

MAJOR RESEARCH INTERESTS

Neurotrophic administration is currently considered for treatment of neurodegenerative diseases like Alzheimer’s disease (AD). However, neurotrophic approaches have yielded unsatisfactory outcomes due to short half-life and poor blood-brain-barrier (BBB) permeability. To overcome permeability limits, viral vectors and mesenchymal stem cells that produce neurotrophic peptides have been directly injected into the brain. However, the invasiveness of surgical delivery and difficulties in the regulation of peptide production are limiting factors for treatment using viral vectors and stem cells.

 Other work had shown that polysaccharides may have neuroprotective effects; moreover, polysaccharides generally have a longer plasma half-life than peptides. However, no polysaccharides had been demonstrated to permeate the BBB. From this starting knowledge, we began work to find a BBB-permeable neurotrophic polysaccharide from natural polysaccharides that are approved by the FDA for human use. This led to our initial interest in midi-GAGR. Midi-GAGR is a relatively small, 4.7kD cleavage product of low acyl gellan gum, and is considered a safe human food additive.

 Our subsequent work has shown that midi-GAGR has properties that make it a promising candidate for treatment for neurodegeneration. We have shown that midi-GAGR protects primary neurons from oxidative insults of free radicals and amyloid Ab42 peptide, and from microglial cells activated by free radical and amyloid Ab42 peptide. We also showed that midi-GAGR increases neuritogenesis and nuclear levels of pCREB in vitro and in vivo. We showed that midi-GAGR penetrates the BBB in living animals, and can exert neurotrophic effects for ~24 h after one-time intranasal administration. At behavior levels, we find that intranasal administration of midi-GAGR improves nesting behavior in AD model animals. Nesting behaviors of rodents depend on cognitive and memory functions of the brain, suggesting that midi-GAGR may improve behavior that depends on cognition and memory brain regions. These regions are involved in neurodegenerative diseases like AD.

Overall, our lab has been a leader in showing that midi-GAGR has good BBB-permeability, long plasma half-life, strong neuroprotective and neurotrophic effects, and cognition/memory dependent behavioral effects. These properties are clearly desirable for protection from neurodegeneration. Our program of studies raises the possibility that midi-GAGR may be a candidate for treatment of neurodegenerative diseases, including AD.

Our long-term goal is focused on clinical development of midi-GAGR for treatment of neurodegenerative diseases such as AD, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Huntington’s disease, traumatic brain injury, and spinal cord injury.

Academic Honors:
NICHD American Recovery and Reinvestment Act (ARRA) grant, 2009
NIH FARE (Fellows Award for Research Excellence) award, 2008
NICHD Transition Career Development K22 Award, 2007
Young Investigator Award of the Summer joint US-European Neuropeptide Conference, 2006
NIH FARE (Fellows Award for Research Excellence) award 2006
Predoctoral Fellowship NIH Training Program at Johns Hopkins University 1998-2003
Predoctoral Fellowship, EPSCOR NSF Training Program in Cell and Molecular Pharmacology

PATENTS:
D2013-69                    Therapeutic Polysaccharide Midi-GAGR and Related Materials and
                                   Methods (US/PCT filed)

D2017-05                 Wound Healing Agent Made From Low Acyl Gellan Gum, Methods of                                                      Making and Methods of Using The Same (US/PCT filed)

EDITORIAL BOARDS:
Stem Cell International
Journal of Diabetes, Endocrinology and Metabolic Disorders
Alzheimer’s and Parkinson’s Diseases
Journal of Brain & Neuroscience Research
Research Advances in Brain Disorder and Therapy


REFERENCES:

1. Ella, K.M., Qi, C., McNair, A.F., Park, J.H., Wisehart-Johnson, A.E., and Meier, K.E. (1997). PhospholipaseD activity in PC12 cells. Journal of Biological Chemistry, 272(20): 12909-12912.

2. Qi, C., Park, J.H., Shirley, D.W., Bradshaw, C.D., Ella, K.M., and Meier, K.E. (1998). Lysophosphatidic acid stimulates phospholipase D activity and cell proliferation in PC-3 human prostate cancer cells. Journal of Cellular Physiology, 174(2): 261-2723.

3. Miliaras, N.C., Park, J.H., and Wendland, B. (2004). The function of the endocytic scaffold protein Pan1p depends on multiple domains. Traffic, 5(12): 963-78. 

