Research team
Expertise
As a dedicated scientist with deep expertise in chemical proteomics, I lead a research group at the forefront of exploring host-pathogen interactions. Just three years after obtaining my PhD, I established this group, demonstrating my commitment and rapid progression in the field. Our work aims to decode how pathogens evade immune defenses, facilitating their virulence and resistance to antibiotics. Through an interdisciplinary toolkit encompassing methods from organic chemistry, proteomics, microbiology and cell biology, we strive to discover new molecular mechanisms and develop innovative therapeutic strategies. Core Expertise: Chemical Proteomics My career began with a highly successful research project at the Harvard University, where I developed peptide-hormone analogues to address diabetes, resulting in a notable first-author publication in the Journal of the American Chemical Society (JACS). This work laid the foundation for my expertise in peptide synthesis and chemical biology. During my PhD, I specialized in creating covalent probes to investigate the activity of virulence-related enzymes in pathogens, integrating chemical proteomics techniques to uncover novel molecular mechanisms. My postdoctoral research at KU Leuven further expanded my skill set, focusing on peptide-based chemical probes for profiling human proteases in complex samples. Interdisciplinary Research: Beyond my focus on chemical proteomics, I possess a broad skill set in biochemical and biological techniques. My research encompasses a range of methods from organic chemistry, biochemistry and microbiology to cell biology, demonstrating my ability to integrate diverse approaches for comprehensive studies. My group's current research revolves around three core projects: 1) Bacterial Proteases: We are developing chemical strategies to understand the role of these enzymes in infections better. 2) Microbial Virulence Factors: Our aim is to innovate chemical proteomic methods to identify bacterial components critical for virulence. 3) In Vivo Imaging Tools: We are pioneering the creation of chemical tools for visualizing bacterial enzymes in live models, enhancing our insight into host-pathogen interactions. In summary, my career is distinguished by a pioneering spirit in chemical proteomics, underscored by the early establishment of my research group. This initiative reflects my commitment to advancing our understanding of infectious diseases and contributing to the development of new therapeutic interventions.
Development of photoactive affinity probes for profiling of Streptococcus pneumoniae IgA1 protease
Abstract
The project aims to develop the first chemical probes for the IgA1 protease (IgA1P) of Streptococcus pneumoniae (S. pneumoniae), a key virulence factor in bacterial pathogenesis. This enzyme plays a crucial role in evading the host immune response by cleaving the IgA1 antibody. S. pneumoniae is a significant cause of bacterial pneumonia and meningitis, posing a global health challenge. The IgA1P of S. pneumoniae specifically targets the IgA1 antibody in the human immune system, cleaving it and thereby helping the bacteria evade immune detection and response. Specifically, the project will involve designing, synthesizing, and testing various probes to enable activity-based profiling of the S. pneumoniae Iga1P. Successful probes of the IgA1 protease could pave the way for new therapeutic strategies against Streptococcus pneumoniae infections. The project aims to contribute valuable insights into the enzyme's mechanism and potential for drug targeting. This research is critical in the context of increasing antibiotic resistance and the need for novel therapeutic strategies against bacterial pathogens. The development of specific inhibitors against bacterial virulence factors like IgA1 protease represents a promising approach in antimicrobial therapy.Researcher(s)
- Promoter: Prothiwa Michaela
- Fellow: Hailu Gebremedhin Solomon
Research team(s)
Project type(s)
- Research Project
Versatile chemical tools for profiling IgA1 protease activity in neisserial infections.
Abstract
This PhD project aims to investigate the virulent roles of IgA1 proteases during infections with pathogenic Neisseria species. Immunoglobulin A1 (IgA1) is a major antibody class that provides the first line of defense on mucosal surfaces. However, some pathogenic bacteria such as Neisseria gonorrhoeae and Neisseria meningitidis secrete IgA1 proteases to evade the immune response, and their specific impact on bacterial virulence remains unclear. Therefore, this PhD project aims to investigate the effect of neisserial IgA1 proteases on virulence. Specifically, we will develop a set of reagents for highly sensitive and selective detection of IgA1 proteases. To achieve the desired outcomes, this PhD project is outlined in three specific aims: (I) synthesizing highly sensitive peptide substrates as potential diagnostic tools, (II) developing activity-based chemical probes for in vivo monitoring of protease activity, and (III) exploring cyclic peptides containing a diphenyl phosphonate warhead as irreversible inhibitors. The successful execution of the project will provide valuable insights into the pathogenesis of neisserial infections and contribute to the development of novel anti-infective drugs and diagnostic tools. Given the emergence of high-level resistance strains of N. gonorrhoeae and the lack of rapid diagnostic tests for N. meningitidis, the project's outcomes can be a great asset to biomedical research on IgA1 proteases.Researcher(s)
- Promoter: Prothiwa Michaela
- Fellow: Thomas Pooja
Research team(s)
Project type(s)
- Research Project
Chemical strategies to understand microbiota-immune interactions in infectious diseases
Abstract
My research group focuses on understanding the complex interactions between pathogens and the human immune system during the infection process. We use a combination of organic chemistry, natural product identification, proteomics, and biology to study how microbial factors such as pathogenic enzymes, toxic proteins, and small molecule metabolites enable pathogens to evade the immune system and contribute to virulence and antibiotic resistance. Our goal is to uncover the unknown molecular mechanisms of these interactions, in order to develop new antibiotics or alternative treatment strategies.Researcher(s)
- Promoter: Prothiwa Michaela
- Fellow: Prothiwa Michaela
Research team(s)
Project type(s)
- Research Project
Modulation of cathepsin activity by pathogenic bacteria.
Abstract
We will investigate how some harmful bacteria can evade the immune system and cause infections. Our focus is on how these bacteria manipulate enzymes called cathepsins, which immune cells use to fight off infections. Some bacteria can evade the immune system by manipulating these enzymes, making the infection worse. Our goal is to understand how they do it and find new ways to treat infections. To do this, we will use special chemical tools called "activity-based probes" that detect and highlight cathepsins. We will isolate these enzymes from immune cells and create chemical probes that specifically target them. By using these probes, we will identify the microbial molecules that can stop the cathepsins working. Finally, we will pinpoint the exact molecules interacting with the cathepsins using analytical techniques. Armed with this knowledge, we can develop new treatments that target these molecules and stop bacteria from causing harm.Researcher(s)
- Promoter: Prothiwa Michaela
- Fellow: Van der Reysen Sarah
Research team(s)
Project type(s)
- Research Project