Josh Andersen

Decoding the Language of Cell Signaling

Cells communicate through an intricate network of signaling pathways that determine whether they grow, divide, migrate, or die. These pathways are controlled by post-translational modifications (PTMs)—chemical modifications that act as molecular switches to regulate protein function. Although modern proteomics has identified more than 500,000 PTMs across the human proteome, we understand the function of only a small fraction of them.

Our lab combines molecular biology, biochemistry, proteomics, structural biology, and computational approaches to discover functional PTMs and understand how they control cell signaling in cancer. By uncovering the mechanisms that regulate tumor growth, survival, and immune responses, we hope to identify new therapeutic vulnerabilities that can be exploited to develop better cancer treatments.

Our research spans several interconnected areas:

Discovering functional PTMs

We develop and apply experimental and computational tools—including quantitative proteomics, 14-3-3 biology, and AlphaFold—to identify previously unknown regulatory PTMs. These discovery platforms generate new projects throughout the lab and have led to studies in kinase regulation, autophagy, immune signaling, and cell-cycle control.

Discovering the mechanisms and functions of understudied kinases

More than one-quarter of the human kinome (roughly 160 kinases) remains poorly characterized despite the central role of kinases in cancer and their importance as drug targets. We investigate the molecular mechanisms that regulate these understudied kinases and their disease-relevant functions. Some of our current work focuses on the ACK family tyrosine kinases (TNK1 and ACK1), combining mechanistic, structural, and translational approaches to uncover new therapeutic opportunities.

Autophagy and innate immunity

Autophagy plays essential roles in cellular homeostasis and immunity, yet many of its regulatory mechanisms remain unknown. We study how autophagy shapes innate immune signaling and explore ways to manipulate this pathway to enhance anti-tumor immunity.

Oncogenic kinase fusions

Many cancers are driven by kinase fusion proteins in which a kinase becomes linked to a non-kinase partner. We investigate how these fusion partners influence kinase localization, signaling, and oncogenic activity, with the goal of understanding why seemingly similar kinase fusions behave so differently in patients and how these insights can guide new targeted therapies.

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Why join our lab?

We are committed to providing a collaborative and supportive training environment where students develop into independent scientists. Students are encouraged to pursue challenging biological questions and cultivate scientific curiosity while gaining expertise across a diverse set of approaches, including molecular biology, biochemistry, quantitative proteomics, computational biology, structural prediction, and cancer cell biology. By integrating multiple disciplines, trainees graduate with the technical skills and scientific perspective needed to tackle complex problems in academia, biotechnology, or medicine.