Top image

Andrew Law: Understanding Molecular Mechanisms of drug Resistance At Single Cell Resolution Using Biomimetic Tissue Engineering

RESEARCH TYPE
T1,T2
PROGRAM
Flagship 3 Scholarships & Awards
TAGS
    Treatment
STATUS
In Progress

Acquired drug resistance of cancer cells is one of the major challenges in having successful cancer treatment. Despite the advances of our understanding in cancer, the mechanisms and effects of other tumour associated cell that drives acquired drug resistance in cancer cells still remains elusive. As such, the overarching aim of this T1T2 project is to integrate two leading edge technologies to 1) uncover the molecular pathways that are involved in cancer drug resistance using single cell RNA sequencing (scRNA-seq) and 2) implement our ALTEN platform (ALginate-based Tissue ENgineering) to the clinical setting - a system for high throughput drug screening in whole tissue that can be used to inform on treatment efficacy and optimising therapies in patient tumours. 

Currently there are no cost-effective high-throughput methods available to study the functional effects of anticancer drugs on whole tumour explants. We want to translate our ALTEN platform, a biomimetic hydrogel system for rapid functional testing of anticancer drugs, into clinical settings to examine the effectiveness of therapies in patient biopsies and develop improved patient-personalised therapies. We will also harness the state-of-the-art high-resolution scRNA-seq technologies to analyse the molecular effects of anticancer treatments within the tumour to study the mechanisms of acquired drug resistance. The unprecedented capacity of these two technologies together in this T1T2 project will provide an innovative avenue for drug screening and understanding cancer drug resistance.

 

Scholarship Awarded:

  • Name: Andrew Law
  • Member Group: Garvan Institute
  • Year and Duration: 2019 for 1 years
  • Amount: Top Up $19,700

 

5 Minutes with Andrew

 

  Law A  | 

Why did you decide to undertake a PhD in this area?

I had always been fascinated in medical research and understnding the complexities of the human body and its reaction to disease. However, what truly inspired me to pursue a PhD in Cancer Biology were primarily thanks to my exceptional supervisor Dr David Gallego-Ortega. We often had meetings to talk about experimental plans for novel ideas and his passion for science was very motivating. The constant support and the passion from my supervisors had made it very easy for me to decide to do a PhD in this field.

 

Why is your research important in the context of Sydney Catalyst and translational cancer research? 

One of the major challenges of successful cancer treatment is acquired drug resistance of cancer cells. Currently, there is a lack of cost effective high-throughput methods to study the functional effects of anticancer drugs on whole tumour explants. Thus, we want to translate our ALTEN platform, a system for high-throughput drug screening in whole tissue, into clinical settings that can be used to inform on treatment efficacy and optimising patient-personalised therapies. Furthermore, we will use state-of-the-art high-resolution scRNA-seq technologies to analyse the molecular effects of anticancer treatments to study the mechanisms of acquired drug resistance. This project will uncover the key mechanisms responsible for therapy resistance and provide an innovatice avenue for drug testing to guide the development of improved therapeutic regimes. Our final aim is to collaborate with clinicians from Sydney Catalyst to translate our research and system into clincial T3 practice.

 

What is the most rewarding part of your PhD?

A very rewarding aspect of my PhD is being surrounded by like-minded people and having a strong supportive group that helps me both personally and professionally. Since research are primarily comprised of inquisitive and curious scientists, you can get some of the most interesting conversations form your colleagues, which in terms leads to developing fascinating ideas.

Another aspect that is particularly satisfying is being able to solve a problem and making a discovery, regardless if it is big or small. There is also a great sense of personal acheivement in knowing that you are capable of independently thinking in a way to solve a unique issue. 

 

How do you achieve a work/life balance with such an all-consuming academic load? What keeps you motivated?

With the flexibility of a PhD I am able to maintain work/life balance by scheduling my days based on my experiements, while also being able to spend time with my family and friends and my hobbies, such as Latin dancing. Learning to prioritise everything happening in my life was an important lesson I learnt during my time as a research assistant. As such, the adjustment to PhD life was not as difficult as I thought it would be.

For me, science is something I have always really enjoyed doing, so the time I spend in the lab has not really been too stressful for me. Having lab mates that are also really fun and joking around also helps in making an easy-going and friendly work environment. 

 

How do your family and friends feel about your PhD? Do they understand what you do?

My family and friends do find that my PhD seems quite complicated, but I enjoy explaining my research in a simplified manner and using simple analogies to describe the complexity of cell biology and cancer. My family and friends are very supportive of it and often they are curious about what I do at work since it is usually quite different from what they are used to.

 

What are your plans once you graduate?

