Brady Lab

Welcome to the Brady Lab

The Brady Lab is part of the Department of Cancer Biology and the Abramson Family Cancer Research Institute in the Perelman School of Medicine at the University of Pennsylvania. Our research program at Penn explores two key areas in cancer biology to understand what fuels cancer cells.

Mapping and Leveraging Metal Signaling in Cancer 

We’re looking beyond the usual nutrients—proteins, fats, and sugars—to examine the contribution of metals to cancer growth. Metals are essential for many cellular processes, supporting the structure and function of DNA, RNA, and a large number of proteins. Our bodies rely on dietary metals, specific transporters to absorb them, and tight regulation to keep metal levels balanced. However, much remains unknown about how metals from our diet fine-tune biological functions or how cells adjust to changes in metal availability. Our research team is investigating these questions by studying how cells maintain metal balance and respond to metal fluctuations, focusing on how metal-protein interactions drive cellular processes by intersecting with cellular metabolic pathways. We’re also exploring whether metal needs shift as stem cells, which drive tissue growth and repair, mature into specialized types or are activated from a resting state to start repairs in a process that can go wrong and may be one of the first steps toward cancer development.  This work could lead to new insights into how metals support tissue health and development, potentially uncovering new ways to treat diseases like cancer where these processes are disrupted.
 

Unlocking the Chemical Space of Cancer-Associated Perturbations

Although detection of genetic differences between cancer and normal cells has led to advances in precision medicine, only a small fraction of patients benefit from these approaches. We’re expanding beyond genetics to focus on proteins, which directly drive cancer initiation, growth, and spread. One reason why previous basic science approaches to monitor proteome rewiring in response to cancer relevant stimuli have failed to deliver of the promise of precision medicine approaches, is perhaps due to the lack of engagement across multiple disciplines. Unfortunately, translation of basic science approaches to monitor changes in oncogenic protein activity as a means to discover tumor cell liabilities and develop molecularly targeted therapeutics has been limited by deficiencies in existing technologies. Penn Therapeutics Mechanisms (PTM), a multidisciplinary team that encompasses expertise in translational oncology, mechanistic tumor cell biology, and chemical biology, was founded in 2019 to develop quantitative approaches that evaluate dynamic changes in the proteome in order to characterize unique features of tumor biology that will motivate novel targeted therapies. By tracking changes in protein function, we can better predict treatment responses, identify new cancer vulnerabilities, and develop targeted therapies. To advance this, we created the Probe Enabled Activity Reporting (PEAR) platform with colleagues from biochemistry, cancer biology, and radiology. PEAR uses a unique probe to capture the full range of proteins in cancer cells, identifying potential drug targets that genetic analysis might miss. This approach could significantly enhance precision oncology and drug discovery, opening doors for better cancer treatments.