Fields: 

  • Cancers

Location: QIMR Berghofer Medical Research Institute

Type of student:

  • Higher Degree Research only i.e. PhD or MPhil (intercalated MD-PhD & MD-MPhil)
  • Honours students

Type of work:

  • Literature review
  • Systematic review
  • Wet lab work

Prerequisite skills

  • Wet lab work experience, data analysis and statistical experience are desirable

Brief synopsis:

Project 1: Plasma protein biomarkers to predict immunotherapy response in lung cancers

Background: Immunotherapy has revolutionized cancer treatment in the recent years. It has been successfully used to treat several melanoma and lung cancer patients. It is reasoned that the efficacy of immunotherapy in melanoma and lung cancers is due to high mutation burden which potentially results in high load of cancer neo-antigens on the surface that can be recognized by immune cells. However, not all lung cancer patients with high mutation burden respond to immunotherapy. There is a clinical need for biomarkers that can identify lung cancer patients that are most likely to benefit from immunotherapy. In this project, we will employ mass spectrometry based proteomics approaches to carry out plasma proteomic profiling of samples from lung cancer patients that undergo immunotherapy. Plasma proteome profiles of patients who respond to immunotherapy and those that do not respond to immunotherapy will be compared to identify biomarkers of response. These markers will be useful to stratify lung cancer patients that are most likely to benefit from immunotherapy from those that are unlikely to benefit.

Aim: Identification of protein biomarkers in plasma to predict immunotherapy response in lung cancers

Hypothesis: Lung cancer patients who respond to immunotherapy have a distinct plasma proteome profile compared to patients who do not respond

Approaches:

  • High abundant protein depletion from plasma
  • Fractionation of plasma proteins using HPLC
  • Proteolytic digestion and sample preparation for plasma proteome profiling using mass spectrometry
  • Global proteomic profiling using mass spectrometry and data analysis
  • Targeted mass spectrometry and ELISA based methods to validate potential biomarkers

Project 2: Novel approaches to augment immunotherapy response in cancers

Background: Immunotherapy has revolutionized cancer treatment in the last decade. This is exemplified by the success of checkpoint inhibitors in treating various cancers. T cells mount immune response by recognizing peptide antigens presented by MHC complex on the cell surface. The nature of specific antigens recognized by T cells remains ill understood in cancers. Mutant proteins that harbor cancer specific coding variations are thought to be the primary source of cancer neo-antigens recognized by T cells. However, immunopeptidomics studies have shown that the number of mutant peptides from coding variations that are presented by MHC complex is extremely low. Mass spectrometry based immunopeptidomics studies from our lab indicates that aberrant expression of proteins from non-coding regions of the human genome is a major source of tumor neo-antigens. Enhancing the expression of these proteins in cancer cells can potentially increase the load of MHC class I presented neo-antigens. We are investigating potential ways to enhance the expression of these non-canonical proteins by cancer cells. This strategy in combination with checkpoint inhibitors has the potential to augment immunotherapy responses in cancers.

Aim: To develop novel approaches to enhance expression of cancer neo-antigens and identification of antigens that can trigger T cell response in cancers.

Hypothesis: Proteins encoded by non-coding regions in the human genome is a major source of cancer neo-antigens.

Approaches:

  • Mass spectrometry based immunopeptidomics
  • Transcriptomics and proteomics studies to identify proteins encoded by ‘non-coding’ regions in the human genome
  • Pharmacological inhibition and siRNA based studies to identify targets to enhance neo-antigen production in cancer cells
  • Assays to identify neo-antigens that trigger T cell response
  • Animal studies to determine immunotherapy response in vivo

Supervisor

A/Prof Harsha Gowda

A/Prof Harsha Gowda

Group leader
QIMR Berghofer
Adjunct Associate Professor
Faculty of Medicine