Editor’s note: Eight young pain researchers were recently selected to provide interviews, news articles, and other content as part of PRF’s Virtual Correspondents Program, which provides a science communications training experience for program participants. The following interview comes courtesy of PRF Correspondent Melanie Schaffler. (Also see the Correspondents’ blog posts here.)
Theanne Griffith, PhD, is an incoming assistant professor at the University of California at Davis (UC Davis), US. She completed her PhD at Northwestern University, Chicago, US, did postdoctoral training in the lab of Dr. Ellen A. Lumpkin at Columbia University, New York City, US, and most recently was an instructor at Rutgers University, Newark, US. Her current work focuses on how peripheral sensory neurons encode different bodily sensations, particularly temperature change and thermal hypersensitivity.
Griffith took time to talk with Melanie Schaffler, a PhD candidate at the University of Pennsylvania, Philadelphia, US, via Zoom. Griffith discussed her journey to pain research, her plans for her new lab at UC Davis, her career as a children’s book author, and more. Below is an edited transcript of their conversation.
What brought you to research in the first place, and ultimately to sensory biology research?
I went to Smith College and was fortunate enough to be part of a scholarship program for underrepresented science students. So instead of working in the kitchen or somewhere else on campus, I could translate that work-study money into hours in the lab. I did research and electrophysiology right out of the gate; I was doing two-electrode voltage clamp in Xenopus oocytes, looking at GABA receptor pharmacology and modulation. Then, in grad school, I continued along the ion channel, ligand-gated receptor route and studied kainate receptors, a member of the ionotropic glutamate receptor family, using patch clamp electrophysiology.
After all of this work on ion channels and receptors, I was very much interested in them, but I wanted to study them in more of a physiological context. I was really attracted to the peripheral nervous system because I felt that the things that it was encoding, these bodily sensations, were very tangible for me; I know what cold feels like, I know what touch feels like, I know what pain feels like. A lot of the work in the glutamate receptor field focuses on learning, memory, fear, and anxiety, and all of those things are very abstract concepts in my opinion – definitely worth studying, but for me the tangibility of somatic sensations was very attractive.
During my postdoc with Ellen Lumpkin, I investigated mechanisms of excitability in dorsal root ganglion [DRG] neurons, and then I homed in on a population of putative cold-sensing neurons, found some really cool physiological aspects, and decided to pursue that line of investigation.
What do you feel are your most significant or exciting findings so far?
I was looking at a population of small-diameter DRG neurons, and the dogma states that in small-diameter neurons, you have a predominant effect of Nav1.8, Nav1.9, and Nav1.7 on excitability; that’s what people think about when they think of small-diameter neurons. On the other hand, when you think about large- or medium-diameter neurons, you think about Nav1.1 and Nav1.6.
I found the exact opposite. The menthol-sensitive DRG neurons that I was studying are small diameter, but I found that their action potentials were entirely TTX-sensitive. TTX is a voltage-gated sodium channel blocker that will block just about everything except Nav1.8 and Nav1.9, so the fact that the action potentials were sensitive to the TTX meant that Nav1.8 and Nav1.9 were not contributing to the excitability of this population under our conditions.
Additional pharmacological studies that I did showed that, indeed, Nav1.1, which is again thought to be predominantly in large-diameter neuron populations, was largely responsible for action potential firing in these small-diameter, menthol-sensitive neurons.
It’s not necessarily surprising that these highly excitable small-diameter neurons could rely on Nav1.1, but people just weren’t thinking about them that way. Most of the data that was out there tended to look at cold pain, and the initial conclusion was that excitability was regulated by Nav1.8; no one was thinking about Nav1.1. So that was pretty exciting.
What are the translational applications of that work?
One thing that I’m really excited about and that I’m actively working on now is determining whether or not Nav1.1 has a role in cold pain. Cold pain is the prominent feature of several human pathological states, one of them being a certain form of chemotherapy-induced peripheral neuropathy. Oxaliplatin is a commonly used chemotherapy drug for colon and rectal cancer patients. However, it has this very unfortunate side effect in that it produces cold hypersensitivity. That can be either acute, like an immediate feeling of cold, or it can become chronic with prolonged treatment whereby even opening a refrigerator is very uncomfortable and painful.
I also plan to study pain in sickle cell anemia, but this is a little bit more long term because it’s somewhat complicated to address. One of the main neurological consequences of having sickle cell is severe pain, and how and why that happens is not clear. We know that cold can trigger these pain crises, but the mechanisms behind this are very unclear. So I’m really excited to tackle that question because it’s interesting scientifically, but also because sickle cell is most common in Black people, and I would love to be able to address a research question that will specifically help my community. Largely, research tends to overlook diseases that predominantly impact Black people.
More broadly, where do you see the field moving in the future?
I would definitely love to see more in vivo approaches – using optogenetics or in vivo imaging in freely moving animals to really understand how synaptic integration and synaptic transmission are happening in an in vivo context. This gets complicated when you’re looking at the spinal cord or DRG. When you’re looking at the brain, you can head fix a mouse and have them move on a ball, but it’s much more difficult to image or record from neurons in vivo if you’re looking at the part of the body that’s moving. But I think that will be important in the future.
You recently announced that you’re starting your own lab at UC Davis! What are some of the first projects or experiments you want to get up and running in your new lab?
