Tomasz Nowakowski, PhD

Asst Professor in Residence
Anatomy
+1 415 476-0878

Dr. Nowakowski received his Ph.D. from the University of Edinburgh (UK) in 2012, where he developed his passion for understanding molecular mechanisms of brain development. Subsequently, he pursued postdoctoral training at the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research at UCSF. In 2017, where he used single cell RNA sequencing to study the heterogeneity of cellular populations in the developing brain and discovered the biomarkers of outer radial glia.

He synthesized the current understanding of brain development and cortical expansion in the Supragranular Cortex Expansion Hypothesis, which extends the classic view of cortical development embodied in the Radial Unit Hypothesis to account for the massive expansion of the cortical OSVZ progenitor population, the protracted neurogenesis period in humans and primates, the loss of pial surface-contacting radial glia fibers mid-way through cortical neurogenesis, and the disproportionate expansion of supragranular cortical layers within primates. This updated model has important implication for neuronal migration, area patterning, and cortical folding.

Dr. Nowakowski established his own research group in 2017. His group seeks to understand how the human genome, a fundamental unit in biology, reproducibly generates the neuronal cell types of the brain that support its complex cognitive functions. In particular, Dr. Nowakowski is fascinated by inherited developmental mechanisms that recapitulate key morphological features of the body plan, while allowing sufficient flexibility to achieve the phenotypic variation we observe in nature. 

Recently developed technologies of single-cell sequencing, genome engineering, and in vitro modeling of tissue development have transformed our ability study the complex universe of cellular processes with unprecedented precision. Dr. Nowakowski’s independent research group seeks to utilize these technologies to uncover genetic control mechanisms underlying neurodevelopmental events and tissue organization in the cerebral cortex. These approaches may highlight cellular patterns of selective vulnerability in neurodevelopmental and neuropsychiatric disorders, including Autism Spectrum Disorders and Schizophrenia.

Research Summary: 
Developmental origins of cellular diversity in the nervous system. Molecular and cellular mechanisms of cortical development.

Websites

Publications: 

Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.

Cell

Pollen AA, Bhaduri A, Andrews MG, Nowakowski TJ, Meyerson OS, Mostajo-Radji MA, Di Lullo E, Alvarado B, Bedolli M, Dougherty ML, Fiddes IT, Kronenberg ZN, Shuga J, Leyrat AA, West JA, Bershteyn M, Lowe CB, Pavlovic BJ, Salama SR, Haussler D, Eichler EE, Kriegstein AR

Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex.

Neuron

Mayer S, Chen J, Velmeshev D, Mayer A, Eze UC, Bhaduri A, Cunha CE, Jung D, Arjun A, Li E, Alvarado B, Wang S, Lovegren N, Gonzales ML, Szpankowski L, Leyrat A, West JAA, Panagiotakos G, Alvarez-Buylla A, Paredes MF, Nowakowski TJ, Pollen AA, Kriegstein AR

Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function.

Cell reports

Pai EL, Vogt D, Clemente-Perez A, McKinsey GL, Cho FS, Hu JS, Wimer M, Paul A, Fazel Darbandi S, Pla R, Nowakowski TJ, Goodrich LV, Paz JT, Rubenstein JLR

Neuroserpin expression during human brain development and in adult brain revealed by immunohistochemistry and single cell RNA sequencing.

Journal of anatomy

Adorjan I, Tyler T, Bhaduri A, Demharter S, Finszter CK, Bako M, Sebok OM, Nowakowski TJ, Khodosevich K, Møllgård K, Kriegstein AR, Shi L, Hoerder-Suabedissen A, Ansorge O, Molnár Z

Regulation of cell-type-specific transcriptomes by microRNA networks during human brain development.

Nature neuroscience

Nowakowski TJ, Rani N, Golkaram M, Zhou HR, Alvarado B, Huch K, West JA, Leyrat A, Pollen AA, Kriegstein AR, Petzold LR, Kosik KS

Building blocks of the human brain.

Science (New York, N.Y.)

Nowakowski TJ

Identification of cell types in a mouse brain single-cell atlas using low sampling coverage.

BMC biology

Bhaduri A, Nowakowski TJ, Pollen AA, Kriegstein AR

Transcriptional fates of human-specific segmental duplications in brain.

Genome research

Dougherty ML, Underwood JG, Nelson BJ, Tseng E, Munson KM, Penn O, Nowakowski TJ, Pollen AA, Eichler EE

The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.

Cell

Willsey AJ, Morris MT, Wang S, Willsey HR, Sun N, Teerikorpi N, Baum TB, Cagney G, Bender KJ, Desai TA, Srivastava D, Davis GW, Doudna J, Chang E, Sohal V, Lowenstein DH, Li H, Agard D, Keiser MJ, Shoichet B, von Zastrow M, Mucke L, Finkbeiner S, Gan L, Sestan N, Ward ME, Huttenhain R, Nowakowski TJ, Bellen HJ, Frank LM, Khokha MK, Lifton RP, Kampmann M, Ideker T, State MW, Krogan NJ

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

An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder.

