Development of novel anticancer drugs able to target and switch off cancer cells

Cancer is responsible for about three of every ten deaths and is the leading cause of disease burden in Australia. This is largely because conventional chemotherapeutic agents have low specificity for tumour cells, high toxicity for healthy cells and susceptibility to the development of resistance. Thus, there is a need for more effective cancer treatments that are tailored for a specific cancer and are not toxic to healthy cells. As each type of cancer is unique and results from alterations in intracellular pathways, inhibition of specific protein-protein interactions involved in the development of a certain type of cancer is a potential strategy to design safer cancer therapeutics. We are developing peptide-based therapeutics to target and deliver tailored drugs able to cross the cell membrane of tumour cells and specifically inhibit cancer pathways involved in breast cancer, leukaemia and melanoma. From the inside, we can deactivate cancer cells and stop these cancers from growing and spreading, without affecting healthy organs.

Breaching membrane barriers to modulate intracellular pathways

Cell membranes are barriers that control what can get inside cells. The ability to cross these barriers and deliver biological macromolecules, such as biomarkers, therapeutics and research tools, inside cells has endless opportunities that can be used to modulate cell’s activity. We are working on the development of novel molecular transporters to deliver macromolecules inside cells/microorganisms with therapeutic and biotechnological relevance. This technology is based on the use of stable cyclic peptides to deliver genes, proteins, probes or biomarkers into distinct cell types (e.g. cancer cells, bacteria, algae). We are specifically interested in the use of cell-penetrating peptides to target and monitor cancer biomarkers and to deliver nucleic acids inside model organisms with cell wall (e.g. bacteria, algae) to improve their potential as biofactories to produce therapeutics and biofuel.

Host-defence peptides to treat cancer and infectious diseases

Host-defence peptides are produced by our innate immune system and are expressed in response to fungal and bacterial infections and some have been shown to be able to kill tumour cells. We are interested in designing more selective and potent anticancer and antimicrobial drugs using host defence peptides. This will be achieved by unravelling the mode-of-action and identifying the features responsible for the anticancer and antimicrobial properties of host-defence peptides. We are particularly interested in redesigning host defence peptides to confer to them ability to selectively target breast cancer, blood tumours, metastatic circulating cells, or multi-resistant Staphylococcus aureus (MRSA) infections.

Collaborators and partners include:

• Professor David Craik (IMB, UQ)
• Professor Mibel Aguilar (Monash University)
• Professor Frances Separovic (University of Melbourne)
• Dr Christina Schroeder (IMB, UQ)
• Professor Miguel Castanho (University of Lisbon, Portugal)
• Professor David Andreu (University Pompeu Fabra, Spain)
• Professor Luis Bagatolli (University of Southern Denmark, Denmark)
• Professor Patrick Daugherty (University of California Santa Barbara, USA)
• Professor Fabrice Homblé (Université Libre de Brussels, Belgium).

Dr Henriques is a biochemist/biophysicist. Her work in mechanistic studies of peptides and peptide-membrane interactions is highly multidisciplinary and places her research at the interface of chemistry, biochemistry, structural biology, membrane biology, biotechnology and medical research. She is the co-author of over 50 publications on cyclic peptides, drug design and/or the mechanism of action of peptides, and has presented >20 oral communications in international scientific conferences including invited talks in prestigious national and international conferences (e.g. Gordon Conference on antimicrobial peptides, Australian Biophysics Symposium).

Dr Henriques has participated in several outreach activities for non-scientific and community audiences. Recently she wrote a chapter for a children’s book to promote science among Portuguese-descendent children (6-12 years) living in the United Kingdom. This book was released in late 2016 in Portugal. Following her award to attend a Nobel Laureate meeting in Germany in 2014 she was given the opportunity to share her story with the community through the media. Her abstract submitted to 60^th Biophysical Meeting in 2016 was selected by the American Institute of Physics and biophysical society journal editors as one that should be of great interest to reporters. As a proof of that, her work was featured in several international (e.g. UK, USA) news websites/online magazines, such as ABC news, Medical News Today, Tech times, International Business Times). She has presented a seminar “the Pharma revolution: growing medicinal drugs in your backyard” at the Global Leadership Series to UQ alumni and the community; her work on cell-penetrating peptides was featured in Chemistry World, a news magazine from the Royal Society of Chemistry.

Dr Henriques’ work is at the interface of fundamental and applied research, together with her team she is trying to create new knowledge in the field of peptide drug research and cancer cell biology, and in potentially developing better and safer therapeutics to treat blood, skin and breast cancers than traditional drugs. This research has the potential to create a new generation of targeted cancer treatments that would deliver many benefits to cancer patients and the community. Developing better therapeutics with fewer side effects could potentially reduce the healthcare costs associated with treating patients diagnosed with cancer.