I am so excited. Right now I have a mouse model that allows me to look at the contribution of Nav1.1 specifically in DRG neurons, so I’m really excited to do some behavioral testing to determine whether or not Nav1.1 is playing a role, in vivo, in thermal sensation, as well as use that same mouse model in different pathological states that involve cold-sensing neurons, such as the oxaliplatin model of chemotherapy-induced peripheral neuropathy.
Now that you have the freedom of being a PI, what is a piece of lab equipment you’re very excited to buy, and why?
I’m really looking forward to building – I guess it’s not just one piece of equipment – but building an electrophysiology rig that can be used for both in vitro and in vivo recordings or imaging; that’s definitely something that I’m hoping to do. I’m all about moving in vivo as much as possible.
With in vivo DRG recording, you can look more directly at excitability and how that could be affected by either loss of a given channel or a pathological condition. Or you could look more at the population-encoding level and do some in vivo calcium imaging to determine, using different Cre drivers, for example, what cells are responding to what stimuli and how that can be altered under pathological states or a different context.
To shift gears a bit, I want to ask you about your career as a children’s book author. Can you tell me a bit about your books, The Magnificent Makers, and how you got started writing them?
I’ve always been an avid reader, and I’ve always really enjoyed writing, but I don’t think I ever saw it as a career per se, despite always wanting to eventually write something and publish a book. But then fast forward through grad school and to my postdoc. I was on maternity leave, so I had a lot of time to sit and think about what I wanted to do with my life, and I decided that now is the moment; I’ve always had this dream and I wanted to make it a reality.
At this point I’d really developed a scientific career, and so I wanted the books to be focused on science. I’ve always been interested in writing for kids; their imagination is just so vivid, and it’s such a fun age to tap into and write for. I just launched myself into it: I created a website, I started participating in Twitter contests, and obviously, I started writing.
Then I had an editor – this was very serendipitous and not common – at Random House directly reach out to me because she saw that I was a scientist, and she was looking to acquire a STEM [science, technology, engineering, and mathematics]-themed chapter book series. So I did some research and put together this idea for her, and after a lot of back and forth, and six to eight months, The Magnificent Makers were born, and we had a contract for three books.
The Magnificent Makers follow best friends, Violet and Pablo, on these out-of-this-world science adventures in a magical laboratory called the Maker Maze, and once they’re in the Maker Maze they go on science challenges, and they have 120 Maker Minutes to finish; otherwise, they don’t get to come back. Because they love science so much and they have so much fun in the Maker Maze, they’re always rushing to finish these challenges.
Also, at the end of the books, there are hands-on activities for kids to do at home that are pretty easy and usually involve things that you find around the house. That was important to me because science is about doing, most of the time – it’s not just about reading and memorizing facts – and I definitely wanted to weave that in there.
It definitely has some Magic School Bus vibes going on, but a big difference is that the two characters are Black and Brown kids, and that was also really important for me. It’s not something that I explicitly tackle in the books because I didn’t want to; I wanted to make it about kids having fun doing science, and enjoying it and being good at it, but I wanted those kids to look like me. I didn’t see kids that looked like me doing that much science when I was younger, so there definitely was a gap in the market for these books.
What keeps you motivated to be both an active researcher and an active children’s book writer?
We know that day-to-day science can be challenging, and you have bad days and you have great days. For me, sometimes when I’m having a bad day and I go into The Magnificent Maker world, I’m like, oh, yeah, science is fun. I don’t hate science; I actually love it, and I want other people to love it. So it helps me recharge my batteries.
I want to highlight that there are so many aspects of our training as scientists that make writing, even fiction writing, a pretty nice side hustle. As a trainee I attended a ton of writing workshops, and even though the style is different, there are so many things that are directly applicable – even the process of revising, going back and forth with an editor, and receiving critiques on your work and not feeling upset about those critiques. We’re so used to this back and forth and making things better; there are so many aspects of our training that can really be directly related to this side writing career. So it makes it not as much of a tangent as it seems, especially when you’re writing about science.
So would you say that your new career in writing influences your perspectives or experiences as a researcher?
It does remind me why I’m doing what I’m doing – it’s that initial spark and joy that I had when I was 16 years old in AP [Advanced Placement] bio and learned about the sodium-potassium pump for the first time. It refreshes me and motivates me to keep moving forward even with something that’s frustrating and not working out. There are kids who want to be doing what I’m doing, and they need to see me doing it, so keep at it.
Do you have any advice for young investigators or others trying to get involved in science communication?
If we’re talking about science communication through writing fiction books, or writing children’s books, or even nonfiction books for adults, the important thing is to just get started – just go for it. The market is there, and publishers love to have someone with the credentials that we have. Even if you haven’t finished your PhD yet, you’re still a scientist, you’re still trained in science, you have expertise that publishers are really excited about.
It’s not easy, and my experience is not typical; it typically takes a lot longer to break into the publishing industry. So just keep at it. We’re very accustomed to failure and repetition in science, so harness that energy and take that to the publishing world and just go for it. Our stories are necessary and needed and wanted, so just start writing.
Is there anything else that you would like to mention?
I want to reiterate that there is definitely a need and a want for science writers to write mainstream books for kids. So if that’s something that people are interested in doing, the opportunity is there. Also, I’ll eventually be hiring grad students and postdocs for my lab, so stay tuned for that!
Melanie Schaffler is a PhD candidate at the University of Pennsylvania, Philadelphia, US.