Tomasz Nowakowski, PhD

Associate Professor
Anatomy
Psychiatry
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
Primary Thematic Area
Neurobiology
Secondary Thematic Area
Developmental & Stem Cell Biology
Research Summary
Developmental origins of cellular diversity in the nervous system. Molecular and cellular mechanisms of cortical development.

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.

Websites
Nowakowski Lab
UCSF Profiles

Publications

An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.

Neuron

Furlanis E, Dai M, Leyva Garcia B, Tran T, Vergara J, Pereira A, Gorissen BL, Wills S, Vlachos A, Hairston A, Dwivedi D, Du S, McMahon J, Huang S, Morabito A, Vazquez A, Kim S, Lee AT, Chang EF, Razzaq T, Qazi A, Vargish G, Yuan X, Caccavano A, Hunt S, Chittajallu R, McLean N, Hewitt L, Paranzino E, Rice H, Cummins AC, Plotnikova A, Mohanty A, Tangen AC, Shin JH, Azadi R, Eldridge MAG, Alvarez VA, Averbeck BB, Alyahyay M, Vallejo TR, Soheib M, Vattino LG, MacGregor CP, Chatain CP, Banks E, Olah VJ, Naskar S, Hill S, Liebergall S, Badiani R, Hyde L, Hanley E, Xu Q, Allaway KC, Goldberg EM, Rowan MJM, Nowakowski TJ, Lee S, Favuzzi E, Kaeser PS, Sjulson L, Batista-Brito R, Takesian AE, Ibrahim LA, Iqbal A, Pelkey KA, McBain CJ, Dimidschstein J, Fishell G, Wang Y

An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.

bioRxiv : the preprint server for biology

Furlanis E, Dai M, Garcia BL, Vergara J, Pereira A, Pelkey K, Tran T, Gorissen BL, Vlachos A, Hairston A, Huang S, Dwivedi D, Du S, Wills S, McMahon J, Lee AT, Chang EF, Razzaq T, Qazi A, Vargish G, Yuan X, Caccavano A, Hunt S, Chittajallu R, McLean N, Hewit L, Paranzino E, Rice H, Cummins AC, Plotnikova A, Mohanty A, Tangen AC, Shin JH, Azadi R, Eldridge MAG, Alvarez VA, Averbeck BB, Alyahyay M, Vallejo TR, Soheib M, Vattino LG, MacGregor CP, Banks E, Olah VJ, Naskar S, Hill S, Liebergall S, Badiani R, Hyde L, Xu Q, Allaway KC, Goldberg EM, Nowakowski TJ, Lee S, Takesian AE, Ibrahim LA, Iqbal A, McBain CJ, Dimidschstein J, Fishell G, Wang Y

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

An organotypic atlas of human vascular cells.

Nature medicine

Barnett SN, Cujba AM, Yang L, Maceiras AR, Li S, Kedlian V, Pett JP, Polanski K, Miranda AMA, Xu C, Cranley J, Kanemaru K, Lee M, Mach L, Perera S, Tudor C, Joseph PD, Pritchard S, Toscano-Rivalta R, Tuong K, Bolt L, Petryszak R, Prete M, Cakir B, Huseynov A, Sarropoulos I, Chowdhury RA, Elmentaite R, Madissoon E, Oliver A, Campos L, Brazovskaja A, Gomes T, Treutlein B, Kim CN, Nowakowski TJ, Meyer KB, Randi AM, Noseda M, Teichmann SA

Temporally distinct 3D multi-omic dynamics in the developing human brain.

Nature

Heffel MG, Zhou J, Zhang Y, Lee DS, Hou K, Pastor-Alonso O, Abuhanna KD, Galasso J, Kern C, Tai CY, Garcia-Padilla C, Nafisi M, Zhou Y, Schmitt AD, Li T, Haeussler M, Wick B, Zhang MJ, Xie F, Ziffra RS, Mukamel EA, Eskin E, Nowakowski TJ, Dixon JR, Pasaniuc B, Ecker JR, Zhu Q, Bintu B, Paredes MF, Luo C

Type-I-interferon-responsive microglia shape cortical development and behavior.

Cell

Escoubas CC, Dorman LC, Nguyen PT, Lagares-Linares C, Nakajo H, Anderson SR, Barron JJ, Wade SD, Cuevas B, Vainchtein ID, Silva NJ, Guajardo R, Xiao Y, Lidsky PV, Wang EY, Rivera BM, Taloma SE, Kim DK, Kaminskaya E, Nakao-Inoue H, Schwer B, Arnold TD, Molofsky AB, Condello C, Andino R, Nowakowski TJ, Molofsky AV

A foundational atlas of autism protein interactions reveals molecular convergence.

bioRxiv : the preprint server for biology

Wang B, Vartak R, Zaltsman Y, Naing ZZC, Hennick KM, Polacco BJ, Bashir A, Eckhardt M, Bouhaddou M, Xu J, Sun N, Lasser MC, Zhou Y, McKetney J, Guiley KZ, Chan U, Kaye JA, Chadha N, Cakir M, Gordon M, Khare P, Drake S, Drury V, Burke DF, Gonzalez S, Alkhairy S, Thomas R, Lam S, Morris M, Bader E, Seyler M, Baum T, Krasnoff R, Wang S, Pham P, Arbalaez J, Pratt D, Chag S, Mahmood N, Rolland T, Bourgeron T, Finkbeiner S, Swaney DL, Bandyopadhay S, Ideker T, Beltrao P, Willsey HR, Obernier K, Nowakowski TJ, Hüttenhain R, State MW, Willsey AJ, Krogan NJ

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

Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.

Nature communications

Guo H, Bettella E, Marcogliese PC, Zhao R, Andrews JC, Nowakowski TJ, Gillentine MA, Hoekzema K, Wang T, Wu H, Jangam S, Liu C, Ni H, Willemsen MH, van Bon BW, Rinne T, Stevens SJC, Kleefstra T, Brunner HG, Yntema HG, Long M, Zhao W, Hu Z, Colson C, Richard N, Schwartz CE, Romano C, Castiglia L, Bottitta M, Dhar SU, Erwin DJ, Emrick L, Keren B, Afenjar A, Zhu B, Bai B, Stankiewicz P, Herman K, Mercimek-Andrews S, Juusola J, Wilfert AB, Abou Jamra R, Büttner B, Mefford HC, Muir AM, Scheffer IE, Regan BM, Malone S, Gecz J, Cobben J, Weiss MM, Waisfisz Q, Bijlsma EK, Hoffer MJV, Ruivenkamp CAL, Sartori S, Xia F, Rosenfeld JA, Bernier RA, Wangler MF, Yamamoto S, Xia K, Stegmann APA, Bellen HJ, Murgia A, 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