Alex Pollen, PhD

Assistant Professor
Neurology
Research Overview: 

Over the last six million years, human cognition has changed in remarkable ways to support symbolic language, long-term planning, cooperation on vast scales, and the rapid cultural accumulation of technology. During this time, patterns of brain development and life history changed to triple the number of neurons produced prenatally, extend synaptic plasticity through a prolonged phase of development, and restructure connectivity between brain regions. At the same time tens of millions of mutations accumulated as fixed changes in the human genome through the processes of selection and drift. A portion of this new genomic information guides the development of uniquely human traits and contributes to disease vulnerabilities shared by all humans. However, connecting human-specific mutations to recently evolved traits remains a major challenge because we lack experimental systems for comparative and functional studies of great ape cortical development. To identify genomic differences underlying unique features or vulnerabilities of the human brain, we are incorporating advances in single cell genomics and genome engineering with great ape cerebral organoid models of brain development. We are enthusiastic for new graduate students to join the team, and the lab is well suited for those with an interest in evolution, neuropsychiatric disorders, neuronal cell diversity, stem cell models, or bioinformatics.

Primary Thematic Area: 
Neurobiology
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
We study how genetic changes that accumulated over the last 6 million years of human evolution influence specialized features of brain development using single cell genomics, cerebral organoid models of ape brain development, and genome engineering.

Websites

Featured Publications: 

Molecular Identity of Human Outer Radial Glia during Cortical Development.

Cell

Pollen AA, Nowakowski TJ, Chen J, Retallack H, Sandoval-Espinosa C, Nicholas CR, Shuga J, Liu SJ, Oldham MC, Diaz A, Lim DA, Leyrat AA, West JA, Kriegstein AR

Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex.

Nature biotechnology

Pollen AA, Nowakowski TJ, Shuga J, Wang X, Leyrat AA, Lui JH, Li N, Szpankowski L, Fowler B, Chen P, Ramalingam N, Sun G, Thu M, Norris M, Lebofsky R, Toppani D, Kemp DW, Wong M, Clerkson B, Jones BN, Wu S, Knutsson L, Alvarado B, Wang J, Weaver LS, May AP, Jones RC, Unger MA, Kriegstein AR, West JA

Human-specific loss of regulatory DNA and the evolution of human-specific traits.

Nature

McLean CY, Reno PL, Pollen AA, Bassan AI, Capellini TD, Guenther C, Indjeian VB, Lim X, Menke DB, Schaar BT, Wenger AM, Bejerano G, Kingsley DM

How unique is the human neocortex?

Development (Cambridge, England)

Molnár Z, Pollen A

Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.

Cell stem cell

Nowakowski TJ, Pollen AA, Di Lullo E, Sandoval-Espinosa C, Bershteyn M, Kriegstein AR