Ideally, I would like to get a post-doc position overseas in the same field or similar enough field to what I am currently studying. At this point, I am also quite open to going into the R&D area in industry. I would like to take a holiday and travel around Europe to go to different Latin dance festivals and visit some friends.

 

If you could be anywhere in the world right now, where would you be?

I would like to be travelling around Japan again as that is my favourite country. Last time I went there, I really loved the food there and the sights were amazing at Mt. Sakurajima. Being near one of the main fishing districts, we also got a lot of fresh seafood. It was memorable seeing everyone at cosplay at Tenjin for Halloween and just enjoying themselves.

 

You might also be interested in...

  • T1,T2
    Andrew Hoy & team: Unraveling the metabolic link between the host and breast cancer disease progression
    Obese and diabetic patients have a far higher risk that lean, healthy people of getting breast cancer, and have worse outcomes when they do get cancer. These examples highlight the crucial and ...
      Breast Cancer
      Metastasis
  • T1,T2
    Angela Ferguson & team: Exploring functional capabilities of immune cells in the Tumour microenvironment (TME) to determine patient responses to immunotherapy
    LAY SUMMARY Although immunotherapy has made a huge impact on cancer patient care, it is still unclear how immunotherapy actually works. It is believed that reinvigoration of T cells is likel...
      Biomarkers
      Immunotherapy
  • T1
    Ashleigh Parkin: From mice to men: biomarker driven classification of pancreatic cancer to define novel targetable molecular subtypes
    Due to the extremely poor prognosis of pancreatic cancer, and current therapies only being marginally effective, there is an urgent need to develop novel therapeutic strategies. This study aim...
      Biomarkers
      Personalised medicine
      New therapies and diagnostics
  • T1
    Aster Pijning: Mechanisms of evasion of innate immunity in ovarian cancer
     |  This project aims to understand the role of a protein called ERp57, which is expressed by ovarian cancer cells, in the suppression of a part of the innate immune ...
      Urogenital
  • T1
    Ben Kong: Towards a therapeutic vaccination for glioblastoma multiforme
    The ultimate objective of Ben's research is to create an effective dendritic cell based vaccine for glioblastoma multiforme by exploiting knowledge of DC biology to find the optimum combinatio...
      Dendritic cell
      Immunotherapy
  • T1
    CINSW RIGs and REGs
    The CINSW Research Equipment and Infrastructure Grants Program is directed to providing substantial funding for key research platforms, core equipment and capacities to enhance the cancer rese...
      Research Equipment
      Research Infrastructure
      CINSW
  • T1
    Claire Vennin: Preclinical targeting of the extracellular matrix to improve chemotherapy and reduce metastasis in patient-stratified models of pancreatic cancer using innovative imaging technologies
    A major challenge in cancer research is to understand and counteract mechanisms of drug resistance. This project will (1) shed light on the role of the ECM in chemoresistance and (2) guide the...
      Biomarkers
      New therapies and diagnostics
  • T1
    David Croucher: Mapping and manipulating therapeutically induced JNK network architecture to tackle breast cancer chemoresistance
    The current generation of cancer therapies mostly target components of signalling pathways, being either small molecule inhibitors or monoclonal antibodies to cell surface receptors. It is fas...
      Breast Cancer
      Chemo resistance
  • T1,T2
    David Herrmann & team: Intravital imaging to overcome pancreatic cancer resistance to immunotherapy
    Survival rates in pancreatic cancer have been at a low standstill (5-year survival of ~9%) for the last decades. There is therefore an urgent need to assess new treatment strategies to effecti...
      Imaging
      Immunotherapy
      Pancreatic cancer
  • T1,T2
    David Thomas: Molecular Screening and Therapeutics Program (MOST)
    The rapid advance in genomic technologies presents the unprecedented opportunity to molecularly phenotype cancers and link genetic information to therapeutic opportunities for individual patie...
      Genetics/genomics
      Personalised medicine
      New therapies and diagnostics
  • EnRICH Sub-Studies
    WHAT IS EnRICH? The EnRICH program is a prospective clinical cohort of 1000 patients with lung cancer, which aims to better define, treat and care for patients in Sydney Catalyst member hosp...
  • T1
    Fast Linear Laser Scanning Technology: The ZEISS LSM 800 Confocal Microscope for the Open Access, Bosch Institute Advanced Microscopy Facility
    Funding was awarded for revolutionary technology, the ZEISS LSM 800 confocal microscope with Airyscan, for the Open-Access, Multi-User Bosch Institute Advanced Microscopy Facility (AMF) at the Uni...
