NIH Grant Advances Alzheimer’s Research – And Launches a Career

Tiara Schwarze-Taufiq traces her love of science to a young age. She recalls browsing educational websites that detailed a wide variety of diseases and medical conditions. After zeroing in on the brain as a fifth grader, the future scientist began to think about a career in medicine.

“From a philosophical and a scientific standpoint, I am really drawn to the intersection between the brain, from a molecular perspective, and how brain functioning influences the rest of your life and how you interact with the world.”

Ten years later, Schwarze-Taufiq is still fascinated by the brain, but her path to medical school has detoured – at least for now – to the lab. As an undergraduate at UW, she studied neuroscience and public health, and found a research mentor in Dr. Paul Crane, who is affiliated with the UW Alzheimer’s Disease Research Center.

While perusing papers with Dr. Crane, Schwarze-Taufiq came across an intriguing figure that highlighted neuropharmacology and immunocytochemistry as lenses for understanding what happens in the neurons in the context of Alzheimer’s disease. That led her to ISCRM faculty member Jessica Young, PhD – her next mentor and current boss.

The Young Lab generates neurons and other brain cell types from human patient-derived human induced pluripotent stem cells (iPSC). This modeling technology allows Young and her team to study how genetic and epigenetic factors contribute to risk of Alzheimer’s disease (AD), and to identify potential therapeutic targets.

Neurons grown from the brain tissue of a patient with Alzheimer’s disease.  [Photo Courtesy of Allison Knupp]

Schwarze-Taufiq joined the Young Lab as an undergraduate researcher. In the summer of 2021, she received a state-funded ISCRM fellowship that allowed her to probe a pivotal question about the protein tau.

If tau is essential for neuronal cell structure and functioning, yet toxic when it accumulates excessively in Alzheimer’s disease, is the toxicity due to the aggregation of the protein itself, or to the loss of tau’s normal functions? In other words, would the problems triggered by the loss of tau resemble the dysfunction associated with abnormal tau in Alzheimer’s?

Alzheimer’s Disease and Neuroinflammation

“We know clumping of tau causes a lot of the neurodegeneration seen in Alzheimer’s,” says Schwarze-Taufiq. “We wanted to better understand how the various functions of tau are altered or lost and how those disruptions contribute to disease beyond the abnormal protein aggregation.”

By isolating loss of tau function from tau aggregation, the researchers were able to produce a clearer picture of the variables that seem to contribute to complications associated with Alzheimer’s disease.

RNA sequencing revealed a surprising discovery related to one disease indicator – neuroinflammation. Specifically, the gene-edited neurons displayed an unexpected immune response. “The cells were not infected with a virus, but they responded as if they were,” says Young. “This was a completely novel finding that suggests both loss of tau function and aggregation of tau contribute to problems we see in Alzheimer’s disease.”

The work Schwarze-Taufiq did as an ISCRM undergraduate fellow has led to other exciting developments. Young leveraged the preliminary data from the tau knockout experiments into an NIH R21 grant which will support a deeper dive into the consequences of tau mutations. And funding from the grant allowed Young to hire the formerly part-time undergraduate researcher as a full-time research scientist.

Becoming a Research Scientist

For Schwarze-Taufiq, who graduated in the fall of 2022, the new role means significantly more time in the lab. “As a student, I had limited bandwidth. As a research scientist, I’ve been really happy to focus on the investigation, to design some of my own experiments, and learn new methods.”

At the lab level, the grant will allow Young and her team to build on the early results by cultivating more cell lines, examining the implications of the tau mutations in neurons alongside non-neuronal cells (together in a more complex organoid model), and looking at neuronal function using electrophysiology. The upshot, according to Young, is a better grasp of the role neuroinflammation plays in Alzheimer’s disease.

While Schwarze-Taufiq is absorbed in her grant-funded research, she has not left behind thoughts of medicine. “I definitely still think about medical school, but mostly about an MD/PhD program. Research has become a non-negotiable part of my career path. That’s what’s rewarding right now and what keeps my curiosity going.”