Miguel A. Valvano

IF YOU WANT TO KNOW MORE ABOUT MY RESEARCH AND MY STYLE PLEASE VISIT THE VALVANO LAB HOME PAGE http://publish.uwo.ca/~mvalvano/

THOSE INTERESTED IN JOING MY GROUP, PLEASE READ FIRST

http://publish.uwo.ca/~mvalvano/Advice-to-grads.html

Valvano Lab Mission Statement

• To carry out hypothesis-driven research in microbiology
• To train graduate students and postdoctoral fellows to become outstanding biomedical scientists
• To develop and foster an environment of scientific inquiry, and at the same time respect for each individual's expertise and contribution
• To place an emphasis on personal and scientific integrity and on team player skills

What do we do?

Our research involves an interdisciplinary approach using molecular genetics, biochemistry, cell biology, and structural biology to understand the infection biology of opportunistic Gram-negative bacteria at molecular and cellular levels. Burkholderia, Enterobacter and Achromobacter species, are the primary model model organisms we use in various aspects of our research program. 

Our main goals are to elucidate how these opportunistic pathogens interact with innate immune cells (e.g., macrophage and epithelial cells) to promote or suppress inflammation, and the molecular basis of their extreme intrinsic resistance to antimicrobial agents, especially resistance to antimicrobial peptides and last resort antibiotics.

Why is it important?

Opportunistic infections pose a significant threat to human health, especially to those individuals who benefit most from advancements in the treatment of genetic diseases, cancer, and organ transplantation, but who become immunosuppressed.

Burkholderia cepacia complex bacteria (Bcc) and Achromobacter species are a major health risk for children and young adults with genetic conditions like cystic fibrosis and chronic granulomatous disease. These individuals commonly suffer from lung and airways infections that are very difficult to treat given the extraordinary resistance of these bacteria to clinically useful antimicrobials. Through our research, we hope to find novel ways to prevent or ameliorate the effect of these infections in susceptible individuals.

Enteric bacteria such as Enterobacter species are important opportunisitic multi drug resistant pathogens in the hospital setting. Very little is known about the infection biology of Enterobacter species despite these pathogens are a global health priority, as they are grouped within the ESKAPEE bacteria.

Lipopolysaccharide (LPS) is a complex glycolipid molecule located on the surface of Gram negative bacteria that is also a critical structural component of the bacterial outer membrane. Bacteria with defects in the LPS molecule are more sensitive to a variety of antibiotics and they can be easily killed by host defensive mechanisms such as the serum complement and antimicrobial peptides.

Therefore, by understanding how the LPS is made and assembled on the bacterial cell surface we hope to design inhibitors that will interfere with this process, which may be useful as novel antimicrobials. Also, we are looking at ways to alter LPS biosynthesis at various levels to increase the overall permeability of the outer membrane to antibiotics and antimicrobial peptides.

Examples of key questions we currently investigate

We discovered that genetic ablation of LPS synthesis or chemical inhibitors of certain LPS biosynthesis enzymes can "weaken" the bacterial outer membrane and facilitate the entry of conventional antibiotics and antimicrobial peptides, especially in B. cenocepacia and other Bcc bacteria. We have also conducted detailed studies on proteins required for the synthesis of core oligosaccharide and O antigen moieties of the LPS molecules. Now we want to learn:

We discovered that Bcc bacteria survive intracellularly in free-living amoebae and macrophages by altering the maturation of the phagosome, and this research has led to the hypothesis that these cells become a reservoir for the persistence and dissemination of these bacteria in the host. We have also discovered a novel secretory system in B. cenocepacia (T6SS) that secretes effectors altering the cytoskeleton of infected macrophages and is required for infection in an animal model of chronic lung infection. We want to learn:

Appropriate genetic tools are not always available for our specific research needs. Therefore, we place special effort in developing new tools and reagents or modifying those available to our own needs. Our lab has contributed novel molecular tools to handle Bcc bacteria and Achromobacter species.

We have recently discovered that Enterobacter species can survive in human macrophages without bacterial replication. We are therefore investigating:

How do Enterobacter species survive intracellularly?

How do macrophages respond to infection by Enterobacter?

What is the role of the highly active T6SS system in Enterobacter's ability to colonize the gut and other mucosal sites?

• Visiting Professor, University of Pavia, Italy.
• Awarded Postgraduate Supervisory Excellence Award, The Graduate School, Queen's University Belfast, 2017.
• Research contributions listed in the "51 Firsts (http://www.uwo.ca/research/51_firsts/), University of Western Ontario, 2015.
• Visiting Professor, Institute of Genetics and Microbiology, Wroclaw University, Poland, 2015
• Zeller Senior Scientist Award, in recognition to outstanding contributions to Cystic Fibrosis Canada as an established investigator. 2011.
• Certificate of Recognition for outstanding service as an online mentor of the ASM Minority Mentorship Program, American Society for Microbiology. 2011
• Tier I Canada Research Chair in Infectious Diseases and Microbial Pathogenesis. 2009-2016 (resigned in 2012 to take Chair at Queen's University).
• Senior Scientist, Research Training Award, Canadian Cystic Fibrosis Foundation. 2009
• CSM/Roche Award, Canadian Society of Microbiologists, given to outstanding Canadian microbiologists.
• Dean’s Award of Excellence for outstanding contributions, Schulich School of Medicine and Dentistry, UWO. 2006
• Certificate of Excellence in Undergraduate Medical Education for the Infection and Immunity block in 1^st year, Hippocratic Council Undergraduate Medical Education Committee, Schulich School of Medicine and Dentistry. 2005
• Tier I Canada Research Chair in Infectious Diseases and Microbial Pathogenesis. 2002-2009
• Honour's Degree for Academic Excellence, School of Medicine, University of Buenos Aires (Academic Cumulative Average of 91.5 %).

CURRENT LAB MEMBERS

Postdoctoral Research Assistant

J. Monjaras Feria, 2017 -

P. Zarodkiewwicz, 2024 -

Post-Graduate Students

Primary Supervisor:

L. MacDonald, BSc, University of St. Andrews; PhD student, 2021 -.

H. Parks, BSc, Queen's University, PhD student, 2022 -.

A. Anderson, BSc, Queen's University, PhD student, 2021 -.

Second Supervisor:

B. Mullan, Queen's University (School of Pharmacy), PhD Student, 2024 -.

R. Miskimmin, Queen's University, PhD Student, 2023 -.

D. Lockwood, Queen's University, PhD Student, 2021 -.

P. Bendale, QUB School of Pharmacy, PhD student, 2021-24.

3rd Y Research Project Students

M. Mitchell, QUB, 2024-25

C. Beattie, QUB, 2024-25

Visiting Post-Graduate Students

N. Adade, PhD candidate, Univ. of Ghana, 2019-24

Over the years, I have trained more than 300 people. For a complete list of past  lab alumni  visit https://publish.uwo.ca/~mvalvano/past-labmembers.html