Trainees

Current Trainees

Luigi Adamo, MD, PhD

“B lymphocytes are the second most prevalent leukocyte population in the heart and they have been shown to play a key role in the myocardial response to injury. Surprisingly very little is known about them. I am working to broaden our understanding of the biology of myocardial B lymphocytes with the goal of the developing innovative B cell focused therapies for the treatment of heart failure.”

Recent Publications:

Adamo L, et al. Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury. JCI Insight. 2018 Jun 7;3(11)

Adamo L, et al. Abnormal Global Longitudinal Strain Predicts Future Deterioration of Left Ventricular Function in Heart Failure Patients With a Recovered Left Ventricular Ejection Fraction. Circ Heart Fail. 2017 Jun;10(6).

Adamo L, et al. Prevalence of lactic acidaemia in patients with advanced heart failure and depressed cardiac output. Eur J Heart Fail. 2017 Aug;19(8):1027-1033.

Joshua Brettmann, PhD

Kir2.1 is crucial for setting the resting membrane potential and misregulation of this channel have significant impact on the timing of cardiac action potentials, with mutations leading to both long and short QT syndromes. My project looks to understand the molecular mechanism of this crucial channel by using single molecule FRET to determine the structural and dynamic consequences of lipid binding.

Recent Publications:

Wang S, et al. Studying Structural Dynamics of Potassium Channels by Single-Molecule FRET. Methods Mol Biol. 2018;1684:163-180.

Brettmann JB, et al. Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel. Proc Natl Acad Sci U S A. 2015 Dec 15;112(50):15366-71.

Michael Cooper, PhD

Michael is examining the role of acetylation and deacetylation of lipin 1 by HDAC1, a protein known to be activated in failing heart. Preliminary work suggests that maintaining lipin 1 expression in the hearts of animals undergoing transaortic constriction preserves cardiac function. Future works will examine the effects of over expressing acetylation deficient lipin 1 to examine the effect on cardiac metabolism and the response to pathological stimuli.

 

Recent Publications:

Cooper MA, et al. A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice. Exp Neurol. 2018 Aug;306:149-157.

Cooper MA, et al. Intrinsic Activity of C57BL/6 Substrains Associates with High-Fat Diet-Induced Mechanical Sensitivity in Mice. J Pain. 2018 May 24. pii:S1526-5900(18)30193-7. doi: 10.1016/j.jpain.2018.05.005. [Epub ahead of print]

McKenna Feltes, PhD Candidate

DBBS Pre-Doc Trainee, Washington University School of Medicine

 

Exogenous cholesterol is acquired principally through receptor-mediated endocytosis of cholesteryl ester-laden low-density lipoproteins and trafficked to the lysosome where it is distributed to other cellular organelles. While it is well established that bulk export of lysosomal cholesterol is dependent on lysosomal protein NPC1, NPC1- dependent and lower flux, NPC1-independent post-lysosomal cholesterol trafficking pathways are poorly understood. My work aims to identify the proteins involved in this trafficking using novel cholesterol probes.

Recent Publications:

Pugach EK, et al. High-content screen for modifiers of Niemann-Pick type C disease in patient cells. Hum Mol Genet. 2018 Jun 15;27(12):2101-2112.

Castellano BM, et al. Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling complex. Science. 2017 Mar 24;355(6331):1306-1311.

Jesus Jimenez, MD, PhD

The Notch signaling pathway is a key player in early cardiovascular development that becomes quiescent in the healthy adult heart. During periods of stress, such as myocardial infarction, Notch can be reactivated in adults to promote cardiomyocyte survival, enhance progenitor proliferation, promote angiogenesis and reduce fibrosis. In addition, Notch reactivation can induce cardiac electrical remodeling, which may alter the electrical properties of the heart and result in a pro-arrhythmic state that increases the risk for sudden cardiac death. The primary goal of my project is to elucidate the role of Notch signaling with regards to cardiac electrical remodeling in the setting of cardiac injury.

Recent Publication:

Lynn ML, et al. The structural basis of alpha-tropomyosin linked (Asp230Asn) familial dilated cardiomyopathy. J Mol Cell Cardiol. 2017 Jul;108:127-137.

Billy Kang, MD, PhD Candidate

I am studying the structure and function of the voltage-gated potassium channel KCNQ1. KCNQ1 is a critical ion channel in the heart and plays an important role in the heart’s ability to respond to stress. Utilizing electrophysiological and optical techniques, I’m trying to learn about how KCNQ1 works on the molecular level and how dysfunction in KCNQ1 can lead to human disease.

Andrew Koenig, PhD

My project focuses on using zebrafish to define the mechanisms by which identified human gene variants associated with dilated cardiomyopathy result in heart failure. Additionally, I am utilizing murine models to investigate the role of macrophage heterogeneity in response to acute myocardial injury.

