Keystone Symposia

Eldorado Hotel & Spa Floorplan

This meeting took place in 2023



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Heart Failure: All Cells Considered (Z7)


Organizer(s) Merry L. Lindsey, Crystal Ripplinger and Zamaneh Kassiri
June 25—28, 2023
Eldorado Hotel & Spa • Santa Fe, NM USA
Abstract Deadline: Apr 19, 2023
Scholarship Deadline: Apr 19, 2023
Discounted Registration Deadline: Apr 25, 2023

Sponsored by AstraZeneca, Ionis Pharmaceuticals, Inc., Merck & Co., Inc. and Novo Nordisk A/S


Summary of Meeting:
Heart failure (HF) has conventionally been defined as the inability of the heart to pump sufficiently to meet the needs of the body for oxygen. In addition to HF with reduced ejection fraction (HFrEF), nearly half of patients who present with HF signs and symptoms have preserved ejection fraction (HFpEF). HFrEF presentation includes reduced contractile function and dilation of the left ventricle (LV), while HFpEF presentation includes abnormal LV relaxation and diastolic stiffness. Both HF types have similar hospitalization, morbidity, and mortality rates, and medications that improve outcomes for patients with HFrEF do not show similar benefit to patients with HFpEF. Understanding the cell signaling pathways and molecular mechanisms that trigger HF is a major challenge in cardiovascular medicine. Our conference is conceptually framed around the hypothesis that while HFrEF and HFpEF clearly have distinct etiologies and driving mechanisms, they may share modifiable pathways and biological mediators in common. The convergence among cells involved in inflammation and extracellular matrix deposition will be a major theme. The meeting program includes specific focus on cell heterogeneity, cell-cell cross-talk, individual cell responses, cardiac interactions with other organs, cardiometabolic aspects of all cell types, and approaches to identify new pharma targets. Scientific Relevance: There is a strong need to better understand the cellular and molecular mechanisms of heart failure development. Gaps: 1. Clarify concepts of cardiac remodeling, inflammation, fibrosis, and cell heterogeneity. 2. Develop standard procedures for rigorous assessments. 3. Examine exacerbation of HF development in the setting of co-morbidities. 4. Harness knowledge from other research arenas to develop new strategies to combat HF. 5. Define the use of animal models for optimal use in HF research. 6. Define phenotypes that distinguish subtypes of heart failure (HF): HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Specific Aims: 1. to disseminate and share new knowledge about heart failure, focused on cell and molecular signaling that yields HF; 2. to focus on controversies and knowledge gaps that prevent or limit therapeutic translation; and 3. to promote the educational growth and careers of young scientists. Anticipated outcomes: 1. Attendees will leave this meeting with clear ideas on the most critical experiments needed to accelerate the field forward. 2. There will be a better understanding of the methods that can be applied to better translate basic science to clinical use. 3. Trainees will understand how to advance their careers in the heart failure field. 4. Scientific knowledge and clinical practice will be advanced in that we will have a comprehensive evaluation of the current state of understanding of heart failure and better understand the challenges that remain before we can more completely translate the dynamics of cellular interactions in heart failure. Innovation: We know of no other conference that focuses on the cellular components of heart failure. We will challenge current concepts and fill in the knowledge gaps to help propel the field forward. Bringing together interdisciplinary groups of investigators will ample provide opportunity for cross-fertilization. In particular, we will use approaches in proteomics and big data science to seek paradigm shifts in research strategies.

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No registration fees are used to fund entertainment or alcohol at this conference

Conference Program    Print  |   View meeting in 24 hr (international) time


The meeting will begin on Sunday, June 25 with registration from 16:00 to 20:00 and a welcome mixer from 18:00 to 20:00. Conference events conclude on Wednesday, June 28 with a closing plenary session from 17:00 to 19:00, followed by a social hour. We recommend return travel on Thursday, June 29 in order to fully experience the meeting.

