Through partnerships with her colleagues in bioinformatics, epidemiology and hematopathology, Anne J. Novak. Ph.D., is interested in characterizing the genomic landscape of B-cell lymphomas and identifying new molecules of interest that are relevant to the biology of lymphoma in hopes to identify novel therapeutic targets.
B-cell lymphomas are a heterogeneous group of neoplasms that arise from lymphocytes and produce tumors in the lymph nodes, lymphatic organs and extranodal lymphatic tissue. Lymphoma subtypes are considered to be clonal tumors of immature or mature B cells arrested at various stages of differentiation.
From a tumor genomics perspective, the current understanding supports the hypothesis that lymphomas are aberrant outcomes of normal physiologic mechanisms used by the both the innate and the adaptive immune system. Once B cells have matured from the bone marrow, they migrate to peripheral lymphoid organs where they can go through the germinal center reaction, which includes clonal expansion, somatic hypermutation affecting the variable regions of Ig genes, class-switch recombination, and affinity maturation or apoptosis.
While these physiologic mechanisms allow for the creation of immense antibody diversity and specificity, they come with a trade-off of susceptibility to neoplasia. Chromosomal translocations involving Ig genes and several partners are a hallmark of many lymphoma subtypes. Additional drivers of lymphomagenesis include chromosomal copy number alterations (amplifications and deletions) and somatic mutations.
- Genetic predictors of early clinical failure in diffuse large B-cell lymphoma (DLBCL). Systematically discover, validate and integrate tumor and host genetic biomarkers into actionable clinical information focused on early clinical failures in DLBCL.
- Genomic predictors of early relapse in immunochemotherapy-treated follicular lymphoma (FL). Systematically discover, validate and integrate tumor and host genetic biomarkers into actionable clinical information focused on early clinical failures in high-tumor-burden FL.
- Genomic, transcriptomic and immune profiling of low-grade lymphomas. Use state-of-the-art genomic and immune profiling of low-grade lymphomas to determine if omics can better define pathology and improve therapeutic decisions. Identify a genomic signature that is associated with early clinical failure and can be used to profile the immune signatures of low-grade lymphomas and correlate them with omics or early failure.
- Lymphoma Genome Project. Characterize the genome and transcriptome of newly diagnosed and relapsed refractory follicular and diffuse large B-cell lymphoma in up to 1,000 patients.
Significance to patient care
Dr. Novak uses genetic data to interrogate the biology of novel variants to better understand their contribution to disease pathogenesis and patient outcome. The ultimate goal of these studies is to translate findings into clinical biomarkers of disease outcome and to identify novel biology and therapeutic targets.
- Member, Executive committee, Mayo Clinic Department of Immunology, 2018-present
- Ad hoc member, Mechanisms in Cancer Therapeutics-2 Study Section, National Institutes of Health, 2017-present
- Immunology course leader, Mayo Clinic Alix School of Medicine, 2015-present
- Associate translational chair, hematology Research, Mayo Clinic, 2014-present