Episode 16: Ellen Lumpkin, PhD

Illustration by Eli Minaya

The following interview was conducted in-class, during the Fall 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 by Maggie Pietsch, Kaitlyn Cheng, Jordan Freud, Sonia Patel, Katherine Silbermann, Justin Lumpkin, and Rachel Lemley, who also drafted Dr. Lumpkin’s biography. The final editing was by Dr. Adema Ribic. The original recordings are available in Podcasts.

Dr. Ellen Lumpkin is a Professor of Neuroscience at the University of California in Berkeley. She received a B.Sc. in Animal Science from Texas Tech University. During her years as an undergrad, she studied the effects of stress on the behavior of domesticated animals. She completed a Ph.D. in Neuroscience from UT Southwestern and Rockefeller University in James Hudspeth Lab. Dr. Lumpkin started her own lab at Columbia University, and she recently moved to UC Berkeley. Her laboratory has been the first to perform the molecular and functional characterization of Merkel cells that are found at our fingertips. Dr. Lumpkin’s findings have advanced our understanding of touch and touch perception, and her lab continues to elucidate how touch shapes our behavior.

 Dr. Lumpkin, thank you for joining us from your family home in Texas today-can you tell us more about it?

My dad grew up on this property. It was my grandmother's property, and it was a dirt floor house until he was an adult and had a job and could pay to have the flooring installed. a flooring, put in her house and in fact what he did is paid to have a new house built, where their old cabin had been and that's this house that I'm sitting in now. This house didn't have indoor plumbing until I was in high school. Although we certainly didn't consider ourselves poor, we were only one generation away from the sort of abject rural poverty that you may have read about during the post-depression era.

How did you come to be a scientist? 

I'm a first-generation college student from the piney woods of Texas and if I was standing in front of a window you would see pine trees all around the house. This is a rural, socio-economically depressed area. As a kid I drove tractors, I raised cows and pigs, and I dreamed of being a rancher. In ninth grade, I enrolled in vocational agriculture and joined the Future Farmers of America, which I had been wanting to do since I was about four years old when I got my first tractor. Through FFA, I learned a huge number of life skills. I learned public speaking, I became an expert in parliamentary procedure, and I also turned out to be really good at dairy judging. Through Future Farmers of America and Houston Livestock Show and Rodeo, I received enough scholarships that my way through college was completely funded and that was great because my parents couldn’t afford to send me to college, but they told me that I would be going to college even if it meant I would live at home and go to the local university that was 20 miles away. However, the most important thing that I learned in vocational agriculture and in FFA is genetics.  

How did you learn genetics?

I became fascinated with Mendelian genetics, which I learned as a ninth-grade student in vocational agriculture. Mendel devised his laws of inheritance by crossing pees, but in East Texas, I learned about genetics through the study of color and cattle. Angus’s cattle coat color follows Mendel's laws of dominance. If you cross a homozygous black cow, with a homozygous red Angus, you get heterozygous calves, all of which have black coats. And every single time you make this coat cross, you get this outcome, black coat, because black is the dominant trait. Things got really interesting in shorthorn cattle, which is red or white. They turn white independent of the gene that codes for a coat if they lack the gene that is required to deposit the pigment in the hair. This idea that simply by looking at the colors of animals, you could understand the logic of inheritance was beautiful to me. At that point, I decided that I was going to be a geneticist and that I wanted to get a Ph.D. in science, or at least that I wanted to become a scientist. When I talked to my teachers, they said I needed to have a Ph.D. I had never even met anyone with a Ph.D., nor had I met a geneticist, but that's what I decided to do. As an undergraduate, I immediately started looking for a job in a lab, and I got a job in a fantastic lab that studied the effects of stress on health. 

What was your major?