SUNDAY, JUNE 25

4:00—8:00 PM
Arrival and Registration

Cava Santa Fe
6:00—8:00 PM
Welcome Mixer
No registration fees are used to fund alcohol served at this function.

Cava Santa Fe

MONDAY, JUNE 26

7:00—8:00 AM
Breakfast

Anasazi Ballroom
8:00—9:00 AM
Welcome and Keynote Address (Joint)

Eldorado A/B
* Merry L. Lindsey, Meharry Medical Center, USA

* Marlene Rabinovitch, Stanford University, USA

Elizabeth M. McNally, Northwestern University, USA
Genetic Determinants of Heart Failure

9:30—11:15 AM
Cell-Cell Cross-Talk

Eldorado A
* Merry L. Lindsey, Meharry Medical Center, USA

* Upendra Chalise, University of Nebraska Medical Center, USA

Gillian A. Gray, University of Edinburgh Centre for Cardiovascular Science, UK
Intracellular Glucocorticoid Regeneration as a Novel Target to Regulate Infarct Repair and Progression to Heart Failure

Karin Sipido, KU Leuven, Belgium
Cellular Cross-talk in Ischemic Cardiomyopathy

Jennifer E. Van Eyk, Cedars-Sinai, USA
Harnessing Proteomics for Novel HF Diagnostics and Therapies

Jason Maynes, Hospital for Sick Children, Canada
Short Talk: Inherent Inflammatory Characteristics Determine Repair and Transferable Benefit of Cardiac Progenitor Cells in Patients with Congenital Heart Disease

9:30—11:30 AM
The Metabolic Basis of Pulmonary Arterial Hypertension Beyond Glycolysis

Eldorado B
* John Shyy, University of California, USA

* David Fulton, Augusta University, USA

Marlene Rabinovitch, Stanford University, USA
Integrating Pathways in Pulmonary Hypertension

Sadis Matalon, University of Alabama at Birmingham, USA
Oxidative Mitochondrial DNA Injury is a Key Contributor to the Development of Chemical Lung Injury

Stephen L. Archer, Queen's University, Canada
The Role of Altered Mitochondrial Dynamics and Metabolism in Pulmonary Hypertension

Michela Noseda, Imperial College London, UK
Single Cell and Spatial Transcriptomics State-of-the-heart

11:15 AM—5:00 PM
On Own for Lunch

11:15 AM—1:00 PM
Poster Setup

Anasazi Ballroom
1:00—10:00 PM
Poster Viewing

Anasazi Ballroom
2:30—4:30 PM
Workshop 1

Eldorado A
* Nicholas W. Chavkin, University of Virginia, USA

* Mikito Takefuji, Nagoya University School of Medicine, Japan

Preethy Parthiban, University of Minnesota- Twin Cities, USA
Macrophage-derived CCL24 Worsens Cardiac Dysfunction by Promoting Fibrosis and Impeding Compensatory Adaptation during Heart Failure

Upendra Chalise, University of Nebraska Medical Center, USA
Big Data Guided Analysis Reveals Unique Cardiac Remodeling Trajectories by Sex After Myocardial Infarction

Benjamin D. McNair, University of Wyoming, USA
Distinct Mechanisms of Aging in the Right and Left Ventricles

Bryana N. Harris, University of Virginia, USA
Dynamic Map Illuminates Hippo Module Crosstalk Driving Cardiomyocyte Proliferation

Karin J. Bosma, Vanderbilt University Medical Center, USA
Modulation of Prostaglandin E2 Receptors EP3 and EP4 as a Novel Therapeutic Strategy to Improve Cardiac Function in Type 2 Diabetes

Alexa Corker, Medical University of South Carolina, USA
PTSD has a Negative Impact on Cardiac Homeostasis

Abraham L. Bayer, Tufts Graduate School of Biomedical Sciences, USA
T-Cell MyD88 is a Novel Regulator of Cardiac Fibrosis through Modulation of T-cell Activation

