Lukasz M. Szewczyk PHD

My research explores how glial cells shape brain development, circuit maturation, and vulnerability to neuropsychiatric disorders. I focus on astrocytes and microglia as active regulators of neuronal function, asking how their developmental programs integrate genetic susceptibility and environmental stress to influence long-term brain outcomes.

A central theme of my work is canonical Wnt/β-catenin signaling as a developmental gatekeeper in glial cells. While Wnt signaling is widely studied in neurons, my research has demonstrated that its transcriptional effector TCF7L2 plays a critical, cell-type-specific role in astrocytes and microglia. I have shown that astrocytic Wnt/TCF7L2 signaling directly controls synapse development, neuronal excitability, and social behavior, challenging neuron-centric models of circuit formation. More recently, my work indicates that disruption of Wnt signaling in microglia induces stress-adapted, latent vulnerability states that alter glial–glial and glial–neuronal communication.

Building on these findings, my current research program examines how Wnt-dependent glial states interact with developmental and environmental stress to generate persistent circuit dysfunction, with relevance to autism spectrum disorder and related conditions. Using cell-type-specific mouse genetics, single-cell and single-nucleus transcriptomics, electrophysiology, and human iPSC-derived neuron–glia systems, I investigate how maladaptive glial states are initiated, propagated across glial networks, and—critically—whether they remain reversible during defined developmental windows.

In parallel, I study astrocyte-intrinsic mechanisms that support brain plasticity in adulthood, focusing on the role of astrocytic TCF7L2 in hippocampal adult neurogenesis and experience-dependent circuit remodeling. Together, my work aims to establish a unified framework in which glial signaling pathways actively gate neural development, plasticity, and vulnerability across the lifespan

01 - 06.2018 - University of California, San Francisco (UCSF), Anna V. Molofsky Laboratory, CA, US

02 - 04.2015 - Icahn School of Medicine at Mount Sinai, Patrizzia Casaccia Laboratory, New York City, NY, US

01 - 06.2011 - Leibniz Institute for Neurobiology, Neuropharmacology Research Group, Magdeburg, Germany 

08 - 12.2010 - Selvita Inc., Laboratory of Cell Biology, Krakow, Poland 

May 2025 – present: Suelen Baggio, PhD (Postdoctoral researcher)

September 2025 – present: Maciej Niedźwiecki (Undergraduate student)

1. National Science Centre - grant Opus 27  

Project - The role of TCF7L2 transcription factor in developing and in adult hippocampal astrocytes

2024 - 2028 (Principal Investigator) 

Funding: PLN 1 917 962 PLN, National Science Centre

2. National Science Centre - grant Sonata 16  

Project - The role of the astrocytic transcription factor TCF7L2 in synapse development

2021 - 2024 (Principal Investigator) 

Funding: PLN 1 508 953PLN, National Science Centre

in a collaboration with prof. Anna V. Molofsky (UCSF) and prof. Tomasz J. Nowakowski (UCSF)

3. National Science Centre - grant Sonatina 1  

Project - The involvement of LEF1/TCF transcription factors in astrogenesis

2017 - 2020 (Principal Investigator) 

Funding: 831 311 PLN, National Science Centre

in a collaboration with prof. Anna V. Molofsky (UCSF)

Cold Spring Harbor Meeting - Glia in Health & Disease 2022

Cold Spring Harbor Laboratory, NY, US, July 21 - 25, 2022

Talk Title: Astrocytic β-catenin signaling regulates social behavior

16th International Congress of the Polish Neuroscience Society, 2023

20-23 September 2023, Toruń, Poland

Talk Title: Astrocytic ß-catenin pathway – a new player in the regulation of behavior 

NEURONUS IBRO & IRUN Neuroscience Forum, 2016

22 -24 April, 2016, Krakow, Poland

Talk Title: Myelin impairment and axonal degeneration in ST8SIA2-deficient mice

- Review Editor in Frontiers in Molecular Neuroscience - Methods and Model Organisms since 2023

- Conference session co-organizer entitled In sickness and in health: the role of astrocytes in the brain function during 16th International Congress of the Polish Neuroscience Society, 20-23 September 2023, Toruń, Poland

Mentorship & International Collaboration

prof. Anna V. Molofsky, MD, PhD, University of California, San Francisco (UCSF), US

prof. Shane A. Liddelow, PhD, Neuroscience Institute New York University Grossman School of Medicine, US

prof. Maite Solas, PhD, University of Navarra, Spain

Nilhan Gounhalnar, PhD, Erasmus University Rotterdam's Medical Center, Netherlands.

