On this page
Publications of Cardiac Function Laboratory
Dr. Liu has over 350 peer-reviewed publications, many in the most celebrated journals in the world, and his publications have been cited over 20,000 times.
Staff of Cardiac Function Laboratory
Focus of Cardiac Function Laboratory
- Heart Failure/Inflammation/Myocarditis
- Early CV Disease Biomarkers & Vaccines
- CV Disease: Mechanisms to Outcomes
Projects of Cardiac Function Laboratory
Troponin Release Dynamics in Cardiovascular Diseases
Cardiac troponins (cTn) are regulators of cardiac contraction. Their release into the blood detectable by cTn assays is the gold standard for the diagnosis of acute myocardial infarction (MI). Recently approved high sensitivity (hs-cTn) assays can now detect cTn below 10 ng/L, allowing positive diagnosis or rule out of acute MI within 1-3 hours of presentation. Hs-cTn is the new standard of care. Heart failure results from progressive cardiac remodeling following injury, leading to hypertrophy/dilatation and symptomatic deterioration. This can lead to a diagnostic dilemma - when a patient presents in the emergency room with acute shortness of breath or chest distress, does the hs-troponin rise in the blood indicate MI, or HF, or both?
We discovered recently that troponins released in the setting of heart failure are frequently enclosed in membrane bound vesicles or exosomes, possibly mediating intercellular communication. We have subsequently discovered that exosomal troponin release is more frequent in response to hypertrophic remodeling stimuli, whereas release of free (soluble) troponins increases following cardiomyocyte damaging conditions (necrotic injury) commonly observed following MI. We aim to further our understanding of these processes by elucidating more detailed mechanisms controlling troponin release. This will enable us to establish new diagnostic tools and potential therapeutic options for different forms of heart failure.
Novel Regulators of Cardiac Innate Immunity and Post-MI Remodelling
Cardiac remodelling following ischemic injury constitutes the commonest cause of heart failure (Nian, 2004). Appropriate tissue repair and functional restoration lead to favourable outcomes; adverse remodelling leads to cell death, chamber dilation and demise of the host. One of the most fundamental biological processes regulating tissue injury and repair is inflammation. Many of the novel biomarkersdetermining outcomes in heart failure or post-myocardial infarction (MI) are members of the inflammatory signalling/innate immune pathways.
The innate immune system originally evolved as a measure to defend tissues against pathogens but has now adapted to be triggered by damaged proteins from the host. Our laboratory has been investigating the role of the innate immune system in cardiac injury in an effort to understand its regulatory control and to develop measures to improve cardiac tissue repair. So far, we have demonstrated that heart failure results from excessive inflammatory responses originating with the activation of cell surface toll-like receptors (TLR) including MyD88 (Fuse, 2005),IRAK4 (Maekawa, 2009; Valaperti, 2013) or IRF3 (de Couto, 2014). This disproportionate immune response contributes to increased cell death, detrimental matrix transitions, inhibition of angiogenesis, attenuated progenitor cell mobilization and high mortality. On the other hand, up regulation of negative regulators of innate immunity such as A20 (Li, 2007) or cellular FLICE inhibitory protein (cFLIP) (Li, 2010) leads to improved cardiac function and survival.
However, because the innate immune system is essential for defence against infection, the direct mediators of this pathway are unlikely to be viable long-term therapeutic targets. We have, therefore, sought to identify critical intrinsic modulators of innate immune/TLR signalling that effect magnitude of inflammatory response. We expect the expression of such regulators to increase in response to cardiac injury. Thus, we have taken a systems approach, examining gene expression and proteomic analyses in both murine models and humans to identify novel candidates that modulate innate immune activation of cardiac inflammation and remodelling, such as following pressure overload (hypertension) or MI. Informatics analyses revealed, with high probability, multiple potential candidates with significant biological effect and which are modulators of innate immunity. Notable discoveries include a novel signaling network which requires interaction of mitochondrial stress sensors such as MAVS with innate receptor complexes including NOD1 (Lin, 2020) in response to pressure overload. Using our multidisciplinary approach, uncovering more detailed molecular interactions may identify higher-precision treatment strategies to limit disease progression.
Heart Failure Biomarkers
Heart Failure is currently the most costly chronic health condition in developed countries with both high mortality and high costs of hospitalization. There are over 20 million patients living with HF today, with at least another 40 million yet to be diagnosed. The prognosis of HF patients is worse than for most cancers. To improve HF care, we need to make correct early diagnosis, appropriately classifying HF etiology, actionable prognosis, and selection of appropriate HF therapy. Addressing these unmet diagnostic needs will render available HF therapies safer and more cost-effective, and allow the development of novel therapies for HF.
Thus the goals of this project are to (1) improve the classification of different types and etiologies of heart failure; (2) provide tools to better risk stratify patients with different types of heart failure to make the right discharge decisions and reduce costly re-admissions; and (3) to tailor treatment strategies by providing guidance for selection of therapy.
The Heart Failure Biomarker Panel will facilitate appropriate and earlier diagnosis and identify etiologies of heart failure, and personalized therapy, aimed to maximize therapeutic effectiveness and survival of our patients. In addition, we will be able to minimize hospitalizations, re-admissions, unnecessary treatments, adverse events, reduce the enormous economic burden and human suffering in heart failure.
Available Positions of Cardiac Function Laboratory
We have many interesting projects for enthusiastic graduate students and postdoctoral fellows. Highly motivated undergraduate students with strong academic track records are welcome to apply for graduate studies in our laboratory. A few competitive postdoctoral positions are also available for highly motivated recent PhD graduates with strong academic track records and strong letters of recommendation. To be considered, you should familiarize yourself with our work (e.g., browse our website and recent publications) and understand the nature of our research publications before you apply. You should become familiar as to what we do and how this relates to your own academic training and interests. You should understand the requirements and demands of academic research and be confident in your own strengths, potential for academic research, and your ability to communicate in spoken and written English.
We have stimulating projects for graduate students, and I recommend that you look into the Department of Cellular & Molecular Medicine website for information about the programs, as you must first be accepted into the Departmental graduate program departmental graduate program. Prospective undergraduate or MSc students need a strong academic standing to be competitive.
For postdoctoral applicants, the University of Ottawa must recognize your PhD title. We also require proficiency in spoken and written English and a demonstrated command of a relevant scientific discipline. Your resume should demonstrate a proven track record in terms of productivity and long-term independent research potential, as evidenced by first-author peer-reviewed publications and public presentations. Foreigners must be eligible for employment authorization in Canada; please inquire at your local Canadian embassy or consulate about the details for obtaining a suitable work-permit and allow sufficient time to get this organized. You should be acquainted with the general academic requirements, cost-of-living, and available funding sources such as relevant local, national and international fellowships.