What are your current research interests? What is a project you are currently working on?
I am an engineer by training, and my focus is on nuclear mechanics. One of the projects I’m working on is to understand what goes wrong with the mechanical properties of the nucleus in cancer. Pathologists grade cancers based in part on the appearance of the nucleus. The nucleus can lose its smooth regular appearance and develop irregularities in its surface like invaginations, lobulations etc. We have known this for more than a century, but we have little understanding for why the nucleus becomes abnormally shaped in cancer, and how/whether this impacts the process of cancer progression. The nucleus houses the genome, and the way chromosomes are packed in cells seems to have an effect on how genes are expressed. It is possible that abnormal nuclear shapes contribute to changes in gene expression in cancer. We are trying to understand the mechanisms underlying abnormal cancer nuclear shaping in cancer. This involves combining engineering concepts, models and thinking with experimental measurements of mechanical forces on the nucleus and the mechanical properties of the nucleus in living cells, combined with molecular biological studies of gene expression. We are collaborating with Dr. Jon Licht on some of these questions.
Why did you decide to focus on cancer?
I was interested in nuclear mechanics — how the nucleus is positioned and shaped in cells. I was fascinated by nuclear rotation, which is observed in many cell types, and I set out to explain how mechanical torque is generated on the nuclear surface. In talking to my biology colleagues, I realized that the nucleus becomes abnormally shaped in cancer, and that’s how I began interested in cancer research.
What do you want to achieve with your work and/or in your career?
I want to test the extent to which physical properties of the cells and nuclei are important in cancer. If we can explain how nuclei become abnormal in such a diverse variety of cancers, and if we can develop ways to ‘normalize’ nuclear morphology and mechanical properties, that might go a long way in helping us develop new therapeutic approaches to cancer. Beyond cancer, I am very interested in understanding the mechanisms by which cells sense and respond to mechanical forces which are constantly generated in tissues in the body.
What excites you about your work? What is exciting to you about your field right now?
I have found that there is a large number of questions in cell biology, what one could call ‘low-hanging fruit,’ that could be solved with creative infusion of quantitative thinking from the other sciences and engineering technologies. The opportunities for collaborations with biologists who are interested in how physical forces and physical properties of cells might play a role in pathologies are the most exciting thing to me. This is a much underappreciated area that deserves attention.