My way through college was paid through by the Houston livestock show and rodeo, and to accept that scholarship, one had to be in the College of Agriculture. I majored in animal science. I studied the stress effects on health in market hogs. When you ship a market hog from the feedlot to the finishing lot, or from the finishing lot to the slaughterhouse, why do they lose so much weight? How does that stress associated with shipping an animal lead to weight loss? I published as an undergrad in the Journal of Animal Science on the effects of shipping stress as well as social stress on peak performance, immune function, and cortisol levels. Coming from this undergraduate experience, I got really interested in how the nervous system and the endocrine system control immune function. For my Ph.D., I decided I would study this intersection of neuroscience and immunology, and I needed to find a place that had both excellent neuroscience and excellent immunology because the field of neuroimmunology, which is now emerging, wasn't a thing then. 

Where did you do your Ph.D.?

I went to UT Southwestern because they had this umbrella Ph.D. program where all the students came into the same graduate program and learned the same core modern molecular and cellular biology, and then at the end of the first year, they declared a final graduate program. I'd already done a couple of years of research in immunology, and so I thought I should maybe focus on neuroscience. It was hard because I didn’t know much of the terminology used. I had no idea when our genetics instructors started talking about cloning genes. In fact, within the first two weeks of graduate school, I went to one of our graduate advisors in tears because I didn't understand what it meant to clone a gene. She was so kind, sat me down and pulled out the molecular biology manual and talked me through what it meant to clone a gene, and helped me realize that it was just a difference in terminology from my background. She welcomed me to come once a week and play catch up on some of the things that I didn't know because I came from this very non-traditional background into a Ph.D. program. 

Did you have other difficulties fitting into your graduate program?

The other thing I found coming from my rural Texas background is that people didn't want me to rotate in their labs. The first two neuro professors I approached to do a rotation turned me down flat, they wouldn't even let me rotate in the lab. I really felt othered and I really felt the imposter syndrome. I persevered and I approached Jim Hudspeth. Jim was then Chair of the neuroscience graduate program, so I thought he wouldn't be able to turn me down since he was the Chair of the graduate program. Jim made me interview three times before he offered me a rotation. In lab meetings, it didn't take long to realize that his lab was so creative. Their curiosity, their ability to pose questions for which no answer is known, and to just get so excited about scribbling on the board and arguing about the right way to answer the question just filled me with a desire to be half as good as they were. I figured if I could work in that scientific and intellectual environment, and come away even half as good as they were, I would make it as a scientist. So I decided to join Jim's lab and pursue my research with him.

How did you respond to being turned away from labs? How did you overcome that feeling of rejection?

I'm just incredibly stubborn. When I was rejected, I thought, “Okay, your loss.” But at the same time, it took me a long time to get over the embarrassment of being rejected. They were nice about it- they gave good reasons for why they didn't want me in their lab. I felt embarrassed for many years. And how do I get over it? Well, at the end of that year, I won every pre-doctoral fellowship I applied for and had to choose between them, and I got the highest academic GPA of any person in that first-year class. Then, when I became an Ivy League professor, that felt pretty good too. The next time I saw one of those two faculty members, I made sure to let him know that I was a professor at Columbia.

Do you have any tips for going into research and overcoming obstacles in research?

I would say my number one piece of advice is to find mentors who will make a personal connection with you. Don't go for the big names; go for the people who, especially at the undergraduate level, genuinely want to invest in students and want to mentor. Those are the people who are going to help you, the people who will pick up a phone and say, “I've got this great undergrad, you need to recruit them to your graduate program, or to your medical program.” Another thing I would say is don't be afraid to advocate for yourself. At your very earliest level of training, start to learn how to advocate, because you are your best advocate. And then follow your passion. Don't let people tell you what you should be passionate about. For example, I wanted to study Merkel cells, and the first paper that I submitted on Merkel cells got rejected without review because they said that Merkel cells weren’t a science, and I explained to them all of the reasons that this was relevant to neuroscience. When that paper finally came out, it became a highly cited paper because it was the first paper that ever did microarray studies on any skin cell type. Our group was also the first team to use optogenetics in a non-neuronal cell. That paper came out in Nature, and it proved that Merkel cells are actively involved in touch reception. Don't let people define you. You define yourself. Listen to feedback, but trust your gut, and don't let people tell you what you should be, or what you should want to be. 

Do you think sexism in science is a major problem today? 

