Dr. Meg Fox
Assistant Professor of Anesthesiology and Perioperative Medicine Penn State University School of Medicine Postdoctoral Fellow University of Maryland, Baltimore School of Medicine PhD in Biological Chemistry University of North Carolina, Chapel Hill
Although she’d been a self-identified nerd most of her childhood, Dr. Meg Fox never expected that the feral cat next door would inspire her to become a scientist. Although the cat’s hunting gifts, often the carcasses of small rodents, were a little gross, Meg was also “fascinated by how alien everything looked,” so she performed backyard dissections to uncover the internal mechanisms running their little bodies. Meg’s clear interest with how living things work culminated in her dedicating her career to the “final frontier” of human knowledge, the brain. Now, as an Assistant Professor at Penn State University, she and her lab aim to uncover the circuits and molecules that underlie opioid use, opioid withdrawal, and stress.
As an undergraduate chemistry student, Meg had her first research experience in a lab studying water decontamination. Though seemingly orthogonal to her interests in biology, this taught her many of the basic skills required in neuroscience wet labs: pipetting, making buffers, and performing basic assays using reporter dyes. It was during this period of her science training when she picked up an issue of Chemical and Engineering News magazine with a cover article about measuring dopamine signals in vivo using voltammetry. Voltammetry is a technique in which electrical potentials are used to detect the abundance of certain electroactive chemicals. The article captivated Meg and she decided she wanted to go to graduate school to learn how to use voltammetry to study monoamines, like dopamine, in the brain.
As a PhD student in Dr. Mark Wightman’s lab at UNC Chapel Hill, Meg learned how to use voltammetry to study norepinephrine and its role in the neural adaptations that occur in rat models of stress and opioid dependence (which share many symptoms). Understanding the neural bases of processes underlying opiate addiction was very meaningful to Meg as she had personally witnessed the devastation that opioid dependence can cause people, including friends and loved ones. Her thesis work involved measuring the dynamics of dopamine and norepinephrine in response to both exposure and withdrawal of the legal opiate morphine in the awake rat brain. She studied how dopamine and norepinephrine signaling change in two brain areas, the nucleus accumbens and the bed nucleus of the stria terminalis, or BNST. Meg found that, in these two structures, dopamine and norepinephrine work in balance in opioid addiction. Specifically, during morphine exposure, dopamine increases in the nucleus accumbens and norepinephrine remains unchanged in the BNST. During symptoms of withdrawal, dopamine decreases in the nucleus accumbens, but norepinephrine increases in the BNST. Her results highlighted the role of norepinephrine in mechanisms of opioid addiction, which until then had been largely overshadowed by dopamine.
Despite the success of her thesis work, Meg acutely felt the pressure of being a woman scientist in an established lab that often had the atmosphere of “an old boys club.” She had to consistently advocate for herself and her results, and she had to push even harder when her observations challenged the previous findings of the literature. Although she always had a good relationship with her PI, Meg has never forgotten how valuable it was to have a few women labmates and mentors to support her, especially Zoe McElligott (now a professor at UNC), who was a postdoc in the lab at the time.
After learning how to measure the activity of neurotransmitters in neural circuits during her PhD, Meg wanted to learn how altering neurotransmitters could change neurons – when dopamine and norepinephrine are altered in opioid use, how does it affect the cells themselves, and what genes drive these changes? To answer this question, she joined a molecular biology lab led by Dr. Mary Kay Lobo at the University of Maryland School of Medicine. During her postdoctoral research, Meg studied how chronic stress and opioid use alter the growth and shape of dendrites in dopamine-receptive neurons in mice. She found that chronic stress can cause different dendritic changes in two types of nucleus accumbens neurons: dendrites shrink in dopamine receptor D1 neurons, while they become more bumpy in dopamine receptor D2 neurons. Meg wondered whether opioid use led to a similar pattern. When she looked at mice experiencing withdrawal from fentanyl, a powerful and often deadly opioid, she found similar changes in the shape of the dendrites, but not through the same pathway as in stress. Instead, a different pathway regulating gene expression was altered. To make it more complicated, the molecular response to opioid withdrawal was dependent on the sex of the mouse, even though the neurons looked similar across sexes. Although her results were not what she expected, Meg discovered important mechanistic differences between chronic stress and opioid withdrawal. Her postdoc work highlighted an exciting new avenue for drug development to treat the most challenging symptoms of addiction and withdrawal from opioid drugs.
In 2020, Meg accepted a position as an Assistant Professor at Penn State University in the Department of Anesthesiology and Perioperative Medicine, with a dual appointment in the Department of Pharmacology. In doing so, she joined the cohort of young faculty challenged to start their labs in the midst of a global pandemic. Due to hiring challenges and illness during COVID, starting the lab was extremely challenging, and Meg often had to fill the role of PI, lab manager, and lab tech all on her own. “I feel like I’m drowning at least two days out of the week,” she says. Despite the persistent challenges, her lab just celebrated its one-year anniversary, and things are finally getting a little easier. Meg is continuously learning to be patient and flexible with the process, and it’s been especially helpful to hire people who are passionate about science and excited to be there.
Meg’s lab at Penn State combines her graduate and postdoctoral work to study the effects of stress and opioid self-administration in the ventral tegmental area, a brain region that is the source of dopamine to the nucleus accumbens. She hopes for her research to inform not only treatment for addiction, but also things like pain management in clinical settings, like how opioid medication might affect both mother and child during labor and delivery. The field can look forward to the scientific gifts Meg's research uncovers, which will help the scientific community better understand and treat opioid abuse (without the ickiness of the hunting gifts from her feral cat friends).
Find out more about Meg and her lab’s research here.
Listen to Rianne’s full interview with Meg on October 15th, 2022 below.
