Dr. Janine Kwapis
Assistant Professor of Biology, Penn State University
Postdoctoral Fellow University of California, Irvine
PhD in Psychology University of Wisconsin-Milwaukee
written by Caitlin Ashcroft
As an undergraduate, Dr. Janine Kwapis had some trepidation about starting a class in biological psychiatry, having been warned to avoid it because it was “too hard”. Today, however, she’s grateful she wasn’t scared away, as it was that course that helped her discover a lifelong interest in the biological mechanisms of memory. Janine is now an Assistant Professor of Biology at Penn State University, where her lab investigates the epigenetic and molecular processes that underlie memory formation, storage, and updating. While Janine imagines she could have been happy in a range of different careers outside of academic research, she loves having a job where every day is an opportunity to learn something new about the brain.
Janine took the biological psychiatry class as part of her Psychology major in college. The class examined memory at a cellular and molecular level and Janine remembers being astounded that biological mechanisms on that scale could be used to explain processes as complex as memory. “I just thought it was the coolest thing ever!” This newfound fascination with the neuroscience of memory led her to apply to grad school, where she joined the lab of Dr. Fred Helmstetter at University of Wisconsin, Milwaukee.
Janine had little lab experience going into grad school, so the start of her PhD involved a steep learning curve. Looking back, she admits “I had no idea what I was getting into… [and] no idea about any of the basics”. Thankfully, she found herself in a supportive lab with plenty of people who were willing to take her under their wings and teach her the techniques and lab skills she needed to know. Initially, Janine recalls feeling behind compared to the other grad students that started in the lab at the same time. Eventually, through a combination of time, perseverance, and a supportive and collaborative work environment, Janine’s PhD project started to blossom.
The focus of Janine’s PhD was investigating the regions of the brain involved in forming and extinguishing different kinds of fear memories. ‘Fear conditioning’ refers to associative learning paradigms in which animals learn to associate a neutral stimulus (e.g a tone) with an aversive experience (e.g a footshock). Many papers studying fear conditioning use a variant known as ‘delay fear conditioning’, in which the neutral and aversive stimuli are delivered simultaneously or directly after each other. There is another variant of fear conditioning, however, known as ‘trace fear conditioning’ in which the two stimuli are separated by a few seconds. The gap in time between the neutral and aversive stimulus in trace conditioning means animals must rely more on their conscious/explicit memory to learn the association. Janine was interested in whether the mechanisms required to form and extinguish these complex trace memories were different from those required for simpler delay memories.
Using infusions of protein synthesis inhibitors in the basolateral amygdala, Janine first demonstrated that the amygdala is required for the formation of both trace and delay memories. She then tested which regions of the brain were necessary for the extinction of these memories using infusions of glutamate receptor blockers. Here she found a striking difference. While the amygdala was critical for the extinction of simple delay memories, Janine found that complex trace memories appeared to rely on a more distributed, cortically-dependent circuit involving regions of the brain such as the retrosplenial cortex. In addition to demonstrating that the updating of simple and complex memories relies on different neural neural circuits, this finding also suggests that studies only using one kind of fear conditioning may not be capturing the full extent of mechanisms underlying different kinds of memory.
Halfway through her PhD, Janine was asked by a visiting academic if she had any thoughts on what she wanted to do for her post doc. She told him that she was interested in studying the epigenetic basis of memory, having recently become interested in epigenetics following a fascinating class on gene regulation she took in grad school. He suggested she reach out to Dr. Marcelo Wood at University of California – Irvine. A few years later, she set off to sunny California to start her post doc in the Wood lab.
The project that made up the majority of her post doc work arose, as is often the case in research, rather serendipitously. Around the time Janine joined the lab, she learned that the lab’s mouse colonies had not been properly maintained and were now overrun with old mice. She decided to put these old mice through some behavioural paradigms and found that they showed age-related reductions in performance on spatial memory tasks. This age-related deterioration in memory was reversed by deleting or disrupting the histone deacetylase enzyme HDAC3 in the hippocampus: a ‘molecular memory break pad’ that catalyses the removal of acetyl groups from DNA histones and has been found to impair memory. A particularly surprising finding from this work was that the effect of HDAC3 disruption on long-term memory was mediated by the circadian clock gene Per1. Janine observed that HDAC3 deletion increased experience-induced expression of Per1, a gene she later demonstrated through genetic knockdown is critical for long-term memory formation. Janine admits that when she first identified Per1 as a key gene associated with HDAC3-mediated memory changes, she was sure something must have gone wrong as it seemed strange for a circadian gene to be involved in memory. Nonetheless, after double-checking their results and looking back at previous experiments, she gradually became convinced that the effect was real.
With some exciting results under her belt, Janine recalls starting to feel a bit restless towards the end of her post doc. “You get a bit frustrated towards the end because you’re capable of doing the experiments and know how to ask your own questions, but still need to run [everything] by the PI.” She admits that this was likely a good sign that she was ready to become an independent researcher.
Janine set up her lab at Penn State University in 2019. The current focus of her lab’s work is attempting to understand the relationship between memory and circadian systems by studying the expression and role of the circadian gene Per1 in regions of the brain involved in memory. Unpublished work from the lab suggests that Per1 may act as an interface between the circadian clock and memory by exerting local circadian control in whatever brain region it is expressed in. Understanding this effect better could offer insight into why memory performance has been found to change across circadian cycles. Although Janine had a clear vision of what she wanted her lab to study from the start, she still found setting up her own lab very daunting. “The first day of starting my lab felt like it lasted for 45 years. No one came to check on me, it was just me and my research technician…” She admits that if she could go through the process of setting up her own lab again, she would probably try to put less pressure on herself. ‘There was no one competing against me, but it felt like I needed to get that first experiment off the ground and my protocols ready to go on day 1.’ While she acknowledges she could have slowed down a bit in those early days, she still remembers how ecstatic she felt the day her first experiment worked and what a powerful reminder it was that — despite all the stress and occasional bouts of imposter syndrome — she deserved to be there.
Four years in, Janine still gets a huge kick from coming into the lab and seeing her students and postdocs doing experiments. When she first started as a PI, she thought a lot about the elements of her previous supervisors’ mentorship style she wanted to bring to her own lab. She quickly realized, however, that being a mentor is something you have to figure out on your own. ‘I am who I am and there’s only so much I can do to change that!’ Over the last several years, she learned that the mentorship style that worked for her as a student is not necessarily what works for others. She tries to encourage her students to take responsibility for their own projects and develop ideas on their own, but also strives to meet them where they are and tailor the amount of support she gives to individual students’ needs. Ultimately, Janine wants to foster an environment where people have the encouragement, creativity, and independence they need to truly thrive in their scientific careers.
Find out more about Janine and her lab’s research here.
Listen to Rianne’s full interview with Janine on September 12, 2022 below!
