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Professor Robert Pawlak

Chair in Functional Cell Biology

7411

+44 (0) 1392 727411

Hatherly Laboratory C2

Prof. Pawlak graduated from the faculty of Medicine, Medical University of Bialystok, Poland (1994) and received a PhD in Medical Sciences from the same University (1997). Prior to his current appointment at Exeter he studied neuronal plasticity and animal behaviour in Poland (Medical University of Bialystok), Japan (Hamamatsu University), USA (The Rockefeller University) and in the UK (University of Leicester). Prof. Pawlak is the first author or a co-author of over 50 publications.

Broad research specialisms

One fundamental question in modern neurobiology is how memories and emotions are formed in the brain. Our lab is interested in cellular mechanisms involved in experience-induced neuronal plasticity underlying learning, fear and anxiety. We study these phenomena using a combination of genetic, cell biological, pharmacological, electrophysiological and behavioural approaches.

Qualifications

  • 1994 - Diploma of Physician, Faculty of Medicine, Medical University of Bialystok, Poland
  • 1997 - PhD, Medical University of Bialystok, Poland

Research

Research interests

Prof. Pawlak is interested in cellular mechanisms involved in experience-induced neuronal plasticity underlying learning, fear and anxiety.

Psychological stress induces neuronal responses that can be either adaptive and directed toward maintaining homeostasis, or maladaptive leading to severe behavioural abnormalities. Understanding neural bases of stress, fear and anxiety is of an immense importance to modern society. Anxiety disorders affect about 25% of adults at least once in their lives, and make a huge social, family and welfare impact. The most dramatic form, posttraumatic stress disorder (PTSD) is characterized by cognitive impairment, depression, fear, anxiety, and may eventually lead to suicide. Understanding of the neural mechanisms of PTSD and other anxiety disorders could reduce the personal and societal impact through development of more efficient therapies.

How is fear and anxiety formed in the brain? Fear memories are encoded as changes in strength of synaptic connections, a process called plasticity. However, the molecular mechanisms that facilitate stress-induced behavioural abnormalities remain unclear. Two brain regions critically involved in fear responses are the amygdala and the hippocampus. We study stress-regulated genes in these areas using a combination of genetic, cell biological, pharmacological, electrophysiological and behavioural approaches.

Prof. Pawlak has particular interests in the role that extracellular proteases, their receptors (PARs) and the extracellular matrix play in experience-induced plasticity in the limbic system. Another area of interest is the involvement of ephrins and their receptors Eph’s in these processes. He uses an interdisciplinary approach to better understand the role of the above molecules in the central nervous system physiology

Research projects

  • Investigations into the mechanism by which FKBP51 modulates neuronal signalling and behavioural signatures of stress
  • The role of ephrins and Eph receptors in fear and anxiety
  • The role of protease-activated receptors in regulating the emotional status of an animal
  • The role of miRNAs and their target genes in the hippocampus and amygdala

Grants/Funding

  • Cost Action BM1001 (ECMNet).

Key publications | Publications by category | Publications by year

Key publications


Bourgognon J-M, Schiavon E, Salah-Uddin H, Skrzypiec AE, Attwood BK, Shah RS, Patel SG, Mucha M, John Challiss RA, Forsythe ID, et al (2013). Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala. Mol Psychiatry, 18(10), 1136-1145. Abstract.  Author URL.
Mucha M, Skrzypiec AE, Schiavon E, Attwood BK, Kucerova E, Pawlak R (2011). Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation. Proc Natl Acad Sci U S A, 108(45), 18436-18441. Abstract.  Author URL.
Attwood BK, Bourgognon J-M, Patel S, Mucha M, Schiavon E, Skrzypiec AE, Young KW, Shiosaka S, Korostynski M, Piechota M, et al (2011). Neuropsin cleaves EphB2 in the amygdala to control anxiety. Nature, 473(7347), 372-375. Abstract.  Author URL.
Skrzypiec AE, Maiya R, Chen Z, Pawlak R, Strickland S (2009). Plasmin-mediated degradation of laminin gamma-1 is critical for ethanol-induced neurodegeneration. Biol Psychiatry, 66(8), 785-794. Abstract.  Author URL.

