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BOSCH INSTITUTE
SPECIAL TALK
Date
Time
Venue
Friday, 13 November 2015
1.00 - 2.00 pm
Norman Gregg
Lecture Theatre 351
Edward Building (A35)
Speaker Assoc Prof Guillaume Lessene,
Division Head, ACRF Chemical Biology Division
The Walter and Eliza Hall Institute of Medical
Research
Targeting the BCL-2 family of proteins:
Title
Toward therapeutic applications of apoptotic
modulation
Date
Friday, 13 November 2015
Time
1.00 - 2.00 pm
Venue
Norman Gregg Lecture Theatre,
Edward Ford Building (A27)
Associate Professor Guillaume Lessene jointly heads the ACRF Chemical Biology Division at
the Walter & Eliza Hall Institute of Medical Research. The division assembles expertise in
medicinal chemistry, biochemistry and molecular biology; and applies chemical biology approaches
to validating therapeutic targets, and elucidating the biological pathways that drive disease.
Dr Lessene trained as an organic chemist, completing his PhD at the University of Bordeaux,
before undertaking postdoctoral work with Prof Feldman at Penn State in the US. Since moving to
WEHI in 2001, his major research focus has been developing small molecules that target the
apoptotic and, more recently, the necroptotic cell death pathways.
His work on targeting the Bcl-2 family proteins for cancer therapy formed the basis of a major
collaboration between WEHI and two biopharmaceuticals, Genentech and AbbVie. For this work,
he has been recognised by the RACI and WEHI, where he was awarded the Biota Award in 2009,
the Burnet Prize in 2013 and the inaugural Sir John Dixon Hughes Medal for Medical Research
Innovation by the NFMRI in 2014.
Targeting the BCL-2 family of proteins: toward therapeutic applications of
apoptotic modulation
Guillaume Lessene
ACRF Chemical Biology Division, the Walter and Eliza Hall Institute of Medical Research, Melbourne,
Australia
Department of Medical Biology, the University of Melbourne, Melbourne, Australia
Department of Pharmacology and Therapeutics, the University of Melbourne, Melbourne, Australia
Apoptosis, or programmed cell death, is a highly conserved biological process required for the removal of unwanted, damaged or infected cells. The central regulators of apoptotic programmed cell death belong to the BCL‐2 family of proteins. A delicate interplay between members of this family that promote cell survival (e.g. BCL‐2, BCL‐XL, MCL‐1) and those that induce cell death (e.g. BIM, BAD, BAX, BAK) dictates whether a cell will live or die. Deregulation of apoptosis has been linked to life‐threatening conditions such as cancer and auto‐immune diseases (where down‐regulation of apoptosis leads to abnormal survival of rogue cells), or ischemia‐reperfusion injuries and neurodegeneration (where increased apoptosis leads to the premature death of normal cells). Due to their central role in the regulation of apoptosis, the BCL‐2‐family proteins represent highly attractive targets both for chemical biology studies and drug discovery. This presentation describes our approaches to developing potent and selective modulators of apoptosis. The validation of on‐target activity will also be discussed, providing strong validation of their specific mode‐of‐action in a cellular context. These new classes of compounds constitute invaluable probes to explore the impact of induction or inhibition of apoptosis to treat human diseases.