Biography
Margaret A. Shipp, M.D. is an Associate Professor of Medicine at Harvard Medical School and the Director of the Lymphoma Program at both the Dana-Farber Cancer Institute and the newly expanded Dana-Farber/Harvard Comprehensive Cancer Center. Dr. Shipp obtained her medical degree from Washington University School of Medicine and completed her residency in Internal Medicine at Barnes Hospital in St. Louis, Missouri. Thereafter, she completed a fellowship in Medical Oncology at the Dana-Farber Cancer Institute and subsequently joined the faculty. Dr. Shipp’s clinical and laboratory research focuses on the clinical and molecular heterogeneity of the most common lymphoid malignancy, diffuse large B-cell lymphoma (DLBCL). Dr. Shipp coordinated the development of the International Prognostic Index which is used worldwide to individualize treatment approaches to DLBCL and other aggressive lymphomas. More recently, she has led efforts to identify and evaluate rational treatment targets in DLBCL. Dr. Shipp is the recipient of numerous awards including an American Cancer Society Junior Faculty Award, a Leukemia Society of America Scholar Award, membership in the American Society of Clinical Investigation and designation as a Stohlman Scholar of the Leukemia and Lymphoma Society of America.
Abstract
Rational Risk-Related Treatment Strategies in Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is currently curable in only 40% of patients. Clinical prognostic factor models such as the International Prognostic Index identify patients who are unlikely to be cured with standard therapy. However, these clinical models do not provide additional insights regarding more effective treatment strategies. In the absence of molecular insights into the observed heterogeneity of DLBCL, therapeutic approaches to "high-risk" patients have largely focused on modifying doses and schedules of conventional chemotherapeutic agents and adding stem cell support. However, these approaches have not significantly improved DLBCL patient survival, underscoring the need to identify more rational, molecularly defined approaches to treatment. The clinical features used to identify "high-risk" DLBCL are likely to be surrogate variables for intrinsic molecular heterogeneity in the disease. For this reason, we have used a variety of approaches to define the molecular bases for outcome differences, characterize biologically discrete subsets of DLBCL and identify rational treatment strategies in the disease. Most recently, we have successfully utilized gene expression profiling and supervised learning methods to predict outcome and identify novel treatment targets in a pilot series of patients with DLBCL. We propose to build upon our previous studies to:
- Define molecular signatures of cured versus fatal disease;
- Characterize the contribution of cell of origin and specific signaling pathways to these outcome signatures; and
- Utilize the molecular signatures of relapsed and newly-diagnosed high-risk DLBCL to develop rational risk-related approaches to therapy.
To accomplish these goals, we will work closely with colleagues from the university-wide DF/HCC Lymphoma Program with specific expertise in hematopathology, genomics/bioinformatics, biostatistics and basic B-cell biology. In the 5-yr funding period of this grant, our goal is to dramatically increase the cure rate in DLBCL by developing therapeutic strategies based on newly-identified rational targets and testing these approaches in the clinic.