Christopher Park. MD, PhD
Associate Professor, Pathology
Director of Pathology Education and Translational Research
MD, PhD 2001 College of Physicians and Surgeons, Columbia University
NYU School of Medicine
550 First Ave, Medical Science Building 595
New York, NY 10016
Tel: (646) 501-8987
The goal of our laboratory is to identify genes that regulate cancer stem cell self-renewal, differentiation, and chemoresistance in the hematopoietic system using primary patient material as well as mouse model systems. We primarily focus on hematologic cancers that arise from hematopoietic stem/progenitors cells such as acute myeloid leukemia and the myelodysplastic syndromes and strive to develop improved methods to diagnose, monitor, and treat patients. In order to accomplish these goals, we utilize high-throughput”-omics” approaches, including RNA-sequencing and proteomic approaches, to identify genes of interest in purified stem cell populations from normal and diseased individuals, and validate genes that mediate disease phenotypes including stem cell function using in vitro systems as well as xenograft and mouse transplantation systems. Major ongoing projects include:
•Cancer stem cell antigens for prognostic, diagnostic, and therapeutic use.
•MicroRNAs that regulate stem cell function.
•Genes that regulate leukemic stem cell chemoresistance.
•HSC aging/contribution of aging to hematologic disease.
•Cell-of-origin studies in hematologic malignancies
Our studies have allowed us to accomplish the following: 1) Identification of cell surface antigens present on normal hematopoietic stem cells (HSCs), thereby allowing their prospective separation and investigation; 2) Identification of cell surface antigens present on myeloid disease stem cells, allowing their separation from normal residual hematopoietic stem/progenitor cells. This has led to novel insights regard the mechanisms that regulate disease stem cells and made possible their therapeutic targeting with therapeutic antibodies; 3) Characterization of microRNAs that regulate normal and leukemic stem cell self-renewal and lineage commitment; 4) Isolation of the cell-of-origin in diseases thought to arise in hematopoietic stem/progenitor cells [e.g. acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)] as well as those from mature hematologic malignancies such as hairy cell leukemia (HCL); 5) Discovery of novel genes that regulate HSC aging; 7) Identification of novel chemoresistance mediators in AML; 8) Elucidation of novel pathways that regulate protein translation regulation in HSCs/LSCs.
·Shin JY, Hu W, Naramura M, Park CY. High c-Kit expression identifies hematopoietic stem cells with impaired self-renewal and megakaryocytic bias. J Exp Med. 2014 Feb 10;211(2):217-31. PMCID:PMC3920569
·Chung SS, Kim E, Park JH, Chung YR, Lito P, Feldstein J, Hu W, Beguelin W, Monette S, Duy C, Rampal R, Telis L, Patel M, Kim MK, Huberman K, Bouvier N, Berger MF, Melnick AM, Rosen N, Tallman MS, Abdel- Park CY*, Wahab O*, Hematopoietic Stem Cell Origin of BRAFV600E Mutations in Hairy Cell Leukemia. Sci Transl Med. 2014 May 28;6(238):238ra71. doi: 10.1126/scitranslmed.3008004. PMCID: PMC4507573
·Hu W, Dooley J, Chung SS, Chandramohan D, Cimmino L, Mukherjee S, Mason CE, Strooper B, Liston A, Park CY. MiR-29a maintains mouse hematopoietic stem cell self-renewal regulating Dnmt3a. Blood. 2015 Jan 29. pii: blood-2014-06-585273. PMCID: PMC4383797
·S. S. Chung, W. S. Eng, W. Hu, M. Khalaj, F. E. Garrett-Bakelman, M. Tavakkoli, R. L. Levine, M. Carroll, V. M. Klimek, A. M. Melnick, C. Y. Park*. CD99 is a Therapeutic Target on Disease Stem Cells in Myeloid Malignancies. Sci. Transl. Med. 9, eaaj2025 (2017).