Faculty Spotlight: Mechano-sensing Tumor Microenvironments with Guilherme Nader, PhD

Editor’s Note: Meet the diverse, dedicated, and distinctive faculty who are discovering and developing pediatric life-changing solutions at Children's Hospital of Philadelphia Research Institute, in our monthly Faculty Spotlight series. This year, we're learning about the ways our faculty unwind and relax after working hard to improve pediatric health and care. In this Q&A, we meet Guilherme Nader, PhD, an assistant professor in the Department of Pathology and Laboratory Medicine. Stay tuned for more from our Faculty Spotlight series in the new year. 

Why did you choose to focus on your research specialty?

Cell migration constitutes a basic phenomenon critical for both the development and maintenance of life, from embryogenesis to immune responses and tissue healing. It has always fascinated me how such a basic phenomenon can modulate so many biological processes in a living and complex organism. It is commonly appreciated that cells lack space while moving within dense and crowded tissues and dense extracellular matrices.

I’m intrigued by how cells cope with different degrees of physical stress as they explore confining and dense microenvironments. What are the underlying mechanisms that allow cells to move from one organ/tissue to another? How do the mechanical stimuli that cells experience during their migratory process impact their function, fate, and ultimately tissue homeostasis?

Can you tell us about a current research project that you are excited about?

The nucleus is the largest and stiffest organelle in the cell and constitutes a major mechanosensory organelle that translates mechanical input into biochemical signaling. The dense tumor microenvironment (TME) is composed of many cell types and imposes mechanical stress on the cells and their bulky nuclei. Macrophages are one of the most abundant immune cell types in the TME of solid tumors that are often subjected to mechanical stress.

We are currently investigating the consequences of TME-imposed mechanical stress on the nucleus of cancer cells and macrophages. More specifically, we are trying to understand how nuclear mechano-sensing pathways triggered by dense TMEs modulate macrophage function and their crosstalk with cancer cells.

What are the long-term research questions you hope to answer?

We hope to establish a causal link between the activation of nuclear mechano-sensing pathways and the progression of different solid tumors. Furthermore, we would like to use nuclear mechanosensors as biomarkers for cancer prognosis in solid tumors.

What do you enjoy doing in your free time when you’re not working on research?

I love playing soccer with my recreational league, and my favorite professional team is Liverpool. I also enjoy tennis, jogging, and reading a good biography in a coffee shop.

How do you balance your research work with your personal interests?

I always try to build out my schedule and agenda with a good balance between work and my personal interests. Although all my relatives live far in Brazil, they play an important part in my routine and help me keep a good work-life balance, which is essential for everyone.