Project (Shiv K. Singh)

Exploring Epigenomic Plasticity and Immune Interactions in Pancreatic Cancer Subtypes

Our research group at the Clinic for Gastroenterology, Gastrointestinal Oncology & Endocrinology at UMG focuses on the mechanisms underlying the tumor-immune heterogeneity, disease progression, and therapy resistance of pancreatic cancer (PDAC). We specifically explore the role of epigenetic and transcriptional regulators in shaping the interactions between cancer cells and immune cells in the tumor ecosystem, particularly in both therapy-sensitive and therapy-resistant subtypes of PDAC. We investigate the interactions between tumor cells and immune/stromal components, such as inflammatory macrophages, to gain insights into immune evasion, metastasis, and chemoresistance. Our primary objective is to identify epigenetic and immune markers that can assist in patient stratification and the development of personalized treatment strategies for PDAC.
We are seeking a motivated individual for a fully funded PhD position. Our lab offers excellent resources for molecular oncology and access to clinical samples. We encourage applicants who are passionate about cancer biology, genomics, immunology, or translational oncology. While skills in molecular biology, bioinformatics, and cell culture are beneficial, your enthusiasm for learning and collaboration is what matters most. This position involves supervised research, teamwork, experimental design, and data analysis, with numerous opportunities to publish and network at national and international events. For more details, please visit our lab website.

• Urbach L, Wieland L, Penz F, Samuel RD, Küffer S, Klein L, Lenz C, Sax U, Ghadimi M, Schulz-Heddergott R, Hessmann E, Ellenrieder V, Dusetti N, Singh SK (2025). TP53 missense-specific transcriptional plasticity drives resistance against cell cycle inhibitors in pancreatic cancer. Science Advances, 11(27):2339.
  
• Klein L, Tu M, Krebs N, Urbach L, Grimm G, Umair L, Penz F, Blandau A, Xueyan Wu, Samuel RD, Küffer S, Wegwitz F, Chan N, Aliar K, Vyas F, Kishore U, Hessmann E, Trumpp A, Espinet E, Papantonis A, Khokha R, Ellenrieder V, Grünwald BT, Singh SK (2025). Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer. Nature Communications, 16(1):335
  
• Espinet E, Klein L, Puré E, Singh SK (2022). Mechanisms of PDAC subtype heterogeneity and therapy response. Trends in Cancer; 12:1060-1071.
  
• Krebs N, Klein L, Wegwitz F, Espinet E, Maurer C, Tu M, Xu X, Küffer S, Bohnenberger H, Cameron S, Bruner M, Neesse A, Kishore U, Hessmann E, Trumpp A, Ströbel P, Brekken R, Ellenrieder V, Singh SK (2022). Axon Guidance Receptor ROBO3 Modulates Subtype Identity and Prognosis via AXL-associated Inflammatory Network in Pancreatic Cancer. JCI Insight, 16:e154475
  
• Tu M, Klein L, Espinet E, Georgomanolis T, Wegwitz F, Xiaojuan L, Urbach L, Danieli-Mackay A, Küffer S, Bojarczuk K, Mizi A, Günesdogan U, Chapuy B, Gu Z, Kishore U, Neesse A, Ströbel P, Hessmann E, Hahn SA, Trumpp A, Papantonis A, Ellenrieder V, Singh SK (2021). TNFα-producing Macrophages Determine Subtype Identity and Prognosis via AP1 Enhancer Reprogramming in Pancreatic Cancer. Nature Cancer; 2:1185-1203