ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Dharma Pally is first author on ‘ The novel ECM protein SNED1 mediates cell adhesion via the RGD-binding integrins α5β1 and αvβ3’, published in JCS. Dharma is a postdoctoral research associate in the lab of Alexandra Naba at University of Illinois Chicago, USA. His research interest in the Naba lab focuses on deciphering the molecular mechanisms by which SNED1 regulates breast cancer cell migration during metastasis and neural crest cell migration during craniofacial development.
Dharma Pally
How would you explain the main findings of your paper in lay terms?
The extracellular matrix (ECM) is made of over 100 proteins that assemble to form a scaffold outside the cells. The ECM is vital to cellular function and plays key roles in both health and disease. Our laboratory has identified a novel ECM protein called SNED1 and found that it is important for driving cell movement during embryonic development and breast cancer metastasis. When I started my position in the Naba lab, the mechanisms by which SNED1 affects cell movement were unknown. In this publication, we discover that cells can stick to SNED1 by engaging specific cell surface proteins called integrins. Using different assays, we pinpoint two specific integrins, α5β1 and αvβ3, which mediate cell attachment to SNED1. This work lays a foundation for future work aimed at understanding how cell attachment to SNED1 influences cell movement during development and cancer metastasis.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Most of the challenges we encountered during this project were technical in nature. This project relied on our ability to purify SNED1 to perform cell adhesion assays. When I started, our lab lacked expertise in large-scale protein purification with minimal or no batch-to-batch variation. We overcame the initial difficulty through several consultations with collaborators and staff at our protein core facility. Additionally, I had to optimize the cell adhesion assay, as it had never been performed in the lab before. By reading scientific literature and having discussions with my mentor and colleagues, I was able to successfully optimize the assay.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
There were several ‘eureka’ moments throughout the study. One moment I will never forget occurred during the initial phase of the work, when I observed that SNED1 mediated cancer cell adhesion. This was the first time anyone had demonstrated that SNED1 is an adhesive ECM protein. This observation motivated us to identify the first cell surface receptors of SNED1 – integrins α5β1 and αvβ3.
Graph showing the adhesion of cells to SNED1. MDA-MB-231 ‘LM2’ metastatic breast cancer cells are the pink line and O9-1 neural crest cells the black line.
Graph showing the adhesion of cells to SNED1. MDA-MB-231 ‘LM2’ metastatic breast cancer cells are the pink line and O9-1 neural crest cells the black line.
Why did you choose Journal of Cell Science for your paper?
Journal of Cell Science is a highly regarded journal that publishes cutting-edge cell biology research. Its expert scientific editors ensure a rigorous and high-quality peer review process, which motivated us to select this journal. We also aimed to reach a broad readership, which JCS provides. Importantly, the journal offers free access to articles in lower-income countries, making science accessible to everyone, which is important to me. Finally, I personally appreciate the journal's commitment to early-career researchers, as exemplified by opportunities such as this interview.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
I have been lucky to meet several inspiring people throughout my scientific career. Here, I would like to mention two of them: Dr Ramray Bhat, my thesis advisor at the Indian Institute of Science, who introduced me to ECM biology, and Dr Alexandra Naba, my current mentor and a leading expert in ECM biology. Under Dr Naba's mentorship, I have learned to approach my work at the bench with both creativity and rigor, to critically evaluate my findings, and to gain a deep understanding of the field of ECM biology.
What's next for you?
I am excited to take this project forward and identify the molecular mechanisms by which SNED1 drives cancer cell and neural crest cell migration.
Tell us something interesting about yourself that wouldn't be on your CV
I am an amateur photographer. During my free time, I like to walk around my neighborhood or nearby parks to photograph wildlife, nature and urban landscapes. I am also fascinated by the stars and have recently started visiting places with the darkest skies to photograph them.
Dharma Pally's contact details: 1853 W Polk St., CMWT Suite 522, Chicago, IL 60612, USA.
E-mail: [email protected]
