Tomasz Nowakowski, PhD

Associate Professor
Anatomy
Psychiatry
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
Research Overview: 

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.

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.

Websites

Publications: 

Thalamocortical organoids enable in vitro modeling of 22q11.2 microdeletion associated with neuropsychiatric disorders.

Cell stem cell

Shin D, Kim CN, Ross J, Hennick KM, Wu SR, Paranjape N, Leonard R, Wang JC, Keefe MG, Pavlovic BJ, Donohue KC, Moreau C, Wigdor EM, Larson HH, Allen DE, Cadwell CR, Bhaduri A, Popova G, Bearden CE, Pollen AA, Jacquemont S, Sanders SJ, Haussler D, Wiita AP, Frost NA, Sohal VS, Nowakowski TJ

Optimal trade-off control in machine learning-based library design, with application to adeno-associated virus (AAV) for gene therapy.

Science advances

Zhu D, Brookes DH, Busia A, Carneiro A, Fannjiang C, Popova G, Shin D, Donohue KC, Lin LF, Miller ZM, Williams ER, Chang EF, Nowakowski TJ, Listgarten J, Schaffer DV

Improving cellular diversity in human cerebellar organoids.

Cell stem cell

Steyert M, Nowakowski T

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

Single-cell analysis of prenatal and postnatal human cortical development.

Science (New York, N.Y.)

Velmeshev D, Perez Y, Yan Z, Valencia JE, Castaneda-Castellanos DR, Wang L, Schirmer L, Mayer S, Wick B, Wang S, Nowakowski TJ, Paredes M, Huang EJ, Kriegstein AR