Analysis and therapeutic targeting of the immune regulatory and ubiquitination pathways in Anaplastic Large Cell Lymphoma and Hodgkin Lymphoma
Fox Chase Cancer Center
Project Term: July 1, 2022 - June 30, 2027
My lab is focused on the immune regulatory mechanisms and ubiquitin-dependent machinery in lymphoma. We have established multiple high-throughput screening technologies and animal models to rapidly and accurately identify critical pathways that are suitable for targeted therapy and immunotherapy. Gaining insight into the pathological roles of these pathways can lead to improved understandings of the molecular circuitry that drives lymphoma pathogenesis and provide novel therapeutic strategies.
Lymphoma typically occurs in mature and older adults, but it is actually the third most common form of cancer in children aged 0 to 14, and is the most common group of cancers in teenagers and young adults. Among lymphoma subtypes, Anaplastic large cell lymphoma (ALCL) comprises 10-15% of pediatric lymphomas, and Hodgkin lymphoma (HL) is the most common (6,000 to 7,000 new cases per year) cancers in young adulthood, representing about 1 in 6 of all cancers affecting young people between 15 and 24 years old. Although there has been significant progress in treating ALCL and HL over the last few decades, the survival rate for patients diagnosed at an advanced stage or with relapsed/refractory disease remains low. Thus, there is a need to develop novel, preferably small molecule-based targeted therapies or immunotherapies for these lymphoid malignancies. A major barrier to this goal is the lack of a systematic and comprehensive understanding of the deep molecular characteristics of ALCL and HL pathology, which is clearly needed to identify critical therapeutic vulnerabilities. My research mainly focuses on using unbiased genetic screen technologies to address these unresolved questions, to gain a complete understanding of how the specific genes and pathways regulate ALCL and HL pathogenesis. We are particularly interested in the pathways of immune regulatory and ubiquitination (a form of protein modification), oncogenes, and tumor-suppressors required for lymphoma pathogenesis and immunotherapy. We have established to use multiple high-throughput screening technologies, clinical samples, and animal models to rapidly and accurately identify critical pathways suitable for targeted therapy and immunotherapy. We hope these studies will form the basis for clinical trials that can be opened at our Cancer Center. Therefore, we have the unique opportunity to exploit the full spectrum of “translational research”, from “big data” (high-throughput technologies), to patient specimens, animal models, and mechanistic biochemical analyses, eventually leading to novel therapeutic interventions. Gaining insight into the answers to these essential unresolved questions can lead to improved understanding of the cornerstone pieces of scientific knowledge and high-quality publications, and provide novel intervention strategies for targeted therapy and immunotherapy in these unique groups of lymphoid malignancies.