      CINSW Research Equipment Grant
  • T1
    Hayley Suen & team: Restoring the Function of Clonal Cytotoxic T cells in Multiple Myeloma to Develop Novel Therapies and Define the Antigenic Landscape
    Multiple myeloma is an incurable disease so new treatments are required to provide a cure for patients. An attractive form of treatment is the use of a patient's own T cells to fight their can...
      Immunotherapy
      New therapies and diagnostics
      Myeloma
  • T1
    Helen McGuire: Development of a novel test to predict clinical response to checkpoint therapy in lung cancer and mesothelioma
    Immune checkpoint inhibitor therapy has provided new hope to cancer patients whose tumours have resisted conventional therapy. One of the most recent success stories has been effective treatmen...
      Immunotherapy
      New therapies and diagnostics
      Lung cancer
      Mesothelioma
  • T1
    Jarem Edwards: Identification & Development of efficacious alternative immunotherapies for melanoma patients resistant to current anti-PD1 and anti-CDLA-4 treatments
    Melanoma is Australia's national cancer and the most deadly cancer in young Australians. Despite the success of anti-PD1/anti-CTLA-4 therapy in advanced stage melanoma, the majority of patient...
      Skin cancer
  • T1
    Jeff Holst & team: Targeting glutamine metabolism to starve triple-negative breast cancer
    Jeff's team are studying nutrient pumps that bring the amino acid glutamine into cancer cells. They have discovered that these pumps are increased in triple-negative breast cancer, a subset tha...
      Cancer metabolism
      New therapies and diagnostics
      Breast Cancer
  • T2
    John Simes: MDT scoping project
    The aim of this research was to describe the multi-disciplinary teams (MDTs) in our consortium and to share findings with survey participants to provide them an opportunity to learn more abou...
      MDT
  • T2
    Jolyn Hersch: Supporting informed choice for management of screen-detected Ductal Carcinoma in Situ (DCIS) among older women (70 years and over)
    Breast screening often finds ductal carcinoma in situ (DCIS) - cell changes which may or may not become cancer later on. Treatments for DCIS (surgery, radiation and drugs) have harmful side ef...
      Psychosocial
      Breast Cancer
  • T1,T2
    Julius Kim & team: Systematic effects of Gioblastoma multiforme (GBM) and GBM-released extracellular vesicles on immune suppression
    Despite recent improvements in cancer therapies, the median survival for patients with brain tumours is only 15 months. We need to urgently develop better treatment options. Anti-tumour vaccin...
      Dendritic cell
  • T2
    Kate White & team: The financial impact of cancer treatment on Australian patients and families
    It is recognised that individuals and their families experience financial costs associated with the diagnosis of cancer and subsequent treatment.  Little attention has been paid to identi...
      Psychosocial
      Cancer costs
  • T1
    LC-PLAT - Lung Cancer Cohort - a Platform to Study Serial Biospecimens and Matched Clinical Data
    The project aimed to optimise a platform for the collection of serial lung cancer tissue and blood biospecimens for research during routine clinical practice. Prospective biobanking and collection...
      Lung cancer
      Biobanking
  • T1
    Lorraine Chantrill and team: IMPACT Trial
    Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) aimed to improve outcomes for patients with advanced pancreas cancer by using molecular analysis of tumor tissue to guide treatment ...
      Personalised medicine
      Clinical Trials
      Pancreatic cancer
      Treatment
  • T1
    Magdalena Budzinska: Discovering Novel Non-Invasive Diagnostic and Prognostic Markers in Hepatocellular Carcinoma
    Magdalena's research addresses the urgent need in HCC management for markers that predict HCC propensity and behaviour. It has the potential to be translated into clinical practice at the level...
      Biomarkers
      New therapies and diagnostics
  • T1
    Mark Larance: Nutrient Deprivation and the Protective Proteome for the Prevention of Disease
    Cancer is a major cause of illness and death in Australia. Key risk factors for colorectal cancer and many other cancer types are poor diet, obesity and age. In animals, short periods of nutrie...
      Cancer metabolism
      Colorectal cancer
      Proteomics
  • T1,T2
    Megan Barnet: Genetic biomarkers for predicting response to immune checkpoint inhibitors in non-small cell lung cancer
    The 5-year survival for patients treated with anti-PD-1 in NSCLC is ~16%. We currently have no reliable tool for predicting who will benefit from this relatively tolerable single drug, and who ...
      Biomarkers
      Genetics/genomics
      Immunotherapy
      Lung cancer
  • T1,T2
    Natalia Pinello: RNA 5-hydroxymethylation in Haemopoiesis and Leukaemia
