What’s the recipe for success in a modern-day laboratory? What drives discovery: technological advancements or big ideas? Khalid Shah, MS, PhD, vice chair of research for the Department of Neurosurgery and director of Stem Cell Therapeutics and Imaging wants to share answers on these big-picture questions and more. But first, he wants you to consider a humble tea bag.
Shah draws an image of a pyramid-shaped tea bag on the white board in his office. He explains that, to be cost-efficient, tea bags are crafted in large batches. Once the processing technology is constructed, the company can change the type of tea – ginger, lavender, mint, etc. – to create hundreds of flavor possibilities.
This process is analogous to generating new research solutions. Once the technology is in place, a scientist can begin to fill it with as many different ideas as there are flavors of tea.
The Shah lab is equipped with cutting-edge tools and technologies for investigating questions about cancer, including hundreds of tumor cell lines as well as different types of mouse models, DNA expression constructs, stem cells and oncolytic viruses. Today, they are tackling some of the hardest problems in treating primary and metastatic tumors, using a unique blend of ingenuity and open-mindedness that allows them to think outside of the box.
“We seldom look at a competitor’s work when we’re thinking about how to solve a problem,” Shah explains. “That would take much of the innovation out of it for us. Instead, we approach the problem with a fresh perspective. We have a vision that guides us and a unique way of doing things – but it’s a way that’s worked for us.”
A Fresh Eye Toward Brain Tumor Research
Recent advancements in biomedical engineering are accelerating brain tumor research. For example, researchers can now use engineered stem cells that home and kill tumor cells, tumor-targeting oncolytic viruses to infect and kill cancer cells, or engineer immune cells, such as chimeric antigen receptor (CAR) T-cells and natural killer (NK) cells, to attack cancer cells. They can also control stem cells and train ‘good’ cancer cells to kill ‘bad’ ones.
“My belief is that biological therapies such as engineered stem cells, oncolytic viruses, redefined immune-cells, or maybe even controlled and repurposed cancer cells may become useful clinical treatments for brain tumors,” Shah said.
Recent research also suggests that the gut microbiome may play a critical role in immune system function. The Shah lab is currently examining the effect of the gut microbiome on brain tumors to enhance the effectiveness of their cell-based immune therapies.
Growing Research from the Ground Up
Now is a time for major discovery and development in the field of neuro-oncology, and Shah remains focused on growing his research from the ground up. For the first eight years of his research career, for example, he examined primary brain tumors such as glioblastoma.
“I have always tried to keep clarity of mind,” Shah said. “Rather than spreading myself too thin, I work to channel my energy and efforts into a singular focus.”
Over the years, topics in his lab have progressed to include metastasized melanomas, breast tumors and lung tumors that have reached the brain. The emphasis on researching and treating brain tumors continues to unite his lab.
“We have not lost our connection with the roots of where we started,” said Shah. “This is the best way to impact the field.”
And Shah’s team has done just that, demonstrated by a proven track record of productivity and innovation. Over the summer, his lab published a paper in Science Translational Medicine about using CRISPR/Cas9 gene-edited and ‘tamed’ cancer cells to attack and kill harmful cancer cells in mouse models. The team envisions that these cell-based therapies could be adjusted for individual patients as part of a personalized care and treatment plan in the future. The work was widely publicized across the scientific community and through media outlets.
Shah acknowledges that it can be difficult for a novel research idea to take hold. He recalls that in the beginning, when his team first proposed killing cancer by using cancer cells, many in the field doubted them. But Shah believes that there are two keys to the successful development of a bold idea: patience and perseverance.
“The reality is that research is more about long-term goals and short-term experimental solutions. We have an amazing group of people in our center that have detailed experimental plans to execute experiments. For me, I am always looking ahead. When you have vision, you’re looking for long-term solutions. It’s the subconscious mind or perhaps beyond that brings forth unique and innovative ideas,” said Shah.
The Modern-Day Investigator
Shah also recognizes that the role of principal investigator is evolving as research funding opportunities become increasingly competitive. Today, conducting research and writing grants is no longer enough to thrive in a competitive research environment.
“To be successful, you have to be skilled in multiple areas, including writing grants, attracting new people, marketing your work, interacting with industry and collaborating with other researchers,” explained Shah, who views science as a global effort.
As part of his role, he regularly travels to present lectures around the world. Just last month, he traveled to the United Kingdom, Italy, Belgium and the Netherlands to share his ideas and speak about his latest research.
Yet, Shah remains grounded. When he is not traveling or guiding research efforts, he can be found teaching his son and daughter the value of deconstructing and understanding simple technologies, such as a tea bag, so that they can, one day, fill new technologies with their own ideas.