Alex Pollen, PhD

Assistant Professor
M_Neurology

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.

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.

Publications

Rapid and repeated evolution of myosin copy number in threespine stickleback.

bioRxiv : the preprint server for biology

Yoxsimer AM, Daugherty RR, Hare EE, Chan YF, Jones FC, Kingman GAR, Offenberg EG, Howes TR, Zhang H, Pollen AA, Brady SD, Xie KT, Chen HI, Lowe CB, Au EH, Grimwood J, Schmutz J, Myers RM, Schluter D, Heins DC, Reyes ML, Baker JA, Jónsson B, Reimchen TE, Bell MA, Kingsley DM

The new frontier in understanding human and mammalian brain development.

Nature

Nowakowski TJ, Nano PR, Matho KS, Chen X, Corrigan EK, Ding W, Gao Y, Heffel M, Jayakumar J, Kaplan HS, Kronman FN, Kovner R, Mannens CCA, Song M, Steyert MR, Venkatesan S, Wallace JL, Wang L, Werner JM, Zhang D, Yuan G, Zuo G, Ament SA, Colantuoni C, Dulac C, Fan R, Gillis J, Kriegstein AR, Krienen FM, Kim Y, Linnarsson S, Mitra PP, Pollen AA, Sestan N, Tward DJ, van Velthoven CTJ, Yao Z, Bhaduri A, Zeng H

Fate plasticity of interneuron specification.

iScience

Mostajo-Radji MA, Leon WRM, Breevoort A, Gonzalez-Ferrer J, Schweiger HE, Lehrer J, Zhou L, Schmitz MT, Perez Y, Mukhtar T, Robbins A, Chu J, Andrews MG, Sullivan FN, Tejera D, Choy EC, Paredes MF, Teodorescu M, Kriegstein AR, Alvarez-Buylla A, Pollen AA

Implementation and validation of single-cell genomics experiments in neuroscience.

Nature neuroscience

Colonna M, Konopka G, Liddelow SA, Nowakowski T, Awatramani R, Bateup HS, Cadwell CR, Caglayan E, Chen JL, Gillis J, Kampmann M, Krienen F, Marsh SE, Monje M, O'Dea MR, Patani R, Pollen AA, Quintana FJ, Scavuzzo M, Schmitz M, Sloan SA, Tesar PJ, Tollkuhn J, Tosches MA, Urbanek ME, Werner JM, Bayraktar OA, Gokce O, Habib N

Structurally divergent and recurrently mutated regions of primate genomes.

Cell

Mao Y, Harvey WT, Porubsky D, Munson KM, Hoekzema K, Lewis AP, Audano PA, Rozanski A, Yang X, Zhang S, Yoo D, Gordon DS, Fair T, Wei X, Logsdon GA, Haukness M, Dishuck PC, Jeong H, Del Rosario R, Bauer VL, Fattor WT, Wilkerson GK, Mao Y, Shi Y, Sun Q, Lu Q, Paten B, Bakken TE, Pollen AA, Feng G, Sawyer SL, Warren WC, Carbone L, Eichler EE

Three-dimensional genome rewiring in loci with human accelerated regions.

Science (New York, N.Y.)

Keough KC, Whalen S, Inoue F, Przytycki PF, Fair T, Deng C, Steyert M, Ryu H, Lindblad-Toh K, Karlsson E, Zoonomia Consortium?, Nowakowski T, Ahituv N, Pollen A, Pollard KS, Andrews G, Armstrong JC, Bianchi M, Birren BW, Bredemeyer KR, Breit AM, Christmas MJ, Clawson H, Damas J, Di Palma F, Diekhans M, Dong MX, Eizirik E, Fan K, Fanter C, Foley NM, Forsberg-Nilsson K, Garcia CJ, Gatesy J, Gazal S, Genereux DP, Goodman L, Grimshaw J, Halsey MK, Harris AJ, Hickey G, Hiller M, Hindle AG, Hubley RM, Hughes GM, Johnson J, Juan D, Kaplow IM, Karlsson EK, Keough KC, Kirilenko B, Koepfli KP, Korstian JM, Kowalczyk A, Kozyrev SV, Lawler AJ, Lawless C, Lehmann T, Levesque DL, Lewin HA, Li X, Lind A, Lindblad-Toh K, Mackay-Smith A, Marinescu VD, Marques-Bonet T, Mason VC, Meadows JRS, Meyer WK, Moore JE, Moreira LR, Moreno-Santillan DD, Morrill KM, Muntan? G, Murphy WJ, Navarro A, Nweeia M, Ortmann S, Osmanski A, Paten B, Paulat NS, Pfenning AR, Phan BN, Pollard KS, Pratt HE, Ray DA, Reilly SK, Rosen JR, Ruf I, Ryan L, Ryder OA, Sabeti PC, Sch?ffer DE, Serres A, Shapiro B, Smit AFA, Springer M, Srinivasan C, Steiner C, Storer JM, Sullivan KAM, Sullivan PF, Sundstr?m E, Supple MA, Swofford R, Talbot JE, Teeling E, Turner-Maier J, Valenzuela A, Wagner F, Wallerman O, Wang C, Wang J, Weng Z, Wilder AP, Wirthlin ME, Xue JR, Zhang X

Tropism of SARS-CoV-2 for human cortical astrocytes.

Proceedings of the National Academy of Sciences of the United States of America

Andrews MG, Mukhtar T, Eze UC, Simoneau CR, Ross J, Parikshak N, Wang S, Zhou L, Koontz M, Velmeshev D, Siebert CV, Gemenes KM, Tabata T, Perez Y, Wang L, Mostajo-Radji MA, de Majo M, Donohue KC, Shin D, Salma J, Pollen AA, Nowakowski TJ, Ullian E, Kumar GR, Winkler EA, Crouch EE, Ott M, Kriegstein AR

High-resolution comparative analysis of great ape genomes.

Science (New York, N.Y.)

Kronenberg ZN, Fiddes IT, Gordon D, Murali S, Cantsilieris S, Meyerson OS, Underwood JG, Nelson BJ, Chaisson MJP, Dougherty ML, Munson KM, Hastie AR, Diekhans M, Hormozdiari F, Lorusso N, Hoekzema K, Qiu R, Clark K, Raja A, Welch AE, Sorensen M, Baker C, Fulton RS, Armstrong J, Graves-Lindsay TA, Denli AM, Hoppe ER, Hsieh P, Hill CM, Pang AWC, Lee J, Lam ET, Dutcher SK, Gage FH, Warren WC, Shendure J, Haussler D, Schneider VA, Cao H, Ventura M, Wilson RK, Paten B, Pollen A, Eichler EE

Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis.

Cell

Fiddes IT, Lodewijk GA, Mooring M, Bosworth CM, Ewing AD, Mantalas GL, Novak AM, van den Bout A, Bishara A, Rosenkrantz JL, Lorig-Roach R, Field AR, Haeussler M, Russo L, Bhaduri A, Nowakowski TJ, Pollen AA, Dougherty ML, Nuttle X, Addor MC, Zwolinski S, Katzman S, Kriegstein A, Eichler EE, Salama SR, Jacobs FMJ, Haussler D