Faculty of Biological Sciences

Dr Jamel Mankouri

BSc Pharmacology, PhD 2006 Leeds
Royal Society University Research Fellow / University Academic Fellow
School of Molecular and Cellular Biology

Background: Post-doctoral researcher with Prof Mark Harris in the School of Molecular and Cellular Biology, University of Leeds (2006 - 2009); Post-doctoral Researcher with Prof Mark Harris and Dr Stephen Griffin (2009-2011) in the School of Molecular and Cellular Biology, University of Leeds. Royal Society University Research Fellow (2011-present).

Contact:  Garstang 8.55a, +44(0) 113 34 35646, email address for  

You can read more about Dr Mankouri's interests here:
http://www.astbury.leeds.ac.uk/people/staff/staffpage.php?StaffID=JM

Research Interests

Investigating host cell ion channel function as a novel target during virus infection

Newly identified factors shown to be important in leading virus entry, survival and release are cellular ion channels, proteins that act as a pore in the membranes of all cells within the body, permitting the selective passage of ions (such as potassium ions, sodium ions, and calcium ions). Through controlling ion passage, these channels serve many critically important cellular functions including chemical signaling, the regulation of pH, and the regulation of cell volume. Malfunction of ion channels can cause diseases in many tissues.

Our research has shown that by pharmacologically modulating cellular ion channels, we can impede the lifecycles of an array of important human viruses. My laboratory focuses on understanding the interaction between viruses and cellular ion channels in more detail. By doing so, we wish to reveal the potential of ion channel modulating compounds (many of which are clinically available) as new anti-viral drugs. 

 

Current Projects

  • Identifiying new virus-ion channel interactions.   
  • Investigating the potential of restoring the function of virus-ion channel targets as a new anti-viral strategy.
  • Defining the molecular mechanisms by which viruses require cellular ion channel activity.
  • Dynamic visualization of host cell ion channel and viral protein trafficking in virus infected cells.

We apply these studies to negative sense RNA viruses including bunyaviruses, human respiratory syncytial virus and rabies virus.

 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Virus-host interactions in zoonotic viruses
  • Ion channel modulators as new anti-viral compounds

Postgraduate studentship areas:

  • Targeting Ion Channel Function for Rabies Virus Therapy
  • Information on this programme can be found at the following:
  • http://www.findaphd.com/search/ProjectDetails.aspx?PJID=52204&LID=735
  • In addition, we welcome applications at any time from self-funded students that are well qualified and highly motivated. Contact us via email (J.mankouri@leeds.ac.uk).

See also:

Modules taught

BIOC3111/12/BIOL3112/MICR3120 a - ATU - Visualising Viruses
BIOC3160 - Laboratory/Literature/Computing Research Project
BIOC3900 - Cancer Biology
BIOL2210/BIOC2301 - Integrated Biochemistry/Biological Membranes
BIOL2301/05 - Skills for Biol Sci & Biosciences
BIOL3398 - Research Tools and Applications
BIOL5296M - Treatment of Infectious Disease and Cancer
BIOL5382M - Extended Research Project
BMSC1212 - Introduction to Pharmacology
BMSC2210 - Chemotherapy
MICR1120 - Introduction to Microbiology
MICR2120/BIOC2301 - Integrated Biochemistry/Medical Bacteriology
MICR3110 - Medical Microbiology Research Project

Postgraduates

Ibrahim Al-Masoud (Primary supervisor) 50% FTE
Frank Charlton (Primary supervisor) 50% FTE
Samantha Hover (Primary supervisor) 50% FTE
Hayley Pearson (Primary supervisor) 34% FTE
Eleanor Todd (Primary supervisor) 50% FTE
Holli Carden (Co-supervisor) 50% FTE
Becky Foster (Co-supervisor) 50% FTE
Jack Fuller (Co-supervisor) 50% FTE
Margarita Panou (Co-supervisor) 20% FTE
Ghada Shawli (Co-supervisor) 33% FTE

Mankouri J, Dallas ML, Hughes ME, Griffin SDC, Macdonald A, Peers C, Harris M Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence. Proc Natl Acad Sci U S A 106 15903-15908, 2009
DOI:10.1073/pnas.0906798106
View abstract

Mankouri J, Taneja TK, Smith AJ, Ponnambalam S, Sivaprasadarao A Kir6.2 mutations causing neonatal diabetes prevent endocytosis of ATP-sensitive potassium channels EMBO J 25 4142-4151, 2006
DOI:10.1038/sj.emboj.7601275

Hover S, Foster B, Barr JN, Mankouri J Viral dependence on cellular ion channels - an emerging anti-viral target? J Gen Virol 98 345-351, 2017
DOI:10.1099/jgv.0.000712
View abstract

Mohl BP, Bartlett C, Mankouri J, Harris M Early events in the generation of autophagosomes are required for the formation of membrane structures involved in hepatitis C virus genome replication Journal of General Virology 97 680-693, 2016
DOI:10.1099/jgv.0.000387
View abstract

Hover S, King B, Hall B, Loundras EA, Taqi H, Daly J, Dallas M, Peers C, Schnettler E, Mckimmie C, Kohl A, Barr JN, Mankouri J Modulation of potassium channels inhibits bunyavirus infection Journal of Biological Chemistry 291 3411-3422, 2016
DOI:10.1074/jbc.M115.692673
View abstract

