JOSHUA PARK, Ph.D.
Office: Block Health Science Building, Room 184
1991: B.A., Korea University
1998: MS, Medical University of South Carolina
2003: Ph.D., Johns Hopkins University
Our first research project is to develop a new drug for the treatment of neurodegenerative diseases. Over 5
million people in the US and 35 million worldwide suffer from Alzheimer's disease
(AD), a devastating disease that costs the US over $100 billion every year. Enormous
efforts have been poured on the development of therapeutic agent(s) that can slow
AD while current treatments only address symptoms without disease-modifying effect
and have side effects. Conversely, increasing evidence points to the effectiveness
of neurotrophic agents for AD treatment. However, the BBB-impermeability and short
half-life of protein neurotrophic factors limit their use for AD treatment. Hence,
neurotrophic agent that overcomes those shortcomings should be a better neurotrophic
treatment of AD. We discovered a neuroprotrophic polysaccharide named ‘midi-GAGR’
that has good BBB-permeability, strong neuroprotective and neurotrophic effects in
primary neurons and in animals, and >12-h half life. Our current research focuses
on the examination of the efficacy of midi-GAGR in slowing pathogenesis in AD animals.
Achieving our goal will provide a strong scientific basis for the clinical development
Our second research project is to develop a stem cell-based treatment that can modify osteoarthritis (OA). OA
is a disease caused by degradation of extracellular matrix at the cartilage of inflamed
synovial joints, resulting in joint deformation and dysfunction. An estimated 27 million
Americans, especially aged people, suffer from OA and the population is expected to
reach 67 million in USA by 2030. Traditional OA treatments including non-steroidal
anti-inflammatory drug, joint replacement, etc., have no disease-modifying effect.
Given most OA treatments cannot overcome synovial inflammation that decreases cartilage
formation and increases cartilage breakdown, OA-modifying treatment should suppress
inflammation and increase cartilage formation. We have developed an innovative stem
cell-based OA therapy device named CHAMPthat is designed to enhance cartilage formation
and decrease inflammation. In our study, CHAMP could generate type II collagen-containing
chondrocytes in human inflammatory OA synovial fluid while current MSC-based OA therapy
could not, showing that CHAMP is superior to current MSC-based OA therapy. Given that
all three CHAMP components are already used for human treatment or in clinical trial,
it is expected to take a short regulatory process to obtain the approval of the use
of CHAMP for human OA treatment. The current goal of our research is to examine the
efficacy of CHAMP in treating OA in anterior cruciate ligament transaction (ACLT)
animal model. Achieving our goal will provide solid pre-clinical and clinical bases
for the clinical development of CHAMP for OA treatment.
Our third research project is to reveal the molecular mechanism that underlies the control of the directionality
of vesicle movements. Hormone secretion is fundamental to the very existence of an
organism, regulating important physiological functions such as neurotransmission,
energy use, reproduction, and behavior, all required for the survival and maintenance
of homeostasis. Understanding the mechanisms underlying how cells within the hypothalamic-pituitary
axis secrete hormones is therefore of paramount importance. For example, regulated
secretion of adrenocorticotropic hormone (ACTH) allows the endocrine, immune, and
central nerve systems to cope with stress, while dysregulation can lead to metabolic,
immune, and psychiatric disorders. Likewise, regulated secretion of the hormone oxytocin
in the brain is important for controlling caloric homeostasis and social behavior,
while dysregulation leads to obesity, diabetes, and psychiatric disorders such as
anxiety. Nevertheless, little is known about the microtubule-based transport of vesicles
containing the hormones to the secretion sites. We have discovered that A-kinase anchor
protein 5 (AKAP5) is involved in the actions of protein kinase A (PKA) and protein
kinase C (PKC) to control the anterograde transport of ACTH- and OXT-containing vesicles
to the secretion sites in the pituitary corticotrophs and hypothalamic neurons, respectively.
We found that activated PKA increases association of kinesin-2 with the AKAP5-ANXA1
complex and anterograde transport of the peptidergic vesicles while activated PKC
decreases both. This evidence suggests that PKA enhances and PKC decreases the anterograde
transport of the peptidergic vesicles by controlling the association of kinesin-2
with AKAP5-ANXA1 complex on the vesicles. Our goal is to identify AKAP5-mediated molecular
mechanism that controls the directionality of microtubule-based transport of ACTH-
and OXT-containing vesicles in the pituitary corticotrophs and hypothalamic neurons,
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,
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
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.
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): 261-272.
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.
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.
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.
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. (co-first author) Journal of Neurochemistry, 114(3): 886-896.
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.
Park,J.J. and Loh, Y.P. (2011) Visualization of peptide secretory vesicles in living nerve
cells. Methods in Molecular Biology, 789:137-45.
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.
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.
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. (co-first author) Journal of Molecular Neuroscience. 49: 1-10.
Gondre-Lewis, M., Park, J.J., and Loh, Y.P. (2012) Cellular Mechanisms for the Biogenesis and Transport of Synaptic
and Dense-Core Vesicles. (co-first author) International Review of Cell and Molecular Biology 299:27-115.
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.
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.
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,
Christopher, K., Makani, V., Judy, W., Lee, E., Chiaia, N., Kim, D.S., and and Park, J.J. (2015) Use of fluorescent ANTS to examine the BBB-permeability of polysaccharide.
MethodsX, 2: 174-181.
Makani, V., Jang, Y., Christopher, K., Judy, W., Eckstein, J., Hensley, K., Chiaia,
N., Kim, D., and Park, J.J. BBB-permeable polysaccharide, midi-GAGR, has a strong neuroprotective and neurotrophic
effects. Under revision for ‘PLOS ONE’.
Heck, B., Park, J.J., Makani, V., and Kim, D. PPAR-delta agonist with mesenchymal stem cells induces type
II collagen-producing chondrocytes in human arthritic synovial fluid. Under revision
for ‘Cell Transplantation’.