Dr Nikki Verrills

Dr Nikki Verrills
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2010 Project Grant
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2008 Project Grant
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What are your research interests?

My research is focused on developing new therapies for treating cancer that target specific changes in cancer cells, but do not affect normal healthy cells. My work is applicable to all cancer types, but I focus primarily on two diseases: Acute myeloid leukaemia (AML) – the most common adult leukaemia, with a dismal 5year survival rate of just 24%; and breast cancer – a disease that kills over 3,000 Australian women every year.

By understanding the molecular changes that occur when a normal cell becomes cancerous, my team is identifying specific molecules inside cancer cells that we can use as new drug targets.

By understanding the molecular changes that occur when a cancer cell becomes resistant to therapy, we can develop new therapies that target relapsed and therapy-resistant cancers

Because we take a basic scientific approach of better understanding the biology of a disease, and then developing drugs to target biological changes, our work is also applicable to other diseases. For example, in collaborative work our targeted drugs are showing great promise in a range of inflammatory diseases such as asthma, rheumatoid arthritis and emphysema.

Why did you get into research?

Like most people in our community, my family has been affected by cancer. During my Honours year my cousin’s husband was diagnosed with leukaemia. He was only 26, with two young daughters, and he died within six months of diagnosis. I remember visiting him in the hospital and thinking that the drugs he was taking were only making him sicker.

During my Honours year I used what was then the new technology of ‘proteomics’ to study melanoma cells. I found that cancer was such an interesting disease to study, because it encompassed all the facets of cell biology that I found fascinating (how a cell divides, how cells signal to each other and how they interact with the surrounding tissue etc). I felt that by truly understanding what a cancer cell is that surely we could develop specific treatments to kill cancer cells. Indeed, I recall my Honours supervisor telling me on a day I was particularly stressed, “You know Nikki, you’re really not expected to cure cancer in this one year!”

I know it takes a fair bit longer than that, but I am even more convinced today than back then that that our contributions to the basic understanding of cancer cell biology can, and is, leading to better treatments and improved survival for cancer patients.

The best advice I give to others is to follow your passion, no matter what it is. My passion is for research, and this keeps me going strong. I’m proud to say that my contributions to the basic understanding of cancer cell biology has led to the development of novel treatments that one day (I hope) will ultimately lead to improved survival rates for cancer patients.

What would be the ultimate goal for your research?

My greatest achievements include discovering that a protein, called PP2A, is inactivated in some myeloid leukaemia’s and breast cancers, and can be re-activated using pharmacological agents – and this is showing great potential for a new anti-cancer therapy. I hope to be able to show that these new PP2A activating drugs can kill cancer cells without adversely affecting normal cells in clinical trials in acute myeloid leukaemia (AML) and breast cancer patients, with the ultimate goal of improving the survival.

I also aim to develop techniques and infrastructure to be able to determine which treatment is most likely to benefit which patient i.e. personalised therapy. We understand so much more about individual tumours now than ever before, however the ability to use that information at the individual patient level is hampered by limitations and costs in our laboratory testing. Our laboratory has been developing new techniques to be able to grow patients cancer cells and test large numbers of potential therapies, in the laboratory. This has the potential to provide information to the clinician as to which treatment to use to maximize the clinical benefit, and minimize unnecessary side effects associated with chemotherapy.

Biography

Dr Nikki Verrills is a cancer biologist at the University of Newcastle and the Hunter Medical Research Institute (HMRI). Dr Verrills was awarded her PhD In cell biology and biochemistry from Macquarie University. Her PhD studies were conducted at the Children’s Cancer Institute Australia and the Australian Proteome Analysis Facility, where she investigated the molecular mechanisms behind chemotherapy resistance in childhood leukaemia.

She then moved to Newcastle for postdoctoral studies, and in 2006 was awarded an NHMRC Peter Doherty Fellowship, together with an HMRI Award for Early Career Researchers supported by the Jennie Thomas Foundation. Together, this allowed her to establish her own laboratory investigating the molecular causes of cancer, and novel treatment therapies.

The work in the Verrills lab centres on understanding the molecular changes that occur in cancer cells so they can identify molecules that can be targeted with novel therapies that aim to kill the cancer cells, without affecting normal cells.

A major part of her work is breast cancer, where she is focusing on developing improved therapies for patients who currently don’t respond, or who relapse, on current therapies. Medical research has led to a massive improvement in survival rate for breast cancer patients – today, nine out of 10 will survive the disease. However, still more needs to be done to reach our goal of 100% survival.

