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Professor David Ascher
Professor

David Ascher

Email: 
Phone: 
+61 7 336 53991

Overview

Background

Prof David Ascher is currently an NHMRC Investigator and Director of the Biotechnology Program at the University of Queensland. He is also Head of Computational Biology and Clinical Informatics at the Baker Institute.

David’s research focus is in modelling biological data to gain insight into fundamental biological processes. One of his primary research interests has been developing tools to unravel the link between genotype and phenotype, using computational and experimental approaches to understand the effects of mutations on protein structure and function. His group has developed a platform of over 40 widely used programs for assessing the molecular consequences of coding variants (>7 million hits/year).

Working with clinical collaborators in Australia, Brazil and UK, these methods have been translated into the clinic to guide the diagnosis, management and treatment of a number of hereditary diseases, rare cancers and drug resistant infections.

David has a B.Biotech from the University of Adelaide, majoring in Biochemistry, Biotechnology and Pharmacology and Toxicology; and a B.Sci(Hon) from the University of Queensland, majoring in Biochemistry, where he worked with Luke Guddat and Ron Duggleby on the structural and functional characterization of enzymes in the branched-chain amino acid biosynthetic pathway. David then went to St Vincent’s Institute of Medical Research to undertake a PhD at the University of Melbourne in Biochemistry. There he worked under the supervision of Michael Parker using computational, biochemical and structural tools to develop small molecules drugs to improve memory.

In 2013 David went to the University of Cambridge to work with Sir Tom Blundell on using fragment based drug development techniques to target protein-protein interactions; and subsequently on the structural characterisation of proteins involved in non-homologous DNA repair. He returned to Cambridge in 2014 to establish a research platform to characterise the molecular effects of mutations on protein structure and function- using this information to gain insight into the link between genetic changes and phenotypes. He was subsequently recruited as a lab head in the Department of Biochemistry and Molecular Biology at the University of Melbourne in 2016, before joining the Baker Institute in 2019 and the University of Queensland in 2021.

He is an Associate Editor of PBMB and Fronteirs in Bioinformatics, and holds honorary positions at Bio21 Institute, Cambridge University, FIOCRUZ, and the Tuscany University Network.

Availability

Professor David Ascher is:
Available for supervision
Media expert

Research impacts

We have successfully translated our computational tools into the clinic and industry, including:

  • Clinical detection of drug resistance from whole-genome sequencing of pathogens, including Tuburculosis and Leprosy
  • Genetic counselling for rare diseases and cancers with Addenbrooke's Hospital and Brazilian Ministry of Health
  • Patient stratification within clinical trials
  • Implementation within industry drug and biologics development programs

The tools we have developed have also been widely adopted within existing academic programs including:

  • Integration of intermolecular interaction calculations using our tool Arpeggio in the PDBe, the European resource for the collection, organisation and dissemination of data on biological macromolecular structures.
  • Integration of our missense tolerance scores within the widely used VEP tool for variant characterisation.
  • Implementation of our resistance prediction tools within the London School of Hygiene & Tropical Medicine's TB-Profiler tool.

Works

Search Professor David Ascher’s works on UQ eSpace

177 works between 2008 and 2024

141 - 160 of 177 works

2016

Journal Article

mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance

Pires, Douglas E. V., Blundell, Tom L. and Ascher, David B. (2016). mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance. Scientific Reports, 6 (1) 29575, 29575. doi: 10.1038/srep29575

mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance

2016

Journal Article

Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

Phelan, Jody, Coll, Francesc, McNerney, Ruth, Ascher, David B., Pires, Douglas E. V., Furnham, Nick, Coeck, Nele, Hill-Cawthorne, Grant A., Nair, Mridul B., Mallard, Kim, Ramsay, Andrew, Campino, Susana, Hibberd, Martin L., Pain, Arnab, Rigouts, Leen and Clark, Taane G. (2016). Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance. BMC Medicine, 14 (1) 31, 31. doi: 10.1186/s12916-016-0575-9

Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

2016

Journal Article

Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab′ Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity

Chan, Linda J., Ascher, David B., Yadav, Rajbharan, Bulitta, Jürgen B., Williams, Charlotte C., Porter, Christopher J. H., Landersdorfer, Cornelia B. and Kaminskas, Lisa M. (2016). Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab′ Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity. Molecular Pharmaceutics, 13 (4), 1229-1241. doi: 10.1021/acs.molpharmaceut.5b00749

Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab′ Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity

2016

Journal Article

Tumour risks and genotype–phenotype–proteotype analysis of patients with germline mutations in the succinate dehydrogenase subunit genes SDHB, SDHC, and SDHD

