The Karakikes Lab aims to elucidate disease mechanisms of rare cardiac diseases and potential therapeutic strategies.
Precision Medicine for Rare Cardiovascular Disease
CRISPR-based technologies to probe the functional impact of genetic mutations at the cellular and molecular level. Trends in Genetics 2021
CRISPR-Cas9 based genome editing technologies to correct or introduce disease-implicated gene variants in patient-derived iPSCs and differentiate to relevant cell types such as cardiomyocytes. Circulation 2021
Beating Cardiomyocytes Stained with TMRM
Beating Engineered Heart Tissue
The overarching goal of our studies is to improve our understanding of the pathogenesis of familial cardiomyopathies, such as Hypertrophic Cardiomyopathy (HCM) and Dilated Cardiomyopathy (DCM). We utilize isogenic patient specific induced pluripotent stem cells (iPSCs) as a platform for disease modeling to again insights on how rare mutations affect the cardiomyocyte biology and cardiac performance. By establishing a deep understanding of the biology of the disease, our studies represent a first definitive step in elucidating the genotype-phenotype associations in HCM and DCM toward applying a precision medicine approach to the treatment of cardiomyopathies.
Functional Genetics (in vitro)
Fabricating GRID of 256 isolated chambers for iPSC Seeding using IsoCell from iotaSciences
Grogu/baby Yoda hanging out with baby iota
Harvesting iPSC Clones using IsoCell from iotaSciences
Functional Genetics (in vivo)
Strain Analysis of a Beating Mouse Heart
A major focus of the Karakikes Lab is to define the role of Phospholamban (PLN) in heart physiology and pathophysiology. Currently, we are performing a comprehensive characterization of the PLN interactome using proximity-dependent biotin identification (BioID) to identify protein-protein interaction (PPI) in living cells. In addition, we are investigating the mechanism(s) underlying the pathogenesis of DCM associated with the PLN R14del mutation using patient iPSCs.
CURE-PLaN, funded by the Leducq Foundation, brings together experts in molecular and cell biology with clinicians, and most importantly, PLN R14del patients eager to participate (PLN Foundation). Our overarching common goal is to understand the PLN R14del pathophysiological pathways, which will enable us to develop novel therapeutic strategies for treating inherited DCM. A shared platform of patient data coupled with in vitro and in vivo models will facilitate efforts to achieve this goal.