Since the founding of our laboratory, we have committed our research program to determining the mechanisms that cause motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS). As our understanding of these mechanisms improves, we gradually seek to translate our discoveries into new therapeutic options for patients.
Kevin Eggan, Ph.D.
- Professor of Stem Cell and Regenerative Biology
- Principal Faculty
Harvard Stem Cell Institute
- Institute Member
Broad Institute of MIT and Harvard
As a young investigator in the burgeoning field of stem cell biology, Kevin Eggan has garnered international recognition for his seminal work and a number of high profile awards for his creativity and productivity, including the MacArthur Foundation Genius Grant in 2006. He has made fundamental contributions to the fields of stem cell biology and cellular reprogramming, which in turn led his group to pioneer an entirely new strategy for studying human disease.
While training, Eggan performed nuclear transfer studies that challenged preconceived notions concerning the limits of cellular plasticity (Eggan et al., 2000, 2001, 2004). His own lab then became the first to demonstrate that human somatic cells could be reprogrammed to an embryonic stem (ES) cell state (Cowan et al., 2005). This demonstration that human ES cells harbored reprogramming activities has been cited as an inspiration for the discovery of factors used to generate induced pluripotent stem cells (iPSCs). Through persistent reprogramming attempts, his lab became the first to generate patient-specific iPSCs and use them to produce the cell type that degenerated in that individual (Dimos et al., 2008).
As these patients suffered from ALS, he was inspired to explore stem cells as a renewable source of motor neurons for studying mechanisms leading to neural degeneration. These experiments were the first “stem cell models” of disease and enabled the discovery that astrocytes are important non-cell autonomous contributors to motor neuron degeneration in ALS (DiGiorgio et al.., 2007 and 2008). Subsequently, Eggan’s group used this novel approach to study disorders that were intractable in rodents (Mekhoubad et al., 2012), discover new mechanisms that lead to motor neuron degeneration (Suzuki et al., 2013 Kiskinis et al., 2014), and finally to identify a candidate ALS therapeutic (Wainger et al., 2014).
Eggan completed his B.S. in microbiology at the University of Illinois in 1996. A two-year pre-doctoral internship at Amgen at the National Institutes of Health in Bethesda solidified his desire to pursue a career in academic research. He enrolled at the graduate school of Massachusetts Institute of Technology in 1998 shortly after the cloning of Dolly the Sheep was reported. During his Ph.D. training, he actively pursued projects focused on cloning, stem cells and reprogramming after nuclear transfer under the guidance of genetics pioneer, Dr. Rudolf Jaenisch. He stayed in the Jaenisch lab after his graduation for a one-year postdoc training in 2002. During that time, he conducted a collaborative study with Dr. Richard Axel, a Nobel Prize winner at the Howard Hughes Medical Institute. In 2003, he moved to Harvard University as a junior fellow, then became an assistant professor of Molecular and Cellular Biology at the Stem Cell Institute in 2005. In 2009, Eggan was selected as one of 50 Howard Hughes Medical Institute Early Career Scientists receiving six years of dedicated support to conduct transformative research. He was promoted to Professor in the Department of Stem Cell and Regenerative Biology in 2012.
The success of his laboratory in the study of motor neuron disease led to his appointment as the Director of the Stem Cell Program at the Stanley Center for Psychiatric Research at the Broad Institute. In this role, he leads a group of scientists to expand the platform to increase reproducibility of stem cell and reprogramming technologies with the ultimate goal of improving understanding and treatment of psychiatric diseases.
Based on our initial successes in contributing to the understanding of motor neuron disease, we have now begun to expand our interests, applying similar strategies to the study of psychiatric conditions in collaboration with The Stanley Center at The Broad Institute.
In many ways, our research is best described the kind of collaborations we foster.
Stanley Center Stem Cell Biobank at the Broad Institute
Ralda Nehme and her group are interested in investigating the genetic, cellular, and molecular mechanisms underlying neurodevelopmental and psychiatric diseases. They are using stem cell-derived neurons and genome editing technologies to build human cellular models for these disorders. In line with these goals, in collaboration with the Eggan and McCarroll labs, the group established the Stanley Center Stem Cell Biobank at the Broad Institute, a resource of human pluripotent stem cells and genetic data from hundreds of donors, aimed at expanding the scalability of experimental systems.
Genomics and genetics
Lindy Barrett and her lab use a combination of human pluripotent stem cell biology, genome-engineering technologies, and in vitro differentiation to study the impact of genes and variants implicated in neurodevelopmental and neuropsychiatric diseases on neuronal function.
Steve McCarroll and his lab work to study how human genomes vary and how genetic variation shapes human biology.
Sulagna (Dia) Ghosh is a Computational Biologist at the Stanley Center for Psychiatric Research. Dia currently focuses on analyzing genomic and transcriptomic data from cellular models to learn about risk variation in neurodevelopmental and psychiatric disorders.
Steve Hyman is director of the Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard, a core member of the Broad, and Harvard University Distinguished Service Professor of Stem Cell and Regenerative Biology.
Kasper Lage‘s lab develops and applies computational technologies to functionally interpret massive genomic datasets using biological networks. Through their approaches they aim to understand and model how biological networks are perturbed by genetics and can be targeted by therapeutics in complex diseases such as psychiatric disorders, cancers, and metabolic diseases.
Brian Wainger‘s laboratory investigates clinically relevant research questions that could lead to rapid translation and innovation for treating diseases of the motor and sensory nervous systems.
Clifford Woolf‘s lab is devoted to investigating the way in which the functional, chemical and structural plasticity of neurons contributes both to the normal function and diseases of the nervous system.
Adam Cohen‘s lab invents new physical tools to probe biological structures. They choose problems by looking in unexplored regions of time and space. They combine protein engineering, lasers, nanofabrication, microfluidics, electronics, biochemistry, and computers to generate data; and apply statistics and physical modeling to understand the data.