Whitsett (CCHMC) Research Hub 06

Jeffrey A. Whitsett, MD

U01 Principal Investigator, 1-U01HL134745-01

Editing Alveolar Progenitor Cells for Correction of Monogenic Disease

Interstitial Lung Diseases (ILDs), represent a large group of chronic pulmonary disorders that are common causes of morbidity and mortality of both children and adults worldwide. Alveolar dysfunction, pulmonary fibrosis, and vascular remodeling associated with chronic ILDs lead to progressive respiratory failure for which they are few effective therapies. Both genetic and environmental factors underlie the pathogenesis of ILDs; including smoking, air pollution, and chronic inflammation and genetic disorders. Mutations in genes regulating surfactant homeostasis or alveolar type 2 (AT2) cell function or survival includes ABCA3, SFTPB, SFTPC, SFTPA, Telomerase (and related genes) that cause respiratory failure in neonates, children, and older individuals. Our PCTC Consortium seeks to develop novel strategies designed to use CRISPR/CAS9 gene editing for lung progenitor cells for correction of a prototypic Childhood Interstitial Lung Diseases (CHILD) disorder that disrupts pulmonary surfactant homeostasis (ABCA3 deficiency) that leads to fatal infantile lung disease. Mutations in in the ABCA3 gene disrupts surfactant lipid and protein production gene causing severe respiratory dysfunction after birth or chronic lung disease in infancy. We will apply CRISPR/CAS9 mediated gene editing to correct ABCA3 in alveolar progenitor cells as disease targets applicable to other genetic and acquired disorders affecting AT2 cells and their progenitors. The identification, targeting and gene editing of alveolar AT2 cells and their progenitors will be widely applicable for the treatment of both genetic and acquired diseases of the peripheral lung in the future.