Domestic Collaboration

prof. Marta Wisniewska, PhD, University of Warsaw,

Ewa Liszewska, PhD, International Institute of Molecular and Cell Biology (IIMCB)

Prof. Jacek Jaworski, PhD, International Institute of Molecular and Cell Biology (IIMCB)

prof. Anna Malik, PhD, University of Warsaw

Mariusz Popek, PhD, Polish Academy of Sciences

Scientific Articles:

Mariusz Popek, Krzysztof Goryca, Dorota Adamska, Joanna Urban-Ciećko, Katarzyna Hryniewiecka, Marcin Lipiec, Tomasz Grzegorz Krawczyk, Kamil Rafalko, Alicja Ławicka, Shane A. Liddelow, Lukasz Mateusz Szewczyk

Astrocytic TCF7L2 Impacts Brain Osmoregulation and Restricts Neuronal Excitability

Glia

Łukasz M. Szewczyk, Marcin A. Lipiec, Ewa Liszewska, Ksenia Meyza, Joanna Urban-Ciecko, Ludwika    Kondrakiewicz, Anna Goncerzewicz, Kamil Rafalko, Tomasz Krawczyk, Karolina Bogaj, Ilia Vainchtein, Hiromi Nakao-Inoue, Alicja Puscian, Ewelina Knapska, Stephan Sanders, Tomasz Nowakowski, Anna Victoria Molofsky, Marta B. Wisniewska 

Astrocytic β-catenin signaling via TCF7L2 regulates synapse development and social behavior 

Molecular Psychiatry, 

Lipiec MA, Bem J, Koziński K,Chakraborty Ch, Urban-Ciećko J, Zajkowski Z, Dąbrowski M, Szewczyk LM, Toval A, Ferran JL, Nagalski A, Wiśniewska MB

TCF7L2 regulates postmitotic differentiation programs and excitability patterns in the thalamus

Development. 2020 Aug 25;147(16):dev190181. doi: 10.1242/dev.190181.

Szewczyk, L. M., N. Brozko, A. Nagalski, I. Röckle, S. Werneburg, H. Hildebrandt, M. B. Wisniewska & J. Kuznicki

ST8SIA2 promotes oligodendrocyte differentiation and the integrity of myelin and axons.

Glia. 2017 Jan;65(1):34-49. doi: 10.1002/glia.23048. Epub 2016 Aug 18.

Misztal, K., N. Brozko, A. Nagalski, Szewczyk L.M., M. Krolak, K. Brzozowska, J. Kuznicki & M. B. Wisniewska 

TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models.

Neuropharmacology. 2017 Feb;113(Pt A):490-501. doi: 10.1016/j.neuropharm.2016.10.027. Epub 2016 Oct 25.

Nagalski, A., Irimia M, Szewczyk L, Ferran J.L, Misztal K, Kuznicki J & Wisniewska M.B.

Postnatal isoform switch and protein localization of LEF1 and TCF7L2 transcription factors in cortical, thalamic, and mesencephalic regions of the adult mouse brain.

Brain Struct Funct. 2013 Nov;218(6):1531-49. doi: 10.1007/s00429-012-0474-6. Epub 2012 Nov 15.

Szewczyk L, Ulańska J, Dubiel M, Osyczka AM, Tylko G.

The effect of acrylamide and nitric oxide donors on human mesenchymal progenitor cells.

Toxicol In Vitro. 2012 Sep;26(6):897-906. doi: 10.1016/j.tiv.2012.04.016. Epub 2012 Apr 20.

Reviews & Book Chapters

Wnt/β-catenin signaling in brain development and mental disorders: keeping TCF7L2 in mind.

Bem J, Brożko N, Chakraborty C, Lipiec MA, Koziński K, Nagalski A, Szewczyk LM, Wiśniewska MB.

FEBS Lett. 2019 Jun 20. doi: 10.1002/1873-3468.13502. 

Mechanisms of astrocyte development  

Patterning and Cell Type Specification in the Developing CNS and PNS- Second Edition, 2020

Debosmita Sardar, Yi-TingCheng, Lukasz Mateusz Szewczyk, Benjamin Deneen Anna, Victoria Molofsky

Blog Host

Astrocytes instance segmentation with Machine Learning

2021 – National Science Centre - Research Grant Sonata 16 

2017 – National Science Centre - Research Grant Sonatina 1 

2016 - PhD magna cum laude

2016 - NEURONUS 2016 IBRO & IRUN Neuroscience Forum Talk: Myelin impairment and axonal degeneration in ST8SIA2-deficient mice

2014 – National Science Centre - PhD Fellowship Etiuda 2

2014 – Best Poster Award at IBRO & IRUN NEURONUS Neuroscience Forum, Krakow, Poland

2013 – National Science Centre - Research Grant Preludium 5

2013 – Travel Grant for Developmental Neurobiology Course at OIST Institute, Okinawa, Japan

2011 – Laureate of European Commission Lifelong Learning Programme - Leonardo da Vinci Fellowship