Dr Verrills also embraces her role as a mentor to early career researchers, and raising awareness of cancer research in the general community. She spends time communicating her research to community groups such as Rotary and Lions Clubs, HMRI, Cancer Council and Cure Cancer Australia’s fundraising events. She is also passionate about encouraging the next generation to pursue science as a career, and gives talks at schools and careers events to generate awareness about careers in medical research.

Future Focus

At the Verrills lab we are using powerful proteomics analysis to identify proteins in cancer cells which could function as new therapeutic targets. We will use our range of preclinical models to test drugs targeting these proteins, as single agents or in combination therapies, and will work closely with our clinical colleagues to translate these findings into clinical trials, and ultimately into improved therapies.

We will also delve further into the area of development. In the process of studying PP2A, we have discovered that this enzyme is essential for embryonic development. We have found specific roles for this protein in skin, brain and limb development, and will now focus on understanding how PP2A is involved in regulating these processes. This will shed light on the fundamental nature of mammalian development, as well as provide new knowledge that may lead to better PP2A-targeted drugs.

Specialised/Technical Skills

  • Molecular and biochemical analysis
  • Proteomics (Discovery and targeted Mass Spectrometry)
  • Pre-clinical models of cancer
  • Ex-vivo cell cultures
  • Functional genomics
  • Models of drug resistance
  • Analysis of cellular signaling

Affiliations

2018

Receptor tyrosine kinase mutations in acute myeloid leukaemia promote PP2A and p53 inhibition through the phosphorylation of SBDS
Project Grant
Description:

AML (acute myeloid leukemia) is a very aggressive form of leukemia. Tumour suppressor proteins are critically important for normal healthy cells to be protected from genetic mutations. However in AML mutations occur in the genes responsible for stem growth and cell differentiation. The growth of the blood stem cells is accelerated but their differentiation into other cells is inhibited.

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2017

Receptor tyrosine kinase mutations in acute myeloid leukaemia promote PP2A and p53 inhibition through the phosphorylation of SBDS
Project Grant
Description:

AML (acute myeloid leukemia) is a very aggressive form of leukemia. Tumour suppressor proteins are critically important for normal healthy cells to be protected from genetic mutations. However in AML mutations occur in the genes responsible for stem growth and cell differentiation. The growth of the blood stem cells is accelerated but their differentiation into other cells is inhibited.

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JAK3 Signalling in T-cell ALL: KU Leuven - VIB, COOLS - UoN-HCRA, DUN collaboration
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Description:

To aid international collaboration with KU Leuven - VIB in Belgium.

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Determining the mechanisms underpinning leukaemic transformation for children suffering from Shwachman-Diamond Syndrome (SDS)
Project Grant
Researchers:

Dr Matt Dun, Dr Nikki Verrills, Dr Jeremy Robertson

Description:

Shwachman-Diamond-Syndrome (SDS) is an inherited disease that affects 1 in every 76,000 children. Dysfunction of the child’s blood and circulatory system occurs in nearly all patients, causing increased rates of infection and decreased capacity to transport oxygen. Unfortunately, the overall survival of a young person with SDS is only 35 years, and this is attributed to sepsis, organ failure and most frequently the development of leukaemia. 

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MRSP Equipment Grant
Equipment Grant
Researchers:

Dr Matt Dun, Prof Hubert Hondermarck, Prof Murray Cairns, Prof Brett Nixon, Phillip Dickson, Dr Nikki Verrills

Description:

ChemiDoc MP System - this equipment will help directly facilitate the advanced research needs of >20 different groups of HMRI: Cancer (Dun, Hondermarck,  Verrills, Skelding, Tanwar, Weidenhofer, Scarlet, Bowden, Thorne etc), Brain and Mental Health  (Cairns, Dickson, Dayas, Jobling, Smith, Brichta, Lim etc) Pregnancy and Reproduction (Nixon,  Aitken, De Iuliis, Roman, Bromfield, Pringle) Information Based Medicine (Scott, Milward, Kiejda), VIVA (Hansbro, Starkey) and therefore an estimated >80 HDR students, ECRs and research assistants. 

