Christina Gavegnano remembers looking out the bus window on her way to elementary school and telling herself, “You will develop a drug that saves a lot of people.”
It was less a dream than a statement of fact.
Now an assistant professor at Emory School of Medicine and the Emory College of Arts and Sciences Center for the Study of Human Health, Gavegnano has developed two anti-inflammatory medicines that help save lives around the world and have the potential to alter treatment for everything from Alzheimer’s disease to sepsis.
Those medications have already changed Emory’s undergraduate landscape. On the same day in 2020 that the U.S. Food and Drug Administration granted emergency use of her second drug for the treatment of severe COVID-19, Gavegnano used all of her royalties — and some of her own money — to create an undergraduate drug discovery lab.
She shared those stories and encouraged members of Emory’s Class of 2028 to start their own remarkable trajectories as the distinguished speaker at the 2024 Atlanta Convocation ceremony, the capstone event for first-year orientation on Tuesday, Aug. 27.
“It is invigorating to see students excited about figuring out what they want to do with their lives,” Gavegnano says. “The beauty of Emory is changing lives.”
Put out the fire, cure the patient
The inner voice that drove Gavegnano to change lives, combined with an undergraduate degree in microbiology and a master’s degree in immunology, encouraged Gavegnano to counter conventional wisdom during her pharmacology PhD studies at Emory.
She first discovered that a class of small molecules known as JAK (janus kinase) inhibitors, including ruxolitinib and baricitinib, shows promise for use in an HIV-1 cure and treatment for other viral infections.
At the time, the prevailing theory for curing HIV called for essentially lighting the virus on fire: reactivating it from the groups of cells infected with dormant HIV particles known as reservoirs, then blasting it with a yet-determined medication.
Gavegnano’s unorthodox idea focused instead on reconfiguring JAK inhibitors — already FDA-approved for inflammatory conditions such as rheumatoid arthritis — to control inflammation from the virus by blocking key pathways that allow the virus to persist.
Instead of lighting a fire, her plan smothered the virus known to deplete the immune system, letting HIV burn itself out while the immune system restored itself.
The discovery became Gavegnano’s PhD thesis. She was in the pre-clinical stage for the use of baricitinib in HIV when the pandemic struck.
She helped treat millions of patients globally by applying the same logic to treat COVID-19’s deadly systemic inflammation and immune dysfunction. The FDA granted her repurposed version of baricitinib emergency-use status in 2020. It has been a first-line treatment drug for severe COVID-19 worldwide since 2022.
That effort has since revealed direct therapeutic paths for the treatment of diverse diseases with JAK inhibitors, and she is pursuing collaborative ongoing human trials for depression, long COVID and HIV-1.
Last year, Gavegnano’s lab showed that ruxolitinib significantly decays the viral reservoir in a subset of people living with HIV, a finding her team presented at the International AIDS Society Conference in Australia.
At the same conference, researchers Asier Saez-Cruz and Alexandra Calmy from the Pasteur Institute and Universite de Geneve presented “The Geneva Patient,” now listed as the sixth person ever cured of HIV following a stem cell transplant — and the first cured without receiving cells that are not resistant to the virus.
Ruxolitinib remains the only intervention for the Geneva Patient, providing hope toward the role of JAK inhibitors for an HIV cure.
“We are burgeoning on the edge of a paradigm shift,” Gavegnano says. “Inflammation is behind so many diseases, and we are poised to act. And our undergraduates are seeing it all, up close and personal.”
Growth with undergraduates
When Emory University licensed Gavegnano’s invention for the method of use of baricitinib for COVID-19 to Eli Lilly, she made what she called “an easy decision” to disperse all of her royalties to creating and directing the Gavegnano Drug Discovery Program.
She also added her own funds to launch the lab that offers students autonomous “front-row seats” to every facet of drug discovery and training.
“There is no kind of program like this on the planet, where saving lives in real-time directly involves, engages and empowers undergraduate students to find their purpose and flourish along that collaborative journey,” Gavegnano says.
Since 2021, undergraduates have been first authors on 40 abstracts from Gavegnano’s lab, with five publications. Two others are co-first authors and, significantly, two of the lab’s five new patents have been awarded to Emory College students.
The success comes from Gavegnano’s approach for her lab to serve as the hands-on demonstration of her undergraduate course on drug discovery, which covers the scientific discovery, policy, public health, research and legal aspects of drug development.
Amanda Michael became one of Gavegnano’s co-authors on a computational analysis of ruxolitinib’s impact on cardiovascular disease in people living with HIV.
Michael enrolled in Gavegnano’s courses on drug discovery and bioethics, thinking they would help her understand the processes behind medications she would prescribe one day as a physician.
She grew so interested in the considerations of drug development, such as access and affordability, that she decided to apply to the Master of Bioethics program at the Harvard Medical School, where Gavegnano had earned a degree following her doctorate.
“I’ve had an amazing experience working with Dr. Gavegnano that’s lasted for three of my four years at Emory and is still going,” says Michael, who graduated from Emory with highest honors in May and began her studies at Harvard this fall. “I still want to go into clinical medicine, but working with a research scientist has opened my eyes to the many ways we can improve lives beyond patient care.”
Students interested in designing and conducting their own research must also consider multiple angles. Gavegnano accepts ideas from anyone if they have first confirmed an unmet clinical need. Participants also must research whether there is open intellectual property space, indicating a gap for a new medication.
“If you put in the work, she is always going to recognize that and keep giving you opportunities,” says senior Kate Siegel, a human health major Gavegnano hired as a second-year student. “It’s endless opportunities. You learn so much when you take things on yourself.”
Siegel spent her first semester in the lab learning different techniques, such as how to culture cells and run the flow cytometry machine, which measures characteristics of samples.
By the second semester, Siegel was designing her own project, trying to replicate Marfan syndrome conditions in cells to see if baricitinib reduces inflammation levels in the genetic disorder that affects the cardiac system.
That’s in addition to her work as one of four undergraduate students assisting with one of two ongoing clinical trials in the lab.
Siegel, who wants to be a physician, has been approved for patient-facing work in a trial studying how baricitinib affects patients with well-controlled HIV. She also transports samples and helps prepare them for analysis in that trial and a second trial, which examines the correlation between inflammation, immune activation and cardiac-related outcomes.
“There are very few universities in this country that offer undergrads this level of research and this level of innovation,” Siegel says. “My biggest hope is that the incoming first-year students understand from her speech that there is a whole other world that Emory has to offer beyond classes.”