Tomasz Nowakowski, PhD

Associate Professor
M_Neurological Surgery

Research Description

Research in the lab focuses on mapping and functionally interrogating molecular and cellular networks in the developing and adult brain. We are taking a multi-disciplinary approach, including molecular genetics, functional genomics, single cell genomics, cell biology, to gain a mechanistic understanding of cell fate specification, intercellular interactions, and higher order phenotypes in the human brain and its models.

Current Projects

Brain Development – we are pursuing studies that seek to decipher the developmental origins of cell diversity in the human cerebral cortex. We are interested in studying how genetic mutations in patients with neurological and neuropsychiatric developmental symptoms disrupt normal brain development.

Gene Regulatory Networks – we are utilizing single cell omics approaches to identify molecular properties of cells in the developing and adult brain. By generating cellular-resolution datasets spanning genomic, epigenomic, transcriptomic, and functional readouts from cells under different states, we seek to identify the hubs of regulatory relationships that shape multiple features of cell identity and function.

Cell-Cell Interactions – we are studying how distinct cell types come together to build what is more than a sum of its parts. Pervasive and dynamic communication between cell types plays critical role in brain development and disease, and we are developing tools and technologies to identify and functionally interrogate those interactions in the human brain.

Lab Members

Galina Schmunk – Postdoctoral fellow

Cathryn Cadwell – Postdoctoral/Clinical fellow

Ryan Ziffra – Graduate Student

Denise Allen – Graduate Student

David Shin – Graduate Student

Derek Bogdanoff – Graduate Student

Kelsey Hennick – Graduate Student

Chang Kim – Staff/Assistant Specialist

Sarah Soliman – Staff/Assistant Specialist

Jayden Ross – Staff/Assistant Specialist

Lab Website

Publications

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

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.

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

An organotypic atlas of human vascular cells.

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.

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.

M_Anatomy-General

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.

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.

eLife

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.

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.

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.

M_Anatomy-General

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.

M_Anatomy-General

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.

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