Příloha 7: Posudek oponenta habilitační práce


Masarykova univerzita


Fakulta

Lékařská fakulta MU

Habilitační obor

Lékařská biologie



Uchazeč

Yuh-Man Wadeley, Ph.D.

Pracoviště

Biologický ústav Lékařské fakulty MU

Habilitační práce

A quest to find out how human brain cells form and brain-related diseases develop



Oponent

Doc. MUDr. Milena Králíčková, Ph.D.

Pracoviště

Ústav histologie a embryologie, Lékařská fakulta v Plzni, Univerzita Karlova v Praze


Text posudku (rozsah dle zvážení oponenta)

The work contains 9 pages of introduction (text and schemes) with around 60 papers citated after
this introduction. Four articles from years 2005, 2008, 2010 and 2013 are attached.

Articles from 2005 and 2008 are dedicated to the RE1 Silencing Transcription Factor (REST) which is
the master regulator of neuronal and glial fate specification. It acts at multiple levels of stem
cell differentiation and it is required for neurogenesis. Generations of nestin-positive, followed
by β-III-tubulin-positive as well as MAP2-positive phenotype are impeded by REST ablation, and
REST-depleted neural stem cells are defective in adherence, migration and survival. Findings of dr.
Sun from both articles shed new light on a previously underemphasized aspect of REST function
during neural differentiation.

In the third attached paper the authors including dr. Sun identified a novel neural initiator,
neuronatin (Nnat) that acts as an intrinsic factor to promote neural fate in mammals as well as
Xenopus. ESCs lacking this intrinsic factor fail to undergo neural induction despite the inhibition
of the BMP pathway. It has recently been described that neuronatin protein has a strong
predisposition to misfold and form cellular aggregates that cause cell death by apoptosis and its
aggregation within cortical neurons can result in a fatal neurodegenerative disease. A better
understanding of these mechanisms may open new therapeutic targets to help modify the progression
of devastating neurodegenerative conditions.

Last attached article describes the role for protein tyrosine phosphatase 1B (PTP1B). This molecule
plays a role in ESC differentiation - PTP1B suppresses p-ERK1/2 signaling to inhibit neural
specification and promote mesendodermal commitment.

All four attached articles were published in journals with high impact factors and their citation
record proves their relevance.



Dotazy oponenta k obhajobě habilitační práce (počet dotazů dle zvážení oponenta)


1.

The author says in the abstract (page 3) that she will employ her derived paradigms to generate
certain types of neural cells from psychiatric patients (schizophrenia and autism) and investigate
what has happened in the individual neural cell types in relation to the disorders. Could she,
please, describe us the hypothesis behind this plan in more details?

2.

The author also says in the abstract (page 3) that she strongly believes that psychiatric disorders
share a common causal mechanism (a defective neurodevelopmental process and synapthopathies). Could
she, please, describe us what is in her opinion the role of society and social environment in the
pathogenesis of psychiatric disorders?



Závěr


Habilitační práce Yuh-Man Wadeley „A quest to find out how human brain cells form and brain-related
diseases develop“ splňuje požadavky standardně kladené na habilitační práce v oboru Lékařská
biologie.




Praha, dne 4. 4. 2015                                                   Doc. MUDr. Milena
Králíčková, Ph.D.