Yes. The obstacle that we still face as women is sexism. There was one instance when I was sitting in a meeting of faculty- I was on a prize selection committee, and one of the other committee members walked in, looked around the room, and said, “Gentlemen, shall we get started?” That was not even a decade ago, and this is not even sexual harassment, which I also experienced. Every woman I know in academia has a story to tell. It never goes away, being told what to do. There are people who don't get it, who will not understand sexual discrimination is a thing. I can't say to you that you have to learn to ignore it because it can't be ignored. But practice with your mentors, with your peers, ways to shoot back in those kinds of events where you just want to stand there with your mouth open, saying, “You can't possibly be saying that to me right now.”

What research did you do in the Hudspeth lab?

I used electrophysiology, high-speed calcium imaging, and computational modeling to identify how calcium concentration is controlled around hair cells’ mechanotransduction channels. To me, that was so exciting, so beautiful, that I decided I could never turn back to immunology. I had to stick with neuroscience, and what's more, I had to stick with sensory neuroscience, where I could watch cells do their thing in real-time, and where we could study these mysteries of how our nervous systems monitor the environment to allow us to not only survive but to thrive. 

How did you get into touch research-specifically, of the somatic sensory system?

I didn't want to stay in hair cells. I decided that I did want to stay in sensory neurobiology, but there were a bunch of people studying hair cells that I really respected, and I hate competition. What I really care about is fundamental paradigms. I wanted to study something that no one knew.  And at the time- this was in the mid-90s- we knew nothing about touch reception. In fact, barely anybody was working in touch reception, and the stuff in the textbooks was done in the 70s or earlier. I thought, “Okay, this is great. Touch is another mechanical sense just like hair cells, but nobody's working on it.” I looked at snake touch receptors, and then I looked at mammals, and it turned out that all vertebrates have Merkel cells. Based on their anatomical features, Merkel cells were pretty similar to hair cells. I knew how hair cells work, and I figured I’d just study Merkel cells and figure out how they work. 

What is your lab working on? 

For the past 20 years, my lab has studied the cellular and molecular basis of our sense of touch. Touch as a sense is often taken for granted, but it is actually quite fundamental for survival. Touch is important for successful child-rearing and proper cognitive development, for obtaining nutrients, and for avoiding becoming a nutrient for another creature. Touch is actually the first sense to develop in the human embryo and the last sense to fade as we age. As we lose our hearing, our vision, even our appropriate receptive sense of limb position that makes us unsteady on our feet, we still feel the pressure of a loved one's hand as we lie in our last moments.

 How does touch work?

Pain, itch, and touch are parts of the somatosensory system. The neurons that initially convert environmental stimuli into a neural signal are located in ganglia, little clusters of nerve cell bodies that are found in little pockets inside our spinal column. These are called dorsal root ganglia. Each of these dorsal root ganglia has a cluster of a few hundred to a few thousand neurons that send axons out into all of our peripheral tissues-our skin, our viscera, etc.-and by doing so, they allow us to monitor the environmental state of the world around us as well as the environment of our internal organs. In response to a potential tissue-damaging chemical thermal or mechanical stimulus, neurons called nociceptors are activated and send signals through pain pathways to allow us to sense pain. It’s a warning signal that tells us that we need to remove our bodies from a potentially damaging environment.

What type of information does our brain get through our sense of touch? 

We rely on touch sensation to distinguish objects in our world such as shapes, edges, and curvature. Touch receptors in our skin constantly send this information to the brain, even when we are not aware of it, to guide fine motor skills. These touch inputs are particularly important when we learn new motor skills, like learning to play a musical instrument. When a musician plays an instrument, it requires the musician (for example, a pianist) to rapidly feel the keys' edges and to adjust their finger position to strike the right notes. The emotional content of the music is conveyed in part by how hard or how soft this musician strikes the keys, which they can feel by the pressure of the keys returning back onto the fingertip surface. 

What are other warning signals we get through the skin?

Neurons that respond to chemicals that produce itch, like after a mosquito bite, warn us of the presence of pathogens that we might want to brush off of our skin. Another class of neurons called mechanical receptors respond to what we call mechanical stimuli, so that could be a steady pressure of vibration, it could be a stretch, either of our skin or of our internal organs, like when we eat too much and our stomach feels really full. We feel full because there are stretch receptors in our stomach wall that give us the conscious awareness that we should probably eat less next time and we won't be quite so uncomfortable.

