Don Nguyen, PhD, BSc
Associate Professor of Pathology and Medical Oncology; Co-Leader, Cancer Signaling Networks, Yale Cancer Center
Research & Publications
Biography
News
Locations
Research Summary
Cancer metastasis remains an unresolved clinical and biological problem. This is particularly relevant in the case of thoracic malignancies, which can spread aggressively to distant organs with limited opportunity for effective therapeutic intervention. Metastatic cancer cells are believed to acquire complex biological properties by deregulating pleiotoropic molecular programs and interacting with their microenvironment. My laboratory is interested in uncovering the genetic, epigenetic, cellular, and physiological determinants of metastasis by different lung cancer subtypes. Lung cancers as well as other tumor types such as breast cancer and melanoma most notably metastasize to the central nervous system. We are therefore also studying how the unique brain microenvironment alters the therapeutic response of disseminated tumor cells across different cancers. In our endeavors, we utilize a variety of approaches such as animal modeling, human biospecimen research, functional genomics, cell biology, and bioinformatics.
Coauthors
Research Interests
Inflammation; Neoplasm Metastasis; Pathology; Genomics; Epigenomics; Tumor Microenvironment; Neoplasm Micrometastasis
Public Health Interests
Cancer; Genetics, Genomics, Epigenetics
Research Image
Co-option of the brain microenvironment by metastatic lung cancer cells
Soon after lung cancer cells (in green) disseminate into the brain, they can utilize extracellular matrix molecules (in red) derived from resident stromal cells (white) to shield themselves from the hostile surroundings.
Selected Publications
- Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancerAdua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.
- Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain MetastasisWingrove E, Liu ZZ, Patel KD, Arnal-Estapé A, Cai WL, Melnick MA, Politi K, Monteiro C, Zhu L, Valiente M, Kluger HM, Chiang VL, Nguyen DX. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. Cell Reports 2019, 27: 1277-1292.e7. PMID: 31018140, PMCID: PMC6592283, DOI: 10.1016/j.celrep.2019.03.085.
- Tumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6Arnal-Estapé A, Cai WL, Albert AE, Zhao M, Stevens LE, López-Giráldez F, Patel KD, Tyagi S, Schmitt EM, Westbrook TF, Nguyen DX. Tumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6. Oncogene 2020, 39: 3726-3737. PMID: 32157212, PMCID: PMC7190573, DOI: 10.1038/s41388-020-1246-z.
- Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulationCai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.
- Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIsColclough N, Chen K, Johnström P, Strittmatter N, Yan Y, Wrigley GL, Schou M, Goodwin R, Varnäs K, Adua SJ, Zhao M, Nguyen DX, Maglennon G, Barton P, Atkinson J, Zhang L, Janefeldt A, Wilson J, Smith A, Takano A, Arakawa R, Kondrashov M, Malmquist J, Revunov E, Vazquez-Romero A, Moein MM, Windhorst AD, Karp NA, Finlay MRV, Ward RA, Yates JWT, Smith PD, Farde L, Cheng Z, Cross DAE. Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs. Clinical Cancer Research 2021, 27: 189-201. PMID: 33028591, DOI: 10.1158/1078-0432.ccr-19-1871.
- Control of Alveolar Differentiation by the Lineage Transcription Factors GATA6 and HOPX Inhibits Lung Adenocarcinoma MetastasisCheung WK, Zhao M, Liu Z, Stevens LE, Cao PD, Fang JE, Westbrook TF, Nguyen DX. Control of Alveolar Differentiation by the Lineage Transcription Factors GATA6 and HOPX Inhibits Lung Adenocarcinoma Metastasis. Cancer Cell 2013, 23: 725-738. PMID: 23707782, PMCID: PMC3697763, DOI: 10.1016/j.ccr.2013.04.009.
- Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancerde Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, DOI: 10.1016/j.ccell.2023.07.005.
- Epigenetic markers and therapeutic targets for metastasisKravitz C, Yan Q, Nguyen D. Epigenetic markers and therapeutic targets for metastasis. Cancer And Metastasis Reviews 2023, 42: 427-443. PMID: 37286865, DOI: 10.1007/s10555-023-10109-y.
- Melanoma central nervous system metastases: An update to approaches, challenges, and opportunitiesKarz A, Dimitrova M, Kleffman K, Alvarez‐Breckenridge C, Atkins MB, Boire A, Bosenberg M, Brastianos P, Cahill DP, Chen Q, Ferguson S, Forsyth P, Oliva I, Goldberg SB, Holmen SL, Knisely JPS, Merlino G, Nguyen DX, Pacold ME, Perez‐Guijarro E, Smalley KSM, Tawbi HA, Wen PY, Davies MA, Kluger HM, Mehnert JM, Hernando E. Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. Pigment Cell & Melanoma Research 2022, 35: 554-572. PMID: 35912544, PMCID: PMC10171356, DOI: 10.1111/pcmr.13059.
- Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSFCheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, Nguyen D, Patel A, Chiang V. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precision Oncology 2021, 5: 163-172. PMID: 34250381, PMCID: PMC8232069, DOI: 10.1200/po.20.00292.
- Specific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brainCai WL, Greer CB, Chen JF, Arnal-Estapé A, Cao J, Yan Q, Nguyen DX. Specific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain. BMC Medical Genomics 2020, 13: 33. PMID: 32143622, PMCID: PMC7060551, DOI: 10.1186/s12920-020-0695-0.
- Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of MicrometastasesStevens LE, Cheung WKC, Adua SJ, Arnal-Estapé A, Zhao M, Liu Z, Brewer K, Herbst RS, Nguyen DX. Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases. Cancer Research 2017, 77: 1905-1917. PMID: 28196904, PMCID: PMC5468792, DOI: 10.1158/0008-5472.can-16-1978.
Clinical Trials
| Conditions | Study Title |
|---|---|
| Lung | Determining Mechanisms of Sensitivity and Resistance to Anti-Cancer Therapy for Advanced Lung Cancer |