Jennifer Viegas; PNAS December 28, 2021 118 (52) e2120493118

Figure: John L. R. Rubenstein. Image credit: Barbara Ries, University of California, San Francisco.

For over three decades, developmental neurobiologist John L. R. Rubenstein has been a leader in research on the forebrain, the seat of higher-order brain functions. The Nina Ireland Distinguished Professor in Child Psychiatry at the University of California, San Francisco (UCSF), Rubenstein has identified transcription factor (TF) genes, transcriptional and signaling pathways, and more recently, TF networks that control regional and cell-type specification in the developing cerebral cortex and basal ganglia. Elected to the National Academy of Sciences in 2020, Rubenstein reports in his Inaugural Article the identification of cortical ventricular zone (VZ) enhancers—short sections of noncoding DNA that regulate gene expression—and a cortical regionalization TF network that regulates cortical regional patterning in radial glial stem cells. The findings may provide insights into human neurodevelopmental disorders. Born and raised in California, Rubenstein was influenced by his parents, particularly his father Edward, who was a professor of medicine at Stanford University. While a student at The Thacher School between 1969 and 1973, and later as an undergraduate at Stanford, Rubenstein obtained summer research positions with Stanford cardiac surgeons Norman Shumway and Randall Morris, studying immune responses to heart transplants.

Antisense RNA and Gene Expression

During his sophomore year at Stanford, Rubenstein went to a scientific meeting where he heard a lecture on the transcriptomic complexity of brain RNA by University of Michigan geneticist Gilbert Omenn. 

Interneuron Migration

Rubenstein’s team discovered and characterized a Dlx-dependent core transcriptional program that controls development and function of cortical GABAergic (inhibitory) neurons.

For his work on cortical development and other achievements, Rubenstein has received numerous awards and honors. For example, he is an elected member of the National American Academy of Arts and Sciences (2016), and he received the Ruane Prize for Outstanding Child and Adolescent Psychiatric Research from the Brain & Behavior Research Foundation (2016). He is especially proud of being an elected member of the National Academy of Medicine (NAM) (2006), since his father also received this honor. Rubenstein says, “We are among the few father–son pairs to have been elected to the NAM.”

Rubenstein has helped show that cell transplantation in rodents can reduce memory loss in an Alzheimer’s disease model and neuropathic pain.

“Like long-distance running, it is not a short-term process to be successful in science. It is a career where you are in it for the long term,” he says.

See https://www.pnas.org/content/118/52/e2120493118