The research interests of Lisa M. Rimsza, M.D., encompass aggressive B-cell lymphomas and the development of clinical molecular diagnostic tools for improved treatment.
Clinical assay development. Lymphoma is a heterogeneous condition that includes over 100 pathologically and clinically distinct malignancies. With the advent of highly sensitive genomic techniques, an increasing number of lymphoid malignancies previously thought to be single disease entities are being resolved into distinct subtypes with significantly different prognoses and survival rates. The emergence of these morphologically indistinguishable subtypes within a given malignancy underscores the clinical need for novel molecular methods for accurate profiling and diagnosis of these malignancies.
Using digital gene expression profiling, Dr. Rimsza and her colleagues developed the cell of origin Lymph2Cx assay to molecularly subtype diffuse large B-cell lymphoma (DLBCL), which comprises three distinct subtypes — namely, GCB, ABC and UNC. Dr. Rimsza subsequently established the first and only College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA)-certified molecular laboratory to offer the Lymph2Cx assay clinically and exclusively to Mayo Clinic patients. This assay is currently undergoing FDA validation for worldwide clinical dissemination. In a similar manner, Dr. Rimsza and her colleagues are pioneers for the development of similar tests within other lymphoid malignancies, including primary mediastinal B-cell lymphoma (PMBCL) and mantle cell lymphoma (MCL).
HIV-related lymphoma. The immunocompromised status of patients with HIV and the inability of their immune systems to execute appropriate responses have long been associated with an increased risk of developing cancer, particularly AIDS-defining cancers including lymphoma. Although the advent of highly efficacious combined antiretroviral therapies (cART) has significantly reduced the rate, individuals with HIV are still 17 times more likely to receive a diagnosis of DLBCL compared with individuals without HIV. Moreover, DLBCL is more aggressive in HIV-positive than HIV-negative cases, frequently presenting at advanced stages with high tumor burdens and poor prognoses.
Original research within Dr. Rimsza's lab examines the transcriptional and genomic differences between lymphomas arising in individuals with HIV versus individuals without HIV. Although immune deregulation is suspected to play a significant role, the lab is predominately interested in altered cancer signaling in the pathogenesis of lymphoma, particularly DLBCL, in individuals with HIV. Preliminary data have shown that HIV-positive DLBCL tumors have augmented DNA damage responses as well as enhanced genomic stability compared with HIV-negative tumors. Additional translational studies to validate these findings are underway, and future in vitro work is planned to identify the mechanisms underlying these observations, as well as novel therapeutic targets.
Immune evasion in lymphoma. Another research focus is the clinical impact and mechanisms of lost major histocompatibility class II (MHCII) antigens in B-cell lymphomas. Loss of expression of these molecules on the surface of lymphoma cells renders the cells unable to present tumor antigens and thus unable to activate the immune system, which results in immune evasion and poor patient survival.
Dr. Rimsza is co-investigator for Genomic Predictors of Early Relapse in Immunochemotherapy-Treated Follicular Lymphoma, a University of Iowa/Mayo Clinic Lymphoma SPORE study which aims to develop a biomarker assay for the identification of patients at high risk of early progression and for which Dr. Rimsza's lab coordinates tissue acquisition.
- Oncogene dysregulation in lymphoma. In immunocompetent DLBCL patients, Dr. Rimsza and her colleagues have documented poor survival when tumors express both MYC and BCL2. The lab also explores the importance of MYC and BCL2 in the context of cells-of-origin, devises mechanisms for detecting these oncogenes, and identifies novel BCL2 antibodies. Dr. Rimsza is the principle investigator directing an international consortium to further this work.
The drive behind Dr. Rimsza's research is to improve the diagnostic and prognostic capabilities of clinicians by arming them with the best diagnostic tools. Better diagnostics means better treatment and, most important, a better quality of life for patients.