How activism and travels shaped academic career and scientific leadership
As told by Kelsey Martin

Childhood
I was born in Seattle, Washington, the second of four children and the only girl. My father, George M. Martin, was a physician-scientist who devoted his career to the biology of aging. My mother, Julaine, was a stay-at-home mom who went back to college to earn a master's degree in art history at the University of Washington and found tremendous joy managing several art galleries in Seattle.

My older brother Peter was born two years before me; my brother Tommy a year after my birth; and my youngest brother Andrew when I was six. My parents were passionate believers in global experience and travel. When I was three, we spent a year in Glasgow. When I was ten, a year in Paris. At fourteen, I was sent to live with a French family and attend school in Paris; at sixteen, to live with a family in Mexico City. When I arrived as a ten-year-old in a French-speaking school I was terrified. But I quickly learned to love France and now have vivid and treasured memories of those years. My mother took us to museums in Paris every weekend, and I have a transcendent memory of standing in front of Monet's Water Lilies in the Orangerie, entirely awestruck. My pathologist father would stop our Volvo station wagon at every cemetery we drove past in Europe and require us to read all the tombstones to determine whether an epidemic had struck the town. The simultaneous pull of art and science in my childhood has shaped me ever since.

College Years
I entered Harvard-Radcliffe as a member of the class of 1979 with two great loves: reading and painting. I happily chose to major in English while taking as many painting courses as I could. I wrote my senior honors thesis comparing Thomas Carlyle’s Sartor Resartus and Herman Melville’s Moby-Dick — two seemingly unrelated works that I came to see as distinct responses to the collapse of theistic certainty in the nineteenth century. Carlyle argued that meaning and truth could only be found through human-made institutions and systems of belief, while Melville pursued truth as something elusive and ultimately impossible to fully capture. Decades later, I still think of them as representing two different scientific temperaments: one that seeks to tell a coherent, hypothesis-driven story, and the other that embraces unbiased, large-scale exploratory biology.

The Peace Corps
After graduating from Harvard in 1979, I joined the Peace Corps and was assigned to a maternal and child public health position in the Kasai Oriental rural zone of Zaire — now the Democratic Republic of Congo — in a village named Bibanga, home of a former American Presbyterian mission hospital. The hospital had no electricity, open wards, one doctor, a small pharmacy, and long daily queues of patients. We were assigned to set up a program for malnourished children but quickly learned that most children sick enough to come to the hospital did not survive more than a day or two.

We re-evaluated and changed directions, developing a preventive health program for maternal and child health care workers that included health education, and immunization. The immunization program was by far the most effective intervention. Each fall, our rural zone was hit with a measles epidemic. After vaccinating 30,000 individuals across the zone, the epidemic did not return. This was a conversion experience for me — making me acutely and permanently aware of the power of science to save lives. Living in a mud hut by kerosene lantern, my father began sending me science books — Ben Lewin's Genes, biographies of John Enders and Jonas Salk. As much as I loved literature, I found myself feeling that it left me empty-handed. I became intent on a career in medicine and science.

The project was going so well that I decided to stay for a third year. Three months in, I got very sick. I was medically evacuated to the U.S. Army Hospital in Frankfurt where I received a diagnosis of necrotizing fasciitis and was told I might lose my foot. I remember lying on the gurney shivering and terrified, cold IV fluids running into my arm. I woke up with my foot intact but with a large area of the dorsum missing after surgical debridement. To this day, I have a scar in the shape of Africa on my right foot.

Graduate Training
I returned to Cambridge to take my remaining premedical courses and found a position as a research technician studying HIV transmission in children in the lab of George Miller at Yale. It was there that I discovered how deeply I loved experimental science — the detective work of designing and interpreting experiments, the joy of working at the bench, and the collaborative process of solving scientific problems. That experience led me to apply to, and ultimately enroll in, the Yale Medical Scientist Training Program.

I chose to do my PhD in the lab of Ari Helenius, a cell biologist and biochemist who pioneered the use of viruses to study membrane trafficking and protein folding. My thesis focused on the transport of influenza ribonucleoproteins into and out of the nucleus of cells. I discovered that the low pH of the late endosome triggered dissociation of the viral matrix protein M1 from the viral ribonucleoprotein, exposing nuclear localization signals and resulting in rapid nuclear import of the viral genome. I further found that the antiviral drug amantadine blocked this dissociation, preventing nuclear import. Later, I showed that M1 synthesized late in infection diffused into the nucleus and escorted ribonucleoproteins back out through the nuclear pores, demonstrating that the directionality of viral nuclear transport depended on M1 and its low-pH-sensitive association with the ribonucleoprotein complex.

