Alessandra Porcu had her sights set on being a forensic detective, analyzing crime scenes for chemical clues. Her colleague Chase Francis once dreamed of becoming an astrophysicist.
Their respective academic journeys led them to new interests and, ultimately, to joining the faculty of USC’s College of Pharmacy, pursuing research aimed at helping people affected by depression, stress and anxiety. That focus is the basis for a developmental research grant from the National Institute of Mental Health shared by the two assistant professors.
Porcu is studying the effects of circadian rhythms, including their effects on administering medications at optimal times of day for maximal efficacy. She also studies how blue light emitted from screen devices affects the adolescent brain.
“We’re especially interested in understanding how the adolescent brain changes in response to very common environmental stimuli: stress and blue light,” says Porcu, a native of the Mediterranean island of Sardinia, who earned a Pharm.D. from the University of Cagliari and a doctoral degree in neuroscience from that university and the University of Basel in Switzerland.
"What I’m focused on would be like an add-on therapy to typical anti-depressants with the goal of preventing a depression relapse."
Francis’ research is focused on the nucleus accumbens, a motivation-related area of the brain that is heavily affected in people who have depression. Francis’ study of the nucleus accumbens and Porcu’s research on circadian disruption are the intersection point for their shared NIMH grant in which they are working to better understand how circadian-driven changes in the nucleus accumbens contribute to susceptibility to mood disorders.
“We’re trying to find new ways of stimulating the exterior of the brain to affect the nucleus accumbens,” says Francis, a Charlotte, North Carolina, native who earned a Ph.D. in neuroscience from the University of Maryland. “There also are targets that we’re interested in that affect the circuits of the nucleus accumbens and could be the basis for novel therapeutics for depression.”
As assistant professors in the drug discovery and biomedical sciences department in the College of Pharmacy, Porcu and Francis are laying the basic science foundations in their respective research areas for future development of new pharmaceutical therapies.
To that end, Francis is collaborating with psychology faculty in the College of Arts and Sciences and with USC School of Medicine Columbia faculty in the Department of Pharmacology, Physiology and Neuroscience. “What I’m focused on would be like an add-on therapy to typical anti-depressants with the goal of preventing a depression relapse,” Francis says. “The hope would be that this new therapeutic would help people with depression get to remission.”
"We’re especially interested in understanding how the adolescent brain changes in response to very common environmental stimuli: stress and blue light."
Francis is focused on pathways that emerge from the nucleus accumbens that mediate depression-related symptoms. He’s particularly interested in a peptide called Substance P that has a major role in mediating how animals perceive stress. Francis points to the possibility of off-label use of existing drugs that suppress the activity of Substance P.
“Substance P enhances attention to stressful stimuli, and so, by blocking it, we hope to decrease reactivity to these significant life stressors,” Francis says.
Francis’ research group uses a technique called whole-cell patch clamp electrophysiology to measure activity in single brain cells of rodent models that have been exposed to different environmental stimuli. The technique lends a better understanding of individual neuron’s response to stress and other stimuli important for survival.
Porcu is using rodent models to study how nocturnal blue light exposure affects stress and anxiety levels in the adolescent brain. Blue light emitted from screen devices — particularly phones and laptops — adversely affects mood, cognition and sleep when the exposure occurs after sunset, a function of circadian rhythms.
“Cells in the back of our retina are very sensitive to the blue wavelength, and they activate brain regions that are not supposed to be active at night. This is what leads to problems in the development of the neural circuit during adolescence,” says Porcu, adding that research has shown dramatic increases in adolescent anxiety since the advent of smart phones in 2008.
Porcu’s team uses a technique called fiber photometry, inserting optical fibers in a mouse’s brain to measure neuronal activity while exposed to different stimuli, including blue light. They also use molecular biology assays to screen for RNA and cellular proteins that change because of environmental exposure.
“It’s like having a microscope inside the brain cell to see what is happening,” Porcu says.
Porcu and Francis devoted their first year in the college to establishing their research labs and both are now teaching College of Pharmacy students. Francis primarily teaches first-year pharmacy students fundamental pathophysiology and pharmacology, including neurotransmission, neuroanatomy and basic principles of neurological and psychiatric disorders.
“I believe in active learning — that's the best way for students to learn,” Francis says. “I also try to provide materials outside such as textbook videos so students can see a topic explained in a slightly different way. Instead of just hearing me drone on or ask them a bunch of questions in class, they can get somebody else's perspective.”
Porcu teaches third-year students pharmacology and pathophysiology, including epilepsy, multiple sclerosis, spasticity, Parkinson’s disease and other neural pathologies.
“In our first class, I tell them that pharmacology is like math — if you understand it, you don't need to memorize anything,” she says. “My goal is to make them understand what is happening because it's just like a mechanism.
“I like them to ask questions, to have them involved as much as I can. If they come to the board and interact with the class, they get a prize. And the prize is coming to my lab and doing some brain sectioning, some microscopy, maybe some immunofluorescence with us. And they love it!”