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Targeting a tumour suppressor for new cancer therapies
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Researchers:
Description:

Previous research has shown that the PPP2R2A gene is ‘lost’ or ‘switched off’, in up to half of all breast cancer, prostate cancer, ovarian cancer, lung cancer, and colon cancer patients.

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2016

Targeting DNA repair for the improved treatment of blood cancers
Project Grant
Description:

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia, and it has the lowest 5yr survival rate at a dismal 24%. Recently, improved technologies have enabled researchers to identify a number of mutations that recur in AML.

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Receptor tyrosine kinase mutations in acute myeloid leukaemia promote PP2A and p53 inhibition through the phosphorylation of SBDS
Project Grant
Description:

AML (acute myeloid leukemia) is a very aggressive form of leukemia. Tumour suppressor proteins are critically important for normal healthy cells to be protected from genetic mutations. However in AML mutations occur in the genes responsible for stem growth and cell differentiation.

more

2015

JAK3 Signalling in T-cell ALL: KU Leuven - VIB, COOLS - UoN-HCRA, DUN collaboration
Project Grant
Improving the effectiveness of a new treatment for acute myeloid leukaemia (AML)
Project Grant
Researchers:

Dr Kathryn Skelding, Dr Mengna Chi, Dr Nicole Verrills, Dr Roger Liang

Description:

Acute myeloid leukaemia (AML) is the most common acute leukaemia affecting adults, and accounts for ~20% of childhood leukaemias.

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A novel approach to cancer therapy - targeting patients with loss of a specific tumour suppressor gene
Project Grant
Description:

Cancer is the leading cause of death in Australia. Each year over 120,000 Australian’s will be diagnosed with cancer, and tragically, more than 42,000 patients will die from this disease. 

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2014

Identification of better diagnostic tools and treatment regimens for children with Shwachman-Diamond Syndrome (SDS)
Project Grant
Description:

Shwachman-Diamond Syndrome (SDS) is an inherited condition affecting bone marrow, the pancreas, skeletal system, and other organ systems. 

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2013

Targeting BAALC as a new treatment for acute myeloid leukaemia
Project Grant
Description:

Improving survival from Acute myeloid leukaemia (AML) with new therapies

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Myr-C310: A new treatment for childhood leukaemia
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Description:

Improving survival and reducing treatment side effects in childhood leukaemia

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Defining the role of shwachman-bodien diamond syndrome protein (SBDS) in PP2A inhibition in acute myeloid leukaemia (AML)
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Description:

A new treatment for acute myeloid leukaemia

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Identifying novel therapeutic targets for the treatment of Acute Myeloid Leukaemia
Project Grant
Description:

Finding the ‘disease-causing’ mutations and proteins in Acute Myeloid Leukaemia to develop new treatment strategies.

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Preclinical testing of a novel therapeutic strategy for breast cancer
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Description:

Testing a new treatment strategy for breast cancer - turning proteins "on" that improve patient survival

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2010

Targeting PP2A as a novel therapeutic Strategy for mutant FLT3+ Acute Myeloid Leukaemia
Project Grant
Researchers:

Dr Nicole Verrills, Dr Kyu-Tae Kim, Anoop Enjeti
 

Preclinical testing of PP2A activating compounds for the treatment of childhood acute lymphoblastic leukaemia
Project Grant
Researchers:

Dr Nicole Verrills, Dr Anthony Don

Epigenetic methylation of PP2A subunit promoters in breast cancer
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2008

Novel Alternative Splice Isoforms of the SET Oncogene in Acute Myeloid Leukaemia
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2007

Investigating the role of protein phosphatise 2A in the oncogenic transformation of myeloid cells in leukaemia
Project Grant
Researchers:

Ms Kathryn Roberts, Dr Nicole Verrills

2006

Bio-Rad Mini-PROTEAN 3 Electrophoresis system
Equipment Grant
Researchers:

Professor Leonie Ashman, Dr P Dickson, Professor Peter Dunkley, Professor J Rostas, Dr J Scott, Associate Professor A Sim, Dr N Verrills

High speed computer for a live cells imaging system.
Equipment Grant
Researchers:

Dr Rick Thorne, Professor G Burns, Dr N Verrills, Associate Professor A Sim

Investigating the functional role of altered expression and point mutations in the tumour suppressor gene, protein phosphatise 2A (PP2A)
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Researchers:
Novel protein phosphatase interactions in cancer
Project Grant
Researchers:

Dr Nicole Verrills, Associate Professor Alistair Sim