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Dr Mohammed Shaker

Research Fellow/Senior Research off

Australian Institute for Bioengineering and Nanotechnology

Research Fellow/Senior Research off

Australian Institute for Bioengineering and Nanotechnology
m.shaker@uq.edu.au
+61 7 334 63894

Overview

Dr. Shaker is an accomplished neuroscientist who earned his PhD in 2017 from Korea University in Seoul, South Korea. His doctoral research focused on the cellular behavior of embryonic neural stem cells during brain and spinal cord development, as well as axial elongation. Dr. Shaker was awarded the prestigious Brain Korea 21 Plus Fellowship from Korea University Medical School, which set the stage for his subsequent role at AIBN-UQ. There, he joined Professor Ernst Wolvetang's laboratory as a Postdoctoral Research Fellow in Organoid Biology, continuing his pioneering research into the human central nervous system in health and disease using cutting-edge organoid technology.

Dr. Shaker has made several groundbreaking contributions to the field, including:

1. Generation of White Matter-like Tissues in Organoids: Dr. Shaker developed a robust and rapid protocol that produces white matter-like tissues enriched with myelinating oligodendrocytes, neurons, and astrocytes within 42 days. This protocol, detailed in publications such as Frontiers in Cellular Neuroscience (2021) and STAR PROTOCOLS (2023), involves the exposure of neuroectoderm-derived organoids to a cocktail of growth factors and small molecules that promote oligodendrocyte specification and survival. His work also led to the discovery of NELL2 expression in human oligodendroglial cell types and its linkage to human white matter development and diseases, as highlighted in Frontiers in Cell and Developmental Biology (2022).

2. Human Cortical Organoid Senescence: Dr. Shaker demonstrated that human cortical organoids exhibit typical hallmarks of senescent cells when maintained in vitro for extended periods. He also found that moderate upregulation of endogenous KL expression in cortical organoids inhibits neuronal senescence, providing new mechanistic insights into human brain aging. This significant finding was published in NPJ Aging and Mechanisms of Disease (2021).

3. Down Syndrome Modelling with Organoids: Dr. Shaker successfully modeled Down Syndrome using patient and isogenic human iPSCs lines with Choroid Plexus-Ventricle-Cortical organoids. This model, published in Science Advances (2024), is instrumental for dissecting the role of the choroid plexus in euploid and Down Syndrome forebrain development and enables screening for therapeutics to inhibit SARS-CoV-2 induced neuro-pathogenesis.

Currently, Dr. Shaker is leading two major research projects:

1. Leukodystrophy Modeling: Using reprogrammed patient iPSCs lines to create oligodendrocyte brain organoids, Dr. Shaker is advancing the understanding and potential treatments for leukodystrophies.

2. Neural Tube Elongation Defects: This project uses spinal cord organoids combined with advanced transcriptomics techniques to study the cellular processes driving neural tube elongation. The goal is to gain insights into the causes of neural tube defects, improving our understanding of how cells arrange into a continuously elongating neural tube.

Dr. Shaker’s innovative work continues to push the boundaries of neuroscience, providing valuable insights into the development and diseases of the human central nervous system

Research Interests

  • Neurogenesis
  • Myelination
  • Organoids
  • Neural tube
  • Mitochondria

Research Impacts

Research Impact

Knowledge Impact Despite decades of animal research aimed at developing treatments for white matter diseases, most interventions that showed preclinical success failed in humans. Our research program aimed to uncover the cellular and molecular mechanisms controlling stem cell behavior, leading to the development of novel platforms for creating complex human central nervous system (CNS) tissues in vitro. These advancements have facilitated a paradigm shift in CNS development and stem cell research.

We pioneered new technologies and methods, such as:

  1. Illustrating the lineage and cellular properties of axial stem cells.
  2. Generating complex human brain and spinal cord tissues that accurately replicate human systems.
  3. Introducing innovative tools to create human white matter-like tissues in vitro.

Technological and Interdisciplinary Advancements Our research has significantly advanced multiple disciplines, including neuroscience, medicine, and technology. Key achievements include:

  1. Rapid production of mature oligodendrocytes in brain organoids, now used globally for modeling white matter diseases and drug screening.
  2. Creation of the first in vitro model of human brain aging and neuronal senescence.
  3. Discovery of the role of NELL2 in human oligodendrocytes, revealing new insights into white matter diseases with the aid of machine learning.

Before our research program, generating reliable human CNS tissues that accurately mimicked in vivo conditions was a challenge. Our early studies (2014-2018) on axial stem cells led to novel in vitro techniques, uncovering new progenitor cells (neuromesodermal progenitors) that form the spinal cord and caudal hindbrain. This work has driven interest in generating human spinal cord tissues for drug screening against neural tube defects.

From 2018-2022, we developed platforms to model different CNS domains using organoids, optimizing conditions to generate white matter-like tissues for drug screening. Our discovery of the anti-aging protein Klotho's role in inhibiting neuronal senescence and the creation of forebrain-like tissues with choroid plexus for modeling SARS-CoV-2 neuropathology in Down syndrome significantly advance disease modeling in vitro.

Recent work identified NELL2 in oligodendroglia, associated with white matter diseases like leukodystrophy. We have established national and international collaborations for further research and drug screening.

My efforts have been recognized with several awards, including the Early Career Researcher Fellowship from the Children’s Hospital Foundation and the European Leukodystrophy International Association Grant. I have presented my work at prestigious conferences and received multiple awards.

Qualifications

  • Doctor of Philosophy, Korea University
  • Masters (Coursework), University of Malaya
  • Bachelor of Biomedical Science, University of Malaya

Publications

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Grants

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Supervision

  • Elucidating the role of Human Aminoacyl multi- tRNA synthetase complex (MSC) in Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL)

    Doctor Philosophy

  • Understanding neuromuscular synaptic loss in motor neuron disease

    Doctor Philosophy

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Publications

Journal Article

Conference Publication

PhD and MPhil Supervision

Current Supervision

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Links

ORCID: 0000-0002-3675-4598

Scopus ID: 56622545100

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