Publications by category


Journal articles

Hall MH, Magalska A, Malinowska M, Ruszczycki B, Czaban I, Patel S, Ambrozek-Latecka M, Zolocinska E, Broszkiewicz H, Parobczak K, et al (2016). Localization and regulation of PML bodies in the adult mouse brain. Brain Struct Funct, 221(5), 2511-2525. Abstract.  Author URL.
Bradley SJ, Bourgognon J-M, Sanger HE, Verity N, Mogg AJ, White DJ, Butcher AJ, Moreno JA, Molloy C, Macedo-Hatch T, et al (2016). M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss. Journal of Clinical Investigation, 127(2), 487-499.
Harlalka GV, McEntagart ME, Gupta N, Skrzypiec AE, Mucha MW, Chioza BA, Simpson MA, Sreekantan-Nair A, Pereira A, Günther S, et al (2016). Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia. Hum Mutat, 37(11), 1157-1161. Abstract.  Author URL.
Baple EL, Maroofian R, Chioza BA, Izadi M, Cross HE, Al-Turki S, Barwick K, Skrzypiec A, Pawlak R, Wagner K, et al (2014). Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures. Am J Hum Genet, 94(1), 87-94. Abstract.  Author URL.
Tsilibary E, Tzinia A, Radenovic L, Stamenkovic V, Lebitko T, Mucha M, Pawlak R, Frischknecht R, Kaczmarek L (2014). Neural ECM proteases in learning and synaptic plasticity. Prog Brain Res, 214, 135-157. Abstract.  Author URL.
Bourgognon J-M, Schiavon E, Salah-Uddin H, Skrzypiec AE, Attwood BK, Shah RS, Patel SG, Mucha M, John Challiss RA, Forsythe ID, et al (2013). Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala. Mol Psychiatry, 18(10), 1136-1145. Abstract.  Author URL.
Skrzypiec AE, Shah RS, Schiavon E, Baker E, Skene N, Pawlak R, Mucha M (2013). Stress-induced lipocalin-2 controls dendritic spine formation and neuronal activity in the amygdala. PLoS One, 8(4). Abstract.  Author URL.  Full text.
Attwood BK, Patel S, Pawlak R (2012). Ephs and ephrins: emerging therapeutic targets in neuropathology. Int J Biochem Cell Biol, 44(4), 578-581. Abstract.  Author URL.
McGeachie AB, Skrzypiec AE, Cingolani LA, Letellier M, Pawlak R, Goda Y (2012). β3 integrin is dispensable for conditioned fear and hebbian forms of plasticity in the hippocampus. Eur J Neurosci, 36(4), 2461-2469. Abstract.  Author URL.
Mucha M, Skrzypiec AE, Schiavon E, Attwood BK, Kucerova E, Pawlak R (2011). Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation. Proc Natl Acad Sci U S A, 108(45), 18436-18441. Abstract.  Author URL.
Attwood BK, Bourgognon J-M, Patel S, Mucha M, Schiavon E, Skrzypiec AE, Young KW, Shiosaka S, Korostynski M, Piechota M, et al (2011). Neuropsin cleaves EphB2 in the amygdala to control anxiety. Nature, 473(7347), 372-375. Abstract.  Author URL.
Poulin B, Butcher A, McWilliams P, Bourgognon J-M, Pawlak R, Kong KC, Bottrill A, Mistry S, Wess J, Rosethorne EM, et al (2010). The M3-muscarinic receptor regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner. Proc Natl Acad Sci U S A, 107(20), 9440-9445. Abstract.  Author URL.
Skrzypiec AE, Maiya R, Chen Z, Pawlak R, Strickland S (2009). Plasmin-mediated degradation of laminin gamma-1 is critical for ethanol-induced neurodegeneration. Biol Psychiatry, 66(8), 785-794. Abstract.  Author URL.
Skrzypiec AE, Buczko W, Pawlak R (2008). Tissue plasminogen activator in the amygdala: a new role for an old protease. J Physiol Pharmacol, 59 Suppl 8, 135-146. Abstract.  Author URL.
Pawlak R, Rao BSS, Melchor JP, Chattarji S, McEwen B, Strickland S (2005). Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc Natl Acad Sci U S A, 102(50), 18201-18206. Abstract.  Author URL.

Publications by year


2016

Hall MH, Magalska A, Malinowska M, Ruszczycki B, Czaban I, Patel S, Ambrozek-Latecka M, Zolocinska E, Broszkiewicz H, Parobczak K, et al (2016). Localization and regulation of PML bodies in the adult mouse brain. Brain Struct Funct, 221(5), 2511-2525. Abstract.  Author URL.
Bradley SJ, Bourgognon J-M, Sanger HE, Verity N, Mogg AJ, White DJ, Butcher AJ, Moreno JA, Molloy C, Macedo-Hatch T, et al (2016). M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss. Journal of Clinical Investigation, 127(2), 487-499.
Harlalka GV, McEntagart ME, Gupta N, Skrzypiec AE, Mucha MW, Chioza BA, Simpson MA, Sreekantan-Nair A, Pereira A, Günther S, et al (2016). Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia. Hum Mutat, 37(11), 1157-1161. Abstract.  Author URL.

2014

Baple EL, Maroofian R, Chioza BA, Izadi M, Cross HE, Al-Turki S, Barwick K, Skrzypiec A, Pawlak R, Wagner K, et al (2014). Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures. Am J Hum Genet, 94(1), 87-94. Abstract.  Author URL.
Tsilibary E, Tzinia A, Radenovic L, Stamenkovic V, Lebitko T, Mucha M, Pawlak R, Frischknecht R, Kaczmarek L (2014). Neural ECM proteases in learning and synaptic plasticity. Prog Brain Res, 214, 135-157. Abstract.  Author URL.

