Projects

Our Research

Dr. Mario Deng's Advanced Heart Failure Research Team is committed to studying the effects and more precisely predicting survival outcomes of Multi-Organ Dysfunction within Advanced Heart Failure Patients undergoing various interventions including Mechanical Circulatory Support, Heart Transplantation, high risk revascularization, high risk valve replacement, and high risk ventricular tachycardia treatment at the UCLA Ronald Reagan Medical Center by developing Multi-Dimensional Molecular Immunology Algorithms.

Advanced Heart Failure "Outcome Research" Motivating Molecular Biomarker Test Development

Early publications focused on organization of multidisciplinary care and clinical outcomes in advanced heart failure, mechanical support, and heart transplantation.

Heart failure affects >6 million people in the United States. For selected patients with advanced heart failure for whom optimal medical management does not provide a good enough longevity & quality of life outlook, we consider the options of coronary artery bypass graft (CABG) surgery, percutaneous coronary interventions (PCI) (recruitment goal n=250) (Stratum #1=Ischemia), aortic valve replacement (AVR) surgery, mitral valve replacement (MVR) surgery, trans-catheter aortic valve replacement (TAVR), transcatheter Mitral Clip (Stratum #2=Overload), ventricular tachycardia ablation and stellate gangliectomy (Stratum #3=Arrhythmia), and mechanical circulatory support (MCS) surgery, heart transplantation (HTx) surgery (Stratum #4=Dyscontractility). For patients who are neither candidates for heart transplantation nor lifelong mechanical circulatory support and are very ill, based on advance care planning, less aggressive therapy focusing on quality of life and alleviation of suffering may be an alternative.

‌Selected Publications

Organ Failure Molecular Biomarker "Test Development"

From this emerged the translational interest of the relationship between immunological activation and cardiovascular outcomes, most visibly in the completed “Immunology of Cardiac Rejection” AlloMapTM project. Over the last >20 years, working in my labs at Stanford University, Muenster University, Columbia University and UCLA, we have co-developed the first diagnostic and prognostic peripheral blood mononuclear cell (PBMC) gene expression profiling (GEP) biomarker test in transplantation medicine that gained US-FDA-regulatory clearance and international evidence-based medicine guideline acceptance to rule out rejection without invasive biopsies.

Collaborators

Selected Publications

Conceptually related to the AlloMapTM project is the ongoing Advanced Heart Failure Organ Dysfunction project. Based on the AlloMapTM success, the NIH-United States Critical Illness and Injury Trials (USCIIT) Group invited us in 2008 to expand this work to develop a similar PBMC-GEP biomarker test to 1) better understand HF-related frailty and organ dysfunction, 2) better diagnose and predict outcomes, and 3) better treat HF-related organ dysfunction. We propose the overall project hypothesis that the interaction between altered leukocyte and endothelial cell biology in hypoperfused organs and tissues has the potential to worsen organ dysfunction and further activate the immune system, leading to uncontrolled systemic inflammatory response, MOD and death. We are now expanding on this work to develop a genomic blood test to better predict outcomes in patients with various forms of heart failure (MyLeukoMAPTM).

Sub-Project 1: Aging & Functional Recovery Potential In Advanced Heart Failure 

Our central hypothesis is that organ dysfunction and patient death after mechanical circulatory support- or heart transplantation-surgery is resulting from innate and adaptive immune cell dysfunction reflecting an age-related reduced “Functional Recovery Potential (FRP)” that can be predicted by a multidimensional molecular biomarker (MMB) test.

Selected Publications

Organ Failure Molecular Biomarker "Systems Biology"

Integrating these clinical-translational projects is the lab’s systems biological conceptual work.

‌Selected Publications

The goal of this project are to conduct systems analyses of heterologous immunity during CMV infection and define the role of CMV infection on the generation of heterologous T cell alloimmunity in renal transplantation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated coronavirus disease (COVID-19) is an evolutionarily unprecedented natural experiment that causes major changes to the host immune system. We propose to develop a test that accurately predicts short- and long-term (within one-year) outcomes in hospitalized COVID-19 patients broadly reflecting US demographics who are at increased risk of adverse outcomes from COVID-19 using both clinical and molecular data. We will enroll patients from a hospitalized civilian population in one of the country’s largest metropolitan areas and a representative National Veteran’s population. (Grant Number: R01AI159946, contact PI: Dr. Deng)

Deng MC. An exercise immune fitness test to unravel mechanisms of Post-Acute Sequelae of COVID-19. Expert Review of Clinical Immunology. 2023 Jul 3;19(7):693-7.

Change "Molecular Biomarkers in Heart Failure with Preserved Ejection Fraction" to "Exercise Immune Fitness Molecular Biomarkers in Heart Failure" and add the following summary and reference:

Cardiorespiratory fitness positively correlates with longevity and immune health. Regular exercise may provide health benefits by reducing systemic inflammation. In chronic disease conditions, such as chronic heart failure and chronic fatigue syndrome, mechanistic links have been postulated between inflammation, muscle weakness, frailty, catabolic/anabolic imbalance, and aberrant chronic activation of immunity with monocyte upregulation. We hypothesize that (1) temporal changes in transcriptome profiles of peripheral blood mononuclear cells during strenuous acute bouts of exercise using cardiopulmonary exercise testing are present in adult subjects, (2) these temporal dynamic changes are different between healthy persons and heart failure patients and correlate with clinical exercise-parameters and (3) they portend prognostic information

Bondar G, Mahapatra AD, Bao T-M, Silacheva I, Hairapetian A, Vu T, Su S, Katappagari A, Galan L, Chandran J, Adamov R, Mancusi L, Lai I, Rahman A, Grogan T, Hsu J, Cappalletti M, Ping P, Elashoff D, Reed E, Deng M. An Exercise Immune Fitness Test to Unravel Disease Mechanisms—A Proof-of-Concept Heart Failure Study. Journal of Clinical Medicine. 2024; 13(11):3200.

The goal of this project is to develop and combine patient-specific clinical MRI and LV pressure data in a computer model to diagnose changes in diastolic myocardial stiffness in patients with HFpEF.

Organ Failure Molecular Biomarker "Science In the Making"

The link between our practice of modern medicine, training of humanism in medicine and research apprenticeship is reflected in our research collaboration on "Science in the Making" with Prof. Federica Raia (UCLA DGSOM and SE&IS).

Collaborators

Organ Failure Molecular Biomarker in Practice "Relational Medicine"

Linking systems biology back into the clinical framework of a humanistically sound high –tech modern medicine encounter is reflected in my most recent research collaboration with Prof. Federica Raia (UCLA DGSOM and GSEIS) in the “Relational Medicine” project.

Collaborators

Selected Publications