 

 

 

Recent Publication:

Davis JA, et al. ETS transcription factor Etsrp / Etv2 is required for lymphangiogenesis and directly regulates vegfr3 / flt4 expression. Dev Biol. 2018 Aug 1;440(1):40-52.

Chien-Jung Lin, MD, PhD

My work focuses on the role of extracellular matrix on the development and remodeling of blood vessels.

Recent Publications:

Lin CJ, et al. Genetics of the extracellular matrix in aortic aneurysmal diseases. Matrix Biol. 2018 Apr 12. [Epub ahead of print].

Lin CJ, et al. Insurance access in adults with congenital heart disease in the Affordable Care Act era. Congenit Heart Dis. 2018 Feb 26. [Epub ahead of print].

Reinhardt S, et al. Non-invasive cardiac testing versus clinical evaluation alone in acute chest pain. JAMA Int Med. 2018 Feb 1;178(2):212-9.

Lin CJ, et al. Cardiomyopathy in patients after posttransplant cyclophosphamide–based hematopoietic cell transplantation. Cancer. 2017 Mar 15;123(10):1800-9.

Kathryn Mangold, PhD Candidate

I develop state-dependent (Markov) models of cardiac sodium channel function to predict tissue excitability effects. I am using this technique to study modulation of the sodium channel by accessory subunits.

Recent Publication:

Mangold KE, et al. (2017) Mechanisms and models of cardiac sodium channel inactivation, Channels, 11:6, 517-533, DOI: 10.1080/19336950.2017.1369637.

Jonathan Moreno, MD PhD

My research focus is on utilizing computational approaches to mathematically describe the biology of ion channels, which are critically important for cellular excitability. These models allow us to design better treatment strategies for the pharmacological management of heart failure and arrhythmia. Using computational tools and clinical datasets, I also am interested in drug-repositioning – using old drugs for new targets in novel ways. My current project is focused on building a computational model of the cardiac Na+ channel that incorporates voltage clamp fluorometry data (VCF) to track voltage-sensing domain (VSD) movement of the Na+ channel during an action potential. By incorporating VSD kinetics into a multi-scale model of the heartbeat, we can better understand the molecular movements that drive antiarrhythmic efficacy (or failure) of certain long-QT mutation carriers in response to commonly prescribed anti arrhythmic drugs.

Recent Publication:

Mangold KE, et al. (2017) Mechanisms and models of cardiac sodium channel inactivation, Channels, 11:6, 517-533, DOI: 10.1080/19336950.2017.1369637.

Arthur Sletten, MD, PhD Candidate

Excess lipid uptake and metabolism cause cell dysfunction and death in a process called lipotoxicity. Our laboratory has identified several novel genes that regulate lipotoxicity, and my project focuses on one of these genes, the small nucleolar hosting gene 3 (snhg3). Disruption of snhg3 protects cells from lipotoxic cell death through rewiring of glucose metabolism. Ongoing work seeks to identify the molecular underpinnings of this phenotype and investigate the role of the snhg3 locus in models of in vivo lipotoxicity.

 

Recent Publications:

Li, M. W., et al. Nuclear export factor 3 regulates localization of small nucleolar RNAs. J Biol Chem. 2017 292:20228-20239.

Schott, M. B., et al. beta-Adrenergic induction of lipolysis in hepatocytes is inhibited by ethanol exposure. J Biol Chem. 2017 292:11815-11828.

Sletten AC, et al. Manifestations and mechanisms of myocardial lipotoxicity in obesity. J Intern Med. 2018 Jan 13. doi: 10.1111/joim.12728. [Epub ahead of print].

 

 

Former Trainees

Peter Crawford, MD, PhD

Professor, Departments of Medicine, and Biochemistry, Molecular Biology, and Biophysics
Vice Chair for Research, Department of Medicine
Director, Division of Molecular Medicine
University of Minnesota

 

Our group performs studies in animal models and humans to learn how alterations of ketone metabolism and related pathways may serve as diagnostic biomarkers and therapeutic targets for obesity, diabetes, nonalcoholic fatty liver disease (NAFLD/NASH), and heart failure. We leverage recent advances in stable isotope tracer based NMR and mass spectrometry-based untargeted metabolomics technologies to study metabolism on a systems level, and we also employ established techniques in molecular cell biology and biochemistry to reveal phenotypic shifts at the cellular level.

Recent Publication:

d’Avignon DA, et al. Hepatic ketogenic insufficiency reprograms hepatic glycogen metabolism and the lipidome. JCI Insight. 2018 Jun 21;3(12).

Sharon Cresci, MD

Associate Professor of Medicine (Tenured) and Associate Professor of Genetics, Washington University School of Medicine

 

The focus of my research is the association of genetic variation with clinical outcomes in patients with cardiovascular disease and in the variable response to pharmacologic treatment. I have specific interest in (1) the contribution of genetic variation to racial disparities in response to medical treatments used to treat coronary syndromes and in outcomes in patients with coronary artery disease and (2) defining the functional mechanism of these genetic associations; the ultimate goal of my research is to promote and advance precision medicine approaches.

