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St. Jude Children's Research Hospital Home
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Explore our cutting edge research, world-class patient care, career opportunities and more.
St. Jude Children's Research Hospital Home
Exploring and understanding the cellular and molecular biology of cancer to advance cures
The Cancer Biology Program (CBP) is the only St. Jude Comprehensive Cancer Center (SJCCC) program focused predominantly on discovery research. The goal of the CBP is to explore and understand the cellular and molecular biology of pediatric cancers and to translate discoveries for patient benefit.
We facilitate integrated, multidisciplinary research with four main goals: to identify driver mutations, genetic abnormalities and chromatin modifications as new targets for clinical trials; to explore key cellular processes in cancers that impact oncogenesis; to understand the mechanisms of repair, cell death and survival that can be targeted for cancer treatment; and to advance our understanding of the interplay between the immune system and the tumor microenvironment as a route to therapy.
To achieve these goals, we focus on these four fundamental scientific areas to address the hypothesis that understanding the cell and molecular biology of pediatric cancer will advance patient cures.
Department of Structural Biology
The CBP brings together scientists with expertise in multiple disciplines ranging from genome science and omics to computational, structural and molecular biology to study chromatin structure and modifications, nuclear organization and gene expression. The overarching objective is to comprehensively understand the influence of genomics and epigenomics on pediatric cancers and determine how these factors impact both the cancer cell and its microenvironment. This knowledge is being applied to the identification of novel therapeutic targets and development of innovative model systems for pediatric cancer research.
Our program brings together investigators interested in developmental and signaling pathways and drug development. Members of the CBP have been critical in understanding the role of Sonic Hedgehog (SHH) signaling in medulloblastoma and determining how this information can be translated into new therapeutic approaches to SHH cancers. Focus has also been placed on elucidating the roles of intrinsically disordered proteins in the formation of biomolecular condensates. Researchers are interested in how aberrant condensate formation contributes to fusion oncoprotein-driven pediatric cancers and Myc-driven cancers. The CBP is also studying protein kinases to inform pharmacological approaches to inhibit these cancer-driving enzymes without resistance mutations leading to relapse.
Programmed cell death plays an integral role in cellular homeostasis. Molecular alterations in these pathways are associated with many types of cancers, and pharmaceutical modulation of proteins involved in programmed cell death has proven to be a promising therapeutic strategy.
Members of the CBP are among the world leaders in studies of programmed cell death pathways, including apoptosis and necroptosis. Program members investigate cellular and environmental stress responses, DNA repair pathways, protein and organelle turnover (e.g., through autophagy and biomolecular condensate dynamics) and metabolic processes that cancer cells need to survive. Research in this field has informed the efficacy of inhibitors of BCL-2 family proteins in acute myeloid leukemia, the development of the next generation of MCL-1 inhibitors and other promising approaches to the treatment of pediatric cancer.
Engineering T lymphocytes to express chimeric antigen receptors (CAR-T) has proven to be a powerful addition to the anti-cancer arsenal. However, transformative advances are necessary to avoid issues with this type of immunotherapy, such as a lack of CAR-T cell expansion, T-cell exhaustion, CAR-T cell toxicity and cancer cell evasion strategies.
Members of the CBP are using innovative single-cell methodology, among other approaches, to understand the evolution of an individual’s cancer when engineered CAR-T cells are employed as a treatment strategy. Identifying the major molecular influencers that impact CAR-T cell function is highly illuminating as this information can be leveraged to engineer the next generation of CAR-T cells. Members of the CBP are focused on translating these fundamental discoveries on the biology of T-cells into clinical trials to improve treatment outcomes of patients receiving CAR-T cell therapy and to expand CAR-T cell clinical indications to cancers that have historically responded poorly to this immunotherapy.
The CBP has made impressive contributions to our understanding of basic cancer biology. A number of these findings have been or are being translated into the clinic through collaborations with the disease-oriented Programs within the SJCCC.
The CBP hosts regular meetings with different formats with the purposes of highlighting the breadth of CBP research and discussing key findings, identifying new research questions and enhancing collaborations and promoting career development of junior scientists within the Program.
During weekly CBP meetings, presentations are given by a member of the CBP and either a research trainee or collaborator. This forum provides an opportunity to present current research findings, obtain feedback and explore potential collaborations.
Several trainees and/or laboratory staff members present lectures on their current research relevant to cancer biology. The CBP co-leaders coach participants in presentation skills and facilitate discussion during these sessions. Research Rodeos promote career development of junior scientists within the CBP by preparing them for presentations beyond the SJCCC.
This format features one or two speakers discussing innovative concepts, technologies and/or methodologies relevant to cancer research. Presenters are often SJCCC Shared Resource directors, members of other SJCCC programs, or visitors from other cancer centers. Science Circus sessions serve to heighten awareness of innovative technologies deployed by our Shared Resources and often catalyze new intra- and inter-programmatic collaborations.
In this format, Developmental Funds awardees provide research progress reports. These sessions are particularly impactful because they highlight to the CBP membership the types of collaborative, translational research projects that are supported by Developmental Funds, providing guideposts for others to apply. This mechanism has increased submissions of Developmental Funds applications from CBP members and their intra- and inter-programmatic collaborators.
The CBP hosts an annual retreat with a theme relating to the SJCCC’s Strategic Plan. Examples of prior retreat themes include community outreach, translating discoveries and enhancing collaborations. The retreat consists of keynote speakers from Cancer Center leadership, cutting-edge presentations from trainees and team building exercises.
The Biomolecular Condensates focus group includes researchers studying the biophysical mechanisms that drive phase separation to form condensates. CBP focus group members and their collaborators in other Programs investigate the role of condensates in tumor suppression and how tumor suppression is altered by cancer mutations, how fusion oncoprotein condensates promote oncogenesis in pediatric cancers, contributions of phase separation to nucleolar structure and function and the influence of phase separation by nucleosomes on chromatin organization and regulation.
The Translational Cancer Immunotherapy working group includes investigators across SJCCC research programs engaging in identifying the most promising immune therapies for pediatric cancer and fostering collaborations to bridge and accelerate discoveries and clinical translation.