    My project will characterise the role of RNA modifications in normal bone marrow development and acute myeloid leukaemia, focusing on understanding how epigenetic drugs work and exploring new ...
  • T2
    Nicole Rankin and Team: Sydney Catalyst Member Experience Survey
    The aim of this research was to qualitatively explore the experiences of members of Sydney Catalyst to identify members' understanding and perceptions of translational research, benefits of me...
      Member Experience
  • T1,T2
    Peter Luk & team: Understanding the Body's Response to Cancer Invasion and Progression
      Cutaneous squamous cell carcinoma (cSCC; skin cancer) is the most common human cancer with the potential to spread to other parts of the body. Australia has the highest rate of cSCC i...
      Head and Neck Cancer
  • T1
    Philip Hogg: ACRF Centenary Cancer Research Centre
    The goal of the ACRF Centenary Cancer Research Centre is to understand the link between diet, metabolism and tumour initiation and development at a molecular level, and to design new therapies usi...
      Cancer metabolism
      New therapies and diagnostics
  • T1,T2
    Philip Hogg: Measure of thrombotic risk in cancer patients
    Thrombotic events are a major cause of death in cancer patients and are associated with worsened short‐term and long‐term survival. Prof Hogg and his team developed a new diagnostic test for ...
      Thrombosis
  • T1
    Roger Bourne & team: Gold-standard assessment of prostate cancer MRI accuracy
    A recent health economics analysis identified doctors' lack of confidence in prostate MRI as a major inhibitor to increased choice of active surveillance for low risk prostate cancer. Furthermore,...
      Imaging
      Urogenital
      Prostate
      MRI
  • T1
    Sarah Sutherland: Novel targets for a new generation of therapeutic cancer vaccines
    DC vaccines are well tolerated and can induce an anti- tumour immune response. Current vaccine strategies use in vitro generated "DC" which are loaded with antigen, stimulated and transfused back ...
      Dendritic cell
      Immunotherapy
      Urogenital
  • T1
    Sonia Yip: Biobanking - Patient and healthcare Professional Attitudes and Experiences of universal consent (B-PPAE)
    The Biobanking Qualitative Evaluation Project was initially developed to explore patient and health professional views of universal consent for biobanking procedures. It was later expanded to ...
      Lung cancer
      Biobanking
      Consent
  • T1,T2,T3
    Sydney Catalyst Scholarships Awarded pre July 2016
    We aim to encourage training and development of outstanding researchers and clinicians from within Sydney Catalyst units, who have the potential to develop highly significant ca...
      Scholarships
  • T1,T2,T3
    Sydney Catalyst: Embedding Research in Cancer Healthcare (EnRICH)
      The EnRICH program is a prospective clinical cohort of 1000 patients with lung cancer, which aims to better define, treat and care for patients in Sydney Catalyst member hospitals...
      Epidemiology and health services research
      Implementation research
      Knowledge translation
      Lung cancer
  • T1,T2,T3
    Tahlia Scheinberg: Implications of Homologous Recombination Deficiency defects in Advanced Prostate Cancer
    Up to 12% of men with metastatic prostate cancer carry a mutation in a gene that predisposes to cancer, independent of age at diagnosis or family history of cancer. The nCCN guidelines have re...
      Prevention and Early Detection
      Urogenital
      Prostate
  • T1
    The Next Wave of Cancer Genomics: Resolving Complex Structural Variants and Tumour Heterogeneity with Linked Short-Read
    Large genomic structural rearrangements are just important as short mutations in cancer pathogenesis. However, these critical events are often missed by conventional sequencing technologies. The f...
      CINSW Research Equipment Grant
  • T1
    Thomas Cox: Biomechanical priming of organotropism in metastasising breast cancer cells
    Breast cancer is the most common cancer in women worldwide. It is estimated that more than 1.7 million new cases of breast cancer occurred among women worldwide in 2012. We already know that ti...
      Breast Cancer
      Tissue stiffness
      Metastasis
  • T1
    Thomas Johnson: YB-1: A central player in the carcinogenesis and malignant behaviour of malignant pleural mesothelioma
    Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-induced malignancy that responds poorly to treatment. The combination of cisplatin and pemetrexed, which is the current standard...
      Biomarkers
      Mesothelioma
  • T1,T2
    Wojciech Chrzanowski & team: HIFUn+ – Nanotechnology-Enhanced High Intensity Focused Ultrasound as the New Generation of Cancer Therapy: advancing HIFU towards mainstream, non-invasive cancer therapy
    Current medicine, predominated by surgery, chemo- and radiotherapy has only taken us so far in beating cancer. Immunotherapy benefits less than 20% of patients (1). Targeting and uptake of pre...
      Treatment