My medical school psychiatry clerkship was a turning point for me. Here was a field of critical public health importance where therapeutic interventions were almost entirely disconnected from any mechanistic understanding of disease. It was a field that urgently needed strong science — and one that was, like literature and art, centrally about human identity, behavior, and what it means to be human. My cell biology background also pulled me toward neuroscience — neurons, with their extraordinary structural polarity and intricate compartmentalization, captivated me. By the end of the clerkship, I decided to pursue postdoctoral training in neuroscience rather than enter residency immediately, believing that I could always return to clinical medicine later.

I was on a preschool field trip with my two-year-old daughter Maya when it dawned on me that some of the Aplysia sensory neurons I had been culturing had bifurcated processes

Postdoctoral Training and the Discovery of Synapse-Specific Plasticity
I joined the laboratory of Eric Kandel at Columbia in 1992. When I joined, the lab was identifying the signaling pathways and gene regulatory switches required to consolidate short- to long-term facilitation at Aplysia sensory-motor synapses. The requirement for new transcription immediately raised two questions that fascinated me as a cell biologist. First: how do signals travel the great distances from stimulated synapses to the nucleus to alter transcription? Second — and more profound: if long-term plasticity requires transcription in the shared nucleus of a neuron, what determines whether plasticity occurs at some synapses but not others within that same neuron?

I was on a preschool field trip with my two-year-old daughter Maya when it dawned on me that some of the Aplysia sensory neurons I had been culturing had bifurcated processes. If I cultured these such that one branch made synapses with one motor neuron and the other branch with a second, spatially separated motor neuron, I could test whether serotonin applied to one branch triggered long-term facilitation only there, or throughout the entire cell.

The results of the experiment were unambiguous: the strength at the serotonin-treated branch had increased, with no change at the untreated branch. I went on to show that this branch-specific long-term facilitation required transcription in the sensory neuron and involved the growth of new synaptic connections exclusively at the stimulated branch. In exploring the underlying mechanisms, I found that local perfusion of translational inhibitors blocked branch-specific plasticity — establishing that local translation of synaptically localized mRNAs in the sensory neuron process was required for synapse-specific plasticity. Together, these studies demonstrated, at the level of a single cell, that long-lasting plasticity can occur at specific synapses made by a single neuron — establishing the synapse, rather than the neuron as a whole, as a fundamental unit of memory storage.

Using the same culture system, I also found that a synaptic "tag" was required for persistent long-term plasticity — that a single application of serotonin at one branch could tag that synapse to capture the products of gene expression induced by stimulation of the cell body, generating persistent, branch-specific growth of new synaptic connections. These studies illuminated the temporal and spatial orchestration of signaling and gene expression within a single neuron that gives rise to the persistence of synaptic plasticity.

The Martin Laboratory at UCLA
I joined the UCLA faculty in 1999, joining two departments: Psychiatry and Biological Chemistry. Over the following two and a half decades, my lab has pursued two intertwined questions: how are mRNAs localized to neuronal processes, and how do signals travel from stimulated synapses to the nucleus?

Working with graduate student Robert Moccia, we prepared cultures of isolated Aplysia sensory neurons, removed all cell bodies, and generated cDNA libraries from the isolated processes — identifying hundreds of localized transcripts.

Michael Poon in the lab developed a preparation for growing mouse hippocampal neurons on filters through which neuronal processes but not cell bodies could penetrate and used this preparation to identify the population of process-localized mRNAs. Both studies revealed a surprisingly rich repertoire of localized transcripts.

Postdoctoral fellow Dan Ohtan Wang developed a brilliant approach to visualizing local translation in real time in Aplysia neurons, fusing the 5' and 3' UTRs of a localized mRNA to the photoconvertible protein Dendra2. By UV photoconverting existing protein from green to red and then monitoring new green signal, she could visualize new translation in real time — and, after removing the cell body and locally perfusing serotonin, showed that translation occurred only at stimulated synapses. Graduate student Sangmok Kim subsequently showed that mRNAs — including transcriptionally induced mRNAs — were delivered throughout the neuronal arbor, but that local translation was restricted to the site of synaptic stimulation, requiring trans-synaptic netrin/DCC signaling. This decoupling of transcriptional and translational regulation was an important insight: stimuli trigger transcription of mRNAs that are delivered throughout the neuron, while local cues independently regulate their translation — allowing all branches to remain in a state of readiness to respond to local experience by changing their local proteome.

