Phagocyte Biology Laboratory

Dr. Bryan Heit, Western University

About Us

Welcome! You have reached the homepage for the laboratory of Dr. Bryan Heit. Our lab is part of the Department of Microbiology and Immunology at Western University, and we are members of the Center for Human Immunology, the lead centre for the CIHR Human Immunology Network.

Our interests surround the function of phagocytes – white blood cells which ingest (phagocytose) pathogens, particles, and dead cells. We focus on the cellular and molecular processes which control the function of these cells during the maintenance of homeostasis, infection and chronic inflammatory disease. Central to most of our studies is the study of efferoctyosis – the phagocytic removal of apoptotic (dying) cells, and how failures in this process lead to inflammation, autoimmunity and infection.

What is a Phagocyte?

Phagocytes are a class of white blood cells which have the capacity to engulf large particles such as bacterial and fungal pathogens, and subsequently destroy the engulfed material. The term phagocyte literally translates to “cell that eats”, which is an apt description of the primary function of these cells in our bodies. While there are many types of phagocytes, the Heit lab focuses primarily on macrophages, which play key roles in both maintaining our bodies and in fighting infections.

Lab News

Charles Yin Wins a Prestigious Vanier Scholarship

We are excited to announce that Charles Yin has won a prestigious Vanier Canada Graduate Scholarship, Canada’s most prestigious scholarship for doctoral students. Charles is a MD/PhD student in the Heit lab, and was 1 of 55 students selected by the CIHR for this award. The Vanier award was established by the Government of Canada “to strengthen Canada’s ability to attract and retain world-class doctoral students and establish Canada as a global centre of excellence in research and higher learning. Vanier Scholars demonstrate leadership skills and a high standard of scholarly achievement in graduate studies in the social sciences and/or humanities, natural sciences and/or engineering and health”.

Charles Yin, Vanier Scholar

Charles Yin

Charles’s Research:

Charles is spearheading our work into the role of Rab17 during efferocytosis – the removal of dying cells from our tissues. This work has revealed a pathway used by immune cells to avoid unwanted immune responses following normal “housecleaning” of our tissues. Charles has published this research over two papers (publication #1, publication #2).

Charles is also spearheading a collaborative study into macrophage dysfunction during atherosclerotic disease, using macrophages isolated from human heart tissue. We hope that this work will provide insight into heart disease and identify future treatments.

For more information, see Charles’s biography at the Schulich School for Medicine and Dentistry.


Rab17 Mediated Antigen Sorting

Model of Rab17 Function

Model of Rab17 Activity (click for full-size). Legend: EE – early endosome, LE – late endosome, LY – lysosome, RE – recycling endosome

We are excited to announce the publication of a follow-up paper to last-years study of Rab17 mediate sorting of antigens. In our first study we identified Rab17 as a protein which allowed macrophages to prevent generating immune responses after engulfing dead cells (a process termed efferocytosis), while still allowing macrophages to generate immune responses after engulfing pathogens. In this new study we have further explored this Rab17-dependent sorting pathway, revealing the details of how this process works.

Background:

To understand what Rab17 is doing we first need to talk – briefly – about how macrophages process pathogens. Macrophages “eat” pathogens, with engulfed pathogens ending up in a “stomach” called the “phagosome”.The phagosome then moves towards the centre of the macrophage, where it can fuse with lysosomes. This fusion delivers  enzymes that destroy the pathogen. The resulting pathogen debris (termed ‘antigens’) are loaded onto a molecule called “MHC II”, which then presents the antigens to the immune system. This antigen presentation allows for other immune cell types to begin targeting the pathogen.

How Rab17 Works:

The problem is that macrophages also phagocytose cells in our bodies are they are turned over during tissue maintenance. The phagocytosis of these cells – termed ‘efferocytosis’ – must avoid presenting any antigens from these cells, as this results in autoimmune disease. This is where Rab17 gets involved – Rab17 “grabs” the phagosome immediately after it fuses with lysosomes, and redirects the phagosome to fuse with another cellular compartment called the “recycling endosome”. Here, the debris are either absorbed by the macrophage or expelled into the extracellular space, thereby avoiding loading onto MHC II. This allows macrophages to “clean” our tissues of old, damaged and unneeded cells, while preventing autoimmunity.

Reference:

Charles Yin, Dean Argintaru & Bryan Heit (2017). Rab17 mediates intermixing of phagocytosed apoptotic cells with recycling endosomes. Small GTPases. Eprint ahead of publication. [Article] [Pubmed]


 

Welcome New Students

The Heit lab is excited to announce that two new students are joining our lab. Adam Tepperman will be joining us as a summer student, and will be investigating antigen sorting following efferocytosis and phagocytosis. Darius Lau, a former honours student in our lab, is staying on as a graduate student and will be continuing his exciting work into the function of CD93 in efferocytosis.


 

2017 RGE Lecturer – Dr. Peter Mugyenyi

Next Thursday we will be hosting the 2017 RGE Murray Lecturer, Dr. Peter Mugyenyi from the Joint Clinical Research Centre. Dr. Mugyenyi is a Ugandan medical doctor, researcher and promoter of equitable medical care. He is currently the Executive Director of Joint Clinical Research Centre, Kampala, the largest provider of HIV care and research in Africa. He was a pioneer in the introduction of antiretroviral therapy to Africa, in the delivery of ARVs to rural areas, and in making life saving AIDS treatment accessible to low and middle income countries. He has received many awards including A Hero of Medicine Award and Science Diplomacy Prize, as well as honorary degrees from Mbarara University in Uganda and the University of Ireland.

Dr. Mugyenyi’s research cover a wide spectrum of HIV/AIDS and related diseases, including paediatric and adult HIV treatment, drug trials, HIV resistance, HIV prevention, immunological studies including HIV vaccine trials, pharmacokinetic, molecular and epidemiological studies as well as social and economic impact of HIV. Internationally, he is on several boards of institutions and organisations in Africa, UK and the USA. He previously served as a temporary Board Member of the Institute of Medicine of the National Academies, and as an advisory member of the HIV Vaccine Trials Network, USA.

Dr. Mugyenyi will be presenting his work on Thursday May 11, 2PM, in 3M Building Room 3250.


 

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