Co-­‐opera(ng  with  industry  in  biomarker  studies  

       Tim  Bowen  

Department  of  Nephrology  Wales  Kidney  Research  Unit  

Cardiff  University  

Diabe(c  nephropathy  (DN):  A  major  UK  health    

problem  with  no  effec(ve  prognos(c  biomarkers  

Inves(ga(ng  the  u(lity  of  urinary  microRNAs    as  diabe(c  nephropathy  biomarkers    

•  22-­‐25  nucleo+de  RNA  regulators  of  gene  expression  

•  Imperfect  base  pairing  to  target  sites  in  the  3’-­‐untranslated  region  (UTR)  –  repress  transla+on  –  enhance  mRNA  degrada+on  

•  Sequence-­‐specific  target  recogni+on  –  seed  region  –  mul+ple  binding  sites  in  3’-­‐UTR  

microRNAs  bind  to  specific    mRNA  targets  and    

inhibit  protein  synthesis  

Urinary  microRNA  biomarker  development  

Knowledge  Economy  Skills  Scholarship  (KESS)    European  Social  Fund  &  BBI  Group  

Inven+on  for  Innova+on  (i4i)  early-­‐stage  product  development  grant  

NISCHR  &  BBI  Group  

BBSRC  &  Gwent  Group  Industrial  CASE  4-­‐year  PhD  studentship  

Knowledge  Economy    Skills  Scholarship  (KESS)  European  Social  Fund  &  BBI  Group    

Iden%fica%on  of  microRNA  biomarkers  of    chronic  kidney  disease  and  development  of  

minimally-­‐invasive  methods  of  molecular  detec%on  

•  Accessible,  non-­‐invasive  sample  type  •  Alterna+ve  to  renal  biopsy  •  Analysis  by  RT-­‐qPCR  

MicroRNAs:  global  regulators  of  gene  expression  with  conserved  func(on  

Evaluate  feasibility  of  miRNA  test  for  diabe(c  kidney  disease  

Urinary  microRNA  biomarker  development  

Knowledge  Economy  Skills  Scholarship  (KESS)    European  Social  Fund  &  BBI  Group  

Inven+on  for  Innova+on  (i4i)  early-­‐stage  product  development  grant  

NISCHR  &  BBI  Group  

BBSRC  &  Gwent  Group  Industrial  CASE  4-­‐year  PhD  studentship  

Innova(on  for  Inven(on  (i4i)  early-­‐stage  product  development  grant  NISCHR  &  BBI  Group    

Development  of  urinary  microRNAs  as  biomarkers  for  diabe%c  kidney  disease  

Prototype  microRNA  biomarker  test  /  Intellectual  property  

RT-­‐qPCR  valida(on  and  development  of  test  plaWorm  

•  Evaluate  microRNA  u+lity  across  disease  stages  •  Evaluate  microRNA  detec+on  in  independent  pa+ent  cohorts  •  Op+mise  sample  prepara+on  /  develop  test  

Urinary  microRNA  biomarker  development  

Knowledge  Economy  Skills  Scholarship  (KESS)    European  Social  Fund  &  BBI  Group  

Inven+on  for  Innova+on  (i4i)  early-­‐stage  product  development  grant  

NISCHR  &  BBI  Group  

BBSRC  &  Gwent  Group  Industrial  CASE  4-­‐year  PhD  studentship  

BBSRC  &  Gwent  Group  

Industrial  CASE    4-­‐year  PhD  studentship   Electrochemical  detec%on  of  microRNAs  

•  Synthesis  of  electrode-­‐tethered  microRNA  probe    •  Preliminary  data  from  synthe+c  urine  analysis  promising  •  Aim  to  develop  a  microRNA  “dips+ck”  probe  

Probe  development  for  electrochemical  miRNA  detec(on  

In  collabora(on  with  Dr  James  Redman,  CU  School  of  Chemistry  

Urinary  microRNA  biomarker  development  Knowledge  Economy  Skills  Scholarship  (KESS)  

 European  Social  Fund  &  BBI  Group  

Inven+on  for  Innova+on  (i4i)  early-­‐stage  product  development  grant  

NISCHR  &  BBI  Group  

BBSRC  &  Gwent  Group  iCASE  4-­‐year  PhD  studentship  

Biomedical  Catalyst    Confidence  in  Concept  (CiC)  

MRC  Development  of  urinary  microRNAs  

as  biomarkers  following    kidney  transplanta%on    

Responsive  Funding  Kidney  Research  UK    

Analysis  of    urinary  microRNAs    as  biomarkers    

for  acute  kidney  injury    

IP  

Responsive  Funding  Wellcome  Trust  

The  role  of  microRNAs    in  the  regula%on    and  response    

to  insulin  signalling    in  the  podocyte    

MRC  

Biomedical  Catalyst  Confidence  in  Concept  (CiC)  

Development  of  urinary  microRNAs    as  biomarkers  following    kidney  transplanta%on    

•  Urine  samples  from  post-­‐transplant  pa+ents  •  Comparison  with  IRI/IPC  rat  models  •  Analysis  of  perfusate  solu+on  underway    

MiRNA  data  from  human  kidney    transplant  pa(ent  urine  samples  

Biomarker  miRNAs  to  predict  transplanta(on  outcomes  

Urinary  microRNA  biomarker  development  

KESS  –  ESF/BBI  Group  

i4i  –  NISCHR  /  BBI  Group  

CASE-­‐BBSRC/Gwent  Group  

IP  Test  development  and  manufacture  

BioCat-­‐DPFS  Partnership  funding  

MRC  /  Innovate  UK  

i4i  early-­‐/late-­‐stage    funding  NISCHR  

 

BioCat-­‐CiC  MRC  

Project  Grant  KRUK    

Acknowledgements  WKRU, Cardiff University Cristina Beltrami Kate Simpson Usman Khalid Robert Jenkins Chris Carrington

Donald Fraser Cardiff University Aled Clayton James Redman Ian Weeks

BBI Group Pete Corish

The Gwent Group Guido Drago

Dept Renal Medicine, QEH, Birmingham Paul Cockwell et al.

Academic Renal Unit, Bristol University Simon Satchell, Richard Coward et al.

All Wales Kidney Research Network

 Tim  Bowen  PhD  

Senior  Lecturer  in  Matrix  and  Molecular  Biology  Department  of  Nephrology  

School  of  Medicine  College  of  Biomedical  and  Life  Sciences  

Cardiff  University  Heath  Park  

Cardiff  CF14  4XN  UK      

Tel  direct:  +44-­‐(0)29-­‐2074-­‐8389  Tel  office:  +44-­‐(0)29-­‐2074-­‐8467  Fax  office:  +44-­‐(0)29-­‐2074-­‐8470  

Web  home:  hip://medicine.cf.ac.uk/person/dr-­‐+mothy-­‐bowen/  

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