'Drug discovery' courses showcase bench-to-bedside process

Emory College undergraduates were among the first people Christina Gavegnano wanted to tell about a new study that confirmed the drug she co-invented is the gold standard in saving the lives of critically ill COVID-19 patients.

The students in question are in the packed drug discovery course that Gavegnano, an assistant professor in the Emory School of Medicine, is teaching for Emory College's Center for the Study of Human Health.

Gavegnano, listed with Emory antiviral expert Raymond Schinazi as sole co-inventors of the drug baricitinib, also has taught a bioethics course this spring and led a course on vaccines and inflammation last fall. The coursework, which returns next year, is part of a new human health initiative to expose students to the full bench-to-bedside process that needs scientists, clinicians, lawyers, policy makers and others to work.

"Science requires collaboration to be empowering in the real world," Gavegnano says. "The students absorb that, because it's happening in real time, and we're just giving context to it."

Applying context is a hallmark for human health, which integrates the liberal arts emphasis on critical thinking with Emory's renowned health sciences research. The COVID-19 pandemic further drove home the many ways the human experience ties to health — and the important role of unconventional thinkers such as Gavegnano.

An unorthodox approach to discovery

Emory professor Christina Gavegnano

Christina Gavegnano's courses related to drug discovery and human health will be offered to Emory College students again next year.

Twelve years ago, conventional wisdom for a cure for HIV called for essentially lighting the virus on fire: reactivating it from reservoirs, then blasting it with a yet-determined medication. Gavegnano's idea was more unorthodox: modulate immune pathways in a virus known to deplete the immune system, in a way that was more akin to putting a lid over the viral fire, letting it burn itself out while the immune system restores itself.

The result was a class of drugs that Gavegnano discovered in 2012 known as JAK (janus kinase) inhibitors for the specific family of enzymes they regulate to tamp down inflammation.

Getting the FDA to approve the first of them — ruxolitinib — took years of study, tests and ultimately human trials that Gavegnano co-led with Vincent Marconi, a professor of infectious diseases and global health at Emory School of Medicine.

Baricitinib, a second-generation JAK inhibitor approved for long-term use and in children as young as two, earned FDA approval for rheumatoid arthritis in 2018.

Gavegnano had begun pre-clinical work with baricitinib for HIV, with the goal of supporting future human studies, when the pandemic struck. In 2020, her work became the foundation of repurposing baricitinib to treat the systemic inflammation and immune dysfunction from COVID-19 that was killing patients.

Understanding immunology in real life

In February, the global COV-BARRIER study revealed baricitinib significantly reduces risk of death for ventilated patients. The World Health Organization has since issued a "strong recommendation" for worldwide use.

"Our goal is to train and educate our students to be leaders in jobs that don't exist yet," says Michelle Lampl, Charles Howard Candler Professor of Human Health and Samuel Candler Dobbs Professor of Anthropology, who directs the Center for the Study of Human Health. "Dr. Gavegnano's depth of scientific knowledge and willingness to be counter-paradigm illustrates the importance of being forward-thinking when it comes to health."

Lampl first invited Gavegnano to be a guest lecturer in her predictive health courses last year, where Gavegnano shared her lab work focused on inflammation as it relates to how viruses cause disease.

college student in class wearing mask

Merissa Coleman, a senior studying human health, says being part of the class has helped show how multifaceted health is.

Students showed so much interest in her discussion of the immune system and inflammation that it led to the vaccine and immune system course last fall.

Keri Kramer, a senior human biology and anthropology major, was among students in that course, where each discussion about what's known about the immune system led to more unanswered questions.

"Dr. Gavegnano did a great job of reminding us inflammation is a huge cause of disease, mental health disorders and so many other things that affect your health," says Kramer, who plans a gap year working before attending medical school. "I 150% want to include immunology in my career, because it is relevant in every field of medicine."

Senior human health major Merissa Coleman, who also took Gavegnano's course last fall, enrolled in the drug discovery course because it seemed like a continuation of questions into the social and biological aspects of health by covering the scientific discovery, policy, public health, research and legal aspects to drug development.

"The class really shows how multifaceted health is," Coleman says. "Too often, drugs are not tried first on people who would benefit the most, but we saw how the special considerations in the pandemic revealed how important it is to consider how we are thinking about all of the pieces that fit together in health care and our own health."

Coleman starts a job connecting health care operations and patient outcomes this fall, after a summer working on protocols and policy in Gavegnano's lab. She is torn between whether she will eventually return to school for a public health master's degree focused on health care policy or a PhD in immunology.

After living two years with a virus that has extracted a terrible human toll, Gavegnano loves to hear that her research may have as much an effect on future researchers as it does research.

"Living immunology and drug discovery in real life has transformed how we work and think," Gavegnano says. "What these students are learning is revolutionary if only because they are seeing the demand for practical knowledge and creative thinking."

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