2:30—4:30 PM
Workshop 1: Imaging and Biomarkers of Disease Altering Therapies

Eldorado B
* Christopher Rhodes, Imperial College London, UK

S M Riajul Wahab, University of Texas at El Paso, USA
Identifying the Role of Prion-like Protein Doppel as a Novel Mediator of Pulmonary Arterial Hypertension

Claudia Mickael, University of Colorado Denver, USA
Classical Dendritic Cells Drive and Maintain Hypoxia-Induced Pulmonary Hypertension

Micheala A. Aldred, Indiana University, USA
Cybrid Analysis Delineates Nuclear and Mitochondrial Contributions to Oxidative Stress in Pulmonary Arterial Hypertension

Cassidy Delaney, University of Colorado, USA
Platelets Participate in Regulation of the Early Immune Response in Experimental PH

Slaven Crnkovic, Medical University of Graz, Austria
Defining Cell-type Specific Disease States in Pulmonary Hypertension

Jingbo Dai, Northwestern University, USA
The RNA m6A Demethylase, FTO, Regulates Vascular Remodeling in the Pathogenesis of Pulmonary Arterial Hypertension

Bin Liu, University of Arizona, USA
Fatty Acid-binding Proteins Promote Pulmonary Arterial Hypertension via Glycolysis

Caitlin Lewis, University of Colorado, USA
Extracellular Superoxide Dismutase Affects Interstitial Macrophage Accumulation, Reprogramming and Hyaluronan Binding during Pulmonary Hypertension

4:30—5:00 PM
Coffee Available

Concourse
5:00—7:00 PM
Cell Heterogeneity in Heart Failure

Eldorado A
* Gillian A. Gray, University of Edinburgh Centre for Cardiovascular Science, UK

* Preethy Parthiban, University of Minnesota- Twin Cities, USA

Amy D. Bradshaw, Medical University of South Carolina, USA
Fibroblast Activation Profiles in Pressure Overload

Jennifer Davis, University of Washington, USA
Mechanical Signaling Networks that Program Fibroblasts

Taben Hale, University of Arizona, USA
Sub-Populations of Resident Cardiac Fibroblasts in Hypertension: Taking a Census

Alessandra Pasut, KULeuven, Belgium
Short Talk: Metabolic Heterogeneity of Endothelial Cells in HFpEF

Richard Keith Babbs, Keros Therapeutics, USA
Short Talk: RKER-012, A Novel Modified ActRIIB Ligand Trap, Attenuated Cardiac Hypertrophy, Fibrosis, and Cardiovascular Remodeling in a Transaortic Constriction Model of Heart Failure

5:00—7:00 PM
How Epigenetic Changes and RNA Translation Govern Disease Susceptibility

Eldorado B
* Ke Yuan, Boston Children's Hospital, USA

* Scott Barman, Augusta University, USA

Sebastien Bonnet, Université Laval, Canada
Epigenetics Targets in PAH: BRD4 and ACLY Novel's Targets for Vascular Remodeling

Soni Savai Pullamsetti, Max-Planck-Institute for Heart and Lung Research, Germany
The Suppressor Function of lnc RNAs in Pulmonary Hypertension

Chen-Shan Julia Woodcock, University of Pittsburgh, USA
Short Talk: RNA Editing Deficiency Induces Pulmonary Endothelial Pathophenotypes and Drives Pulmonary Hypertension

Cheng-Jun Hu, University of Colorado Denver, USA
Short Talk: Pulmonary Vascular Fibroblasts Are Epigenetically Primed for Inflammatory Responses

YouYang Zhao, Northwestern University-Lurie Children's Hospital of Chicago, USA
Short Talk: Endothelial Cell-targeted Nanoparticle Delivery of CRISPR/Cas9 Plasmid DNA Disrupts Endothelial HIF-2a in Adult Rats and Inhibits Experimental PAH: Towards Genome Editing Therapy of PAH

Jingbo Dai, Northwestern University, USA
Short Talk: Therapeutic Genome Editing of Endothelial Fabp4 Inhibits Pulmonary Arterial Hypertension in Rats

7:00—8:00 PM
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.