Andrews, Katrina A, Vialard, Lindsey, Ascher, David B, Pires, Douglas E V, Bradshaw, Nicola, Cole, Trevor, Cook, Jackie, Irving, Richard, Kumar, Ajith, Lalloo, Fiona, Izatt, Louise, Goudie, David, Woodward, Emma R and Maher, Eamonn R (2016). Tumour risks and genotype–phenotype–proteotype analysis of patients with germline mutations in the succinate dehydrogenase subunit genes SDHB, SDHC, and SDHD. The Lancet, 387, S19-S19. doi: 10.1016/s0140-6736(16)00406-2

Tumour risks and genotype–phenotype–proteotype analysis of patients with germline mutations in the succinate dehydrogenase subunit genes SDHB, SDHC, and SDHD

2016

Journal Article

In silico functional dissection of saturation mutagenesis: Interpreting the relationship between phenotypes and changes in protein stability, interactions and activity

Pires, Douglas E. V., Chen, Jing, Blundell, Tom L. and Ascher, David B. (2016). In silico functional dissection of saturation mutagenesis: Interpreting the relationship between phenotypes and changes in protein stability, interactions and activity. Scientific Reports, 6 (1) 19848. doi: 10.1038/srep19848

In silico functional dissection of saturation mutagenesis: Interpreting the relationship between phenotypes and changes in protein stability, interactions and activity

2016

Journal Article

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy

Nemethova, Martina, Radvanszky, Jan, Kadasi, Ludevit, Ascher, David B., Pires, Douglas E. V., Blundell, Tom L., Porfirio, Berardino, Mannoni, Alessandro, Santucci, Annalisa, Milucci, Lia, Sestini, Silvia, Biolcati, Gianfranco, Sorge, Fiammetta, Aurizi, Caterina, Aquaron, Robert, Alsbou, Mohammed, Lourenço, Charles Marques, Ramadevi, Kanakasabapathi, Ranganath, Lakshminarayan R., Gallagher, James A., van Kan, Christa, Hall, Anthony K., Olsson, Birgitta, Sireau, Nicolas, Ayoob, Hana, Timmis, Oliver G., Sang, Kim-Hanh Le Quan, Genovese, Federica, Imrich, Richard ... Zatkova, Andrea (2016). Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy. European Journal of Human Genetics, 24 (1), 66-72. doi: 10.1038/ejhg.2015.60

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy

2015

Journal Article

PEGylated interferon displays differences in plasma clearance and bioavailability between male and female mice and between female immunocompetent C57Bl/6J and athymic nude mice

Landersdorfer, Cornelia B., Caliph, Suzanne M., Shackleford, David M., Ascher, David B. and Kaminskas, Lisa M. (2015). PEGylated interferon displays differences in plasma clearance and bioavailability between male and female mice and between female immunocompetent C57Bl/6J and athymic nude mice. Journal of Pharmaceutical Sciences, 104 (5), 1848-1855. doi: 10.1002/jps.24412

PEGylated interferon displays differences in plasma clearance and bioavailability between male and female mice and between female immunocompetent C57Bl/6J and athymic nude mice

2015

Journal Article

Lst4, the yeast Fnip1/2 orthologue, is a DENN-family protein

Pacitto, Angela, Ascher, David B, Wong, Louise H, Blaszczyk, Beata K, Nookala, Ravi K, Zhang, Nianshu, Dokudovskaya, Svetlana, Levine, Tim P and Blundell, Tom L (2015). Lst4, the yeast Fnip1/2 orthologue, is a DENN-family protein. Open Biology, 5 (12) 150174. doi: 10.1098/rsob.150174

Lst4, the yeast Fnip1/2 orthologue, is a DENN-family protein

2015

Journal Article

Exploring the chemical space of the lysine-binding pocket of the first kringle domain of hepatocyte growth factor/scatter factor (HGF/SF) yields a new class of inhibitors of HGF/SF-MET binding

Sigurdardottir, A G, Winter, A, Sobkowicz, A, Fragai, M, Chirgadze, D, Ascher, D B, Blundell, T L and Gherardi, E (2015). Exploring the chemical space of the lysine-binding pocket of the first kringle domain of hepatocyte growth factor/scatter factor (HGF/SF) yields a new class of inhibitors of HGF/SF-MET binding. Chemical Science, 6 (11), 6147-6157. doi: 10.1039/c5sc02155c

Exploring the chemical space of the lysine-binding pocket of the first kringle domain of hepatocyte growth factor/scatter factor (HGF/SF) yields a new class of inhibitors of HGF/SF-MET binding

2015

Journal Article

Flexibility and small pockets at protein-protein interfaces: new insights into druggability