Mankouri J, Walter C, Stewart H, Bentham M, Park WS, Heo WD, Fukuda M, Griffin S, Harris M Release of infectious hepatitis C virus from huh7 cells occurs via a trans-golgi network-to-endosome pathway independent of very-low-density lipoprotein secretion Journal of Virology 90 7159-7170, 2016
DOI:10.1128/JVI.00826-16
View abstract

Surtees R, Dowall SD, Shaw A, Armstrong S, Hewson R, Carroll MW, Mankouri J, A Edwards T, Hiscox JA, Barr JN Heat shock protein 70 family members interact with Crimean-Congo hemorrhagic fever virus and Hazara virus nucleocapsid proteins and perform a functional role in the nairovirus replication cycle Journal of Virology 90 9305-9316, 2016
DOI:10.1128/JVI.00661-16
View abstract

CesurÖ, Nicol C, Groves H, Mankouri J, Blair GE, Stonehouse NJ The subcellular localisation of the human papillomavirus (HPV) 16 E7 protein in cervical cancer cells and its perturbation by RNA aptamers Viruses 7 3443-3461, 2015
DOI:10.3390/v7072780
View abstract

Ross-Thriepland D, Mankouri J, Harris M Serine phosphorylation of the hepatitis C virus NS5A protein controls the establishment of replication complexes Journal of Virology 89 3123-3135, 2015
DOI:10.1128/JVI.02995-14
View abstract

Igloi Z, Mohl BP, Lippiat JD, Harris M, Mankouri J Requirement for chloride channel function during the hepatitis C virus life cycle Journal of Virology 89 4023-4029, 2015
DOI:10.1128/JVI.02946-14
View abstract

Igloi Z, Kazlauskas A, Saksela K, MacDonald A, Mankouri J, Harris M Hepatitis C virus NS5A protein blocks epidermal growth factor receptor degradation via a proline motif- dependent interaction Journal of General Virology 96 2133-2144, 2015
DOI:10.1099/vir.0.000145
View abstract

Amako Y, Igloi Z, Mankouri J, Kazlauskas A, Saksela K, Dallas M, Peers C, Harris M Hepatitis C virus NS5A inhibits mixed lineage kinase 3 to block apoptosis. J Biol Chem 288 24753-24763, 2013
DOI:10.1074/jbc.M113.491985
View abstract

Mankouri J, Harris M Viruses and the fuel sensor: the emerging link between AMPK and virus replication. Rev Med Virol 21 205-212, 2011
DOI:10.1002/rmv.687
View abstract

Dallas ML, Boyle JP, Milligan CJ, Sayer R, Kerrigan TL, McKinstry C, Lu P, Mankouri J, Harris M, Scragg JL, Pearson HA, Peers C Carbon monoxide protects against oxidant-induced apoptosis via inhibition of Kv2.1. FASEB J 25 1519-1530, 2011
DOI:10.1096/fj.10-173450
View abstract

Mankouri J, Tedbury PR, Gretton S, Hughes ME, Griffin SDC, Dallas ML, Green KA, Hardie DG, Peers C, Harris M Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase. Proc Natl Acad Sci U S A 107 11549-11554, 2010
DOI:10.1073/pnas.0912426107
View abstract

Mankouri J, Fragkoudis R, Richards KH, Wetherill LF, Harris M, Kohl A, Elliott RM, Macdonald A Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection. PLoS Pathog 6 e1000778-, 2010
DOI:10.1371/journal.ppat.1000778
View abstract

Milward A, Mankouri J, Harris M Hepatitis C virus NS5A protein interacts with beta-catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion. J Gen Virol 91 373-381, 2010
DOI:10.1099/vir.0.015305-0
View abstract

Gamlen T, Richards KH, Mankouri J, Hudson L, McCauley J, Harris M, Macdonald A Expression of the NS3 protease of cytopathogenic bovine viral diarrhea virus results in the induction of apoptosis but does not block activation of the beta interferon promoter. J Gen Virol 91 133-144, 2010
DOI:10.1099/vir.0.016170-0
View abstract

Taneja TK, Mankouri J, Karnik R, Kannan S, Smith AJ, Munsey T, Christesen HBT, Beech DJ, Sivaprasadarao A Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism. Hum Mol Genet 18 2400-2413, 2009
DOI:10.1093/hmg/ddp179
View abstract

Mankouri J, Griffin S, Harris M The hepatitis C virus non-structural protein NS5A alters the trafficking profile of the epidermal growth factor receptor TRAFFIC 9 1497-1509, 2008
DOI:10.1111/j.1600-0854.2008.00779.x

Mankouri J, Milward A, Pryde KR, Warter L, Martin A, Harris M A comparative cell biological analysis reveals only limited functional homology between the NS5A proteins of hepatitis C virus and GB virus B J GEN VIROL 89 1911-1920, 2008
DOI:10.1099/vir.0.2008/001131-0

Sivaprasadarao A, Taneja TK, Mankouri J, Smith AJ Trafficking of ATP-sensitive potassium channels in health and disease. Biochem Soc Trans 35 1055-1059, 2007
DOI:10.1042/BST0351055
View abstract

Smith AJ, Taneja TK, Mankouri J, Sivaprasadarao A Molecular cell biology of KATP channels: implications for neonatal diabetes. Expert Reviews in Molecular Medicine 9 1-17, 2007