Nguyen, Phuong-Hien - CAP 19

Deciphering the functional relevance and signal transduction network of protein kinases in the tumor microenvironment

Dr. Phuong-Hien Nguyen
Dr. Phuong-Hien Nguyen

Department I of Internal Medicine

CMMC - PI - A 09 and CAP 19

hien.nguyen@uk-koeln.de

+49 221 478 84120

Lab Website

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed

Department I of Internal Medicine

Joseph-Stelzmann Str. 26

50931 Cologne

Introduction

Tremendous advances in cancer therapy have been made with the development of kinase inhibitors targeting protein kinases, with prominent examples being inhibitors of oncogenic receptor kinases that have substantially improved patient outcomes. 

The definition of cancer hallmarks has significantly expanded in the last decades and cancer is no longer considered a disease of only malignant cells, but a highly complex tissue comprising tumor cells and their tumor microenvironment (TME). All components of the TME interact with tumor cells and with each other in a complex multidirectional manner to promote malignant progression. 

Our research is based on the finding that tyrosine kinases are also functionally essential for the creation of a proneoplastic, microenvironmental niche. The distinct, cell-type specific patterns of substrate activation induced by kinases may lead to a differential activation of transcription factors and, as a consequence, to a cell type-specific modulation of cellular functions.

Figure 1

Fig. 1: The TME strongly influences fundamental processes of leukemia pathogenesis, generating an inflammatory milieu, steering tumor cell homing, inducing tumor cell proliferation and survival, and driving immune evasion (vom Stein et al., Semin Hematol 2023).

Figure 2

Fig. 2: This figure illustrates the consensus interactions between various immune cell subsets and metastatic tumor cells, providing an overview of the immune dynamics in brain metastasis (Schreurs et al., Neuro-Oncology 2024).

Clinical Relevance

Because many kinase inhibitors are readily available, understanding these kinases’ functions in the TME will be useful to design improved anti-cancer therapies, particularly to target the immune- and metastatic niches.

Approach

Employ and combine state-of-the-art methodologies including CRISPR/Cas9-based screening, high-throughput functional assays, complex model systems and advanced drug delivery methods to investigate the interactions of tumor cells and their respective immune microenvironment, aiming to identify actionable targets in the TME across multiple cancer entities.

Lab Website

For more information, please check Laboratory for tumor-host interdependence at University Hospoital Cologne or check the Research Website. 

Affiliations

Publication Record on PubMed - Phuong-Hien Nguyen

2025
  • Schreurs LD, Vom Stein AF, Jünger ST, Timmer M, Noh KW, Buettner R, Kashkar H, Neuschmelting V, Goldbrunner R, Nguyen PH. The immune landscape in brain metastasis. Neuro Oncol. 2025 Jan 12;27(1):50-62. doi: 10.1093/neuonc/noae219. PMID: 39403738; PMCID: PMC11726252.
2024
  • Iqbal S, Schneider TK, Truong TT, Ulrich-Muller R, Nguyen PH, Ilyas S, and Mathur S (2024). Carriers for hydrophobic drug molecules: lipid-coated hollow mesoporous silica particles, and the influence of shape and size on encapsulation efficiency. Nanoscale16, 11274-11289. doi:10.1039/d4nr01420k.
     
  • Jestrabek H, Kohlhas V, Hallek M, and Nguyen PH (2024). Impact of leukemia-associated macrophages on the progression and therapy response of chronic lymphocytic leukemia. Leuk Res143, 107531. doi:10.1016/j.leukres.2024.107531.
     
  • Vom Stein AF, Hallek M, Nguyen PH. Role of the tumor microenvironment in CLL pathogenesis. Semin Hematol. 2024 Jun;61(3):142-154. doi: 10.1053/j.seminhematol.2023.12.004. Epub 2023 Dec 26. PMID: 38220499.
2023
  • Braun T, Pruene A, Darguzyte M, Vom Stein AF, Nguyen PH, Wagner DL, Kath J, Roig-Merino A, Heuser M, Riehm LL, Schneider A, Awerkiew S, Talbot SR, Bleich A, Figueiredo C, Bornhauser M, and Stripecke R (2023). Non-viral TRAC-knocked-in CD19(KI)CAR-T and gp350(KI)CAR-T cells tested against Burkitt lymphomas with type 1 or 2 EBV infection: In vivo cellular dynamics and potency. Front Immunol 14, 1086433. doi:10.3389/fimmu.2023.1086433.
     
  • de Oliveira TD, Vom Stein A, Rebollido-Rios R, Lobastova L, Lettau M, Janssen O, Wagle P, Nguyen PH, Hallek M, and Hansen HP (2023). Stromal cells support the survival of human primary chronic lymphocytic leukemia (CLL) cells through Lyn-driven extracellular vesicles. Front Med (Lausanne) 9, 1059028. doi:10.3389/fmed.2022.1059028.
     
  • Flumann R, Hansen J, Pelzer BW, Nieper P, Lohmann T, Kisis I, Riet T, Kohlhas V, Nguyen PH, Peifer M, Abedpour N, Bosco G, Thomas RK, Kochanek M, Knufer J, Jonigkeit L, Beleggia F, Holzem A, Buttner R, Lohneis P, Meinel J, Ortmann M, Persigehl T, Hallek M, Calado DP, Chmielewski M, Klein S, Gothert JR, Chapuy B, Zevnik B, Wunderlich FT, von Tresckow B, Jachimowicz RD, Melnick AM, Reinhardt HC, and Knittel G (2023). Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies. Blood Cancer Discov 4, 78-97. doi:10.1158/2643-3230.BCD-22-0007.
     
  • Vom Stein AF, Hallek M, and Nguyen PH (2023). Role of the tumor microenvironment in CLL pathogenesis. Semin Hematol. doi:10.1053/j.seminhematol.2023.12.004.
     
  • Vom Stein AF, Rebollido-Rios R, Lukas A, Koch M, von Lom A, Reinartz S, Bachurski D, Rose F, Bozek K, Abdallah AT, Kohlhas V, Saggau J, Zolzer R, Zhao Y, Bruns C, Brockelmann PJ, Lohneis P, Buttner R, Haupl B, Oellerich T, Nguyen PH, and Hallek M (2023). LYN kinase programs stromal fibroblasts to facilitate leukemic survival via regulation of c-JUN and THBS1. Nat Commun 14, 1330. doi:10.1038/s41467-023-36824-2.

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