Episode 07: Theanne Griffith, PhD

The following interview was conducted in-class, during the Spring 2021 session of Hidden Figures: Brain Science through Diversity, taught by Dr. Adema Ribic at the University of Virginia. What follows is an edited transcript of the interview, transcribed and edited by Paavan Bonagiri and Tessa Webster, who also drafted Dr. Griffith’s biography. The final editing was by Dr. Adema Ribic. The original recordings are available in Podcasts.

Dr. Theanne Griffith attended Smith College, where she received a B.A. in neuroscience and Spanish. She completed her post-baccalaureate at the Catholic University of Chile and her Ph.D. at Northwestern University. At Northwestern, Dr. Griffith worked under Dr. Geoffrey T. Swanson studying glutamate receptors using patch-clamp electrophysiology. Her postdoc was in Dr. Ellen A. Lumpkin’s Lab at Columbia University (at the time), where she studied sodium channels’ role in mediating action potential firing. Currently, Dr. Griffith has her own lab at the University of California, Davis, where she studies somatic sensations and aims to understand how temperature is encoded in health and disease. The Griffith Lab studies dorsal root ganglion neurons, specifically looking at menthol-sensitive neurons. In her lab, she found that Nav1.1 is a critical mediator of excitability, suggesting that it could be contributing to cold-sensing in vivo. In addition to her research, Dr. Griffith is the author of The Magnificent Makers, a STEM-themed children’s book series featuring a diverse array of characters. The books in her series aim to close the science-literacy gap and merge core scientific concepts with important life lessons.

Dr. Griffith, can you tell us a bit about your background?

I was born in Pennsylvania but was raised in Springfield, VA, where I attended West Potomac High School. My mother and father were both college professors, my mother in sociology, and my father in economics.

How did you become interested in neuroscience?

I was first introduced to the field of neuroscience through AP programs! Math was not my strong suit, but I always loved science, especially in terms of biology. I was really exposed to neuroscience through AP Biology. I took the class as a junior, while most of the people who took it were seniors. I did very well in the class, but I was kind of lazy in high school. I only scored a 3 or something on the AP exam, but I still did well in the class. I was exposed to neuroscience through the use of the sodium-potassium pump and how that creates an action potential that neurons use, etc. I was enthralled simply by the electrical aspect of neurons.

How did you end up at Smith College?

In high school, I had a very supportive guidance counselor, who was also a black woman. She encouraged me to apply to Smith College. My mother was also very interested in the idea of me going to Smith. I applied to Oberlin (because I had a teacher that was an alum), Washington and Lee, and Bucknell. When I visited Smith, I just fell in love with it. Smith had a Neuroscience Major affiliated with the Biological Sciences Department, something that was uncommon at the time.  Moreover, Smith has the largest animal research facility, where I really found love for neuroscience.  It also gave me ample opportunity to conduct research.

What kind of research did you conduct at Smith?

I participated in research all four years of my undergraduate career. I was able to receive work-study hours due to an underrepresented student grant, which basically means that I was paid to do research with money and credit. In the lab, I used a lot of two-electrode voltage clamps in which we harvest two eggs from a frog (oocytes), inject them with mRNA that codes for a given protein, and then record the current that is passed through that protein/channel. We specifically studied GABA receptors and their roles as anesthetic targets to understand menthol and propofol action. We asked the question of whether or not we could design a novel compound that has the better anesthetic properties of propofol, but without the toxic properties. This gave me my first taste of electrophysiology.

What motivated you to major in Spanish as well? And what were your experiences abroad?

As I was talking about before, I was raised in the Northern Virginia area. This area has a large El Salvadoran population– I had many friends whose families spoke Spanish, and I just wanted to learn Spanish. I took Spanish in high school as well. I studied abroad in Chile and simply loved it. Smith had a summer internship fund in which they would pay for unpaid internships, so that allowed me to go. Here, I kind of left electrophysiology and learned more biochemical techniques– things like western blots and transgenic mouse models. I was then invited back for another two years through a post-bac program. This lab was the first time I really felt pressure to publish something. At Smith, the emphasis was very much on learning, not a real “publish or perish” environment.

