Erika Holzbaur is a pioneer in the field of motor protein research who has spent decades driving cutting-edge cell biological and biophysical research. This includes first defining dynein-associated proteins and their roles in neuron regeneration. More recently, she has intensely focused on neurodegenerative diseases including amyotrophic lateral sclerosis and Huntington’s disease. She is the recipient of numerous awards and honors, including being an inaugural American Society for Cell Biology Fellow for lifetime contributions to cell biology. She is the William Maul Measey Professor of Physiology at the University of Pennsylvania and has published 140 scientific papers, including in Nature and Science. She has also mentored many graduate and postdoctoral trainees, many of whom have gone on to outstanding careers themselves.
Holzbaur grew up in Poughkeepsie, New York, in an environment with close proximity to nature and plenty of contact with the outdoors. As a young adult, she was engaged by American history. In particular, she was fascinated by figures such as Frederick Douglass, who fought for emancipation and also was a vocal advocate for women’s rights. She continued to be drawn to such visionary figures, and pursued a double major in history as an undergraduate. However, it was the study of the periodic table in high school that sparked her interest in science. “At the time, biology was taught as a qualitative science,” Holzbaur explains, “but chemistry made sense! I decided in the eleventh grade that I wanted to be a scientist and to major in chemistry, then go on to graduate school in biochemistry.” Holzbaur completed a chemistry and history double major at the College of William and Mary, and credits training in the study of history with strengthening the writing skills that are so important to a scientific career, particularly the discipline of evidence-based writing. She still enjoys reading about history, however following college she pursued a PhD at Pennsylvania State University in the lab of Kenneth Johnson instead of further study of history.
Holzbaur’s passion for the study of motor proteins was ignited early, at her first interview for graduate school rotations. “I didn’t even interview with anyone else,” she says. “I have been obsessed ever since.” Holzbaur made seminal contributions to the field during this time of her training, including the discovery that identified the rate-limiting step in the kinetic pathway of the dynein ATPase, and demonstrated that this step was specifically activated by microtubules. Following graduate school, she did a quick postdoctoral fellowship with Dr. Ming Tien to learn molecular biology, a field that had exploded during this time. She describes this as being a very different experience from the rigor of understanding motor kinetics. “It was very much about finding ways to approach whatever problem you had,” she shares. She then did a longer postdoc at the Worcester Foundation for Experimental Biology in the laboratory of Richard Vallee. It was during this time that she was the first to clone the full length p150Glued subunit of dynactin, and subsequently was the first to show the direct binding of p150Glued to microtubules and to dynein, work that led to high-impact publications and laid the foundation for her independent investigative program.
Prior to her arrival at the University of Pennsylvania (Penn) as an assistant professor in 1992, Holzbaur had no model for women who were raising a family while also advancing their career. “I didn’t know anyone else who was trying to do that,” she says, “so I just decided to go for it.” She eventually did meet other women who were successfully navigating these challenges. These included some of the “actin ladies,” a group of women at Penn with interests in the cytoskeleton and motor proteins who met weekly. This group included outstanding scientists such as Sally Zigmond, Annemarie Weber, Clara Franzini-Armstrong, Vivianne Nachmias and Jean Sanger. Holzbaur describes this time as a golden age for women in cytoskeletal research at Penn, and was inspired by even their feminist approach to journal club. “They would take a paper, dice it up, and then sew it back together. Most importantly, they wouldn’t limit themselves to just finding flaws in the work, but would instead think deeply about how to improve it and what the next steps would be to advance the science,” she explains. She found other role models within the biophysics and cell biology communities, particularly those doing interdisciplinary, cutting-edge science, such as Tom Pollard, Ron Vale, and Yale Goldman. The ability to combine disciplines and approaches to advance our understanding of important questions is of highest importance to Holzbaur, who calls herself a cell biologist, biophysicist, and neuroscientist by vocation. She feels that the best research is intersectional, and leads to the circular flow of information.
Holzbaur has made many important findings in the motor field, but more recently has been intensely focused on neuronal transport following the discovery that targeted disruption of the dynein-dynactin interaction leads to progressive motor neuron degeneration. This work addresses questions that are still poorly understood despite many years of research. These questions include how to maintain a meter-long cell for up to 100 years and how to transport things along the distance of this cell. Her work has led to important insight into diseases associated with neuronal transport, including amyotrophic lateral sclerosis, a disease that is devastating and still poorly understood. She enjoys communicating with patients and families, explaining what she does and why it is important.
Holzbaur cites the rewards of training the next generation of scientists amongst her greatest accomplishments. Former Holzbaur lab members have gone on to tenure-track positions at Yale, NIH, RPI, McGill University, Tel Aviv University, the University of Massachusetts, the University of Sheffield, the University of Pennsylvania, and Washington University in St. Louis. Watching trainees mature and go out into the world to do amazing things is one of the most rewarding aspects of her job. “I think there is a better understanding of the role of mentorship in shaping careers,” says Holzbaur. “That has changed since the time I was training, when it was very easy to feel unsupported at times.” She encourages trainees and young investigators, particularly women, to be bold and resilient. “I find some of the brightest young women are also the greatest perfectionists. While you need that to a certain extent, at times you just need to go for it. The best advice I can recommend,” she says, “is what I learned accidentally: Just keep going until someone tells you that you can’t, and you will find that most times, you will succeed.”