Overview
The focus of Dr. Rickman’s lab is to elucidate the role of key oncogenic transcription factors in the biology of prostate cancer with an emphasis on the role of ETS family members and N-Myc in gene regulation and response to treatment. His lab has shown that Aurora-A and N-Myc associate with and stabilize each other in neuroendocrine prostate cancer (NEPC) and generated mechanistic data showing that N-Myc over-expression is associated pro-metastatic, dedifferentiation and Polycomb Repressive Complex deregulated genes (Beltran H, Rickman DS et al., Cancer Discovery 2011; Dardenne E., Beltran, et al. Cancer Cell, 2016, Berger A, Brady N., et al. J. Clinical Investigation 2019). The Rickman lab has developed multiple pre-clinical models over-expressing N-Myc (isogenic cell lines, xenografts, genetically engineered mice and organoid cultures) of NEPC and transitioning CRPC to NEPC in order to determine the molecular features driving these cancer entities. Most recently, his lab has also analyzed epigenetic modifications along with the N-Myc transcriptome, cistrome and chromatin-bound interactome by performing ChIP-seq, RNA-seq and RIME in a combination of mouse models, human prostate cancer cell lines, and NEPC patient-derived organoids and found that the expression of MYCN in CRPC and NEPC patients correlates with reduced overall survival, that the N-Myc cistrome is androgen-dependent and drives a transcriptional program leading to epithelial plasticity and the acquisition of clinically relevant neuronal lineage markers. Interestingly, histone marks specifically associated with lineage-defining genes are epigenetically reprogrammed by N-Myc.
Highlights
- 1Nature communications · 2021
- 2
- 3Cancer research communications · 2023
Publications
Funding
Active
5 grants- MPIR01CA301637-02The role of early oncogenic drivers in maintaining lineage fidelity in prostate cancerNational Cancer Institute · 2025–2030
- KP1614289The role of SPOP mutation in opposing lineage plasticity in neuroendocrine prostate cancerAmerican Urological Association · 2026–2028
- MPIR01CA274963-04"DNMT and TET1 reprogramming as a targetable mechanism of resistance in advanced prostate cancer"National Cancer Institute · 2023–2028
- PIR03CA308672-01Characterizing the cooperative role of E2F1 and interacting proteins in driving advanced prostate cancerNational Cancer Institute · 2026–2028
- Co-I24CHAL11Development and optimization of CEACAM5-targeted alpha emittersProstate Cancer Foundation · 2025–2027
Completed grants (14)
- Sub-PIR01CA234162-05NOTCH signaling controls transformation to androgen independent neuroendocrine prostate cancerNational Cancer Institute · 2019–2025 · via Health Research Inc. & Roswell Park Cancer Institute
- PICI 227883-01Development of Next-Generation Therapeutics for Advanced Prostate CancerChimerix, Inc. · 2022–2024BioPharma Alliance
- KPW81XWH-19-1-0666Transferrin Receptor Identifies a Comprehensive pool of Circulating Tumor Cells with unique molecular features from metastatic Prostate Cancer PatientsU.S. Department of Defense · 2019–2024
- PIR01CA230913-05Defining Molecular Determinants of Lineage Plasticity as a Mechanism of Treatment Resistance in Prostate CancerNational Cancer Institute · 2019–2024
- KPW81XWH2110090Interplay of DNA methylation and histone methylation driving neuroendocrine phenotype in advanced prostate cancerU.S. Department of Defense · 2021–2024No publications yet
- PIW81XWH-17-1-0652Temporal Evolution of N-Myc Signalign and Early Targeting of the Neuroendocrine Phenotype in Prostate CancerU.S. Department of Defense · 2017–2023
- MPIP50CA211024-05Weill Cornell Medicine (WCM) SPORE in Prostate CancerNational Cancer Institute · 2017–2023
- KPPF-20-119-01-TBELineage plasticity as a mechanism of therapy resistance in prostate cancerAmerican Cancer Society · 2021–2023
- Co-IW81XWH-19-1-0403Defining the Potential of Early Molecular Subtypes of Prostate Cancer to Progress to AR-Indifferent DiseaseU.S. Department of Defense · 2019–2022
- Co-I88C-16Subtype-specific modes of clinical and molecular progression in prostate cancerDamon Runyon Cancer Research Foundation · 2019–2022
- PICUI 211812-01Role of lineage dynamics in castration-induced plasticity of prostate carcinoma cellsCornell University - Ithaca · 2021–2021
- PIR01CA179100-05Mechanistic Insights Underlying ERG-Induced Taxane Resistance in Castration-Resistant Prostate CancerNational Cancer Institute · 2014–2020
- Co-IJanssen RAAIdentification of Antibody Therapeutics for Treatment of Neuroendocrine Prostate CancerJanssen Research & Development, LLC · 2016–2019Contract
- PIR21CA143496-02EWOUnderstanding the Biology of Taxane Response in the Context of ETS Rearranged Prostate CancerNational Cancer Institute · 2010–2012
News mentions
- Research Suggests How Tumors Evolve to Become Aggressive Form of Prostate CancerJuly 1, 2021
The genetic changes that underlie an especially lethal type of prostate cancer have been revealed in a new study by investigators at Weill Cornell Medicine. Learning more about what causes this type of cancer, called neuroendocrine prostate cancer (NEPC), could lead to new approaches for treating it.
Mentoring
- RGRichard GarnerCell & Developmental Biology (PhD)
- KDKate DunmoreCell & Developmental Biology (PhD) · Class of 2026
- LVLucie Van EmmenisPostdoc mentee · 2021–2022
- ABAlyssa BagadionCell & Developmental Biology (PhD) · Class of 2020
- SHShih-Bo HuangPostdoc mentee · 2020–2022