Jubb, Harry, Blundell, Tom L. and Ascher, David B. (2015). Flexibility and small pockets at protein-protein interfaces: new insights into druggability. Progress in Biophysics and Molecular Biology, 119 (1), 2-9. doi: 10.1016/j.pbiomolbio.2015.01.009

Flexibility and small pockets at protein-protein interfaces: new insights into druggability

2015

Journal Article

Achieving high signal-to-noise in cell regulatory systems: spatial organization of multiprotein transmembrane assemblies of FGFR and MET receptors

Blaszczyk, Michal, Harmer, Nicholas J., Chirgadze, Dimitri Y., Ascher, David B. and Blundell, Tom L. (2015). Achieving high signal-to-noise in cell regulatory systems: spatial organization of multiprotein transmembrane assemblies of FGFR and MET receptors. Progress in Biophysics and Molecular Biology, 118 (3), 103-11. doi: 10.1016/j.pbiomolbio.2015.04.007

Achieving high signal-to-noise in cell regulatory systems: spatial organization of multiprotein transmembrane assemblies of FGFR and MET receptors

2015

Journal Article

Germline mutations in the CDKN2B tumor suppressor gene predispose to renal cell carcinoma

Jafri, Mariam, Wake, Naomi C, Ascher, David B, Pires, Douglas E V, Gentle, Dean, Morris, Mark R, Rattenberry, Eleanor, Simpson, Michael A, Trembath, Richard C, Weber, Astrid, Woodward, Emma R, Donaldson, Alan, Blundell, Tom L, Latif, Farida and Maher, Eamonn R (2015). Germline mutations in the CDKN2B tumor suppressor gene predispose to renal cell carcinoma. Cancer Discovery, 5 (7), 723-729. doi: 10.1158/2159-8290.CD-14-1096

Germline mutations in the CDKN2B tumor suppressor gene predispose to renal cell carcinoma

2015

Journal Article

pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures

Pires, Douglas E V, Blundell, Tom L and Ascher, David B (2015). pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58 (9), 4066-72. doi: 10.1021/acs.jmedchem.5b00104

pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures

2015

Journal Article

Analysis of HGD gene mutations in patients with Alkaptonuria from the United Kingdom: identification of novel mutations

Usher, Jeannette L, Ascher, David B, Pires, Douglas E V, Milan, Anna M, Blundell, Tom L and Ranganath, Lakshminarayan R (2015). Analysis of HGD gene mutations in patients with Alkaptonuria from the United Kingdom: identification of novel mutations. JIMD Reports, 24, 3-11. doi: 10.1007/8904_2014_380

Analysis of HGD gene mutations in patients with Alkaptonuria from the United Kingdom: identification of novel mutations

2015

Journal Article

PEGylation does not significantly change the initial intravenous or subcutaneous pharmacokinetics or lymphatic exposure of trastuzumab in rats but increases plasma clearance after subcutaneous administration

Chan, Linda J., Bulitta, Jürgen B., Ascher, David B., Haynes, John Michael, McLeod, Victoria M., Porter, Christopher J. H., Williams, Charlotte C. and Kaminskas, Lisa M. (2015). PEGylation does not significantly change the initial intravenous or subcutaneous pharmacokinetics or lymphatic exposure of trastuzumab in rats but increases plasma clearance after subcutaneous administration. Molecular Pharmaceutics, 12 (3), 794-809. doi: 10.1021/mp5006189

PEGylation does not significantly change the initial intravenous or subcutaneous pharmacokinetics or lymphatic exposure of trastuzumab in rats but increases plasma clearance after subcutaneous administration

2015

Journal Article

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats

Kaminskas, Lisa M., McLeod, Victoria M., Ascher, David B., Ryan, Gemma M., Jones, Seth, Haynes, John M., Trevaskis, Natalie L., Chan, Linda J., Sloan, Erica K., Finnin, Benjamin A., Williamson, Mark, Velkov, Tony, Williams, Elizabeth D., Kelly, Brian D., Owen, David J. and Porter, Christopher J. H. (2015). Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats. Molecular Pharmaceutics, 12 (2), 432-443. doi: 10.1021/mp500531e

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats

2015

Journal Article

Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides

Hermans, Stefan J, Ascher, David B, Hancock, Nancy C, Holien, Jessica K, Michell, Belinda J, Chai, Siew Yeen, Morton, Craig J and Parker, Michael W (2015). Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides. Protein Science, 24 (2), 190-199. doi: 10.1002/pro.2604

Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides

2015

Book Chapter

Protein-protein interactions: structures and druggability

Ascher, David B., Jubb, Harry C., Pires, Douglas E. V., Ochi, Takashi, Higueruelo, Alicia and Blundell, Tom L. (2015). Protein-protein interactions: structures and druggability. Multifaceted roles of crystallography in modern drug discovery. (pp. 141-163) Dordrecht, Netherlands: Springer Netherlands. doi: 10.1007/978-94-017-9719-1_12

Protein-protein interactions: structures and druggability

2015

Journal Article

Platinum: a database of experimentally measured effects of mutations on structurally defined protein-ligand complexes

Pires, Douglas E V, Blundell, Tom L and Ascher, David B (2015). Platinum: a database of experimentally measured effects of mutations on structurally defined protein-ligand complexes. Nucleic Acids Research, 43 (D1), D387-D391. doi: 10.1093/nar/gku966

Platinum: a database of experimentally measured effects of mutations on structurally defined protein-ligand complexes

2014

Journal Article

Practical lessons in murine thoracic lymph duct cannulations: Observations in female and male mice across four different strains that impact on cannulatability

Caliph, Suzanne M., Shackleford, David M., Ascher, David B. and Kaminskas, Lisa M. (2014). Practical lessons in murine thoracic lymph duct cannulations: Observations in female and male mice across four different strains that impact on cannulatability. Journal of Pharmaceutical Sciences, 104 (3), 1207-1209. doi: 10.1002/jps.24312

Practical lessons in murine thoracic lymph duct cannulations: Observations in female and male mice across four different strains that impact on cannulatability

Funding

Current funding

  • 2023 - 2027
    Improving genetic diagnosis of autoimmune and autoinflammatory disease through an integrated multi-omics approach (MRFF 2022 GHFM - administered by ANU)
    The Australian National University
    Open grant

Supervision

Availability

Professor David Ascher is:
Available for supervision

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Supervision history

Current supervision

  • Doctor Philosophy

    Developing structure-based deep learning methods to predict mutation effects on proteins

    Principal Advisor

  • Doctor Philosophy

    Computer-aided drug design: predicting and mitigating drug toxicity

    Principal Advisor

    Other advisors: Dr Stephanie Portelli

  • Doctor Philosophy

    Exploring Cardiotoxicity Risk Factors

    Principal Advisor

    Other advisors: Dr Thanh-Binh Nguyen

  • Doctor Philosophy

    Post-transcriptional gene regulation: towards a better understanding of pathogenesis and medical applications

    Principal Advisor

  • Doctor Philosophy

    Computational approaches to engineer and modulate G protein-coupled receptors

    Principal Advisor

  • Doctor Philosophy

    Personalising treatments for genetic diseases

    Principal Advisor

    Other advisors: Dr Stephanie Portelli

  • Doctor Philosophy

    Deep Learning Algorithms for Polygenic Genotype-Phenotype Predictions and the development of genetics computation tools

    Principal Advisor

  • Doctor Philosophy

    Towards the accurate functional characterisation of protein coding mutations

    Principal Advisor

    Other advisors: Dr Stephanie Portelli, Dr Thanh-Binh Nguyen

  • Doctor Philosophy

    Improving rational antibody design using machine learning

    Principal Advisor

  • Doctor Philosophy

    Machine Learning for Protein Dynamics: Predicting Post-Translational Modifications and Mutation Effects

    Principal Advisor

  • Doctor Philosophy

    Using Deep Learning in Cell & Gene Therapy

    Principal Advisor

    Other advisors: Dr Thanh-Binh Nguyen, Dr Stephanie Portelli

  • Doctor Philosophy

    Protein structure guided precision medicine

    Principal Advisor

    Other advisors: Professor Phil Hugenholtz, Dr Stephanie Portelli

  • Doctor Philosophy

    Rational protein engineering and inhibition

    Principal Advisor

  • Doctor Philosophy

    Allosteric modulation of synaptic proteins by endogenous and modified sterols

    Associate Advisor

    Other advisors: Dr Evelyne Deplazes, Professor Megan O'Mara

  • Doctor Philosophy

    Breaking the chain of inflammation through targetting NLR proteins

    Associate Advisor

    Other advisors: Professor Avril Robertson

  • Doctor Philosophy

    Therapeutic Resolution of Inflammation in the Central Nervous System for Neuroprotection in Parkinson's Disease

    Associate Advisor

    Other advisors: Professor Avril Robertson

  • Doctor Philosophy

    Use of structural phylogeny and reconciliation in molecular phylogenetics

    Associate Advisor

    Other advisors: Dr Kate Bowerman, Professor Phil Hugenholtz

  • Doctor Philosophy

    Computational design of targeted lipid technologies

    Associate Advisor

    Other advisors: Professor Megan O'Mara

Media

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