How are those neurons so different from one another?

These different sensory neurons achieve these different sensations because they have different molecular receptors that convert environmental stimuli into the electrical signals-the currency of the nervous system. They also send their central axons, their projections, to different pathways that travel to different centers in our brain so that we perceive the inputs differently. 

Can you tell us more about the mechanoreceptors your lab is working on? 

One of the most remarkable things about these touch receptors is that they are specialized both through their anatomy and through their physiology to encode different qualities of a complex tactile stimulus. For example, if I hold up a bottle of sparkling mineral water, I can with my eyes closed feel that there's curvature. I can feel that there are some letters embossed here. I can feel that it's quite a rigid body, it's made out of glass, not out of squishy plastic. And I know how heavy it is so that I can hold it with the right amount of pressure. Without really thinking about what information is being sent to the nervous system, I can use my sense of touch to distinguish all of those features of this rigid body. I can also tell that it's coming out of the refrigerator because the water inside has made the bottle cold-that's what I mean by a complex tactile stimulus, a single bottle that has at least four different perceptual qualities. The way that these neurons can pick out those different sources of tactile information is through anatomical and functional specializations. 

What aspect of these mechanoreceptors is your lab studying?

The goal of my research for the past 20 years or so has been to determine how these different kinds of touch receptors produce unique patterns of neural activity that represent specific tactile features, like the ones that I talked about with my bottle of water. My group has focused much of our efforts on a very special vertebrate touch receptor, called the Merkel cell-neurite complex. These are touch receptors that are found clustered in areas of skin that are specialized for high tactile acuity, like the touch receptors I used to find the edge versus the center of a keyboard when I type emails (since that’s most of what I do now!). 

What areas of the skin are Merkel cells found in?

No surprise here-they are found at high concentrations in mammalian fingertips. That's true in humans as well as non-human mammals such as mice. In mice, we can also see them at very high concentrations around whisker follicles. That makes a lot of sense because whiskers to a rodent are analogous to our fingertips. Whiskers are one of the rodent’s organs of high tactile acuity that they use to explore their environment and to distinguish the objects, textures, and shapes of very small objects. In the skin that covers most of our body, we don’t have whiskers-we have hair. In hair-bearing skin, Merkel cell-neurite complexes are found in these little spots, called touchstones. That's the area where we usually study them.   

How do Merkel cell complexes function?

Neurons that innervate clusters of Merkel cells have a very characteristic firing pattern, called the slowly adapting type I response (SAI). They fire a train of action potentials in response to touch. Our lab uses sophisticated equipment to give very precise touches to the skin while we record the neurons that innervate that piece of skin. Some of that equipment has been fabricated by our collaborator at UVA, Dr. Gregory Gerling in the Department of Engineering Systems and Environment. 

The SAI response special is that it has two phases. It has a dynamic phase when the skin is actually being moved. We call it dynamic because the skin is moving, and that dynamic phase is very fast, very high frequency, and it encodes tactile features such as shapes, textures, and even curvature, as we move our fingertips across an object. When the skin is held at a constant position, the firing rate of the SAI response drops off, it becomes very irregular, and it lasts for as long as the skin is being indented. That's different from other types of touch receptors, which will fire for a few seconds, and then become silent. These SAI responses can continue to fire for up to 30 minutes in response to a single touch. In our experiments, we typically go for 10 minutes, and then we stop, but other scientists have reported responses that last up to 30 minutes. 

But what do Merkel cells do in that complex? 

Sensory receptor cells come in two flavors: in the first, the sensory cell itself is a neuron. We call those primary sensory neurons. In the other type, there is a dedicated secondary sensory receptor cell, a cell that derives from the epithelium. It is an epithelial-like cell that turns on neuron transcription factors, and basically puts on a coat that makes it look like a neuron. By birth, it's an epithelium cell, but by function, it acts as a neuron. These secondary sensory receptor cells transduce the stimulus into an electrical signal and then communicate that with the sensory neuron through neurotransmission. Merkel cells are epithelial cells, which has led to the hypothesis that Merkel cells are sensory receptor cells in the skin. In fact, Merkel himself alluded to this possibility when he first described the cells in 1875. This German anatomist named them “tastzellen”, which translates as touch cells.  

