Dr Loretta Dorstyn is a Senior Research Fellow at the Centre for Cancer Biology (CCB), UniSA and SA Pathology. Loretta has over 18 years experience in caspase biology and understanding of the fundamental process of apoptosis. Loretta received her PhD from the University of Adelaide where she cloned and characterised two novel Drosophila caspases. She then spent 8 years studying the roles and mechanisms of caspase activation and regulation during apoptosis. Over this time she was awarded a RAH Florey Fellowship that fostered her independent research where she initiated several caspase-related projects including examining non-canonical caspase activation mechanisms.
In 2012 she was awarded a South Australian Cancer Collaborative Senior... Read more
About me
Dr Loretta Dorstyn is a Senior Research Fellow at the Centre for Cancer Biology (CCB), UniSA and SA Pathology. Loretta has over 18 years experience in caspase biology and understanding of the fundamental process of apoptosis. Loretta received her PhD from the University of Adelaide where she cloned and characterised two novel Drosophila caspases. She then spent 8 years studying the roles and mechanisms of caspase activation and regulation during apoptosis. Over this time she was awarded a RAH Florey Fellowship that fostered her independent research where she initiated several caspase-related projects including examining non-canonical caspase activation mechanisms.
In 2012 she was awarded a South Australian Cancer Collaborative Senior Research Fellowship and transitioned to project leader at the CCB. Over this time, Loretta established several independent projects that focused on understanding how cell death mechanisms act to maintain cell homeostasis and genomic integrity. Her projects led to numerous seminal findings detailing cell death mechanisms in tumour suppression, DNA damage repair, genomic stability, oxidative stress and healthy ageing. She spent the last 6 years studying different mouse tumour models to better understand caspase function in tumour suppression and has gained extensive expertise in tumour biology, as well as genomic, proteomic and bioinformatic analyses. Loretta's current work aims to understand how cells can evade checkpoint or “safety net” mechanisms during cell division and thereby acquire persistent DNA alterations and mutations that disrupt the balance in gene expression. This phenomenon is known as genomic instability and is one of the key hallmarks ageing-related diseases such as cancer.
About me
Doctor of Philosophy The University of Adelaide
Bachelor of Science (Honours) The University of Adelaide
Bachelor of Science The University of Adelaide
Caspase-2 function in tumour suppression
Caspases are the main enzymes that initiate and execute cell death by apoptosis. Our work has focussed on functional analysis of caspase-2, one of the first caspases discovered and has identified the apoptotic and non-apoptotic functions of this caspase. I was part of the team that described the function of caspase-2 in apoptosis induced by cytotoxic drugs that disrupt the cytoskeleton (Ho et al. 2008, Oncogene). This was followed by the first seminal demonstration that caspase-2 acts as a tumour suppressor in mice (Ho et al., 2009, Proc Natl Acad Sci USA). These findings led to further studies using various different mouse tumour models to define the role of caspase-2 in tumour suppression.... Read more
Research
Excludes commercial-in-confidence projects.
Deciphering the mechanisms of caspase-2-mediated suppression of aneuploidy and tumourigenesis, NHMRC - Project Grant, 01/01/2019 - 31/12/2021
Using mouse models to decipher the function of caspase-2 in limiting aneuploidy tolerance and cancer, NHMRC - Project Grant, 01/01/2018 - 30/06/2021
Deciphering the function of capcase-2 in DNA damage response and tumour suppression, NHMRC - Project Grant, 01/01/2014 - 31/12/2017
Characterisation of the role and mechanisms of caspase-2 in tumour suppression, Cancer Council SA - Beat Cancer, 06/03/2014 - 30/11/2016
Deciphering the mechanisms of a caspase-mediated tumour suppressor pathway, Worldwide Cancer Research (formerly - Association for International Cancer Research), 01/06/2013 - 31/08/2016
Research
Research outputs for the last seven years are shown below. To see earlier years visit ORCID, ResearcherID or Scopus
Open access indicates that an output is open access.
