Pitt Chemist Fights the Clock for Aging and Alzheimer’s Disease Research

Renã A.S. Robinson knows America’s older population is growing — that’s why she’s wasting no time. Robinson, 37, is an assistant professor of chemistry at Pitt who has firmly positioned her work in the context of a critical moment in public health.

Americans age 65 and older will make up more than 20 percent of the country’s population by 2040. As the country ages, the incidence of incurable age-related diseases such as Alzheimer’s and Parkinson’s looms large.

With a grant from the National Institutes of Health last year and a pilot award from Pitt’s Alzheimer Disease Research Center, Robinson is looking at the role proteins play in the aging process.

A major focus of her multidisciplinary “RASR” Laboratory — the name comes from Robinson’s initials — is investigating beyond the brain to see if proteins in so-called “periphery organs” including the liver, heart and kidneys — might contribute to, or even cause aging and neurodegenerative diseases.

In the body, proteins have many functions, such as aiding muscles in movement and translating the instructions from genes to organs and other body parts.

Researchers know that proteins are connected to neurodegeneration. Sometimes proteins misfold and break down. Sometimes they clump and clog up tissues in the brain. But it’s still unclear whether Alzheimer’s originates in the brain or elsewhere in the body.

The full set of proteins in the body is called the proteome and — due to aging and other factors like genetic mutations, metabolic changes, even UV exposure — the human proteome changes over time. Some mutations are small and can be repaired easily. Some are more serious. When enough of these mutations accumulate, it can lead to diseases as diverse as Alzheimer’s and Parkinson’s to cystic fibrosis and some forms of cancer.

By analyzing the proteome Robinson hopes to create a clearer picture of the origin of neurodegeneration — and she’s using brand-new technology to do it.

Traditionally, when scientists analyze protein expression, they only focus on one or two proteins at a time, in part due to limitations of technology. Robinson’s group has developed a way to hit fast-forward on that laborious process, which allows her to get information from tens of thousands of proteins within a matter of hours.

“We took advantage of some of the chemistry that we’ve used throughout the years, and we came up with a novel way to combine technologies together,” Robinson says.

This kind of connective innovation is her M.O. In grad school, Robinson studied disease progression in the proteins of aging fruit flies across all systems. Her doctoral advisor David Clemmer, a distinguished professor in Indiana University Bloomington’s College of Arts and Sciences, told Chemical and Engineering News about how she improvised in his lab, combining techniques that hadn’t yet made it to the market of commercial chemical instruments for her extensive experiments with 25,000 to 100,000 flies.

One result of her research virtuosity is cPILOT, also known as Combined Precursor Isotopic Labeling and Isobaric Tagging. It’s a technology that assigns “chemical barcodes” to thousands of proteins.

Much like how packaged foods are labeled at the grocery story to make sure the right item rings up at the right price, cPILOT allows researchers to tag and monitor many samples in a single experiment — up to 24 right now, though Robinson is hoping to get capacity into the hundreds, maybe beyond. What’s more, samples can be taken from all kinds of contexts — different patients, different stages of disease, various tissues in the body and more — to trace how benign biological pathways can turn sinister.

“We’re making these grand proteome experiments … faster, less expensive and still yield comprehensive information about a given disease state,” she says.

Clemmer couldn’t be a prouder mentor. “Renã is among a handful of what I would call the truly elite young people of her generation.

“I would guess that there are maybe a half a dozen laboratories in the world that are doing this the way that Renã is doing it … but Renã leads the pack,” Clemmer adds.

Another facet of Alzheimer’s on Robinson’s radar is its disproportionate effect on African American and Latino populations. Using these same proteomic technologies, her lab seeks to identify possible molecular differences to explain why these populations are twice as likely to experience the disease. Her mentorship in and outside of the lab continues this goal.

“It became really clear when I was a postdoc that I could make a difference in influencing STEM by being in STEM and continuing to pursue a career as a faculty member,” she says. At Pitt, she’s an avid mentor, especially for students from underrepresented populations.

The undergrad, graduate and even high school students in her diverse and growing laboratory hardly need convincing about the importance of the work they’re doing. “They just really think that studying aging and disease is cool,” she says, “and that chemistry can be used to do those things I think is mind-boggling for them.”

A good thing, for a generation of aging Americans and their caregivers. As always, Robinson knows, time is of the essence.