Title: Novel xenograft models to study racial differences in myeloma progression
Iron plays important roles in tumor initiation, progression, andmetastasis12-14. We have found that intracellular iron accumulates in myeloma cells, and high levels correlate with negative clinical outcomes15,16. This accumulation results from aberrant regulation of Ferroportin (Fpn1)15,16 and Transferrin receptor (TfR) in myeloma cells. A preliminary retrospective study also shows that high levels of serum iron are associated with worse outcomes in MM patients. Primary iron overload is relatively common in the AA population17. Most AAs with primary iron overload are presumed to have inherited putative African iron overload alleles18.
Based on this, the overall goal of this proposal is to investigate the role of iron in MM progression using newly developed MM PDX models under three specific aims:
- Establish and characterize PDX models of MGUS/SMM/MM as it relates to ethnic diversity.
- Determine the role of iron in accelerating myeloma progression.
- Determine whether targeting increased intracellular iron prevents myeloma progression.
Donghoon Yoon, Ph.D., joined the UAMS Myeloma Center as an Assistant Professor in 2013. He had explored hematopoiesis, particularly erythropoiesis, and the role of hypoxia. He has investigated multiple myeloma (MM) pathogenesis. As part of these studies, he discovered that parathyroid hormone (PTH) and its receptor play an important role in the anti-myeloma activity of proteasome inhibitors. His group found that a significant portion (43%) of MMBD patients heal large bone lesions after conventional therapy. It leads to a hypothesis that MMBD can be corrected by the treatment when they are on the right stage. The current goal of his study is to identify the MMBD stage based on the status of osteolysis. In addition, he has developed unique humanized mouse strains to develop patient-derived xenograft models from various diseases.”
Dr. Yoon’s Mentors
Fenghuang Zhan, Ph.D., M.D. is the Director of myeloma research. His research focuses on myeloma drug resistance and disease progression. His research interests include: 1) Understanding how the genetic alterations in cancer cells contribute to tumor progression, alter treatment response, and create vulnerabilities that may be targeted therapeutically and 2) Develop new therapeutic strategies to overcome chemo and immune therapy resistance.
Shuk-Mei Ho, Ph.D., is a vice chancellor for research and a professor in the College of Medicine Department of Pharmacology and Toxicology. Her research interests pertain to the role of hormones and endocrine disruptors, and the interplay between genetics and epigenetics, in disease development as well as how early-life experiences can be a root cause in later development of cancers, asthma, neural disorders and other complex chronic diseases.