Nature genetics

Werling DM, Brand H, An JY, Stone MR, Zhu L, Glessner JT, Collins RL, Dong S, Layer RM, Markenscoff-Papadimitriou E, Farrell A, Schwartz GB, Wang HZ, Currall BB, Zhao X, Dea J, Duhn C, Erdman CA, Gilson MC, Yadav R, Handsaker RE, Kashin S, Klei L, Mandell JD, Nowakowski TJ, Liu Y, Pochareddy S, Smith L, Walker MF, Waterman MJ, He X, Kriegstein AR, Rubenstein JL, Sestan N, McCarroll SA, Neale BM, Coon H, Willsey AJ, Buxbaum JD, Daly MJ, State MW, Quinlan AR, Marth GT, Roeder K, Devlin B, Talkowski ME, Sanders SJ

Evolution of New miRNAs and Cerebro-Cortical Development.

Annual review of neuroscience

Kosik KS, Nowakowski T

Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex.

Science (New York, N.Y.)

Nowakowski TJ, Bhaduri A, Pollen AA, Alvarado B, Mostajo-Radji MA, Di Lullo E, Haeussler M, Sandoval-Espinosa C, Liu SJ, Velmeshev D, Ounadjela JR, Shuga J, Wang X, Lim DA, West JA, Leyrat AA, Kent WJ, Kriegstein AR

Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia.

Cell stem cell

Bershteyn M, Nowakowski TJ, Pollen AA, Di Lullo E, Nene A, Wynshaw-Boris A, Kriegstein AR

The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells.

Nature communications

Gambardella G, Carissimo A, Chen A, Cutillo L, Nowakowski TJ, di Bernardo D, Blelloch R

Zika virus cell tropism in the developing human brain and inhibition by azithromycin.

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

Retallack H, Di Lullo E, Arias C, Knopp KA, Laurie MT, Sandoval-Espinosa C, Mancia Leon WR, Krencik R, Ullian EM, Spatazza J, Pollen AA, Mandel-Brehm C, Nowakowski TJ, Kriegstein AR, DeRisi JL

Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas.

Molecular systems biology

Müller S, Liu SJ, Di Lullo E, Malatesta M, Pollen AA, Nowakowski TJ, Kohanbash G, Aghi M, Kriegstein AR, Lim DA, Diaz A

Transformation of the Radial Glia Scaffold Demarcates Two Stages of Human Cerebral Cortex Development.

Neuron

Nowakowski TJ, Pollen AA, Sandoval-Espinosa C, Kriegstein AR

A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA.

Neuron

Rani N, Nowakowski TJ, Zhou H, Godshalk SE, Lisi V, Kriegstein AR, Kosik KS

SCell: integrated analysis of single-cell RNA-seq data.

Bioinformatics (Oxford, England)

Diaz A, Liu SJ, Sandoval C, Pollen A, Nowakowski TJ, Lim DA, Kriegstein A

Single-cell analysis of long non-coding RNAs in the developing human neocortex.

Genome biology

Liu SJ, Nowakowski TJ, Pollen AA, Lui JH, Horlbeck MA, Attenello FJ, He D, Weissman JS, Kriegstein AR, Diaz AA, Lim DA

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

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

The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells.

Cell stem cell

Ramos AD, Andersen RE, Liu SJ, Nowakowski TJ, Hong SJ, Gertz C, Salinas RD, Zarabi H, Kriegstein AR, Lim DA

Radial glia require PDGFD-PDGFRß signalling in human but not mouse neocortex.

Nature

Lui JH, Nowakowski TJ, Pollen AA, Javaherian A, Kriegstein AR, Oldham MC

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

Loss of functional Dicer in mouse radial glia cell-autonomously prolongs cortical neurogenesis.

Developmental biology

Nowakowski TJ, Mysiak KS, O'Leary T, Fotaki V, Pratt T, Price DJ

MicroRNA-92b regulates the development of intermediate cortical progenitors in embryonic mouse brain.

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

Nowakowski TJ, Fotaki V, Pollock A, Sun T, Pratt T, Price DJ

The expression and activity of ß-catenin in the thalamus and its projections to the cerebral cortex in the mouse embryo.

BMC neuroscience

Pratt T, Davey JW, Nowakowski TJ, Raasumaa C, Rawlik K, McBride D, Clinton M, Mason JO, Price DJ

Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability.

BMC neuroscience

Quinn JC, Molinek M, Nowakowski TJ, Mason JO, Price DJ

Time-Multiplexed Laguerre-Gaussian holographic optical tweezers for biological applications.

Optics express

Lafong A, Hossack WJ, Arlt J, Nowakowski TJ, Read ND