What has your lab discovered about them?

My group’s first hint that Merkel cells might function as sensory receptor cells came from an experimental approach that I took when I started my lab. Studying them is challenging because they make up only about .1% of the epidermis. Whereas the epidermis is less than half of the entire skin, so they're 0.1% of less than half of the skin. The first thing I did when I started my lab was to develop a methodology to purify Merkel cells from the skin. Once we did that, we could then perform DNA microarray analysis to identify genes that are more enriched in Merkel cells compared to other cells in the skin. We were super excited to find that Merkel cells, like hair cells and taste cells, expressed neural transcription factors, voltage-gated ion channels, and dozens of synaptic molecules. This was our first hint that Merkel cells really could be playing a role as sensory cell-like hair cells and taste cells. 

What are the next steps that your lab is taking?

One thing I'm excited to do is to go in new directions. We have molecular questions, but we're also really interested in how touch during development is needed to create healthy neural circuits for adult behaviors. In particular, we're thinking about children who are touch-deprived during development or who are exposed to drugs or abuse in utero, who develop sensory-seeking behaviors. We’re interested in studying what's different about their neural circuits. We're also starting to look at the evolution of mechanical transduction. 

Do you think that the current pandemic has impacted some aspects of our lives that rely on touch?

The last two years have made us all much too aware of how important touch is for our mental health. A life without hugs makes it almost impossible to comfort a grieving friend during loss or in my case to calm a frustrated child. And how can you celebrate a graduation, a dissertation defense without clinking glasses or high fives? It really makes us think about how important that personal skin-to-skin contact is for our emotional health.

 This interview was conducted during the Fall Session of UVA’s Hidden Figures class in 2021. 

Class roster: Brink, Julia Elizabeth; Abraham, Carly Elizabeth; Rose, Odell Bayou; Kang, Elizabeth; Posner, Chloe Grace; Luscko, Caroline Ann; Pappagallo, Julia Dominique; Ware, Liza Elizabeth; Murphy, Ryan Martin; Faisal, Zainab; Fastow, Elizabeth; Walker, Mary-Catherine; Petz, Kaitlyn Dorothy; Terblanche, Alexandra Savenye; Nguyen, Katie; Guttilla, Gianna Marie; Hoang, Chloe Nam; Grace, Ann Brown; Smith, Charles Cornelius; Sears-Webb, Delaney Jean; Abed, Jamil; Miao, Julia Stephanie; Johnson, Catherine Anne; Kim, Evalyn; Lee, Sarah; Pietsch, Maggie Malia; Cheng, Kaitlyn Jiaying; Freud, Jordan Maria; Patel, Sonia; Silbermann, Katherine Elizabeth; Lumpkin, Justin; Lemley, Rachel Ann; Hall, Maria Elizabeth; Nugent, Elise Genevieve; Limon, Safiye; Mangan, Erva; Ali, Sophie; Muse, Morgan Noelle; Miley, Sareena Elizabeth; Bennett, Bailey Grace; Mollin, Hannah Beth; Nguyen, Daniel Van; Englander-Fuentes, Emilu Maria; Pest, Marshall Sinclair; Mahuli, Rhea Mina; Chindepalli, Jahnavi; Malyala, Meghana; Weldon, Nathaniel Andreas; Aschmies, Lindsay Elizabeth; Chakrapani, Krithi; Heintges, Bella Grace; Baker, Gabriella Christine; Bonsu, Tenneh Ina; Hall, Ann M; Rodriguez, Kaitlyn; Simmons, Emma Isabela; Davenport, Julia Barrett; Andrews, Tara; Ramirez, Alexa Hidalgo; Petrus, Sarah Anne; Singh, Aanika; Wilson, Sydney Paige; Younan, Krestina. 

TA: Kipcak, Arda. Instructor: Ribic, Adema, PhD.