Beyond the Paper: A Conversation with Dr. Sreeja Kumari Dhanya and Dr. Bhavana Muralidharan

Interviewed by Dr. Paige N. McKeon, February 18, 2025

In a study led by Sreeja Kumari Dhanya and Bhavana Muralidharan from the Institute for Stem Cell Science and Regenerative Medicine, researchers used mice to identify a new role for RBBP4, a chromatin modifier that regulates gene expression, in neurogenesis: regulating progenitor proliferation and neuronal differentiation in the neocortex. Their study sheds light on RBBP4’s cell-type specificity and mechanisms through which this chromatin modifier influences neocortical development. The researchers also identified a new RBBP4 binding target that supports neurogenesis. This work is informative for those studying mechanisms of cortical development and neurodevelopmental disorders.

“If I had one piece of advice for new faculty, it would be to embrace flexibility. Things will not always go as planned, and resilience, along with a strong support network, makes all the difference.” —Dr. Bhavana Muralidharan

Drs. Dhanya (left) and Muralidharan (right) at SfN’s Neuroscience 2023 in Washington DC, USA.

Dr. Dhanya, what led you to pursue a research career? What experiences have contributed to your success so far?

SD: My interest in neuroscience and cellular biology was ignited during my undergraduate studies. My passion for research, desire to contribute to scientific knowledge, and pursuing a career in academia persuaded me to obtain a PhD and subsequently a postdoctoral position. I was fortunate to work under Prof. Gaiti Hasan at the National Centre for Biological Sciences (NCBS, Bangalore, India) for my PhD where I explored the role of intracellular calcium signalling in gene expression and synaptogenesis in mouse Purkinje neurons, with implications for neurodegenerative disorders like spinocerebellar ataxia. Prof. Gaiti was more than just a mentor; she was instrumental in teaching me how to balance my family life with my research career. Through her guidance, I gained invaluable experience that shaped me into an independent researcher.

My keen interest in exploring the molecular basis by which dysregulated chromatin modifiers affect neocortical development in neurodevelopmental disorders persuaded me to continue my research career as a postdoctoral fellow under the mentorship of Dr. Bhavana Muralidharan at the Institute for Stem Cell Science and Regenerative Medicine (inStem, Bangalore, India). Bhavana has provided exceptional support and guidance throughout my research project, during which we uncovered the functional role of RBBP4 (Retinoblastoma Binding Protein 4) in regulating neurogenesis in the developing mouse neocortex. Bhavana was extremely proactive and enthusiastic as she trained me in new techniques, which greatly expedited my research findings. Furthermore, the comprehensive training I received during my PhD has equipped me with essential skills that are directly applicable to my current postdoctoral research, making it easier for me to address complex research questions. Receiving prestigious MK Bhan Young Researcher Fellowship, instituted by the Department of Biotechnology (DBT), has offered financial support, enabling me to pursue my current research projects in Muralidharan Lab.

“The field of science is constantly evolving, so maintaining a curious mindset and being open to new ideas and methodologies is essential for success.” —Dr. Sreeja Kumari Dhanya

Dr. Dhanya.

What are your future career goals? Do you have any advice for people pursuing a similar career?

My future career goal is to secure a faculty position at a reputable academic institution where I can lead my own research group and contribute significantly to the advancement of understanding neuronal function and development. My focus will be on unraveling the complexities of brain development and investigating the molecular mechanisms that contribute to neurological disorders, with the goal of developing therapeutic interventions. I am passionate about mentoring the next generation of scientists and plan to engage in teaching and training students, fostering an environment of curiosity and innovation in scientific inquiry. I also aim to participate in scientific outreach to communicate complex scientific concepts to broader audiences and collaborate with interdisciplinary teams globally, enhancing the scope and impact of my research.

My advice for aspiring scientists is to set clear short-term and long-term goals that can help guide career progression. Make sure to keep reassessing these goals regularly to adapt to new opportunities and challenges that arise in the scientific landscape. Establishing strong relationships with mentors is crucial and the guidance from experienced researchers provides valuable insights and support throughout one's academic journey. I advise aspiring scientists to embrace challenges as learning experiences and to engage in collaborative projects that can broaden research perspectives and enhance learning opportunities. The field of science is constantly evolving, so maintaining a curious mindset and being open to new ideas and methodologies is essential for success. It is also very important to focus on developing presentation skills and engaging in outreach activities to share your work with diverse audiences.

Dr. Muralidharan, how did your research experiences help you get to where you are now? What motivated you along the way?

BM: My PhD was in molecular biology. However, my growing fascination with neuroscience led me to join Prof. Shubha Tole’s lab at TIFR, Mumbai, for postdoctoral research. There, I worked on uncovering how chromatin dynamics shape the emergence of neurons and glia during cerebral cortical development. This work reinforced my passion for decoding the molecular blueprint of brain formation. Eager to expand my research into neurological disorders, I joined Prof. Adrian Isaacs' lab at the UK Dementia Research Institute, UCL, London, where I used human in vitro disease modelling to explore therapeutic interventions for neurodegenerative diseases.

