AG: Genetic Variants of Proximal Signaling

Our Research Philosophy: Our mission is to uncover new biology unique to human genetic variants and advance indvidualized medicine (iMed) in cancer and autoimmunity by identifying next-generation therapeutic targets.

Current approaches to personalized medicine primarily focus on analyzing tumor DNA to align tumor-specific mutations with approved therapies. While promising, this strategy has significant limitations: only 30% of cancers with driver mutations—representing approximately half of all cancers—have approved treatments, translating to an overall effectiveness of just 15% across all cancers. In effect, 85% of cancer patients remain without the benefits of personalized medicine.
To address this unmet need, this research working group led by Dr. Vijay K. Ulaganathan is dedicated to identifying therapy-relevant germline genetic variants to enhance personalized treatment strategies for cancer patients. We posit that genetically determined membrane-proximal signaling pathways play a significant role in both tumor-intrinsic and tumor-extrinsic mechanisms. These mechanisms contribute to variations among individuals (referred to as individuality) in cancer traits, including anti-tumor immune responses, cancer progression, and sensitivity to therapies like chemotherapy and immunotherapy. Despite their critical role, the functional implications of many cancer-associated human germline genetic variants in immune and oncogenic signaling pathways are not well understood, which poses a substantial knowledge gap that hinders the advancement of precision oncology. To address this gap in knowledge, the research group within the Molecular Genetic Division of the Institute for Medical Genetics and Applied Genomics (IMGAG) engages in clinically oriented basic science research. This research aims to provide foundational insights into how specific genetic variants alter signaling mechanisms, particularly in immune and oncogenic molecular signaling pathways.
Our work is the cornerstone of individualized Signaling Biology (iSignBio)—a novel field dedicated to unraveling the intricate interplay between genetic individuality and signaling biology. Through our efforts, we aim to advance the field of personalized medicine and enhance therapeutic outcomes for the many patients who are currently underserved by existing approaches.

Collaboration with Clinicians: We are eager to collaborate with clinicians interested in gaining hypothesis-driven, mechanistic insights into genetic variants associated with disease or therapy. We also welcome opportunities to contribute to case-study manuscripts. Our approach combines molecular cell biology and immunology experiments, using genome editing and synthetic biology approaches to generate cells expressing patient-specific receptor variants. This helps us understand the mechanistic signaling pathways underlying the associations between genetic variants and cancer traits, including anti-tumor immune responses, cancer progression, and therapy sensitivity, across both chemotherapy and immunotherapy.

Internship/Praktikum/Thesis Opportunities available: We are always looking for enthusiastic students to engage in Internship (Praktikum), Bachelor's, or Master's research projects. If you're interested, feel free to contact me for more information about these opportunities.