The Darbar Lab
Center for Cardiovascular Research | University of Illinois Chicago
Overview
At the Darbar Lab, we are redefining the future of cardiovascular medicine through bold, precision-guided science. Based at the University of Illinois Chicago (UIC), our research focuses on unraveling the complex genetic, molecular, and environmental drivers of cardiac arrhythmias — with a primary emphasis on atrial fibrillation (AF), the most common sustained arrhythmia worldwide.
Our work spans the full translational spectrum: from fundamental discoveries in ion channel biology and stem cell-based disease modeling, to clinical-genomic studies and personalized therapeutic strategies. We integrate cutting-edge technologies — including patient-derived iPSC models, multi-omic analysis, and genotype-guided clinical trials — to develop transformative approaches to risk prediction, diagnosis, and treatment.
Led by Dr. Dawood Darbar, Professor of Medicine and Pharmacology and Chief of the Division of Cardiology, our lab is at the forefront of elucidating the genetic, molecular, and environmental mechanisms of AF and translating this knowledge into individualized therapies.
Our Mission
To advance cardiovascular science through discovery, innovation, and inclusion — transforming the treatment of AF and inherited heart diseases by:
- Decoding genetic and molecular underpinnings of arrhythmias
- Developing personalized and mechanism-based therapies
- Training the next generation of physician-scientists and scientists
- Addressing health disparities through inclusive research
Research Focus
Genomics & Precision Medicine:
Our lab is at the forefront of unraveling the genetic foundations of AF, advancing a precision medicine approach to diagnosis and treatment. We have led pivotal efforts to define the genetic architecture of AF by investigating both common variants and rare, high-impact mutations — particularly in diverse and underrepresented populations.
Our research initiatives include:
- Discovery of key AF risk loci — including variants at chr4q25, chr5, and in genes such as SCN5A, NPPA, and TTN — that shape arrhythmia susceptibility and clinical outcomes.
- Integration of large-scale genomic platforms, such as whole-exome sequencing (WES) and genome-wide association studies (GWAS), to map inherited risk and uncover novel pathogenic pathways.
- Leadership in AF pharmacogenomics, exploring how inherited variation modulates response to antiarrhythmic drugs — laying the foundation for genotype-guided therapy.
By combining cutting-edge genomic technologies with clinical insight, our lab is driving the future of individualized arrhythmia care.
iPSC Modeling of Inherited Arrhythmias
We harness the power of patient-specific induced pluripotent stem cell (iPSC)–derived atrial cardiomyocytes to recreate and study AF in a dish — providing a transformative platform for understanding disease mechanisms and testing therapies in a human-relevant context.
Our work in this area focuses on:
- Modeling genetic forms of AF linked to mutations in TTN, NPPA, SCN5A, and KCNQ1, enabling us to dissect the cellular and electrophysiological consequences of specific variants.
- Engineering advanced, high-throughput platforms for drug screening and functional genomics, using structured cocultures and metabolic/electrical conditioning to produce mature, responsive atrial phenotypes.
By replicating human arrhythmias at the cellular level, our models bridge the gap between genotype and phenotype, accelerating the discovery of targeted, mechanism-based therapies for inherited forms of AF.
Health Equity in Cardiovascular Research
At the Darbar Lab, we are deeply committed to advancing health equity through science that reflects the full spectrum of human diversity. Our UIC Multi-Ethnic AF Biorepository — one of the largest and most racially and ethnically diverse in the country — serves as a powerful resource for uncovering how genetic and social determinants intersect to influence arrhythmia risk.
Through this initiative, we aim to:
- Identify and address racial and ethnic disparities in the incidence, progression, and treatment response of AF.
- Investigate social determinants of health — including access to care, environmental exposures, and structural inequities — that contribute to arrhythmia vulnerability.
- Champion inclusive, representative research that informs more equitable clinical care and precision therapies across all populations.
By embedding equity at the core of our genomic and translational work, we are working to close the gap between scientific discovery and real-world impact — for every community.
Translational Clinical Science
The Darbar Lab bridges bench and bedside through an integrated clinical research platform anchored by the UIC Inherited Heart Disease Program — the only combined adult–pediatric initiative of its kind in Chicago. Our team delivers state-of-the-art care while advancing discoveries that directly shape how inherited cardiovascular disorders are diagnosed and treated.
Key pillars of our translational work include:
- Comprehensive, family-centered care for patients with genetic arrhythmias and cardiomyopathies — from diagnosis and risk assessment to precision-guided management.
