Professor of Medicine; Chief, Infectious Diseases Division
Bio Med Medicine
BiographyDr. Mylonakis is recognized for his research on the study of microbial pathogenesis and host responses. His studies have included clinical and laboratory studies and the use of mammalian and invertebrate model hosts. These surrogate hosts fill an important niche in pathogenesis research and provide us with a unique opportunity to identify novel antimicrobial compounds and study basic, evolutionarily conserved aspects of microbial virulence and host response. His investigations have identified novel virulence factors, cross kingdom pathogen-pathogen interactions, novel agents and evolutionarily conserved traits that are involved in host virulence and immune responses during fungal infection. Taken in their totality, these results indicate that a common, fundamental set of molecular mechanisms is employed by pathogens against a widely divergent array of metazoan hosts. His research has resulted in >150 peer-reviewed scientific articles. Mylonakis, has edited five books on infectious diseases and is the founding editor-in-chief of Virulence.
Research DescriptionThe major focus of my work is the study of microbial pathogenesis. Our studies have developed a novel alternative to study bacterial and fungal infection and host responses: the use of invertebrate model hosts. These surrogate invertebrate hosts fill an important niche in pathogenesis research and provide us with a unique opportunity to identify novel antimicrobial compounds and study basic, evolutionarily conserved aspects of microbial virulence and host response. As part of our efforts we have demonstrated that:
1. There are extensive similarities between infections in mammals and non-vertebrate models including nematode and insect hosts.
2. The model microscopic nematode C. elegans grown on non-pathogenic yeasts has a life span similar to or longer than nematodes fed on the usual laboratory food source, but human pathogenic yeasts kill C. elegans.
3. A number of virulence traits that are involved in mammalian infection from a variety of microbial pathogens are associated with C. elegans disease.
4. C. elegans assays can be used to identify novel virulence factors that are associated with mammalian infection and these virulence factors provide important insights in fungal biology.
5. C. elegans assays can be used to identify and study compounds with antifungal efficacy and multidrug resistance (MDR) mechanisms.
6. During polymicrobial infection, prokaryote-eukaryote interactions modulate fungal virulence.
7. There are evolutionarily conserved pathways for the innate sensing of fungal pathogens. We identified C. elegans receptors that (similar to and their mammalian orthologues) mediate host defense against pathogenic fungi.
Taken in their totality, our results indicate that a common, fundamental set of molecular mechanisms is employed by fungal pathogens against a widely divergent array of metazoan hosts.
Also, my laboratory remains deeply committed in the education of students and in assisting younger scientists and physicians to reach their full potential. Through collaborations with scientists in other countries I have been involved in the education of scientists from other parts of the word such as Australia, China, Greece, Korea, Nigeria and Syria. A significant motivation for these studies and a clear sense of urgency comes from my clinical work as an infectious disease specialist.
In summary, our investigations have identified novel virulence factors, cross kingdom pathogen-pathogen interactions, novel antifungal agents and evolutionarily conserved traits that are involved in host virulence and immune responses during fungal infection. This approach challenges the position that studies in fungal pathogenesis should focus on the analysis of the "host", the "pathogen", or the "antimicrobial compound". I am deeply invested in expanding this work and sharing this vision with the younger members of my "second family" both in the research laboratory, as well as at the bedside.
Grants and Awards1999 "Teacher of the year," Voted by the Senior Medical students of the Brown University
2004 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Young Investigator Award, American Society for Microbiology
2005 Maxwell Finland Award for excellence in Infectious Disease Research, Massachusetts Infectious Disease Society
2010 The Oswald Avery Award, Infectious Disease Society of America (IDSA)
2011- American Society for Clinical Investigation, Member
2011 Partners in Excellence award in Leadership and Innovation
Funded Research1. Title: "A C. elegans high-throughput assay for the identification of new antifungal agents".
Sponsor: NIH R01 AI075286
Funding Amount: Total direct costs over the entire funding period: $750,000
The role of this grant is to develop high-throughput, whole animal assays for the identification of compounds with antifungal activity. We are currently reviewing the chemical characteristics of the compounds identified through a first screen of ̃~6,000 natural products.
2. Title: "Use of NMR technology in the diagnosis of candidemia"
Sponsor: T2 Biosystems
Funding Amount: Total direct costs over the entire funding period: $55,500
The aim of the study is the clinical evaluation of a novel, nanotechnology-based molecular assay for the diagnosis of invasive candidiasis.
3. Title: "Genome-wide investigations in fungal pathogens utilizing an invertebrate model host".
Sponsor: NIH R21 AI079569
Funding Amount: Total direct costs over the entire funding period: $250,000
The studies detailed in this proposal are expected to develop a large collection of random Cryptococus neoformans and Candida albicans mutants and implement C. elegans assays to identify genes associated with evolutionarily preserved fungal virulence traits.
4. Title: "The role of Candida colonization in bacterial VAP".
Sponsor: Astellas Pharma
Funding Amount: Total direct costs over the entire funding period: $102,500
The goal of this proposal is to evaluate the clinical significance of Candida-bacterial interactions in VAP.
5. Title: Harvard-wide Program on Antibiotic Resistance; The title of the Mylonakis subproject is: "Identification of pathways that can be targeted for the development of novel therapies for MRSA."
Role: PI of subproject, PI is M. Gilmore
Sponsor: NIH P01 AI 083214
Funding Amount: Direct cost for subproject 4 (per year): $260,00
(Mylonakis lab portion = 190,422 per year)
This is a multi-investigator program project grant The aim is to explore novel ways to identify antimicrobial compounds effective against methicillin resistant S. aureus and to study the mechanisms by which S. aureus acquires antibiotic resistance.
6. Title: Targeting Multidrug Efflux Systems in Francisella tularensis and Burkholderia psenudomallei.
Role: PI of a Sub-contract, PI: Dr. G. Tegos
Sponsor: Threat Reduction Agency (DTRA)
Funding Amount: Mylonakis lab portion = 104,422/year
This is a multi-investigator project grant. Our sub-contact focuses on the use of invertebrate models for the study of antimicrobial compounds.