I learned many Spanish words of science before I learned them in English, which led to some funny stories when I came back to the US. For example, when doing a Western blot in Spanish, the word for “develop” is revelar, which directly translates to reveal. When I came back to the States, I said I was going to reveal my blot, to which my colleagues responded, “you mean develop?”

How did attending an all-women’s college impact your experience as an undergraduate researcher? Did it make it more or less difficult when going into future research?

I one hundred percent think that it made it less difficult. I’m really happy that I chose to pursue my scientific career at a women’s college because there’s actual data that shows that there are more women scientists who are graduates from women’s colleges than from co-ed colleges. I think it’s because it’s during this very critical time where you’re developing your intellectual identity. When you’re in a single-sex all-women’s classroom, you’re not necessarily worried about “looking dumb,” or you don’t have over-eager male students raising their hand more quickly than you because they don’t have some of the insecurities that you might have about answering a question. I think that’s just a common thread–if you remove some of the contexts, whether it’s the racial context or the gender-based context, it allows for those minoritized groups to feel a little bit more comfortable.

Can you tell us about your doctorate at Northwestern?

I always wanted to return to the States for my doctorate and I ended up at Northwestern. I loved the city and had a particular affinity for the lack of over competitiveness that I saw at some Ivy League schools. Here, I returned to electrophysiology, where we did patch clamp. This is another way of measuring currents; this time for glutamate receptors and how kinase receptors were modulated by auxiliary subunits. I made a bunch of chimeric proteins in order to determine what domain was really doing what. The focus was really ion channel biophysics– studying the physical properties of these biological molecules to see how they worked.

I obviously loved my time studying for my doctorate but I also had a difficult time. Getting a little more personal here, my mother was diagnosed with breast cancer around orientation. And she did pass away my 4th year.  However, I believe that this made me very resilient– I was studying for finals in hospital rooms and flying back and forth between school and Baltimore.  Moreover, I believe that it made me more committed to doing well–if I’m here instead of with my mother, I better be doing well!

We are sorry to hear that. How was your postdoc experience?

I love ion channels and how they worked, but I did not enjoy the biophysical experiments. I was more attracted to somatosensory systems because I felt that it was more tangible; research about memories and ion channels were less easy to conceptualize. I was at Columbia for my postdoc, where I joined the lab of Ellen Lumpkin. I studied mechanosensation and specifically how tactile sensations are sent. I applied my knowledge of ion channels and receptor function in order to try to understand how they regulated action potential firing in different neuronal populations. We need to understand how this works in order to understand somatosensation. This was the first time that I had a woman as my mentor. Moreover, I became a mother during this period, twice in rapid succession; Violetta was born in April of 2017, and Leila was born in November of 2018. I can’t divorce my identity as a mother and as a scientist, they go hand in hand.  Motherhood is a big part of who I am as a scientist and my children are definitely a big motivator to keep moving forward when things get tough.

What did you do after your postdoc?

My postdoc ended somewhat prematurely because Ellen took a position at UC Berkeley. I felt that it was too early for me to enter the job market. So, what happened was that my partner, who was at Rutgers, was able to negotiate a non-tenure position in October of 2019. I then made the move from Columbia to Newark, NJ. Shortly after I started at Rutgers, a position opened up at UC Davis. I had strong mentors at the time that encouraged me to apply, even though I felt as if I wasn't qualified.  I interviewed on March 1 at UC Davis right before there was the first community case of COVID, right before everything shut down.  I was eventually offered the position at UC Davis and was able to negotiate an associate tenure position for my husband as well. I moved in September of 2020 and started October 1, 2020.  I have been studying mammalian thermosensation– what ion channels are critical in transmitting thermal signals in both health and disease.

What does your current lab study?

I study somatic sensations. Our lab is particularly interested in temperature and when that temperature turns into pain. Normally, you go outside and it's cold so you put on a jacket. But for people who have different neuropathies or diseases that cause thermal hypersensitivity, that cool feeling becomes very painful. So even opening a refrigerator and getting a cool burst of air from the refrigerator hurts. We’re very interested in understanding how temperature is encoded in both health and disease. I think that we really take for granted our ability to detect these somatic sensations. Could you imagine if we couldn’t feel touch? You wouldn’t be able to navigate your environment. That’s also reflected in the limited number of genetic diseases in which these sensations are compromised; they are just so fundamental to survival. Therefore, understanding how they work is also a really basic and important question.

