Rodriguez-Bravo Research

Contact

Name: Veronica Rodriguez-Bravo, PhD
Position: Professor

233 10th Street
Philadelphia , PA 19107

Telephone: 215-503-9881
HomeImage Transmission electron microscopy imaging showing in detail Nuclear Pores (NPC) in the nuclear envelope of tumor cells. Red arrow points one NPC (Top left). Diagram of Nuclear Pore Complex and protein components, nucleoporins (Nups) (Top right). Fluorescence microscopy images of mitotic protein Mad1 localization to NPCs. Magnified images show in detail colocalization of Mad1 with a NPC marker. (Green, Mad1; Red, NPC; blue,DNA) (Rodriguez-Bravo Lab images).

The Rodriguez-Bravo laboratory studies nuclear hubs controlling genome functions including transcription and genome stability and their role in prostate cancer. Specifically, they focus on the mechanisms by which Nuclear Pore Complex (NPC) proteins called nucleoporins (Nups) contribute to prostate cancer aggressiveness modulating different biological processes such as nuclear-cytoplasmic transport, gene expression or genome stability. Recent work from the laboratory described for the first time clinically relevant changes in NPC composition during prostate cancer disease progression and identified POM121 as a key Nup promoting lethal PC aggressiveness by enhancing nuclear transport of oncogenic and prostate specific transcription factors (Cell 2018). Another active area of work is the investigation of genome aberrations tolerance mechanisms in lethal prostate cancer. The lab uses multidisciplinary approaches applying genetic, single-cell high-resolution microscopy, biochemical, transcriptomic, proteomic, epigenetic and computational analysis to decipher novel molecules and mechanisms contributing to PC progression in cell models, preclinical patient-derived in vitro (organoids), in vivo xenograft (PDX) models and patient tumor tissues samples. The overarching goal is to unveil novel nuclear networks modulating gene expression and chromosomal stability in aggressive prostate cancer to define novel molecular targetable vulnerabilities for prostate cancer treatment.

Research Projects

Study of Nuclear Pore-regulated Mechanisms in Prostate Cancer.

ProjectOne Representative transmission electron microscopy imaging of localized and advanced metastatic human prostate cancer tumors. Insets display details of nuclear pores perforating the nuclear envelope (scale bar, 5 μm).

Nuclear pore complex (NPC) defects have been identified in a variety of human cancers and linked to oncogenesis however their mechanistic contribution to cancer pathogenesis remains ill-defined. NPCs are nucleocytoplasmic gateways piercing the nuclear envelope (NE) control selective transport of molecules between the nucleus and the cytoplasm. Nucleoporins (NUPs), NPC protein components, have been involved in many other essential biological processes such as genome integrity, chromatin organization or gene expression. However, despite NE and NPC defects being described as classical features of cancer cells, the specific NPC-regulated mechanisms contributing to cancer pathogenesis remains underexplored. Our lab is performing comprehensive studies interrogating the specific Nup-regulated mechanisms that contribute to prostate cancer cell aggressiveness. Integrating transcriptomics, genetics cell biology approaches and validation in patient tumor samples we aim to decipher new mechanisms important in lethal prostate cancer.

Mechanisms of Genome Instability Tolerance in Lethal Prostate Cancer.

ProjectTwo Immunofluorescence microscopy image of prostate cancer cells in culture. A) Cell performing normal anaphase during mitosis. B-D) Cells displaying mitotic errors during chromosome segregation that can lead to chromosomal instability and aneuploidy (Green, tubulin; Red, centromeres; Blue, DNA)(Rodriguez-Bravo Lab image.

The laboratory is interested in understanding mechanistically the roads leading to chromosomal instability and aneuploidy tolerance in aggressive prostate cancer. We combine molecular biology, genetics and proteomics with cancer biology, computational analysis and patient tissue sample validation.

Analyzing cell division and chromosome segregation mechanisms at the single cell level in prostate cancer models allows us more detailed study of how highly aggressive cancer cells  maintain genome stability and to evaluate real time their responses and survival to standard chemotherapy, such as classic anti-mitotic agents called taxanes, used in the treatment of metastatic prostate cancer. Our ultimate goal is to determine novel mechanisms that could serve as targetable vulnerabilities in advanced prostate cancer.