I will briefly highlight two additional studies from the lab that further emphasize the importance of post-transcriptional gene regulation in neurons. JiAnn Lee demonstrated that the cytoplasmic form of an RNA-binding protein interacts with the 3′UTRs of target mRNAs to regulate their stability and translation. Patrick Chen showed that induction of long-term potentiation at hippocampal CA3–CA1 synapses produces substantially greater changes in translation than in transcription. Together with the work of many other talented trainees in the lab over the years, these studies have reinforced the view that post-transcriptional regulation is a central mechanism governing neuronal function and plasticity.

I have come to believe that progress in neuroscience is not the triumph of any single approach, but rather the stitching together of multiple levels of analysis

In addition to our work on mRNA localization, my lab studies synapse-to-nucleus signaling, with a particular focus on the active transport of signaling molecules from stimulated synapses to the nucleus to regulate transcription. Much of this work has centered on the transcriptional co-regulator CRTC1. While in the lab, Toh Hean Ch’ng demonstrated that neuronal stimulation induces the translocation of CRTC1 from synapses to the nucleus through a mechanism involving calcineurin-dependent dephosphorylation, release from 14-3-3 anchoring proteins, and dynein-mediated transport along microtubules. Building on these findings, Sylvia Neumann and Jennifer Achiro showed that stimuli producing either synaptic strengthening or weakening in hippocampal neurons trigger CRTC1 nuclear translocation and activate strikingly similar transcriptional programs. Together, these results suggest that activity-dependent transcription places neurons in a permissive state, primed to respond to localized synaptic signals that reshape the synaptic proteome and modulate synaptic connectivity. More broadly, this work reinforces the central importance of spatially localized regulation of gene expression in neuronal plasticity.

Stepping back over these years of work, I have watched the field of memory research move from excitement about molecular and genetic tools to excitement about circuit-level technologies, theory and computation — each new approach greeted with the hope that it will be the breakthrough that reveals how memories are stored. I have come to believe that progress in neuroscience is not the triumph of any single approach, but rather the stitching together of multiple levels of analysis. At the same time, I know that I am a cell biologist at heart. I find greatest satisfaction thinking about the cells in the brain, the molecules that move within them, and the interactions between them.

I realize that the same sense of activism that led me to join the Peace Corps also shaped my path in academic and scientific leadership.

Academic and Scientific Service Roles
I realize that the same sense of activism that led me to join the Peace Corps also shaped my path in academic and scientific leadership. I co-directed the UCLA Medical Scientist Training Program to strengthen support for trainees, particularly women in science and medicine. I later served as Chair of Biological Chemistry and then Dean of the David Geffen School of Medicine at UCLA, motivated by a deep belief in the power of biomedical research, education, and collaboration to improve human health. I eventually joined the Simons Foundation as Executive Vice President of Autism and Neuroscience, inspired by Jim and Marilyn Simons’s commitment to advancing mathematics and basic science. Each of these roles required me to adapt to new challenges and communities—from graduate education and basic science to healthcare systems, philanthropy, and autism research.

Family
There is no doubt in my mind that my family—my husband Joel Braslow; my children, Ben and Maya Barad; my stepchildren, Seth and Sam Braslow; and their partners, Rachel Morgan, Aaron Khansefid, Doris Li, and Kalie-Ann Nassoura—has been the deepest source of happiness in my life. Joel, a psychiatrist and historian, has changed the way I understand people, illness, and the relationship between mind, brain, and society. Ben’s combination of scientific intensity, humor, and joy in discovery; Maya’s warmth, intellectual seriousness, and love of both medicine and dance; Seth’s extraordinary kindness and global curiosity; and Sam’s fierce intelligence, wit, and moral clarity continually amaze me. Their partners have become fully part of the fabric of our family, each bringing their own strengths, passions, and ways of seeing the world. In one of my favorite poems, The Last Saturday in Ulster, Nick Laird writes that “time is how you spend your love.” That line has always felt true to me. The time I spend with my family has been the clearest and most enduring expression of love in my life.