Anasazi Ballroom
7:30—10:00 PM
Poster Session 1

Anasazi Ballroom

TUESDAY, JUNE 27

7:00—8:00 AM
Breakfast

Anasazi Ballroom
7:30—8:30 AM
Poster Setup

Anasazi Ballroom
8:00 AM—7:00 PM
Poster Viewing

Anasazi Ballroom
8:00—11:00 AM
Cardiopulmonary Crossroads (Joint)

Eldorado A/B
* Zamaneh Kassiri, University of Alberta, Canada

* Gaurav Choudhary, Alpert Medical School of Brown University, USA

Tim Lahm, National Jewish Health, USA
Sex as a Determinant of Right Ventricular Dysfunction in Pulmonary Hypertension

Tami Martino, University of Guelph, Canada
Circadian Rhythms and HF Chronotherapy

Coffee Break

Bradley Maron, University of Maryland School of Medicine, USA
Individualized Interactomes Advance Precision Medicine in Heart Failure Syndromes

Crystal Ripplinger, University of California, Davis, USA
The Nervous Heart: Autonomic Remodeling Post-MI

Yongneng Zhang, University of Alberta, Canada
Short Talk: A Critical Contribution of Cardiac Myofibroblasts in RV Failure and the Role of a UCP2 SNP as a Biomarker Identifying PAH Patients Predisposed to RV Decompensation

Kenzo Ichimura, Stanford University, USA
Short Talk: 3D Deep Tissue Imaging Reveals Complex Remodeling of the Microvasculature in Right Heart Failure

11:00 AM—12:30 PM
Lunch

Anasazi Ballroom
12:00—2:30 PM
Poster Session 2

Anasazi Ballroom
3:00—4:30 PM
Workshop 2

Eldorado A
* Thomas Martin, University of Colorado Boulder, USA

* Alexa Corker, Medical University of South Carolina, USA

Thirupura Sundari Shankar, University of Utah, USA
Adipocyte Enhancer Binding Protein 1 as a Novel Therapeutic Target to Combat Fibrosis in Heart Failure

Mikito Takefuji, Nagoya University School of Medicine, Japan
Cardiac Atypical Kinase Improves Left Ventricular Diastolic Dysfunction in Heart Failure with Preserved Ejection Fraction

Mohit Kumar, Regeneron Pharmaceuticals, Inc., USA
Characterization of Right Ventricle Involvement in MYBPC3-linked Hypertrophic Cardiomyopathy

Patricia Perez-Bonilla, Pfizer Inc., USA
Heart Rate Variability and Chronotropic Incompetence as Prognostic Markers in a HFpEF Preclinical Model

Nicholas W. Chavkin, University of Virginia, USA
Hematopoietic Loss of the Y Chromosome Promotes Cardiac Fibrosis through Epigenetic Regulation of Autosomal Genes in Monocytes and Macrophages

Thomas Martin, University of Colorado Boulder, USA
Activation of FOXO1-dependent Autophagy Mediates Regression of Cardiac Hypertrophy

2:30—4:30 PM
Workshop 2: Narrowing the Gap Between Discovery and Therapy in Pulmonary Hypertension

Eldorado B
* Stephen L. Archer, Queen's University, Canada

* Chanil Valasarajan, Centre for Infection and Genomics of Lung, Justus Liebig University, Germany

Ke Yuan, Boston Children's Hospital, USA
Deficiency of Smooth Muscle ADAR1 RNA Editing Exacerbates Vascular Remodeling and Pulmonary Hypertension

Sarasa Isobe, Stanford University, USA
Loss of BMPR2 Links Unrepaired DNA Damage to Reduced FOXF1 and Pulmonary Arterial Hypertension

Tamanna Islam, University of Texas at El Paso, USA
Bioengineering Models to Study Cell-Specific Durotaxis in Pulmonary Arterial Hypertension

Emily J. Tsai, Columbia University Vagelos College of Physicians & Surgeons, USA
In vivo Cardiac Myocyte-specific Knockdown of Wipi1 Prevents Decompensation of the Pressure-overloaded Right Ventricle

