From a Postdoc’s Perspective: Jagannath Padmanabhan

I'm Jagannath Padmanabhan, and this is why I research.

Dr. Jagannath Padmanabhan is a Research Fellow at Stanford University in the department of Plastic and Reconstructive Surgery. His research, in the laboratory of Dr. Geoffrey Gurtner, aims to uncover the cellular signaling events driving fibrosis during wound healing and foreign body reaction to biomedical implants. To this end, Dr. Padmanabhan leads a multidisciplinary research effort in the collection of tissues from patients with biomedical implants. Additionally, he is interested in developing biomaterial-based strategies towards improving wound repair.

Who or what first sparked your interest in science?

It was a physics class in college, where the professor talked to us about biomaterials as an off-topic discussion. I was fascinated by the idea of biomaterials – lifeless materials interacting with life. This discussion got me interested in science and research. Following this, I volunteered at a biomaterials lab during the school year and really enjoyed it and have remained in the field ever since. This was more than 10 years ago, since then, I have been involved in interdisciplinary biomedical research in various capacities, but focused on different aspects of biomaterial-tissue interactions.

Is there a specific mentor that inspired you to become a scientist or that has significantly influenced your goals in research?

Absolutely! There are four to be exact. I started my research work in Dr. Narayana Kalkura’s lab at Anna University in India – he was the physics professor in college who talked about biomaterials. After this, I went to Cornell and worked with Dr. Jonathan Butcher, who introduced me to biomaterials research in the context of 3D bioprinting. Following this, there was Dr. Themis Kyriakides, who was my PhD advisor at Yale. I spent five years in his lab and his mentorship was crucial for my development as an independent scientist. And finally, my current mentor is Dr. Geoffrey Gurtner, a surgeon-scientist at Stanford, who is helping me develop an expertise in translational biomedical research, which is really important to be able to contribute towards the betterment of real-life patients.

You have been active in teaching different courses, from basic science disciplines to a course on nanobiomaterials? Tell us about some key rewards and challenges of your teaching activities.

Teaching is my way of paying forward what my mentors have done for me. Sharing the inspiration for science is what teaching is all about, and the job is really a reward in itself.

As for challenges, I think the major challenge I have faced is that sometimes the students are really focused on their grades and that takes away the fun of learning something new. I worked on a series of basic science courses with Dr. Surjit Chandhoke – who’s the Dean of Trumbull college at Yale now – who taught me how to capture the students’ attention back and that has been my goal with every course I have taught since.

My teaching philosophy is that when you equip students with the right tools and let them explore a topic of their choice, they not only learn on their own initiative but they also find the joy in learning and have fun. And that’s really the job of the teacher - to share the inspiration, to provide tools for exploration and then let the students take it from there. I do agree that exams and tests are important to assess learning, but sometimes too much testing gets in the way of learning in the sense that learning becomes about doing well on tests. My mission, when I teach, is to help students rediscover that curiosity and passion about learning for the sake of learning.

Which training activities (e.g., teaching, mentoring and committee services) have you found more rewarding and critical for your career development?

As mentioned above, I find teaching / mentoring in a class setting or in labs extremely gratifying. My summer class for high school students is particularly rewarding because I get to develop their scientific inquisitiveness. And I must say, looking at the caliber and enthusiasm of these students, I’m confident that our science will be in the right hands in the coming years.

Besides teaching, I enjoy organizing and being a part of science conferences and meetings to interact with the experts of the field. I had the chance to chair the 2015 Gordon Research Seminar (GRS) on Biomaterials and Tissue Engineering held in Girona, Spain. I learned a lot of new skills such as fundraising and organizing a conference, and it was also a lot of fun because I got to meet so many talented scientists from all around the world. The network that I built through that conference is still strong and I keep in touch with many of them – students and professors alike. So, I would count organizing the GRS as one of the most rewarding experiences.

Among your many science-related activities, you have great interest in science communication. Could you elaborate on your participation as editor for Sciencers.org?

Science is the best tool we have at our disposal to solve some of the world’s most pressing problems. Science is our best bet to gain an objective understanding of ourselves and the world around us. Through scientific pursuit, we can transform the quality of living for all of us. But the details of what problems scientists think and work on, remain with the scientists, although most science is funded by the public.

I started Sciencers.org in the summer of 2017 with a mission to invite everyone to join the conversation about science. But unlike other blogs, I don’t actually write all the articles. I serve as editor and invite my friends, colleagues and students to write articles for the blog. This helps expand the scope of the blog – so far, it has covered topics ranging from antibiotic resistance to quantum computing to nanobiomaterials. Articles change in format and content from time to time, but have the same theme: Academic rigor meets popular science meets journalism. Scientists of all levels, science enthusiasts and skeptics are welcome alike.

Your current research aims to characterize biological responses to biomaterials. How did you become interested in this field?

I have been interested in the general area of biomaterials research since college. For my PhD thesis at Yale, I worked on understanding the foreign body reaction to nanobiomaterials. Foreign body reaction is a complicated multifactorial process through which the body rejects implanted biomaterials. As a grad student, I explored how we can engineer better materials to evade the foreign body response (FBR). Complimenting that, in my postdoc, I wanted to further delve into the biology of FBR, in the context of clinical implants currently in use.

I joined Dr. Geoffrey Gurtner’s laboratory at Stanford in Aug 2016. Dr. Gurtner is a plastic surgeon by training, and plastic surgeons care a lot about foreign body reaction because of the volume of breast implant surgeries and the associated complications. To address this, I use my background in bioengineering to explore the different mechanisms through which biomaterials get rejected by the body and how we can try and make the biomaterial-based implants last longer. Working in Dr. Gurtner’s lab is a unique experience because I get to look at the problem from both surgeon’s and scientist’s perspectives.