Armed with expertise in both neurodevelopment and disease modelling, I established my independent research group in October 2019 as an Assistant Professor at the Institute of Stem Cell Science & Regenerative Medicine (inStem), Bangalore. My lab focuses on the chromatin control of cerebral cortical development in health and disease, leveraging stem cell models to bridge fundamental neuroscience with translational potential. inStem, as a premier institute dedicated to stem cell research and training, provides the perfect environment to pursue this vision.

Throughout my journey, I have been driven by a fundamental question: How does chromatin regulation orchestrate brain development, and how do disruptions contribute to neurological disorders? My research experiences—ranging from molecular biology and developmental neuroscience to patient-derived disease models—have provided me with the tools to tackle this question from multiple angles, shaping my scientific path and fuelling my motivation to uncover new insights into brain health and disease.

What advice or information do you wish you had before becoming an assistant professor? What have you learned about setting up your own lab?

Before becoming an Assistant Professor, I had experience mentoring students and working collaboratively within a team from my postdoc in Shubha’s lab, which helped me navigate lab leadership early on. However, no matter how well-prepared you are, some lessons can only be learned on the job.

One key realization was that running a lab isn’t just about executing a research plan—it’s about managing people, troubleshooting unexpected challenges, and fostering a productive, supportive environment. For example, the COVID-19 pandemic began soon after I started my lab, forcing me to adapt in ways I hadn’t anticipated. Coordinating research in shifts, maintaining team morale, and ensuring both scientific progress and well-being became just as important as the experiments themselves.

I wish I had been more prepared for the administrative aspects—funding cycles, hiring processes, and the logistics of setting up lab infrastructure, all of which require time and strategic planning. Learning to delegate effectively and balance research with mentoring and grant writing has been a continuous process.

If I had one piece of advice for new faculty, it would be to embrace flexibility. Things will not always go as planned, and resilience, along with a strong support network, makes all the difference. Investing in team dynamics and open communication is just as crucial as investing in research itself.

How did you develop the methodology for this study?

SD and BM: Studying a complex process like progenitor proliferation and neurogenesis in the mouse neocortical primordium requires a combination of multiple methodologies and experiments. This publication presents data from various techniques, including sectioning of embryonic mouse brains followed by in situ hybridization, ChIP-seq from neocortical primordia, in utero electroporation, and nucleofection of neocortical progenitors.

Some of the key methodologies used in this study build on techniques previously optimized by Bhavana during her postdoctoral research, particularly ChIP-seq on precisely dissected neocortical tissue from early embryonic mouse brains. Further optimization, such as refining nucleofection protocols in isolated neocortical progenitors, was carried out in the lab to ensure successful execution of the experiments.

Were there any surprises as you collected data for this study?

The data for this study comes from multiple experiments, each exploring different aspects of RBBP4 function. Some experiments delineate RBBP4 expression levels, while others investigate its role in vivo and in vitro using cultured progenitors. At the molecular level, ChIP-seq experiments reveal its downstream effector functions, identifying Cdon as a key target.

While it wasn’t entirely unexpected, we were thrilled to see how all the data aligned seamlessly toward the end. The rescue experiment—where overexpression of Cdon in RBBP4 knockdown conditions restored progenitor proliferation and neuronal output—provided strong functional validation, reinforcing our findings.

Are there future directions for this project that we should stay tuned for?

Putative risk variants in RBBP4 have been implicated in autism spectrum disorders (ASD). Our next goal is to investigate how these variants contribute to the pathophysiology of ASD. Gaining this insight could help identify key neurodevelopmental pathways that are disrupted in individuals with ASD, potentially uncovering novel therapeutic targets for neurological disorders.

How was your experience with the eNeuro review process? Feel free to share how you feel about the science review process in general and what you think could be done to improve it.

Our experience with eNeuro was very constructive. The practice of collating all reviewer comments into a single, detailed document greatly benefits authors, making it easier to address feedback comprehensively. The suggested experiments were critical in establishing the functional link between RBBP4 and its downstream effector, Cdon. Importantly, no extraneous experiments were requested, and the review process had an efficient turnaround time. Overall, it was a very positive experience.

The scientific peer-review process is a fundamental pillar of science, yet it is often overlooked as an unpaid, voluntary task. Given its critical role in maintaining the integrity of scientific publishing, there is merit in considering a system that compensates reviewers for the time and effort spent critically analyzing manuscripts and providing constructive feedback. Ensuring transparency by disclosing reviewer identities could further enhance accountability and credibility in the peer-review process.

Laser tag outing for lab members celebrating their collective science successes.