Maiyon Park, Ph.D.
Assistant Professor of Biochemistry and Microbiology
Marshall University Joan C. Edwards School of Medicine
Education
B.S., University of Michigan
Ph.D., University of Michigan
Postdoctoral, University of Washington
Contact Information
parkm@marshall.edu
Office phone: 304-696-3680
Lab phone:304-696-7033
Fax: 304-696-7253
1700 Third Avenue
Huntington WV 25755
| My research has focused on elucidating the function(s) and mechanism(s) of Chmp1A (Charged Multivesicular Body Protein/Chromatin Modifying Protein) in human cancer development. Chmp1A is a member of the ESCRT-III (Endosomal Sorting Complex Required for Transport) family. ESCRT complexes play central roles in endosomemediated protein trafficking via multivesicular body (MVB) formation and sorting. An increasing amount of data indicates that ESCRT complexes are also involved in tumor development. However, the implication of the ESCRT complex, especially of Chmp1A in tumor development has not been investigated. Recently we provided evidence that Chmp1A functions as a novel tumor suppressor in the pancreas ATRA (published in Cell Cycle). Our conclusion is based on the results that first, non-tumorigenic HEK 293T cells form tumors in nude mice when Chmp1A is silenced. Second, Chmp1A protein is either reduced and/or mis-localized in the ducts of human pancreatic tumors. Third, doxycycline induced over-expression of Chmp1A in human pancreatic ductal tumor cells (PanC-1) resulted in cell growth inhibition and tumor xenograft inhibition, respectively. Fourth, overexpression of Chmp1A strongly increased the protein level of P53 and phospho-P53. We identified putative Chmp1A interacting proteins using affinity chromatography and MS/MS. We also identified many post-translational modification motifs including ubiquitination and sumoylation (paper in submission). In addition, we found that Chmp1A mediates growth inhibition of all trans Retinoic Acid (published in Molecular Cancer) in human pancreatic tumors. Presently, we are working on elucidating the mechanisms of Chmp1A in cell cycle progression leading to tumor suppression. We generated Chmp1A knockout mice that inactivate the gene globally which led to heterozygous infertility and homozygous lethality. However, the survived heterozygotes exhibited severe abnormalities in pancreas and colon indicating that Chmp1A inactivation might induce tumors in the colon and pancreas. We plan to generate Chmp1A knockout mice to inactivate Chmp1A either time or tissue specifically or both time and tissue specifically using Cre- and Tet-system (submitted NIH R21 grant for knockout mice generation). This knockout mouse will provide an excellent opportunity to study Chmp1A function(s) and mechanism(s) in vivo, and to develop and test peptides to mimic Chmp1A function as a promising therapeutic approach to treat human cancers of colon and pancreas. In the future we would like to focus more extensively on elucidating cell cycle mediated signaling mechanisms of Chmp1A in tumor development. P53 and Retinoblastoma (RB) signaling pathways are our present interest. We are also interested in understanding the involvement of motifs and translational modifications of Chmp1A in cell cycle progression and tumor development. |
|
|
Chmp1A stable overexpression induces an increase in phospho-P53 (serine 15)
Publications: