Overview
Dr. Paraskevi Giannakakou s laboratory focuses on the cellular events that depend on the microtubule cytoskeleton, and on gaining a deeper understanding of the mechanism of action of clinically used microtubule targeting drugs (MTDs) in order to develop more effective and individualized therapies. Dr. Giannakakou s laboratory uses functional cellular and molecular biology assays coupled with highresolution microscopy and live-cell imaging to gain new information on the spatial and temporal regulation of microtubule-cytoskeleton dynamics and its effects on cancer-cell survival. The clinical success of taxanes, and other microtubule inhibitors, together with their broad spectrum of antitumor activity, argue that tubulin represents the single best target identified in clinical oncology. However, today, 15 years following the FDA approval of Taxol for clinical oncology, there is still no understanding of the molecular basis of clinical response to Taxol treatment. Dr. Giannakakou believes that important, heretofore unrecognized, determinant underlying taxane sensitivity is the involvement of the microtubule cytoskeleton in intracellular trafficking and signaling. As such, her laboratory has identified new roles for the microtubule cytoskeleton in the transport and activation of important cancer transcription factors such as the tumor suppressor p53, the hypoxia-inducible factor 1 , and most recently the androgen receptor in prostate cancer. Dr. Giannakakou s laboratory has previously shown that MTDs exert their antiangiogenic effects through significant down-regulation of HIF-1alpha protein levels and transcriptional activity. More recently, her laboratory has demonstrated that the androgen receptor, a major driver of prostate cancer that remains active even after androgen-deprivation therapy, traffics on microtubule tracks for its translocation from the cytoplasm to the nucleus where it activates target genes such as PSA. Her team has also showed that MTDs, by disrupting the microtubule cytoskeleton, sequester the androgen receptor within the cytoplasm, therefore inhibiting its subsequent transcriptional activation. These results provide a rationale for why the taxanes represent the sole class of chemotherapy agents that improves survival of metastatic prostate cancer patients. [...]
Highlights
- 1Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
- 2eLife · 2022
- 3
Publications
Funding
Active
4 grants- Sub-PIR01CA266704-04Enhancing the Efficacy of Docetaxel in Prostate CancerNational Cancer Institute · 2022–2027 · via Beth Israel Deaconess Medical Center, Inc.
- Sub-PIR44CA290913-03Development of Small Molecule therapeutics targeting AR-V7 for prostate cancer.National Cancer Institute · 2024–2027 · via Arma Bio, Inc.
- PIBP 242175-02First-in-Class Dual AR-V7/AR-fl Molecular Glue Degrader for Prostate Cancer TreatmentDaedalus Fund for Innovation (Weill Cornell) · 2024–2027BioPharma Alliance
- Co-IW81XWH-20-1-0706Heating cold prostate tumors with PSMA-targeted alpha therapy and pembrolizumabU.S. Department of Defense · 2020–2026
Completed grants (17)
- Co-IW81XWH-18-1-0527Molecular and clinical correlates with prostate-specific membrane antigen (PSMA)-targeted radionuclide therapyU.S. Department of Defense · 2018–2024
- PIW81XWH-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
- MPIR01CA228512-05A novel, short isoform of the +TIP microtubule (MT) binding protein CLIP170 confers taxane resistance by obstructing the MT pore.National Cancer Institute · 2018–2024· 2 renewals
- Sub-PI75N91022C00062Automated Rapid Dual-Extraction of DNA and RNA from Single Cells in MicroplatesNational Cancer Institute · 2022–2024 · via Inso Biosciences, Inc.
- PICU 231248-01Nanostructure-Enhanced Infra-Red Absorption Spectroscopy (NEIRAS) assay to improve Prognosis and Personalized Therapy of Drug-resistant Prostate CancersCornell University - Ithaca · 2023–2023
- KPP50CA211024-05Weill Cornell Medicine (WCM) SPORE in Prostate CancerNational Cancer Institute · 2017–2023
- MPIT32CA203702-05Molecular and Translational Oncology ResearchNational Cancer Institute · 2017–2023Training
- PIBP 214751-01Development of Selective Small Molecule AR-V7 Inhibitors for Prostate Cancer TreatmentDaedalus Fund for Innovation (Weill Cornell) · 2021–2023BioPharma Alliance
- PIR21CA216800-02Biomarkers of Taxane Chemotherapy Response/Resistance in Prostate CancerNational Cancer Institute · 2018–2021
- Co-IDU 14111569-01Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men With Metastatic CancerProstate Cancer Foundation · 2014–2020 · via Duke University
- PIR01CA177165-05Microtubule-Regulated RNA Translation: Implications for Taxane ChemotherapyNational Cancer Institute · 2014–2020
- Co-IR01CA179100-05Mechanistic Insights Underlying ERG-Induced Taxane Resistance in Castration-Resistant Prostate CancerNational Cancer Institute · 2014–2020
- PIR01CA137020-05EWOMicrotubule Dependent AR Signaling Predicts Taxane SensitivityNational Cancer Institute · 2009–2016
- KPU54CA143876-05 EWCenter on the Microenvironment and MetastasisNational Cancer Institute · 2009–2015 · via Cornell University - Ithaca
- PIR01CA100202-05Antitubulin drugs: Mechanisms of action and resistanceNCI · 2003–2009 · via NIH RePORTER
Available technologies
News mentions
- WCM Investigators Empowering Cancer Researchers with AIApril 13, 2026
A team of Weill Cornell Medicine investigators is working to cross-train the next generation of cancer researchers in cancer biology and the use of artificial intelligence tools for research.
- Prostate Cancer Foundation Awards Grants to Weill Cornell Medicine InvestigatorsMarch 26, 2026
Six researchers from Weill Cornell Medicine have received Young Investigator Awards from the Prostate Cancer Foundation.
- Study Identifies Gene Linked to Chemotherapy Resistance in Prostate CancerMarch 10, 2026
A gene called FOXJ1 may drive resistance to taxane chemotherapy during treatment for advanced prostate cancer, according to a new study led by investigators at Weill Cornell Medicine and Beth Israel Deaconess Medical Center.
- Innovators Encourage Scientists and Physicians to Dive into Technology CommercializationJanuary 9, 2025
In its eighth year, the annual Dean's Symposium on Innovation and Entrepreneurship celebrates innovation and Weill Cornell Medicine’s entrepreneurial spirit, while encouraging and motivating the next generation of innovators, inventors and entrepreneurs.
- Protein Variant Identified that Renders Chemotherapy Ineffective in Gastric CancerDecember 6, 2021
A new protein variant underlies the ability of gastric cancers to resist an otherwise effective family of chemotherapy drugs, according to a study by a multidisciplinary team at Weill Cornell Medicine. The results suggest a treatment strategy that could improve the prognoses of many patients with cancer.
Show 1 more mention
- Al Algorithm Predicts Drug Targets, Leads to Promising Results for Experimental Cancer TreatmentJanuary 2, 2020
Weill Cornell Medicine scientists have developed a machine-learning algorithm capable of predicting biological targets of prospective drug molecules.
Mentoring
- NANaira Abou-GhaliPharmacology (PhD) · Class of 2025
- EMEiman MukhtarPostdoc mentee · 2020–2020
- SKSeaho KimPostdoc mentee · 2019–2019
External relationships
Ownership
Arma Bio, Inc.
Professional Services
Arma Bio, Inc.