Lari Lehtiö: Structural and Chemical Biology of ADP-ribosylation

Illustration of protein and DNA structures.

Research group description

Human ADP-ribosyltransferases like PARPs catalyze a transfer of ADP-ribose from NAD+ to target proteins and to nucleic acids. The modification serves as a catalyst for recruitment of proteins to e.g. DNA damage site and the signaling event is limited by ADP-ribosylhydrolases. We use structural studies and a range of assay technologies to discover and further develop inhibitors for writers, readers and erasers of ADP-ribosylation. The small molecule inhibitors will serve as tools to study ADP-ribosylation events and also as potential scaffolds for future anti-cancer and anti-viral drugs. 

While many structures of individual domains have been elucidated by protein crystallography, we are now reaching towards understanding how the multidomain PARPs function by addressing several key questions in their oligomerization, protein-protein and protein-DNA interactions. We aim to elucidate the structures of these macromolecular complexes at atomic resolution with protein crystallography, cryoEM and NMR, and complement this with biophysical and biochemical methods.

Research Group Members

  • Lari Lehtiö, PhD, Professor
  • Tuomo Glumoff, PhD, Docent, Vice-Dean of Education
  • Albert Galera Prat, PhD
  • Johan Pääkkönen, PhD
  • Sven Sowa, PhD
  • Sarah Wazir, PhD
  • Carlos Vela Rodríguez, Doctoral researcher
  • Chiara Bosetti, Doctoral researcher
  • Juho Alaviuhkola, Doctoral researcher
  • Saurabh Singh Dhakar, Doctoral researcher
  • Men Duong, Doctoral researcher
  • Heli Alanen, Research technician
  • Anna Tuovinen, MSc student
  • Mahamuda Mow, MSc student
  • Bukunmi Adediran, MSc student

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Alumni

  • Mirko Maksimainen, PhD (2015-2022)
  • Jere Hukkanen, MSc thesis (2020-2021)
  • Mikko Hukkanen, MSc thesis (2019-2021)
  • Renata Prunskaite-Hyyryläinen, PhD (2018-2021)
  • Samina Kazi, Doctoral researcher (2018-2021)
  • Audrey Savolainen, Doctoral researcher (2018-2021)
  • Yashwanth Ashok, PhD (2015-2021)
  • Sudarshan Murthy, Doctoral researcher (2015-2020)
  • Ilaria Scarpulla, MSc thesis (2019-2020)
  • Ezeogo Obaji, Doctoral researcher (2013-2018)
  • Danilo Kimio Hirabae De Oliveira , MSc thesis (2017-2018)
  • Alexander Ignatev, PhD (2014-2018)
  • Yves Nkizinkiko, MSc thesis & Doctoral researcher (2010-2012, 2015-2018)
  • Teemu Haikarainen, PhD (2012-2017)
  • Reduanul Bari, MSc thesis (2016-2017)
  • Elena Rolina, MSc thesis (2016-2017)
  • Harikanth Venkannagari, Doctoral researcher (2010-2016)
  • Vesa Hautaniemi, MSc thesis (2014-2015)
  • Ekaterina Biterova, PhD (2013-2014)
  • Mohit Narwal, Doctoral researcher (2009-2014)
  • Saman Nosheen, MSc thesis (2012-2013)