Melissa Wong, Ph.D.
Oregon Health & Science University
Department of Dermatology
3181 SW Sam Jackson Park Rd
Portland, OR 97239
Melissa Wong is an Associate Professor in the Department of Dermatology, holds an adjunct appoint to the Department of Cell and Developmental Biology, the Oregon Stem Cell Center and is a member of the Knight Cancer Institute. She earned her Ph.D. degree in Molecular Pathobiology at Wake Forest University and trained with Dr. Jeffery Gordon at Washington University School of Medicine in St. Louis, MO. Dr. Wong came to OHSU in 2001.
My research program focuses on understanding the molecular mechanisms underlying stem cell regulation in the context of intestinal development, tissue regeneration and disease. While stem cell biology is at the forefront of regenerative medicine, there lacks a clear understanding of the general mechanisms that regulate stem cell proliferation and ultimate lineage differentiation in tissue. This lack in knowledge hampers potential to harness stem cell biology for therapeutic purposes. The individual research projects in my laboratory encompass investigation of establishment of the regulatory stem cell niche during intestinal development, the dynamic remodeling of the intestinal stem cell niche during injury and disease, and the role of cellular fusion with intestinal stem cells in intestinal carcinogenesis.
The implication of circulating bone marrow-derived stem cells and cell fusion on tumor progression.
Our laboratory has shown that circulating BMDCs fuse with intestinal stem cells upon tissue injury, inclusive of intestinal tumorigenesis. We now extend these studies to identify the cellular mediators of fusion, the underlying mechanism, and the long-term fate to the cell fusion hybrids. We have currently identified the macrophage population as a key bone marrow derived cell population in this fusion process. Our studies are now focused upon determine the fate of the cell fusion hybrids in participating to intestinal pathogenesis, as we examine genomic instability of the fusion hybrids, the ability of these cells to express macrophage genes under certain contexts, and the contribution of these cells to tumorigenesis. Our studies offer an exciting alternative view of how epithelia regenerate and have the potential to explain how chronic injury can lead to promote malignant tumors.
Identification of markers for intestinal stem cells and intestinal cancer stem cells
The cancer stem cell theory for why many cancers may recur after treatment presents a novel target for cancer therapeutics. However, the notion that cancer stem cells arise from mutations in tissue stem cells suggests that these two cell populations may share similar features and targetable epitopes. We have taken a systematic approach to defining surface antigens on these two populations by generating novel monoclonal antibodies. Our studies will establish a link between these two populations and may provide novel epitopes that are unique to the cancer stem cell that can be used for targeted therapy.
Davies PS, Powell AE, and Wong MH. Inflammation and proliferation act synergistically to mediate intestinal cell fusion. PLOS One.
Davies PS, Dismuke, AD, Powell AE, Carroll KH, and Wong MH. Wnt signaling regulates proliferation of murine early progenitor cells in the intestine and is differentially stimulated in response to injury. (2008) BMC Gastroenterol, 8:57.
Jiang S, Bailey AS, Goldman DC, Swain JR, Wong MH, Streeter P, and Fleming WH. (2008) Hematopoietic stem cells contribute to lymphatic endothelium. PLoS ONE 3:e3812.
Rizvi AZ, Swain JS, Bailey AS, Davies PS, Decker AD, Willenbring H, Grompe M, Fleming WH, and Wong MH. (2006) Bone marrow-derived cells fuse with normal and transformed intestinal progenitor cells. PNAS USA,103:6321-5.