To do this research, I employ novel single cell transcriptional technologies that allow me to characterize the heterogeneity in cellular response, but also appreciate the commonality in FBR across various tissues. We are particularly interested in molecular mediators that convert mechanical signals such as stress / strain to biological signals (called mechanotransduction pathways), which in turn contribute to biomaterial rejection. The mechanotransduction pathways that we identify as critical in biomaterial rejection could also be important in other forms of fibrosis. I think there’s a lot of potential, and we are working hard. And I think we will come up with some promising solutions – so stay tuned!

In your recent work published in Journal of Investigative Dermatology you reported the development of a novel scar therapy that overcomes the limitations of current therapies and could improve the outcomes for millions of patients worldwide. Can you elaborate on the novel approach?

Recent research has elucidated many mechanisms and molecular targets for scar therapy, but clinical translation of these therapies has had limited success. The challenges with translating these therapies to the clinic is two-fold. Firstly, the efficacy of drugs is usually very specific to the type of wound / animal model being studied. Secondly, delivery of drugs to the site of wound repair is inefficient.

In this work, we reported a novel scar therapy based on drug-eluting hydrogels that overcomes both limitations and clears the way for clinical translation. Building on many years of basic science research on focal adhesion kinase (FAK), a key molecule involved in scar formation, we have formulated an engineered hydrogel that can be tuned to release FAK-inhibitor (FAK-I) to the wound site at varying rates. We show that this strategy can be used to treat multiple types of wounds / scars including excisional wounds and burn wounds in mice.

All in all, this paper is important for the field because it describes a versatile drug therapy that is effective in treating multiple types of wounds. Additionally, the drug delivery technique developed here can be easily translated to the clinic because it is a topically applied hydrogel (similar to a band-aid), which can be used as wound dressings.

In your study published in Scientific Reports, you explored the effects of nanotopography on cell fusion? Could you elaborate on the signaling pathways that play a predominant role in these responses?

Cell-cell fusion is a fundamental process involved in multiple physiological phenomena in the body. I became interested in cell fusion because macrophages – which are key regulators of FBR fuse on the surface of biomaterials. A lot is known about the biochemical regulators of fusion, but we knew very little about the effect of biophysical cues such as the material topography or stiffness in promoting fusion. Our work found that specific geometries of nanostructures (55nm nanorod arrays) on biomaterial surface could significantly reduce cell fusion. Following this finding, we showed that this was correlated to the activation of p38 MAP Kinase - a biochemical regulator of fusion. These findings suggest that there exists a complex interaction between the biophysical and biochemical environment of cells that regulates the fusion process. But the picture is far from complete, and will need many more years of research to fully understand the different mechanisms and signaling pathways that are involved in cell fusion and how they interact and respond to biophysical cues.

Finally, how do you convey the importance of your research to friends and family?

I really enjoy talking about research to friends and family. I often walk away with more clarity about the topic of discussion after talking about it with a friend or family, because when you don’t use jargon and explain research in everyday language it forces you to think about everything from first principles. And that’s important for clarity. Also, as a scientist working on a highly specific problem, it is only when you talk to someone outside of the field that you are able to zoom out and connect your thoughts, and that’s refreshing. As with anything, practice makes perfect. So, I have become better at conveying the importance of research over time, but I also learn from my scientist friends including my wife, Vaishaali who is a postdoctoral fellow at Gladstone Institutes in San Francisco. These conversations with friends and family gave me the initial inspiration that led to me to start sciencers.org

Select Publications by Dr. Jagannath Padmanabhan:

Gurtner, G. C., & Padmanabhan, J. (2017). Disease models: Method in the madness of fibrosis. Nature Materials. https://doi.org/10.1038/nmat5044

Shayan, M., Padmanabhan, J., Morris, A. H., Cheung, B., Smith, R., Schroers, J., & Kyriakides, T. R. (2018). Nanopatterned bulk metallic glass-based biomaterials modulate macrophage polarization. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2018.05.051

Ma, K., Kwon, S. H., Padmanabhan, J., Duscher, D., Trotsyuk, A. A., Dong, Y., … Gurtner, G. C. (2018). Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation. Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2018.04.034

Januszyk, M., Kwon, S. H., Wong, V. W., Padmanabhan, J., Maan, Z. N., Whittam, A. J., … Gurtner, G. C. (2017). The role of focal adhesion kinase in keratinocyte fibrogenic gene expression. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms18091915

Fujiwara, T., Dohi, T., Maan, Z. N., Rustad, K. C., Kwon, S. H., Padmanabhan, J., … Gurtner, G. C. (2017). Age-associated intracellular superoxide dismutase deficiency potentiates dermal fibroblast dysfunction during wound healing. Experimental Dermatology. https://doi.org/10.1111/exd.13404

Padmanabhan, J., Augelli, M. J., Cheung, B., Kinser, E. R., Cleary, B., Kumar, P., … Kyriakides, T. R. (2016). Regulation of cell-cell fusion by nanotopography. Scientific Reports. https://doi.org/10.1038/srep33277

Padmanabhan, J., & Kyriakides, T. R. (2015). Nanomaterials, inflammation, and tissue engineering. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. https://doi.org/10.1002/wnan.1320

Padmanabhan, J., Kinser, E. R., Stalter, M. A., Duncan-Lewis, C., Balestrini, J. L., Sawyer, A. J., … Kyriakides, T. R. (2014). Engineering cellular response using nanopatterned bulk metallic glass. ACS Nano. https://doi.org/10.1021/nn501874q

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