Year | Output |
---|---|
2017 |
Open access
45
43
10
|
2016 |
Open access
19
21
10
|
2016 |
Open access
25
25
10
|
2014 |
Open access
24
22
1
|
2013 |
Open access
54
52
16
|
Year | Output |
---|---|
2022 |
3
3
4
|
2021 |
Open access
12
12
15
|
2021 |
Open access
13
13
5
|
2019 |
Open access
2
2
5
|
2018 |
Open access
100
100
14
|
2018 |
Open access
9
9
3
|
2017 |
Open access
45
43
10
|
2017 |
Open access
6
6
2
|
2016 |
Open access
19
21
10
|
2016 |
Open access
25
25
10
|
2016 |
Open access
14
14
1
|
2015 |
Open access
11
18
7
|
2015 |
Open access
30
30
10
|
2014 |
2
|
2014 |
Open access
18
18
1
|
2014 |
Open access
42
40
1
|
2014 |
Open access
243
768
17
|
2014 |
Open access
24
22
1
|
2013 |
Open access
76
73
1
|
2013 |
Open access
54
52
16
|
2012 |
Open access
80
80
|
2012 |
Open access
61
53
|
2011 |
Open access
33
32
|
2011 |
Open access
39
40
|
2011 |
Open access
67
61
|
2009 |
Open access
|
2009 |
Open access
133
127
|
2009 |
Open access
84
83
|
2009 |
14
11
|
2008 |
Open access
48
45
|
2008 |
Open access
111
104
|
2008 |
Open access
105
100
|
Research
Caspase-2 function in tumour suppression
Caspases are the main enzymes that initiate and execute cell death by apoptosis. Our work has focussed on functional analysis of caspase-2, one of the first caspases discovered and has identified the apoptotic and non-apoptotic functions of this caspase. I was part of the team that described the function of caspase-2 in apoptosis induced by cytotoxic drugs that disrupt the cytoskeleton (Ho et al. 2008, Oncogene). This was followed by the first seminal demonstration that caspase-2 acts as a tumour suppressor in mice (Ho et al., 2009, Proc Natl Acad Sci USA). These findings led to further studies using various different mouse tumour models to define the role of caspase-2 in tumour suppression. In particular, the mouse thymoma model (Atm knockout mice) was used to demonstrate genetic interaction between Atm and caspase-2 in tumour suppression and enhanced tumour development in a caspase-2 knockout background (Puccini et al., 2013, Proc Natl Acad Sci USA). Interestingly, I also demonstrated that loss of caspase-2 can in fact delay tumour onset in a MYCN transgenic neuroblastoma mouse model (Dorstyn et al., 2014, Cell Death Dis). These findings indicated that caspase-2 has very defined tissue specific and context specific roles in tumour suppression and we are currently investigating the mechanisms by which it mediates these opposing functions.
Caspase-2 regulation of cellular stress pathways
By preventing genomic instability and regulating the oxidative stress response, caspase-2 acts as a key cell surveillance protein and as a consequence is important to prevent pre-mature ageing in mice. We are currently interestend in understanding the molecular basis of these caspase-2 functions in cancer and ageing.
External engagement & recognition
Organisation | Country |
---|---|
Baker Heart and Diabetes Institute | AUSTRALIA |
Baylor College of Medicine | UNITED STATES |
Boston University | UNITED STATES |
CSIRO Australia (Commonwealth Scientific Industrial Research Organisation) | AUSTRALIA |
Deakin University | AUSTRALIA |
Genentech, Inc. | UNITED STATES |
Griffith University | AUSTRALIA |
Hanson Institute | AUSTRALIA |
Harry Perkins Institute of Medical Research | AUSTRALIA |
Jilin University | CHINA |
La Trobe University | AUSTRALIA |
Medical University of Innsbruck | AUSTRIA |
Monash University | AUSTRALIA |
Queensland Institute of Medical Research | AUSTRALIA |
SA Pathology | AUSTRALIA |
St. Jude Children's Research Hospital | UNITED STATES |
State University of New York Buffalo | UNITED STATES |
University of Adelaide | AUSTRALIA |
University of Cambridge | UNITED KINGDOM |
University of Iowa | UNITED STATES |
University of London | UNITED KINGDOM |
University of Melbourne | AUSTRALIA |
University of New South Wales | AUSTRALIA |
University of South Australia | AUSTRALIA |
University of Sydney | AUSTRALIA |
University of Western Australia | AUSTRALIA |
Walter and Eliza Hall Institute of Medical Research | AUSTRALIA |
External engagement & recognition
Engagement/recognition | Year |
---|---|
Senior Research FellowshipSouth Australian Cancer Collaborative |
2012 |
Teaching & student supervision
Supervisions from 2010 shown
Thesis title | Student status |
---|---|
High fat diets and breast cancer | Current |
Deciphering the role of caspase-2 in protecting against genetic instability and tumour suppression | Completed |