- Clinical-genomic research that seamlessly links patient phenotypes with molecular insights, driving discovery and immediate application in care pathways.
- Leadership in precision clinical trials, including genotype-guided therapies and interventions targeting specific molecular mechanisms of atrial fibrillation and related conditions.
By embedding research within clinical practice, we accelerate the development of therapies that are not only innovative but also personalized, equitable, and scalable.
Training & Mentorship
The Darbar Lab is deeply committed to cultivating the next generation of physician-scientists and cardiovascular researchers through rigorous training, personalized mentorship, and a strong culture of inclusion.
We provide a dynamic and supportive environment that integrates basic science, translational discovery, and clinical investigation — preparing trainees to lead at the forefront of precision cardiovascular medicine.
Our leadership and track record include:
- Co-Director, UIC Medical Scientist Training Program (MSTP, MD/PhD)
- Mentorship of 35+ early-career investigators over the past decade, including:
- 12 NIH K awardees
- 10 investigators with independent R01 funding
- A sustained commitment to mentoring URiM (Underrepresented in Medicine) students, residents, fellows, and junior faculty
Collaborations & Funding
The Darbar Lab is embedded in a global network of innovation, leading and collaborating on transformative research initiatives that span genetics, precision medicine, and cardiovascular health equity.
We actively contribute to and lead efforts within major national and international programs, including:
- NIH TOPMed (Trans-Omics for Precision Medicine) – advancing multi-omic insights into atrial fibrillation and related conditions
- NIH RECOVER – investigating the cardiovascular effects of long COVID and post-acute sequelae
- VA Merit Award – exploring obesity-mediated mechanisms of AF
- Qatar Foundation Grant – defining the genetic architecture of AF in Arab populations
- UK Biobank – leveraging large-scale, deeply phenotyped population data to identify genetic determinants of arrhythmia risk
Our collaborative ecosystem spans:
- Genomics and pharmacogenomics
- iPSC disease modeling and stem cell biology
- Electrophysiology, bioengineering, and computational biology
- Health disparities and public health research
Through these multidisciplinary partnerships, we translate discovery into clinical impact — accelerating science that is inclusive, data-driven, and globally relevant.
Join Us
Are you driven to advance cardiovascular science through innovation, precision, and equity?
The Darbar Lab is always looking for curious, committed, and collaborative minds — including undergraduate and graduate students, medical trainees, postdoctoral fellows, and research collaborators — who are eager to make an impact in the fight against atrial fibrillation and inherited heart diseases.
We offer:
- A dynamic, interdisciplinary research environment
- Hands-on mentorship and career development
- Opportunities to work at the intersection of genomics, stem cell biology, and clinical science
Join a team that translates discovery into transformative care.
Location:
Division of Cardiology, Department of Medicine, Center for Cardiovascular Research, UIC College of Medicine
Contact: darbar@uic.edu
UIC Center for Cardiovascular Research
UIC MSTP Program – Medical Scientist Training
Recent High-Impact Publications
1. NOX2 Modulation Drives Obesity-Mediated Atrial Fibrillation
Sridhar A, DeSantiago J, Pavel MA, Chen H, Ly OT, Owais A, Barney M, Jousma J, Nukala SB, Abdelhady K, Massad M, Rizkallah LE, Ong SG, Rehman J, Darbar D. J Clin Invest 2024. https://doi.org/10.1172/JCI175447.
Reveals that NOX2-dependent oxidative stress is a key mediator of AF in obesity, offering a novel therapeutic target. Combines iPSC-derived atrial cardiomyocytes with in vivo and human tissue validation.
2. Titin-Dependent Ventricular Defects Result in Atrial Arrhythmia
Jiang X, Ly OT, Chen H, Zhang Z, Ibarra BA, Pavel MA, Brown GE, Sridhar A, Tofovic D, Swick A, Marszalek R, Vanoye CG, Navales F, George AL, Khetani SR, Rehman J, Darbar D#, Saxena A#. ISCIENCE (2024), doi: https://doi.org/10.1016/j.isci.2024.110395 #corresponding author. Explores how transient ventricular defects caused by TTN mutations lead to adult atrial arrhythmias.
Significance: Demonstrates systemic effects of sarcomeric gene mutations beyond structural cardiomyopathy.
