Dhiman Sankar Pal
I did my postdoctoral research with Peter Devreotes in the Department of Cell Biology. Traditionally, research in the Devreotes lab has been focused on chemotaxis using the soil amoeba Dictyostelium as the model organism of choice. Chemotaxis is the directed movement of cells along extracellular gradients, which plays an important role in development and immunity. Although chemotaxis studies of the model system have been invaluable, there has been an urgent need to understand mechanisms of migration in immune cells for the research to be useful to human health and disease. Since studies in immune cell lines are technically more difficult than in the model system, it has discouraged all but a few laboratories from making significant progress in these cellular systems.
When I joined Peter’s lab, I saw this roadblock as an opportunity to make fundamental discoveries in the field whilst honing my technical and analytical skills. To this end, I developed new approaches for powerful optogenetic studies in human neutrophils and macrophages. With these optical tools, I elucidated the role of the Ras/PI3K/Akt pathway in immune cell migration. Ras signaling is typically associated with cell growth, but not direct regulation of motility or polarity. However, my studies demonstrated that local activation of Ras-mediated classical growth-control pathways directly modulate actin polymerization, cell shape and migration modes. Thus, my work provided the first mechanistic description of the role of Ras GTPases and Akt in directly controlling human cell migration. I further continued my pursuit of the role of Ras growth pathways in immune cell migration by noting the effects of locally inhibiting Ras GTPases. Based on my previous results, we expected that suppressing Ras activity would stop migration. But I saw the opposite: Reducing Ras activity on the cell membrane polarized cells and improved their migratory ability by increasing actomyosin contractility at the back. The surprising ability of Ras inhibition to promote migration presents a warning that targeting Ras to inhibit proliferation could have the unanticipated effect of promoting migration and metastasis.
Questions & Answers
Why did you choose Johns Hopkins for your work?
During my graduate studies, I tried to understand the molecular basis of how intracellular pathogens negotiate the harsh phagolysosomal environment of host immune cells. For my postdoctoral work, I was interested to look at host-pathogen interaction from the point of view of the host, specifically in the context of immune cell migration. And what better place to understand the signaling mechanisms governing cell migration than the Devreotes lab at Johns Hopkins! In addition to the expertise, Johns Hopkins attracted me with its rich history of basic/biomedical research and funding.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
It is a huge honor for me to be selected by a committee of accomplished scientists for this award. It will surely be helpful for my career progression. The fact that this award is named after none other than the great biochemist Albert Lehninger gives me added satisfaction, as well as motivation to do more impactful work!
What contributed to your project’s success?
The Devreotes lab has a friendly and collaborative environment, which I believe has played a substantial role in the development of my multiple projects. I would like to point out that my adviser Peter Devreotes’ holistic approach to data analysis and big-picture thinking has greatly helped my work. Additionally, collaboration with Pablo Iglesias at the Whiting School of Engineering and discussions with Douglas Robinson in our department have proven to be highly productive. I am also thankful to the Microscope Facility at the school of medicine, where I was able to generate all the beautiful movies for my papers! Finally, the versatile training in biochemistry/molecular biology/cell biology that I received during my Ph.D. with Rupak Datta at the Indian Institute of Science Education and Research Kolkata, drove this work to its success.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
I think it is a wonderful platform to have brilliant students and fellows present their work in front of the Johns Hopkins scientific community. It also provides a great opportunity for young scientists from across the school of medicine to discuss scientific ideas and open new collaborations. Ultimately, it is very motivating for any young trainee to get recognition from their host institute, so I wholeheartedly support Young Investigators’ Day.
What has been your best/most memorable experience while at Johns Hopkins?
I had always wanted to learn live-cell fluorescence imaging, which I was able to do extensively during my time at Johns Hopkins and have really enjoyed. Specifically, for my own project, I have an amusing memory. My project was stuck for many months initially, and I was banging my head against a brick wall. However, a wonderful bacterial contamination in one of my cell culture plates on an August afternoon in 2021 solved my problems and changed my fortunes. It goes to show that contaminations may not always be bad! Outside of work, I have always enjoyed time with my labmates and our colorful, “after 3 p.m.” conversations in the computer lab or over a few beers at the Ministry!
What are your plans over the next year or so? Graduating, looking for faculty positions, etc.?
I plan to finish up my remaining projects and start looking for faculty positions.
Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?
I enjoy traveling, and take every opportunity to take a trip and explore. I love photography, and have been clicking photos since I was a kid. Throughout my school years, I did martial arts and swimming and did fairly well in tournaments. In the near future, I would like to take up pottery.