Professor Jerry Adams

Details

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Division: Molecular Genetics of Cancer

Research Overview

The research of my laboratory is focused on the molecular control of apoptosis by the Bcl-2 family of proteins, how this control is disrupted in cancer and how apoptotic mechanisms can be exploited to improve cancer therapy.

Background

Most apoptotic pathways converge on the mitochondrion, where the interactions of three sub-families of the Bcl-2 protein family determine whether the cell will live or die (Adams and Cory, Oncogene, 2007). While Bcl-2 itself and its closest relatives (eg Bcl-xL and Mcl-1) promote cell survival, two other factions instead promote cell death. Members of the first pro-death faction share with the wider family only the short BH3 domain, by which they engage their pro-survival relatives and initiate apoptotic signalling. Subsets of these ‘BH3-only proteins’ are activated by different cytotoxic signals, including those used in cancer therapy. Subsequently, Bax and Bak, which comprise the other pro-death faction, change conformation and form oligomers that permeabilize the mitochondrial membrane and thereby free proteins such as cytochrome c, which then activate the proteases (caspases) that dismantle the cell.

My research, often together with senior colleagues such as David Huang, Andreas Strasser, Suzanne Cory, Philippe Bouillet and Ruth Kluck, is addressing major unresolved issues about the molecular control of apoptosis. Together with other laboratories in the Division, and with Structural Biology and Chemical Biology colleagues, we are also interested in exploring the potential of targeting pro-survival Bcl-2 proteins as a new approach to cancer therapy.

Research Interests

Selected Publications

  1. Michalak EM, Vandenberg CJ, Delbridge AR, Wu L, Scott CL, Adams JM and Strasser A. 2010. Apoptosis-promoted tumorigenesis: gamma-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death. Genes Dev 24(15): 1608-13.[cit. 3] PMID: 20679396
  2. Dewson G, Kratina T, Huang DCS, Adams JM and Kluck RM. 2009. Bak activation for apoptosis involves oligomerization of dimers via their alpha6 helices. Mol Cell 36(4): 696-703. [cit. 18] PMID: 19941828.
  3. Fletcher JI, Meusburger S, Hawkins CJ, Rigla, DT, Lee EF, Fairlie WD, *Huang DC and *Adams JM. 2008. *Joint senior authors. Apoptosis is triggered when prosurvival Bcl-2 proteins cannot restrain Bax. Proc Natl Acad Sci U S A 105(47): 18081-7.[cit. 25] PMID: 18981409.  Inaugural article. Faculty of 1000 ‘Recommended’. 
  4. Dewson G, Kratina T, Sim HW, Puthalakath H, Adams JM, Colman PM and Kluck RM. 2008.  To trigger apoptosis Bak exposes its BH3 domain and homodimerizes via BH3: groove interactions. Molecular Cell 30(3):369-380. [cit. 30] PMID: 18471982
  5. Kelly PN, Dakic A, *Adams JM, *Nutt SL and *Strasser A. 2007.  Tumor growth need not be driven by rare cancer stem cells.  Science 317:337. *Joint senior authors [cit. 262] Faculty of 1000 'Must Read' PMID: 17641192
  6. Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P, Strasser A, Kluck RM, *Adams JM and *Huang DC. 2007.  Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak.   Science 315:856-859. *Joint senior authors [cit. 391] Faculty of 1000 'Must Read' PMID: 17289999
  7. van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE, Willis SN, Scott CL, Day CL, Cory S, *Adams JM, *Roberts AW and *Huang DCS. 2006.  The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized.  Cancer Cell. 10:389-399. *Joint senior authors [cit. 258] Faculty of 1000 'Must Read' PMID: 17097561
  8. Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, *Adams JM and *Huang DC. 2005.  Pro-apoptotic Bak is sequestered by Mc1-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins.  Genes Dev 19:1294-1305. *joint senior authors [cit. 400] Faculty of 1000 'Must Read' PMID: 15901672
  9. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, *Adams JM and *Huang DCS. 2005.  Differential targeting of pro-survival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function.  Mol Cell 17:393-403. *joint senior authors [cit. 605] Faculty of 1000 'Must Read' PMID: 15694340
  10. Villunger A, Michalak EM, Coultas L, Müllauer F, Böck G, Ausserlechner MJ, Adams JM and Strasser A. 2003.   p53- and drug-induced apoptotic responses mediated by BH3-only proteins Puma and Noxa.  Science 302:1036-1038. [cit. 515] Faculty of 1000 'Must Read' PMID: 14500851

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Current Laboratory Members

Faculty Member: Jerry Adams, BSc Emory PhD Harvard FAA FRS

Postdoctoral Fellow: Dana Westphal, MSc Technical PhD Otago

Postdoctoral Fellow: Bin Wang, BSc Beijing PhD Beijing

PhD Student: Colin Hockings (with Ruth Kluck), BA(Hons) Cantab

Research Assistant: Leonie Gibson, BAppSc RMIT