2013

Bourgognon J-M, Schiavon E, Salah-Uddin H, Skrzypiec AE, Attwood BK, Shah RS, Patel SG, Mucha M, John Challiss RA, Forsythe ID, et al (2013). Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala. Mol Psychiatry, 18(10), 1136-1145. Abstract.  Author URL.
Skrzypiec AE, Shah RS, Schiavon E, Baker E, Skene N, Pawlak R, Mucha M (2013). Stress-induced lipocalin-2 controls dendritic spine formation and neuronal activity in the amygdala. PLoS One, 8(4). Abstract.  Author URL.  Full text.

2012

Attwood BK, Patel S, Pawlak R (2012). Ephs and ephrins: emerging therapeutic targets in neuropathology. Int J Biochem Cell Biol, 44(4), 578-581. Abstract.  Author URL.
McGeachie AB, Skrzypiec AE, Cingolani LA, Letellier M, Pawlak R, Goda Y (2012). β3 integrin is dispensable for conditioned fear and hebbian forms of plasticity in the hippocampus. Eur J Neurosci, 36(4), 2461-2469. Abstract.  Author URL.

2011

Mucha M, Skrzypiec AE, Schiavon E, Attwood BK, Kucerova E, Pawlak R (2011). Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation. Proc Natl Acad Sci U S A, 108(45), 18436-18441. Abstract.  Author URL.
Attwood BK, Bourgognon J-M, Patel S, Mucha M, Schiavon E, Skrzypiec AE, Young KW, Shiosaka S, Korostynski M, Piechota M, et al (2011). Neuropsin cleaves EphB2 in the amygdala to control anxiety. Nature, 473(7347), 372-375. Abstract.  Author URL.

2010

Poulin B, Butcher A, McWilliams P, Bourgognon J-M, Pawlak R, Kong KC, Bottrill A, Mistry S, Wess J, Rosethorne EM, et al (2010). The M3-muscarinic receptor regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner. Proc Natl Acad Sci U S A, 107(20), 9440-9445. Abstract.  Author URL.

2009

Skrzypiec AE, Maiya R, Chen Z, Pawlak R, Strickland S (2009). Plasmin-mediated degradation of laminin gamma-1 is critical for ethanol-induced neurodegeneration. Biol Psychiatry, 66(8), 785-794. Abstract.  Author URL.

2008

Skrzypiec AE, Buczko W, Pawlak R (2008). Tissue plasminogen activator in the amygdala: a new role for an old protease. J Physiol Pharmacol, 59 Suppl 8, 135-146. Abstract.  Author URL.

2005

Pawlak R, Rao BSS, Melchor JP, Chattarji S, McEwen B, Strickland S (2005). Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc Natl Acad Sci U S A, 102(50), 18201-18206. Abstract.  Author URL.

Awards

2007 Marie Curie Excellence Grant, European Commission.

2002 Young Investigator Award, 2ndAsia-Pacific Congress of Thrombosis and Hemostasis, Seoul, Korea

2000 The Young Investigator Award, XVth International Congress in Fibrinolysis and Proteolysis, Hamamatsu, Japan.

1998, 2000 Research Excellence Award, Ministry of Health of Poland.


Committee/panel activities

University of Exeter Ethical Review Group

University of Exeter Research Advisory Committee

Vice-Chair and grant evaluator, Life Sciences Panel, European Commission, FP7 Marie Curie Actions

FP7 COST Action BM1001 Brain Extracellular Matrix in Health and Disease – the Management Committee.


Invited lectures

‘Physiological and Molecular Regulation of Amygdala Circuits’, Amygdala in Heath and Disease: Gordon Conference, 2013 (accepted).

“Control of anxiety and fear by extracellular proteolysis in the amygdala”, Department of Pharmacology Seminars, University of Oxford, UK, 2013.

“Regulation of anxiety by neuropsin in the amygdala”, Frontiers in stress and cognition: From Molecules to Behaviour, Ascona, Switzerland, September 2012.

“Molecular Mechanisms Linking Stress and Mental Health”, Brain Mind Institute, Lausanne, Switzerland, 2012.

RIKEN Brain Research Institute, Wako, Japan, 2011. Neuropsin in the amygdala – a new role for an old protease.

32nd Naito Conference “Biological Basis of Mental Functions and Disorders”, Yamanashi, Japan, 2011. Regulation of anxiety at the neuron-matrix interface

Max Planck Institute for Experimental Medicine, Goettingen, Germany, 2011. Regulation of anxiety and fear by extracellular proteolysis in the amygdala.

“Topical Problems in Biophotonics”, St. Petersburg, Russia, 2011. Regulation of stress-induced anxiety by extracellular proteolysis in the amygdala.


Media Coverage

Brain chemistry linked to source of stress disorders: British Neuroscience Association

The pill that beats stress? Researchers discover how fear develops into anxiety and hope to find a cure: Mail Online.

Brain study reveals stress code: Sciencedaily.com.

Pill that can ease bad memories after scientists discover lipocalin-2 stress link: Mail Online.

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