3. A Titin Missense Variant Causes Atrial Fibrillation
Pavel MA, Chen H, Hill M, Sridhar A, Barney M, DeSantiago J, Owais A, Sandu S, Darbar FA, Ornelas-Loredo A, Al-Azzam B, Chalazan B, Rehman J, Darbar D. A titin missense variant causes atrial fibrillation. medRxiv preprint doi: https://doi.org/10.1101/2024.12.06.24318402. Reveals a novel titin variant as a genetic driver of atrial fibrillation using iPSC-derived atrial cardiomyocytes.
Significance: First direct mechanistic link between a TTN variant and AF pathogenesis.
4. Engineered Cocultures for Modeling Atrial Fibrillation
Brown GE, Han YD, Michell AR, Ly OT, Vanoye CG, George A, Darbar D#, Khetani SR#. Microscale co-cultures of human iPSC-derived atrial cardiomyocytes and fibroblasts for drug development. Sci Adv. 2024 Jan 19;10(3):eadg1222. doi: 10.1126/sciadv.adg1222. #corresponding author. Describes a novel high-throughput iPSC-based platform for modeling atrial arrhythmias.
Significance: nables personalized disease modeling and drug screening in a human-relevant system.
5. Rare Genetic Variants and Early-Onset AF in Ethnic Minorities
Chalazan B, Mol D, Darbar FA, Ornelas-Loredo A, Al-Azzam, Chen Y, Tofovic D, Sridhar A, Alzahrani Z, Ellinor PT, Darbar D. Association of rare genetic variants and early-onset atrial fibrillation in ethnic minority. JAMA Cardiol. 2021;6:811-819. Identifies underappreciated genetic risk in minority populations with early-onset AF.
Significance: Promotes inclusivity and representation in cardiovascular genetic research.
6. Atrial Fibrillation Burden and Social Determinants of Health
Shah A, Alonso A, Sweis J, Griza S, Chen Y, Barney M, Diaz A, Al-Azzam B, Rodriguez-Ziccardi M, Ornelas-Loredo A, Darbar FA, Benjamin E, Darbar D. Association of atrial fibrillation burden with social determinants of health. Accepted for publication J Am Coll Cardiol Advances
This study provides novel insights into how key social determinants of health—including race-based inequities and neighborhood deprivation—shape symptom burden and recovery in patients with AF.
Significance: Underscores the importance of integrating social determinants into clinical decision-making and research.
Meet the Team
Hanna Chen, PhD
Lab Manager
Project Focus:
- Generate human induced pluripotent stem cells (hiPSCs) from human peripheral blood mononuclear cells (hPBMCs).
- Apply CRISPR/Cas9 genome editing to knock down or correct mutation genes associated with atrial fibrillation (AF).
- Differentiate gene-edited hiPSCs into atrial cardiomyocytes (hiPSC-CMs) to uncover the genetic mechanisms underlying AF.
- Provide mutation-specific hiPSC-CMs to MD/PhD students and mentor them through experimental design, data analysis, and project completion.
Laboratory Management:
- Overseeing and managing the daily operations of the laboratory
- Implement and monitor safety and biosafety protocols in compliance with institutional and regulatory standards
- Develop and manage the laboratory budget, ensuring cost-effective use of resources.
- Oversee daily lab operations, ensuring quality control for genome editing, stem cell culture, and cardiomyocyte differentiation workflows.
- Ensure the maintenance, calibration, and proper functioning of laboratory equipment and instruments.
- Implement and monitor health, safety, and biosafety measures in compliance with institutional and regulatory requirements.
Handle and resolve technical, operational, and personnel issues that arise within the laboratory
Abhinaya Baskaran
PhD Candidate
Project: Mechanisms of TTN Truncation–Driven Atrial Fibrillation
Abhinaya’s research investigates how a truncating variant in the TTN gene contributes to early-onset atrial fibrillation (EOAF) — a major but underexplored form of inherited arrhythmia. She utilizes a human-relevant disease model based on iPSC-derived atrial cardiomyocytes (iPSC-aCMs) generated from a genetically affected proband. These are compared with CRISPR-corrected isogenic controls and unaffected family-derived lines to dissect variant-specific phenotypes. To enhance physiological relevance, iPSC-aCMs are cultured on micropatterned substrates that promote cellular alignment and facilitate the maturation of electrical and mechanical properties. Her work integrates electrophysiological, structural, and contractile analyses with bulk RNA-seq–based transcriptomic profiling to identify the molecular networks perturbed by TTN truncation.
