Pioneering human brain model systems

I’ve always been fascinated with how things come to be. Especially us. As human beings, everything we are starts from a single cell that develops into other cells that form organs and a fetus that continues to grow and mature into a person. Understanding how development occurs from a single cell is an interest that led me down the path of working with stem cells and now directing the Human Neural Organoid Laboratory (HNOL) in the Department of Developmental Neurobiology. 

I was first introduced to this field during my undergraduate studies in India. I quickly developed an interest in stem cells in the context of neuroscience, specifically how stem cells give rise to the brain and spinal cord. At the time, not many people were doing neuroscience research in India, so I went to Göttingen, Germany, to pursue my doctoral studies in developmental neuroscience at the Max Planck Institute for Experimental Medicine.  

My academic journey then took me to California for postdoctoral research, where I learned how pluripotent stem cell technology can be used to model the human brain. For five years, I learned how to differentiate these cells into different types of mature and functioning neurons that make up the human brain. These experiences led to my expertise in both developmental neurobiology and stem cell technology, which was a unique combination that the Department of Developmental Neurobiology needed. 

Building an innovative laboratory at St. Jude 

To really understand what causes pediatric brain tumors and other debilitating neurological diseases and how we can diagnose and treat them, we need human disease models. These would validate what we learn from mouse models, facilitate medical breakthroughs and bring us one step closer to significantly improving the success rate of drug discovery. Michael Dyer, PhD, Department of Developmental Neurobiology chair, understands this.  

I have always been interested in developing novel tools and technology and improving current methods and model systems that would allow investigators to answer the questions of “why” and “how” in biology. At St. Jude, I was given the space and autonomy to do just that. When I came in 2016 to start building a lab that would pioneer modeling of the human brain, it was a dream come true.  

At the time, the idea of human brain model systems was very new since the first model of its kind had only been published three years earlier. At St. Jude, I got the opportunity to build an entire lab dedicated to developing robust, reliable and physiologically relevant three-dimensional models that faithfully recreate various parts of the very complex human brain. 

As we built the HNOL, the goal was to integrate this innovative technology into the discovery pipeline and help principal investigators understand how they could use our models to further their research goals. To date, we have developed protocols to recreate the human cortex, retina, thalamus, cerebellum and other structures in the form of “organoids.” We have also successfully recreated brain circuitry relevant to neuropsychiatric disorders, such as schizophrenia. Our models have been used in studies ranging from patient-specific retinoblastomas to learning and memory in humans to novel neuroprotective pathways. 

I am incredibly proud of my dedicated, self-motivated and hardworking team, which includes a scientist and an associate scientist. Together, we have been actively collaborating with investigators in the department for more than a decade and helping them with their scientific discoveries. 

At the forefront of discovery 

Building the HNOL has been a journey. There were lots of unknowns to navigate, but my work has been beyond gratifying. I love the mission of St. Jude, and combining this with the opportunity to do something not many people have had an opportunity to do in the field of science has been incredibly rewarding.  incredibly rewarding.  

That’s the fun of doing scientific research: We are trying to accomplish something nobody has done before through discovery and innovation. It is extremely challenging because we are on the forefront, which means we continually discover new problems that no one has a solution to because we are the ones leading the development of these tools and systems. We are constantly trying to improve the model systems we create to make them more physiologically relevant, so they are better for studying diseases and for drug discovery.  

When we are able to solve a problem, that’s the greatest sense of accomplishment. For me, knowing our work in developing human disease models is advancing our collective understanding of how we develop, how diseases come to be and how we can better treat these conditions is the most rewarding of all.