Xavier Clemente-Casares

Assistant Professor, Faculty of Medicine & Dentistry - Medical Microbiology and Immunology Dept

Contact

Assistant Professor, Faculty of Medicine & Dentistry - Medical Microbiology and Immunology Dept
Email
jclement@ualberta.ca
Phone
(780) 492-4070

Overview

Area of Study / Keywords

Immunology T cell biology Heart Disease Viral Myocarditis Cancer-associated cachexia Macrophages and Dendritic Cells


About

I am a new recruit to the Department of Medical Microbiology and Immunology at the University of Alberta.

A native of Barcelona, I obtained my undergraduate degree in Biology, with specialization in Health Care Biology, from the University of Barcelona in 2006 and worked as a research assistant from 2005-2007 in the Laboratory of Immunobiology for Research and Application to Diagnosis specializing in dendritic cell biology and Type 1 Diabetes.

I moved to Canada in 2008 and trained as a PhD student under Dr. Pere Santamaria at the University of Calgary. During my PhD training, I studied CD4+ T cell memory in autoimmunity and the mechanisms of action of an antigen-specific nanovaccine against autoimmune diseases using pre-clinical models of type 1 diabetes, multiple sclerosis, and arthritis.

In 2014, I moved to the University Health Network (Toronto) for my postdoctoral training. First, in the laboratory of Dr. Slava Epelman, I characterized the subsets and life-cycles of resident cardiac Dendritic cells. Later, in the laboratory of Dr. Daniel Winer, I researched the role of Insulin receptor in T cell Biology and the interactions between metabolic diseases (obesity and tumor-induced wasting), the heart and its immune system.

My lab was established in 2019 thanks to the generous support of the Faculty of Medicine and Dentistry, the Medical Microbiology and Immunology department and the Li Ka Shing Institute of Virology.


Research

My lab works in the broad field of Cardiac Immunopathology, trying to study the complex relationship between the heart and the immune system. 

Upon sterile or non-sterile injury of the heart a series of processes, both molecular and cellular, occur that lead to the recruitment into the myocardium and/or activation of cells specialized on defense and repair. This is referred to as inflammation and when it occurs within the myocardium, myocarditis. The evolutionary purpose of inflammation is to defend our tissues against pathogens in order to prevent further damage and to promote, more or less efficient, reparative programs. However, inflammation is a double-edged sword that can both limit or enhance the tissue damage depending on the circumstances. The defensive mechanisms (i.e: cytotoxic cell death, complement activation or antibody production) and changes in the environment (i.e: pro-inflammatory or pro-fibrotic milieu) can break the homeostasis of highly specialized tissues, like the heart, and affect its function in the short and long run, leading in some cases into heart failure (HF).

Cardiac immune cell components

The immune system is an essential component of a healthy heart. The myocardium is home to a rich population of different immune cell subsets with functional compartmentalization both during steady state and during different forms of inflammation. In addition, different forms of myocardial stress or injury, including ischemic (ischemia-reperfusion or myocardial infarction) and non-ischemic (hypertension or myocarditis), promote the recruitment of inflammatory cells with reparative and protective, but also pathogenic properties.

Through the combination of digestion, flow cytometry, and transcriptomics, we have characterized the major populations of macrophages and dendritic cells residing in the heart. The most abundant population of cardiac immune cells during steady state are CD64+MerTK+ macrophages, which can be further divided based on their expression of CCR2 or CD11c. CCR2+ macrophages originate from adult bone marrow hematopoiesis, whereas the majority of CCR2- macrophages, which can express high or low levels of MHC-II, are mainly of prenatal origin. Macrophages perform key functions such as repair and removal of debris during injury or supporting electrical connectivity in steady state. A significantly smaller, but important, population of cells residing in the myocardium of healthy individuals is composed of dendritic cells. The two major subsets of cardiac conventional DCs (cDCs) have been recently characterized: cDC1 (CD103+ DCs) and cDC2 (CD11b+ DCs). DCs play important roles in defense against infection but can also promote self-injury during inflammation, particularly during myocardial infarction.

During different forms of inflammation, an influx of immune cells into the myocardium change the cardiac landscape and environmental milieu. Both cells of the adaptive (T and B lymphocytes) and innate immune system (such as monocytes or neutrophils) participate in cardiac inflammation processes potentially determining beneficial or deleterious outcomes.

Lines of research

The Clemente Lab currently has three proposed axes of research: Cancer, Infectious and Autoimmune myocarditis, and Hypertension (in progress).

The Cancer axis has an active line of research on the immune mechanisms (primarily cell-mediated) involved in the development of tumor-induced cachexia or muscle wasting. Another important line of research under development studies the immune-mediated cardiotoxicity effects of cancer drugs (doxorubicin or checkpoint inhibitors).

The Infectious/Autoimmune Axis has an active line of research on the developmental signals of cardiac Dendritic cells and their role in adaptive immune responses during myocardial infection. In addition, we are currently exploring a line of research on the generation of cardiac autoantibodies and their role in myocarditis outcomes. 

Featured Publications

Lee M., Chu K., Chakraborty M., Kotoulas N., Akbari M., Goh C., Clemente-Casares X., Winer D.A., Shrestha A., Tsai S.

STAR Protocols. 2022 June; 3 (2) 10.1016/j.xpro.2022.101233


Chakraborty M., Chu K., Shrestha A., Revelo X.S., Zhang X., Gold M.J., Khan S., Lee M., Huang C., Akbari M., Barrow F., Chan Y.T., Lei H., Kotoulas N.K., Jovel J., Pastrello C., Kotlyar M., Goh C., Michelakis E., Clemente-Casares X., Ohashi P.S., Engleman E.G., Winer S., Jurisica I., Tsai S., Winer D.A.

Cell Reports. 2021 January; 34 (2) 10.1016/j.celrep.2020.108609