Caring for his grandmother as her health deteriorated after being diagnosed with a rare neurodegenerative disease inspired Wyss researcher Ayush Noori to commit to finding better treatments
By Jessica Leff
Ayush Noori grew up amidst a large extended family divided by geography – spread across California, Washington, and India – but united by shared core values of integrity, dedication, and resilience. At the center of this family was his grandmother, Munira Brooks, or as Ayush lovingly called her, his Nani. Ayush remembers, “We were very close. She would travel the world and always return with these incredible stories of her vibrant life – and with little gifts for me.”
Munira was born in India in the 1950s, a time when career prospects for women were incredibly limited. Although she dreamed of pursuing higher education, she was denied the opportunity. Despite not having a college degree, Munira was determined to build a better future for her family, exploring opportunities in the Middle East, England, and the United States. Overcoming all obstacles, she eventually earned the position of senior vice president at a global telecommunications company. As she rose through the ranks, she used her position to open doors for others.
When she reached the height of her career, her family noticed a change. “When I was around six or seven, my grandmother’s facial expressions became less pronounced,” Ayush explains. “In her job, she regularly spoke to crowds of hundreds of people, but slowly, her speech became less expressive. Then she began to stumble in her gait.”
Ultimately, Munira was diagnosed with progressive supranuclear palsy, or PSP. This devastating, rare neurodegenerative disorder affects approximately six out of every 100,000 people. PSP is caused by damage to the cells in certain areas of the brain that control movement, coordination, and other important functions. As the disease advances, patients lose the ability to move their eyes, muscles, and body. PSP is currently a fatal disease with no known cure.
A few years after her diagnosis, Munira was forced to retire because she couldn’t sufficiently control her body anymore.
A tough pill to swallow
The diagnosis of PSP was not only life-changing for Munira, but it also affected her loved ones. Ayush and his family became her primary caretakers. As a child, Ayush often stayed up through the night to take care of his grandmother. He remembers, “I would take her to the bathroom, feed her, and put her to sleep. When you care for someone so deeply, you form a bond and a connection that goes beyond just a grandson and a grandparent. When you see that person’s disease progress and there’s nothing you can do about it, it breaks your heart every day.” That was one of the most challenging things for her family to accept – the fact that even the best medicines and specialists could do nothing to save her.
Although there is no known disease-modifying treatment or cure for PSP, Ayush refused to take no for an answer. Motivated by his experiences of caring for his Nani, Ayush developed an early passion for science and medicine. Unable to see his grandmother suffer, he resolved to find some way to help. So, at the age of only twelve, he reached out to leading scientific researchers, and Josh Russell, Ph.D., a postdoctoral fellow in the lab of Matt Kaeberlein, Ph.D. at the University of Washington in Seattle, agreed to take Ayush under his wing.
The first time Ayush entered the lab, he remembers there was a distinctly sweet smell of agar, E. coli, and C. elegans. Someone was running a gel, and another researcher was working over an open flame. The lab benches were piled high with boxes filled with strains of nematodes and yeast. Ayush recalls, “I thought, this must be what scientific paradise is like.”
Ayush worked in the Kaeberlein Lab to study extracellular vesicles in Alzheimer’s disease and related neurodegenerative disorders. This research was scientifically impactful, but also personally meaningful for Ayush: “For the first time, with my own hands and mind, I could contribute something towards this fight. It was the most empowering thing in the world. Exposure to the domain of scientific research also helped me understand how complex these diseases truly are.”
Pursuing a scientific passion
Galvanized by his early experiences in the lab, Ayush was determined to keep making a difference. He knew that Boston was a mecca of scientific, medical, and technological innovation – but it was also 2,500 miles away from his grandmother. Once he was accepted to Phillips Exeter Academy, a rigorous and selective high school in New Hampshire, he faced a challenging decision: to stay in Seattle with his Nani, or to travel to New England and continue his scientific training. “I was ready to stay back and care for my Nani, but my grandmother pushed me to take the plunge. She said, ‘You’re not passing up this educational opportunity on my account.’”
Munira was right – studying on the East Coast was an invaluable experience. The faculty at Phillips Exeter dedicated themselves to their students’ growth – both intellectually and personally. Plus, with his proximity to Boston, Ayush sought out opportunities to continue his scientific research. First, he worked in the lab of Clotilde Lagier-Tourenne, M.D., Ph.D., in the Department of Neurology at Massachusetts General Hospital (MGH), helping to characterize a genetic repeat sequence that is the most common cause of familial amyotrophic lateral sclerosis, or ALS, and frontotemporal dementia.
After a year and a half, and with far more wet lab experience than most high schoolers, Ayush broadened his research focus from the bench to bytes. “Although wet lab science was my first love,” he says,“I realized that the advent of new computational technologies would allow me to ask and answer bigger questions beyond the bench.”