Her goal is to define atrial-specific mechanisms of disease — including altered ion channel function, impaired conduction velocity, and dysregulated sarcomere signaling — and to advance the development of precision therapies for inherited AF syndromes.
Sami Muslmani
MD/PhD Candidate
Project: Exploring Caveolin-1’s Role in the Development and Progression of Atrial Fibrillation
Sami’s research focuses on Caveolin-1 (Cav1), a membrane scaffolding protein, and its mechanistic role in the development and progression of AF. Using a previously established mouse model from his co-mentor, Dr. Richard Minshall, he utilizes electrophysiologic, biochemical, and transcriptomic analyses to understand better how this influential protein contributes to changes in the electrical and structural landscape of the atria.
His preliminary findings suggest that endothelial cell dysfunction, in conjunction with standard atrial fibrosis, may increase the severity of AF. He also aims to identify how Caveolin-1 interacts with common AF risk factors, such as hypoxia, and to explore a potential mechanistic link between AF and vascular dementia. These insights offer a direct translational connection to patients entering the cardiology clinic and may provide valuable information on therapeutic targets beyond the currently recognized arrhythmia standard of care.
Asia Owais, MBBS
PhD Candidate
Project: Genetic Mechanisms of Atrial Fibrillation in Lamin A/C Cardiomyopathy
Asia’s research focuses on the intersection of rare and common genetic variants in atrial fibrillation (AF), particularly within the context of Lamin A/C (LMNA) cardiomyopathy. Using patient-specific iPSC-derived atrial cardiomyocytes (iPSC-aCMs) from a family carrying the pathogenic LMNA-S143P variant, she integrates epigenetic, transcriptomic, and electrophysiologic analyses to unravel how these variants shape arrhythmogenic risk.
Her recent findings reveal that alterations in chromatin accessibility disrupt regulatory interactions involving key cardiac transcription factors and AF-associated loci. Notably, her work demonstrates how impaired accessibility near a region controlling SCN5A expression leads to reduced action potential amplitude and slowed conduction velocity — mechanisms that likely promote AF via re-entry. These insights offer a compelling mechanistic model for how rare variant–common variant interactions contribute to arrhythmia in inherited cardiomyopathies.
Arvind Sridhar, PhD
Postdoctoral Fellow
Project: Investigating Mechanisms Through Which Obesity Induces Atrial Fibrillation
Arvind’s research investigates how obesity predisposes to AF through molecular mechanisms involving oxidative stress, ion channel remodeling, and transcriptional reprogramming. His work bridges metabolic dysfunction and atrial electrophysiology, using both mouse models and human iPSC-derived atrial cardiomyocytes (iPSC-aCMs) to explore how obesity alters the atrial substrate.
In his first-author Circulation: Arrhythmia and Electrophysiology study, he demonstrated that obesity-induced AF is driven by ion channel remodeling and atrial fibrosis, both of which were reversed with mitochondrial antioxidant therapy. Building on these findings, his JCI paper showed that NOX2-derived ROS in obesity promotes AF via PITX2 activation, leading to atrial electrical remodeling in obese mice, palmitic acid–treated iPSC-aCMs, and atrial tissue from obese patients.
Currently, Arvind is investigating how HDAC5 and LKB1, two key metabolic and epigenetic regulators, integrate metabolic and transcriptional signaling to drive atrial remodeling in obesity. His work combines animal models, transcriptomics, ChIP-Seq, and pharmacologic interventions, aiming to uncover novel therapeutic targets for obesity-related AF.
Mahmud Arif, MPhil, PhD
Research Assistant Professor
Project: Mechanism by which a common genetic variant of SCN5A causes Atrial Fibrillation.
Arif’s research centers on the role of common genetic variants in the cardiac sodium channel gene SCN5A, which has been strongly linked to increased AF risk. Despite extensive genetic associations, the precise mechanisms by which such variants contribute to arrhythmogenesis remain poorly defined. To address this gap, Arif has developed a heterozygous SCN5A-S1103Y knock-in mouse model, which exhibits elevated late sodium current in the atria. His research integrates both in vivo and in vitro approaches to investigate how this variant disrupts ion homeostasis to create a vulnerable substrate for AF. Additionally, his work explores the interaction between genetic predisposition and clinical risk factors such as obesity, age, and hypertension. Through this multifaceted approach, the research aims to uncover fundamental insights into AF pathogenesis and contribute to the development of precision therapies tailored to individuals carrying common SCN5A variants, with the ultimate goal of improving patient-specific management of cardiac arrhythmias.