Which types of neurons do you study?

The neurons I study are these DRG neurons (called dorsal root ganglion neurons). They form these ganglia which line the spinal cord. Each neuron is called pseudo unipolar; all that means is that it has one axon coming out, and that axon then splits into two.

Can you tell us about your research on voltage-gated sodium channels?

I was really curious about voltage-gated sodium channels. There wasn’t a lot known at the time about which voltage-gated sodium channels were working in these cold-sensitive neurons. Voltage-gated sodium channels are really critical for action potential generation; their opening is what leads to the upshoot of the action potential and so they’re going to be key regulators for excitability. We took a pharmacological approach where we can use selective blockers to try and figure out which of the isoforms that are expressed in adult DRG are contributing to action potential firing. In the end what we found using all of our different blockers was that Nav1.1 was a critical mediator of excitability in this population. That was really exciting and unexpected.

Can you tell us more about this?

What we found is that when you block Nav1.1, you lose action potential firing. So in theory, if there’s no Nav1.1, you’re going to reduce transmission from these cold sensing neurons. If we delete Nav1.1 in a mouse, does it then have trouble sensing cold?

Nav1.1 is not just in DRG, it’s everywhere. It’s in the brain and is really important for brain function. Mutations in Nav1.1 are really common and cause epilepsy. You can’t just knock out Nav1.1 in the entire mouse. So, we used a genetic strategy that allowed us to specifically knock out Nav1.1 in dorsal root ganglion neurons.

Can you explain the two-plate temperature preference test you use?

What we can do with this setup is that we have two plates, and we can set them to two different temperatures (one warmer and one colder), and see which plate the mouse spends the most time on.

When the mice were given a choice between 25 degrees Celsius and 21 degrees Celsius, both the conditional knock-out animals and the control animals spent the same amount of time on the 21degree plate– there were no altered preferences there. But, when we lowered the plate from 21 to 15, and then asked the mice to choose between them, the knockout animals spent significantly more time exploring this cold plate than the controlled animals did. This was an exciting in vivo demonstration that indeed Nav1.1 could be contributing to cold sensing in vivo.

How did you come up with the idea to look specifically at the sodium channels in your research? Can you explain your thought process and how you focused on those specific sodium channels?

When I was doing these experiments, I was using an approach called current-clamp that allows me to look at changes in membrane voltage, which is what in the end an action potential is. We can do different analyses to quantify this data: some of the parameters that I quantified were the number of action potentials that were generated, how quickly they occurred, and how big they were. I also did this analysis called phase-plot analysis, which basically takes the derivative of the change in voltage over time and plots that against different membrane voltages. In doing this, we can determine when the action potential threshold occurs. Voltage-gated sodium channels are really going to be the ones determining action potential threshold. I saw that in these menthol-sensitive putative cold sensing neurons, the action potential firing initiated at a more hyperpolarized membrane potential. Another thing that I noticed was that the cells’ resting membrane potential was pretty depolarized. Cells in culture will normally sit at -70 mV– that’s our resting membrane potential. But dorsal root ganglion neurons tend to sit at more depolarized potentials. These cells were sitting at -40 mV and their action potential threshold was close to -30 mV; they’re sitting at a membrane potential that’s really close to their ability to generate action potentials. Both of these things together made me think that there was something special about the voltage-gated sodium channels.

Which techniques are most used in your lab?

The main techniques that we use are electrophysiology, where we’re either measuring action potentials using current-clamp or recording voltage-gated currents using voltage-clamp. We’ve also ventured into the world of transgenic and mouse models, and conditional knock-out animals. We use them to behaviorally examine the way in which ion channels are functioning in thermosensory neurons. We also do a fair amount of immunohistochemistry and molecular profiling using a technique called RNAscope, which allows us to look at mRNA expression using fluorescent probes. We can look at several different mRNAs in one cell, which is not feasible when using traditional and in situ hybridization techniques is not feasible.