Yingjie Chen, University of Mississippi Medical Center, USA
Natural Killer Cells Regulate Heart Failure-induced Cardiopulmonary Inflammation, Pulmonary IFN-γ Production, and Pulmonary Remodeling

Pontian Adogamhe, Indiana University School of Medicine, USA
NAMPT Overexpression Decreases Sirt 3 Deacetylase Activity in Human Pulmonary Artery Endothelial Cells

Olin Liang, Brown University, USA
Targeting RUNX1 as a Novel Treatment Modality for Pulmonary Arterial Hypertension

4:30—5:00 PM
Coffee Available

Concourse
5:00—7:00 PM
Cell Responses to Myocardial Injury and Growth

Eldorado A
* Taben Hale, University of Arizona, USA

* Chi Fung Lee, Oklahoma Medical Research Foundation, USA

Leslie A. Leinwand, University of Colorado Boulder, USA
The Sarcomere is a Very Busy Place: From Bench to Bedside in Myosin Myopathies

Kristine Deleon-Pennell, Medical University of South Carolina, USA
T Cell Regulation of MI Remodeling

Kathleen Woulfe, University of Colorado Anschutz Medical Campus, USA
Short Talk: Age-specific Decreases in Sarcomeric Acetylation Modulates Myofilament Function in Skeletal and Cardiac Muscle

Ann Chiao, Oklahoma Medical Research Foundation, USA
Short Talk: Aging Exacerbates Diastolic Dysfunction and Proteostatic Imbalance in Heart Failure with Preserved Ejection Fraction

5:00—7:00 PM
Using Big Data to Understand Complex Disease

Eldorado B
* Micheala A. Aldred, Indiana University, USA

Christopher Rhodes, Imperial College London, UK
The Significance of Noncoding Variants in Pulmonary Hypertension

Wendy K. Chung, Columbia University, USA
Penetrance of Mutations in Pediatric Pulmonary Hypertension

Jose Gomez-Arroyo, University of Cincinnati, USA
Role of FOXF1 in the Pathobiology of Pulmonary Arterial Hypertension

Gabriel Maldonado-Velez, Indiana University School of Medicine, USA
TBX4 Loss-of-function within the Embryonic Lung Mesenchyme Disrupts Lung Alveolar Development and Increases Susceptibility to Pulmonary Hypertension

7:00—8:00 PM
On Own for Dinner
No registration fees are used to fund alcohol served at this function.


WEDNESDAY, JUNE 28

7:00—8:00 AM
Breakfast

Anasazi Ballroom
8:00—11:00 AM
Cardiometabolic Aspects of HF

Eldorado A
* Ann Chiao, Oklahoma Medical Research Foundation, USA

* Abraham L. Bayer, Tufts Graduate School of Biomedical Sciences, USA

Rebecca Ritchie, Monash Institute of Pharmaceutical Sciences, Australia
Diabetic Effects on Cardiac Remodeling

Susan E. Howlett, Dalhousie University, Canada
The Many Effects of Aging and Frailty on the Heart

Coffee Break

Helen E. Collins, University of Louisville, USA
Mechanisms Contributing to Pregnancy-Induced Cardiac Growth

Chi Fung Lee, Oklahoma Medical Research Foundation, USA
Short Talk: SARM1 Deficiency Prevents NAD Decline, Improve Mitochondrial and Cardiac Function in Cardiometabolic Disease

Kayla J. Rayford, Meharry Medical College, USA
Short Talk: Trypanosoma Cruzi Alters Expression of piRNAs That Target Profibrotic and Inflammatory Molecules During Acute Infection of Primary Human Cardiac Fibroblasts

Kenneth Rockwood, Dalhousie University, Canada
Short Talk: Assessing Frailty-related Mortality Risk in Older Adults Hospitalized with and without Congestive Heart Failure