4. Park,J.J., Cawley N.W., and Loh, Y.P. (2008). Carboxypeptidase E cytoplasmic tail anchors hormone vesicles to microtubule motors for transport and activity–dependent secretion. Molecular Endocrinology, 22(4): 989-1005. 

5. Park,J.J., Cawley N.W., and Loh, Y.P. (2008). Carboxypeptidase E cytoplasmic tail anchors BDNF vesicles to microtubule motors for transport and activity – dependent secretion. Molecular and Cellular Neuroscience, 39(1): 63-73.

6. Park,J.J. and Loh, Y.P. (2008). How peptide hormone vesicles are transported to the secretion site for exocytosis. Molecular Endocrinology, 22(12): 2583-95.

7. Lou, H., Park, J.J., Sarcon, A., Adams, T., Cawley, N.X., and Loh, Y.P. (2010). Carboxypeptidase E cytoplasmic tail mediates localization of synaptic vesicles to the pre-active zone in hypothalamic nerve terminals. Journal of Neurochemistry, 114(3): 886-896. (co-first author)

8. Park, J.J., Gondre-Lewis, M., Kim, T., and Loh, Y.P. (2011). A distinct trans Golgi network subcompartment for sorting of synaptic and granule proteins in neuroendocrine cells. Journal of Cell Science, 124(5): 735-44.

9. Park, J.J. and Loh, Y.P. (2011). Visualization of peptide secretory vesicles in living nerve cells. Methods in Molecular Biology, 789:137-45. 

10. Hensley, K., Venkova, K., Christov, A., Gunning, W., and Park, J.J. (2011). Collapsin response mediator protein-2: An emerging pathologic feature and therapeutic target for neurodisease indications. Molecular Neurobiology, 43(3): 180-91. 

11. Cawley, N.X., Wetsel, W., Murthy, S., Park, J.J., Pacak, K., and Loh, Y.P. (2012). New roles of carboxypeptidase E in endocrine and neurological function and cancer. Endocrine Reviews, 33:216-53. 

12. Lou, H., Park, J.J., Phillips, A., and Loh, Y.P. (2012). Gamma-adducin promotes process outgrowth and secretory protein exit from the Golgi apparatus. Journal of Molecular Neuroscience. 49: 1-10. (co-first author)

13. Gondre-Lewis, M., Park, J.J., and Loh, Y.P. (2012). Cellular Mechanisms for the Biogenesis and Transport of Synaptic and Dense-Core Vesicles. International Review of Cell and Molecular Biology 299:27-115. (co-first author)

14. Park, J.J., Rubio, M.V., Zhang, Z., Um, T., Xie, Y., Knoepp, S.M., Snider, A.J., Gibbs, T.C., and Meier, K.E. (2012). Effects of lysophosphatidic acid on calpain-mediated proteolysis of focal adhesion kinase in human prostate cancer cells. Prostate, 72: 1595-610.

15. Makani, V., Hall, J, Qamar, K., Jain, P., Hensley, K., and Park, J.J. (2013). Antidepressant inhibits microtubule organization and hormone secretion in pheochromocytoma cells. Molecular and Cellular Endocrinology, 381:175-87.

16. Makani V, Sultana R, Sie KS, Orjiako D, Tatangelo M, Dowling A, Cai J, Pierce W, Butterfield DA, Hill J, Park, J.J. (2013). Annexin A1 complex mediates oxytocin vesicle transport. Journal of Neuroendocrinology, 25: 1241-54.

17. Christopher, K., Makani, V., Judy, W., Lee, E., Chiaia, N., Kim, D.S., and Park, J.J. (2015). Use of fluorescent ANTS to examine the BBB-permeability of polysaccharide. MethodsX, 2: 174-181.

18. Makani, V., Jang, Y., Christopher, K., Judy, W., Eckstein, J., Hensley, K., Chiaia, N., Kim, D., and Park, J.J. (2016). BBB-permeable polysaccharide, midi-GAGR, has a strong neuroprotective and neurotrophic effects. PLOS ONE, 11(3): e0149715.

19. E. Heck, B., Park, J.J., Makani, V., Kim, E.C., and Hyun Kim D. PAPR-delta agonist with mesenchymal stem cells induces type II collagen-producing chondrocytes in human arthritic synovial fluid. Cell Transplantation, Epub ahead of print.

20. Murphy, K.E. and Park, J.J. (2017). Can Co-Activation of Nrf2 and Neurotrophic Signaling Pathway Slow Alzheimer's Disease? International Journal of Molecular Science, Epub ahead of print.

Last Updated: 8/17/17