Recent Publication:

Cresci S, et al. Cytochrome p450 gene variants, race, and mortality amongclopidogrel-treated patients after acute myocardial infarction. Circ CardiovascGenet. 2014 Jun;7(3):277-86.

Slava Epelman, MD, PhD

Assistant Professor of Medicine
University of Toronto
Loretta Rogers Chair in Immunobioengineering
Toronto General Hospital Research Institute
Peter Munk Cardiac Centre

 

We study cardiac immune cell heterogeneity and the role of individual immune cell subsets in cardiac tissue injury, repair and regeneration.

Recent Publication:

Clemente-Casares X, et al. A CD103(+) Conventional Dendritic Cell Surveillance System PreventsDevelopment of Overt Heart Failure during Subclinical Viral Myocarditis.Immunity. 2017 Nov 21;47(5):974-989.

Brian Finck, PhD

Associate Professor in Medicine, Washington University School of Medicine

 

The Finck lab studies basic aspects of intermediary metabolism in heart, skeletal muscle, and liver. We have ongoing projects to study the role of key proteins that control lipid synthesis and mitochondrial metabolism of fatty acids and pyruvate.

 

Recent Publication:

McCommis KS, et al. Loss of Mitochondrial Pyruvate Carrier 2 in the Liver Leads to Defects in Gluconeogenesis and Compensation via Pyruvate-Alanine Cycling. Cell Metab. 2015 Oct 6;22(4):682-94.

Christopher Holley, MD, PhD

Assistant Professor of Medicine, Duke University

 

The goal of my laboratory at Duke University is to understand how emerging aspects of RNA biology contribute to cardiovascular health and disease, then translate those findings into novel therapeutic approaches for patients. Right now, I am particularly interested in studying how non-coding RNAs and RNA modifications play a role in heart failure.

Recent Publication:

Fry NJ, et al.N(6)-methyladenosine is required for the hypoxic stabilization of specific mRNAs. RNA. 2017Sep;23(9):1444-1455.

David Lanfear, MD

Head, Advanced Heart Failure and Transplant Cardiology, Professor of Medicine, Henry Ford Hospital

 

Research focus is genomics and precision medicine for heart failure, HF clinical trials, and the care of the adv. Hf patients (LVAD outcomes, pt selection, etc.).

 

 

Recent Publication:

Lanfear DE,et al.Targeted Metabolomic Profiling of Plasma and Survival in Heart Failure Patients. JACC Heart Fail. 2017 Nov;5(11):823-832.

Kory Lavine, MD, PhD

Assistant Professor, Washington University School of Medicine

 

The primary goal of our laboratory is to identify new approaches to treat patients with heart failure. Specific projects in the laboratory are focused on unraveling the mechanisms that initiate disease pathogenesis using a precision medicine approach and defining the role of the immune system in cardiac tissue homeostasis, heart failure progression, and myocardial tissue repair.

Recent Publication:

Bajpai G, et al.Thehuman heart contains distinct macrophage subsets with divergent origins andfunctions. Nat Med. 2018 Jun 11. doi: 10.1038/s41591-018-0059-x. [Epub ahead ofprint].

Babak Razani, MD, PhD

Assistant Professor of Medicine -and- Pathology/Immunology
Washington University School of Medicine

 

Babak Razani’s research broadly focuses on the mechanisms of atherosclerosis and related
metabolic conditions. We have taken a particular interest in the autophagy-lysosome system
as it is a cellular process that appears to be affected in a variety of these diseases.

Recent Publication:

Sergin I, et al. Exploitingmacrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis. NatCommun. 2017 Jun 7;8:15750.

Michael Sack, MD, PhD

Chief, Cardiovascular Branch, Division of Intramural Research NHLBI and Director of Laboratory of Mitochondrial Biology and Metabolism

 

Studying the role of nutrient sensing and acetylation in the control of mitochondrial biology and metabolism. My laboratory has extended this work into the translational space exploring these concepts in the control of immune function and inflammation.

 

Recent Publication:

Wang L, et al. GCN5L1modulates cross-talk between mitochondria and cell signaling to regulate FoxO1stability and gluconeogenesis. Nat Commun. 2017 Sep 12;8(1):523.

Joel Schilling, MD, PhD

Assistant Professor of Medicine, Pathology & Immunology

 

My lab is focused on understanding the effects of obesity and diabetes on macrophage function. Our goal is to dissect the biology of distinct macrophage populations in vivo to design novel approaches to treat complications of metabolic disease.

 

 

Recent Publication:

He L, et al. Inhibition of mTOR reduces lipotoxiccell death in primary macrophages through an autophagy-independent mechanism. JLeukoc Biol. 2016 Nov;100(5):1113-1124.