Adaysha Williams, Medical College of Wisconsin, USA
Short Talk: High Inorganic Phosphate Treatment Reduces Rat Neonatal Cardiomyocyte Viability

8:00—11:00 AM
Using Biology to Guide Vascular Regeneration

Eldorado B
* James Klinger, Alpert Medical School of Brown University, USA

* YouYang Zhao, Northwestern University-Lurie Children's Hospital of Chicago, USA

Vinicio de Jesus Perez, Stanford University, USA
Restoring Normal Microvessels in Pulmonary Hypertension

Rubin M. Tuder, University of Colorado Hospital - Anschutz, USA
Disease Heterogeneity and the Challenges in Evaluating Therapies for a Complex Disease

Coffee Break

David B. Frank, Children's Hospital of Philadelphia, USA
Ontogeny and Cellular Heterogeneity in Pulmonary Vascular Development and Disease

Akiko Mammoto, Medical College of Wisconsin, USA
Short Talk: Endothelial Senescence in Pulmonary Hypertension

11:00 AM—5:00 PM
On Own for Lunch

3:00—4:30 PM
Career Roundtable (Joint)

DeVargas
Vinicio de Jesus Perez, Stanford University, USA

Michael Dunn, Regeneron Pharmaceuticals, USA

Chi Fung Lee, Oklahoma Medical Research Foundation, USA

4:30—5:00 PM
Coffee Available

Concourse
5:00—6:45 PM
Pharma Targets for Heart Failure

Eldorado A
* Helen E. Collins, University of Louisville, USA

* Yongneng Zhang, University of Alberta, Canada

Zamaneh Kassiri, University of Alberta, Canada
Metalloproteases Make It or Break It

Rachel J. Roth Flach, Pfizer Inc., USA
Metabolic Targets for Heart Failure

Michael Dunn, Regeneron Pharmaceuticals, USA
Sustained Vasodilation in Preclinical Species and Humans by an Investigational Agonist Monoclonal Antibody to a Membrane-bound Guanylate Cyclase Receptor, Natriuretic Peptide Receptor 1

Aina Hirofuji, Asahikawa Medical University, Japan
Short Talk: Mycn Induces Cardiomyocyte Mitosis in Adult Mice

5:00—6:45 PM
The Inflammatory Basis of Pulmonary Hypertension

Eldorado B
* Thomas Resta, University of New Mexico HSC, USA

* Andrew Bryant, University of Florida College of Medicine, USA

Harry Karmouty-Quintana, University of Texas Health Science Center, USA
RNA Translation and the Proteome of Pulmonary Hypertension

Kurt R. Stenmark, University of Colorado Denver, USA
The Interplay Between Fibroblasts and Monocytes in Pulmonary Hypertension

Simon Bousseau, National Jewish Health, USA
Short Talk: 17β-estradiol Regulates Angiogenesis and Right Ventricle Endothelial Cell Metabolism in Pulmonary Arterial Hypertension

Benjamin Korman, University of Rochester, USA
Short Talk: Single Cell RNA Sequencing of Mice with TNF-mediated Pulmonary Hypertension Demonstrates Marked Changes in Endothelial and Mesenchymal Cell Populations and Aberrant BMP Signaling

6:45—7:00 PM
Meeting Wrap-Up: Outcomes and Future Directions (Organizers)

Eldorado A
6:45—7:00 PM
Meeting Wrap-Up: Outcomes and Future Directions (Organizers)

Eldorado B
7:00—8:00 PM
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.

Anasazi Ballroom

THURSDAY, JUNE 29

8:00—8:00 AM
Departure


*Session Chair †Invited, not yet responded.



Keystone Symposia thanks our Sponsors(s) for generously supporting this meeting:

AstraZeneca Ionis Pharmaceuticals, Inc.
Merck & Co., Inc. Novo Nordisk A/S

We gratefully acknowledge the generous grant for this conference provided by:


National Institutes of Health

Grant No. 1R13HL168861-01

Funding for this conference was made possible (in part) by 1R13HL168861-01 from the National Institutes of Health. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.


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