Dr Kai Hilpert is a reader in infection and immunology.
The widespread use of antibiotics over the last few decades has been closely followed by the development of antibiotic resistance in many pathogens, to the extent that multidrug-resistant bacteria are now a major global threat. Dr Hilpert's research interests lie in the design and development of anti-microbial peptides against multidrug-resistant bacteria and fungi.
Bacterial resistance to conventional antibiotics is quickly becoming a global public health emergency, resulting in a push to develop new treatment strategies and substances with novel modes of action. Despite massive screening and sequencing approaches by the pharmaceutical industry, antibiotics with a novel mechanism of action appear particularly difficult to find. Dr Hilpert’s team develop short cationic antimicrobial peptides (AMPs) as new drug candidates against multidrug-resistant bacteria and fungi. We also work with several companies to test or validate their novel compounds.
The fact that AMPs can kill multidrug-resistant bacteria effectively indicates that their mode of action is different when compared to conventional antibiotics. Thus, AMPs are particularly interesting as lead structures. Short AMPs are exceptionally well suited because the production cost of short peptide drugs is reasonable and they may not trigger undesired immune responses.
Dr Hilpert’s research group designs, synthesises, screens and optimizes peptides against multidrug resistant bacteria strains like Pseudomonas aeruginosa, Staphylococcus aureus and Mycobacterium tuberculosis. They have recently also started working on antifungal peptides. In order to synthesize these peptides the group use Fmoc-based solid phase synthesis on cellulose support. The group were the first to adapt this approach to study peptide dimerization and also apply it to antimicrobial peptides. They have screened more than 10,000 peptides against Pseudomonas aeruginosa and understand now what makes a peptide antibacterial. In order to accelerate drug development further, the group also investigate the toxic effects of these peptides. They use standard haemolytic assays and confirm data in cell culture and zebra fish. So far they determined toxicity for 3,000 peptides and start to understand how to predict peptides with superior therapeutic potential. As a result the group have several patents for a number of peptide sequences that have great potential for further drug development.
Dr Kai Hilpert joined St George's in 2012 as a Reader in Infection and Immunology. His work currently focuses on antimicrobial peptides and their use as drug candidates for the treatment of infections with resistant and multi-drug resistant bacteria and fungi.
Previously, he worked at the Karlsruhe Institute of Technology (KIT) in Germany (2007 – 2011) where, he was junior research group leader. From 2011 to 2012, he worked as a Research Associate with Dr Frank Breitling, a world leader in high density peptide arrays.
Dr Hilpert studied biochemistry at Humboldt University in Berlin and obtained his PhD in the Biochemical Department of the medical school (Charité) where he also carried out his postdoctoral training with Professor Wolfgang Höhne (2001- 2003). Following this he was a Postdoctoral Fellow at the University of British Columbia in Vancouver, working with Professor Bob Hancock, a pioneer in the field of antimicrobial peptides.
Ramón-García S, Mikut R, Ng C, Ruden S, Volkmer R, Reischl M, Hilpert K, Thompson CJ. Targeting Mycobacterium tuberculosis and other microbial pathogens using improved synthetic antibacterial peptides. Antimicrob Agents Chemother. 2013, May; 57(5): 2295-303.
Cornejo A, Oliveira CR, Wurtele M, Chung J, Hilpert K, Schenkman S. A novel monoclonal antibody against the C-terminus of β-tubulin recognizes endocytic organelles in Trypanosoma cruzi. Protein Pept Lett. 2012, Jun 1; 19(6): 636-43.
Gao G, Lange D, Hilpert K, Kindrachuk J, Zou Y., Cheng JTJ, Kazemzadeh M, Yu K, Wang R, Straus SK, Brooks DE, Chew BH, Hancock REW, Kizhakkedathu JN. Implant coating that is highly biocompatible, antimicrobial and biofilm resistant in vitro and in vivo. Biomaterials. 2011, 32(16): 3899-909.
Hilpert K. Identification of novel antimicrobial peptides with therapeutic potential. Mini-Reviews in Organic Chemistry. 2011, 8(2): 157-163.
Wieczorek M, Jenssen H, Kindrachuk J, Scott WR, Elliott M, Hilpert K, Cheng JT, Hancock RE, Straus SK. Structural studies of a peptide with immune modulating and direct antimicrobial activity. Chem Biol. 2010; 17(9):970-80.
Knappe D, Henklein P, Hoffmann R and Hilpert K. Easy strategy to protect antimicrobial peptides from fast degradation in serum. Antimicrob Agents Chemother. 2010, 54(9): 4003-5.
Hilpert K, Volkmer-Engert R, Walter T, Hancock RE. High-throughput generation of small antibacterial peptides with improved activity. Nat Biotechnol. 2005, Aug; 23(8):1008-12.
Hilpert K, Winkler DF, Hancock RE. Peptide arrays on cellulose support: SPOT synthesis, a time and cost efficient method for synthesis of large numbers of peptides in a parallel and addressable fashion. Nat Protoc. 2007, 2(6):1333-49.
Hilpert K, Elliott MR, Volkmer-Engert R, Henklein P, Donini O, Zhou Q, Winkler DF, Hancock RE. Sequence requirements and an optimization strategy for short antimicrobial peptides. Chem Biol. 2006 Oct; 13(10): 1101-7.
Dr Kai Hilpert is currently building a research team.
Martin Ashby joined as a PhD student in 2013.
Asya Petkova joined as a trainee in 2013.
Wenona Barnieh joined as a BSc student in 2013.