Excited by the promise of computational biology, he taught himself how to code in R and Python. Advised by Sudeshna Das, Ph.D., Alberto Serrano-Pozo, M.D., Ph.D., and Bradley T. Hyman, M.D., Ph.D. he worked in both a data science lab and a wet lab at the Mass General Institute for Neurodegenerative Disease. Ayush continued to research neurodegeneration, developing artificial intelligence (AI) methods to reveal changes in astrocytes and microglia in Alzheimer’s disease and diagnose patients with dementia from electronic health records.
Moving on to the next phase
While Ayush grew as a researcher, at home his grandmother’s condition rapidly deteriorated. He recalls, “She wanted to stay alive as long as possible to see her grandchildren go to college and get married, and to be the grandma that she always dreamed she would be.”
As his Nani was repeatedly admitted to the ICU, Ayush and his family spent 2019 in and out of the hospital. That summer, he flew back and forth from Boston, where he was working at MGH, to California, where Munira received treatments to ease her PSP symptoms. In November, she made it to her 69th birthday. The entire extended family came together to celebrate her life.
At this point, Ayush was a senior in high school. He had applied to Harvard College, and would soon find out whether he was admitted. As his peers anxiously awaited their admission decisions, Ayush was focused on getting to Palo Alto to see his grandmother in the ICU, fearing this would be the end.
Ayush recalls, “By fate or by fortuity, my Nani was discharged on the day that my admission to Harvard was released. The decisions were released at 4:00PM, which I remember because it was the same time that the ambulances were bringing her home. The paramedics opened the double doors, wheeled her in, and set her up on the sofa. She had an oxygen canister, a breathing mask, and a nasogastric tube. Only once she was settled, we opened my decision letter together and learned that I was offered admission to Harvard. For the last time that I can remember, she really tried to smile.”
That same year, 12 years after her initial diagnosis, Munira passed away on December 21. Ayush calls this one of the defining moments of his life, “I was holding her hand as she passed away. It’s a privilege and a gift to be there with the people you love in their final moments. Right before she passed, I made a promise to my grandmother that I would do something about this horrific disease that stole years from her life, years from my family, and years of happy memories that we could have shared together.”
Reimagining personalized treatment for challenging diseases
Following his personal experiences, Ayush envisions a different future. “If I could Reimagine the World, every patient would have ready access to high-quality, personalized, and effective medical care. In this world, we’d treat the whole person, delivering treatments for those with neurological diseases and other challenging medical conditions that we cannot treat yet. It would be a world where we can provide every person with the opportunity to live a complete, fulfilling life surrounded by the people they love.”
To realize his vision, Ayush has continued his research, using AI to discover novel diagnostics and therapeutics for neurological disease. Ayush soon joined the lab of AI expert Marinka Zitnik, Ph.D., in the Department of Biomedical Informatics at Harvard Medical School. To date, he has published over 20 scientific papers, and his research efforts have been recognized by many national awards and competitive fellowships, including the prestigious Barry Goldwater Scholarship.
Two years ago, Ayush joined the lab of Core Faculty member George Church, Ph.D., and started working on the CircaVent project. The CircaVent team is focused on finding new treatments for bipolar disorder using a high-throughput drug screening platform that combines predictive algorithms, preclinical models, and human brain organoids. Bipolar disorder is estimated to affect 40 million people worldwide, significantly impacting their quality of life. The current standard of treatment is lithium, but most patients will stop responding to the drug in five years. Plus, it is still unclear how lithium works in the brains of bipolar patients.
Ayush is leading the computational arm of the CircaVent project. He uses AI to better understand the mechanisms of bipolar disorder and search for existing drug candidates that could be repurposed to treat this condition. These drugs are already approved for medical use, so they’re cheaper and faster to develop for bipolar disorder. The CircaVent team is also working to design new drugs for bipolar that are more effective. Ayush explains, “Not only do we care about this problem, but the Wyss equips us with the tools, resources, and technologies needed to convert that passion into scientific impact.”
“Given my family experiences with neurological disease, I have an intimate understanding of how these diseases can rob everything from you. So, it’s incredibly empowering to be able to try and address bipolar disorder, a neurological disease, at the Wyss. With our culture of innovation, scientific discovery, and translation, I am motivated to produce even better science that I know will have an impact.”
Making good on a promise
Despite everything Ayush has been through and contributed at a young age, he still feels an overwhelming sense of gratitude and awe. He says, “I’m grateful to the Wyss and Harvard Medical School, and to all of my mentors throughout my research career thus far who took a chance on me and enabled me to make meaningful contributions. Eight or nine years after I first stepped foot in a lab, I still feel the same sense of wonder and excitement at the promise in our work.”
Speaking of promises, Ayush spends each day trying to live up to the one he made his grandmother right before she passed away. He explains, “This promise was not just to her – it’s a promise to other grandparents and grandchildren, that through the work we’re doing, we can help save other families from the horrors of these diseases – whether neurodegeneration or other challenging neurological disorders that still lack effective treatments.”
