Please give us an overview of your lab’s research focus.
Our lab studies neuronal development, specifically how different subtypes of cells in the central nervous system (CNS) are generated from seemingly similar progenitors. This is a major question in developmental biology because the CNS has a vast diversity of cell types.
From a practical standpoint, understanding how cells are made can help us regenerate them to replace those lost due to injury or neurodegenerative disorders. It also provides a roadmap for targeting specific cells related to specific behaviors, as the genes that specify cell identity are the instructions for building neural circuitry.
We focus on two systems: the retina and the hypothalamus. The retina, with its seven major cell types and 130 subtypes, allows us to study the basic mechanisms of neural development, particularly temporal patterning, which is crucial for generating cell diversity in the CNS.
The hypothalamus regulates a wide range of behaviors and homeostatic functions like appetite, sleep-wake cycles, and body temperature. By applying principles learned from the retina, we aim to identify key cell types in the hypothalamus that regulate these behaviors, potentially leading to therapies for disorders like Alzheimer’s and neuropsychiatric conditions.
Additionally, we explore comparative regeneration. While species like zebrafish and salamanders can regenerate neurons after injury, mammals have largely lost this ability. Our studies show that glial cells can be reprogrammed to act as progenitors in zebrafish. In mammals, injury downregulates genes that keep glial cells in a resting state, but these genes quickly reassert themselves, preventing regeneration. By disrupting these genes, we aim to induce glial cells to generate neurons, particularly in the retina and hypothalamus.
Who are your collaborators?
We’ve had the privilege of working with several outstanding collaborators. Our longest-term collaborator is Jiang Qian at Wilmer, our go-to informatics expert. We’ve also worked closely with Loyal Goff and Genevieve Stein O’Brien on single-cell RNA-seq analysis of retinal development. They developed new tools to identify patterns of co-expressed genes and compare these patterns across datasets.
Currently, we’re collaborating with a large group at Wilmer as part of the ARPA-H initiative, focusing on the transplantation of human eye tissues to treat blindness. This team includes researchers from the University of Colorado, University of Southern California, University of Wisconsin, and Indiana University, led by Tom Johnson and Jeff Mumm.
Additionally, I work closely with Heng Zhu in the Pharmacology department. Together, we developed the human proteome microarray, a tool for functional proteomics. This collaboration led to the founding of CDI Labs, a biotech company with 35 employees across offices in Puerto Rico, Highlandtown, and Toronto.
We’ve also collaborated with Solange Brown’s group on analyzing specific cell types in the hypothalamus that regulate sleep, focusing on LHX6-positive cells. We’re continuing this work with Mark Wu, who has shown that thalamic nuclei neurons project directly to the LHX6 neurons we identified. His research has further demonstrated that these neurons influence the amount of sleep needed rather than the transition between sleep and wakefulness.
What made you become a scientist?
Seth Blackshaw: I’ve been drawn to science for as long as I can remember, driven by curiosity and a bit of fear. My earliest memory is of a picture of a faceless man standing on a dusty surface with a black sky in the background. Later, I learned it was Buzz Aldrin on my wall, which sparked my obsession with astronomy around age four. Understanding that the “spaceman” wasn’t something to fear but something wonderful fueled my curiosity.
Photo Credit: Astronaut Buzz Aldrin walks on the surface of the moon near the leg of the lunar module Eagle during the Apollo 11 mission. NASA
How did you end up at Hopkins?
Seth Blackshaw: In high school, I became more interested in the humanities—history, philosophy, political science, and literature. However, I eventually returned to my original passion: understanding human nature.
Realizing that debates on human nature had persisted for millennia without resolution, I decided to approach the topic through the physical sciences. I majored in biochemistry in college, then came to Hopkins for grad school and worked with Sol Snyder. Towards the end of my studies, I saw the need to understand cell diversity to grasp behavior fully. This led me to a postdoc at Harvard, studying retinal development with Connie Cepko. In 2004, I returned to Hopkins as faculty and have been on this path ever since.
Do you have any special words of advice for students and postdocs going into research?
Seth Blackshaw: Absolutely. First, choose your training environment carefully. I had a tough experience as an undergrad in a poorly managed lab, which ended badly. I was told I had no talent for bench work and should quit, but it only made me more determined.
Do your homework before joining a lab. Ask around about the lab’s environment and the outcomes for people who have worked there. Lab culture and institutional culture will significantly impact your happiness and success, so choose carefully.
What do you enjoy doing in your free time?
Seth Blackshaw: I love spending time with my family. My kids are in their 20’s, but I cherish any opportunity to spend time with them and my wife. We also have two cats that I enjoy being around. In addition to family time, I like to read, travel, swim, and hike.