What were your goals when writing the Magnificent Makers series?

When I wrote these, I had two kinds of broad goals: one was to get kids more excited about science and to make sure that all kids felt represented by my books, but I also wanted them to be tools for teachers. I know that teachers are often already stretched so thin, and I feel that there’s this literacy-science gap whereby language arts and science are taught separately. I wanted teachers to use these books to merge those two fields because creative arts and creative thinking are important to science. I think combining literacy and science is a really good strategy to help teachers tackle these two things that they have to accomplish more effectively.

What important themes or lessons do you include in your books?

Each book tries to incorporate a life lesson. In the end, these are fiction books, and what moves a fiction book forward is the characters, what’s happening to the characters, and how the characters are growing. So in these books, while they’re about science, I try to make science the backdrop; science is the world in which they’re maneuvering, but the story is about these characters.

I try to connect the life lessons to science. In Brain Troubles, it’s all about working as a team because our brain has to work together as a team in order to get things done. In Riding SoundWaves, the life lesson was about accepting differences. I introduced a character here who has sensory processing disorder, and so we get to talk about our senses and also how sometimes people perceive and experience senses differently. For The Great Germ Hunt, I was really excited. I really aimed to make these books as inclusive as possible and one marginalized group that I have historically overlooked, and I would say that society has continued to overlook, is the disabled community. I really wanted to represent a disabled scientist who’s also a kid, and I thought that The Great Germ Hunt would be a good place to do that because we can talk about why some people are maybe more afraid of germs than others and how we need to be cognizant not only of keeping ourselves healthy but of keeping everyone around us healthy.

How important have your mentors been for you in your career?

I’ve been fortunate in that I’ve had pretty much stellar mentors throughout my career. From undergrad, Adam basically welcomed me with open arms into his lab, and supported me, and taught me some fundamental electrophysiological techniques. He always wrote my letters of recommendation on time, helped me get into grad school, all of that stuff. The same goes for my grad mentor, Geoffrey Swanson.

Ellen also has been extremely supportive. I will say, the one difference is that I feel like with my male PIs, they have their experiences with how they achieve things, but those are based on them being men. It’s different… they’re a little bit less strategic. I feel like as a woman, and especially as a black woman, I can’t just let things happen organically– I really need to make them happen and I really need to be strategic in how I do things. I learned that from Ellen. Ellen was an excellent sponsor, in addition to being a good mentor. She made phone calls for me, she advertised me, and she talked about me. I’m going to be a faculty for this neurobiology course this summer because she’s the co-director, so she invited me. She really gave me as many opportunities as she could and exposed me to as many people as she could. In addition to showing me how to be a good scientist, she made sure that I became a tenured track scientist.

Do you have any advice for finding a mentor?

Initially, when I reached out to Ellen, I didn’t hear anything for several weeks. I followed up again, and two hours later I had a response. She just missed my email. I can attest to this, PIs get so many emails, so many things get bumped down. Had I taken that first silence as a rejection, then I might not be where I am today. So be persistent, don’t worry about bugging people. You don’t want to miss opportunities by being nervous about being too pushy.

 This interview was conducted during the Spring Session of UVA’s Hidden Figures class in 2021. Class roster:

Addis, Lucas; Ahmed, Anushey; Akram, Amman; Alam, Maisha; Anderson, Sydney; Bhatia, Rhianna; Bonagiri, Paavan; Booth, Morgan; Clarke, Casey; Fisher, Grayson; Gandhi, Shreyal; Hossain, Mohammed; Rayan; Jensen, Kate; Kim, Michael; Lahham, Zina; Lea-Smith, Kori; Leffler, Schuyler; Leventhal, Emily; Mehfoud, Matthew; Morrisroe, Erin; Pham, Twindy; Sajonia, Isabelle; Sisk, Emma; Suram, Ananya; Wang, Jessica Beth; Webster, Tessa; Wilson, Gina. TA: McDonald, Amalia. Instructor: Ribic, Adema, PhD.