members: 
Lead Principal Investigator
User Name Full Name Institute Affiliation Topic tags People tags
jwhitsett's picture
jwhitsett Jeffrey A. Whitsett, M.D. CCHMC
Co-PI/Co-Investigator
User Name Full Name Institute Affiliation Topic tags People tags
emorrisey's picture
emorrisey Edward E. Morrisey, Ph.D. University of Pennsylvania cardiovascular development
Post-Doctoral Fellow/Trainee
User Name Full Name Institute Affiliation Topic tags People tags
Sbell's picture
Sbell Sheila M Bell Ph.D Cincinnati Children's Hospital Medical Center
Cbolte's picture
Cbolte Craig S Bolte Ph.D. Cincinnati Children's Hospital Medical Center
YAdu's picture
YAdu Yina Du Cincinnati Children's Hospital Medical Center
JAgokey's picture
JAgokey Jason J Gokey Ph.D. Cincinnati Children's Hospital Medical Center
MAguo's picture
MAguo Minzhe Guo Cincinnati Children's Hospital Medical Center
Lhan's picture
Lhan Lu Han Ph.D University of Cincinnati
mherriges's picture
mherriges Michael Herriges Boston University
EAhoskins's picture
EAhoskins Elizabeth E Hoskins M.Sc. Cincinnati Children's Hospital Medical Center
JAmunera's picture
JAmunera Jorge O Munera Ph.D Cincinnati Children's Hospital Medical Center
MAperna's picture
MAperna Marla K Perna M.A.,Ph.D Cincinnati Children's Hospital Medical Center
Hpoling's picture
Hpoling Holly M Poling Cincinnati Children's Hospital Medical Center
SAray's picture
SAray Samriddha Ray Ph.D Cincinnati Children's Hospital Medical Center
MAriccetti's picture
MAriccetti Matthew R Riccetti Cincinnati Children's Hospital Medical Center
TArindler's picture
TArindler Tara N Rindler Ph.D Cincinnati Children's Hospital Medical Center
MAsimsek's picture
MAsimsek Muhammed F Simsek Ph.D Cincinnati Children's Hospital Medical Center
SAsitaraman's picture
SAsitaraman Sneha Sitaraman M.Sc. Cincinnati Children's Hospital Medical Center
JAsnowball's picture
JAsnowball John M Snowball M.Sc. Cincinnati Children's Hospital Medical Center
CAstockman's picture
CAstockman Courtney A Stockman Cincinnati Children's Hospital Medical Center
NAstuart's picture
NAstuart Nagako A Stuart Ph.D Cincinnati Children's Hospital Medical Center
PAsudha's picture
PAsudha Parvathi Sudha M.S. Cincinnati Children's Hospital Medical Center
YAsun's picture
YAsun Yuliang Sun Boston University School of Medicine
XAtang's picture
XAtang Xiaofang Tang Ph.D Cincinnati Children's Hospital Medical Center
RAvagnozzi's picture
RAvagnozzi Ronald Vagnozzi Ph.D Cincinnati Children's Hospital Medical Center
PVummidi's picture
PVummidi Premkumar Vummidi Giridhar Ph.D Cincinnati Children's Hospital Medical Center
pwagh's picture
pwagh Purnima Wagh, Ph.D. CCHMC
Administrative Coordinator
User Name Full Name Institute Affiliation Topic tags People tags
LAkorbee's picture
LAkorbee Leslie Korbee CCRA Cincinnati Children's Hospital Medical Center
EAsmith's picture
EAsmith Erika Smith Cincinnati Children's Hospital Medical Center
Affiliated Investigator
User Name Full Name Institute Affiliation Topic tags People tags
HAakinbi's picture
HAakinbi Henry T Akinbi M.D. Cincinnati Children's Hospital Medical Center
KAVISHA's picture
KAVISHA Kavisha Arora Ph.D. Cincinnati Children's Hospital Medical Center
PAarumugam's picture
PAarumugam Paritha Arumugam Ph.D Cincinnati Children's Hospital Medical Center
AAasai's picture
AAasai Akihiro Asai M.D., Ph.D Cincinnati Children's Hospital Medical Center
BAblaxall's picture
BAblaxall Burns C Blaxall Ph.D Cincinnati Children's Hospital Medical Center
BAcarey's picture
BAcarey Brenna Carey, M.Sc., Ph.D. CCHMC
HAdeshmukh's picture
HAdeshmukh Hitesh Deshmukh M.D., Ph.D Cincinnati Children's Hospital Medical Center
AAjobe's picture
AAjobe Alan H Jobe M.D., Ph.D Cincinnati Children's Hospital Medical Center
TAkalin's picture
TAkalin Tatiana Kalin M.D., Ph.D Cincinnati Children's Hospital Medical Center
VAkalinichenko's picture
VAkalinichenko Vladimir Kalinichenko M.D.,Ph.D Cincinnati Children's Hospital Medical Center
MAkofron's picture
MAkofron Matthew Kofron Ph.D Cincinnati Children's Hospital Medical Center
TAlecras's picture
TAlecras Timothy LeCras Ph.D Cincinnati Children's Hospital Medical Center
SAmadala's picture
SAmadala Satish K Madala Ph.D Cincinnati Children's Hospital Medical Center
JAmaguire's picture
JAmaguire JeanAnn Maguire Ph.D. Children's Hospital of Philadelphia
CormMcCarthy's picture
CormMcCarthy Cormac McCarthy M.D. Ph.D Cincinnati Children's Hospital Medical Center
AAperl's picture
AAperl Anne Karina T Perl Ph.D Cincinnati Children's Hospital Medical Center
JeffRobbins's picture
JeffRobbins Jeff Robbins Ph.D Cincinnati Children's Hospital Medical Center
DAswarr's picture
DAswarr Daniel Swarr M.D. Cincinnati Children's Hospital Medical Center
BAtrapnell's picture
BAtrapnell Bruce C Trapnell M.D. Cincinnati Children's Hospital Medical Center
bvarisco's picture
bvarisco Brian M Varisco M.D. Cincinnati Children's Hospital Medical Center
Tweaver's picture
Tweaver Timothy E Weaver Ph.D. Cincinnati Children's Hospital Medical Center
JAwells's picture
JAwells James Wells Ph.D Cincinnati Children's Hospital Medical Center
YANAxu's picture
YANAxu Yan Xu Ph.D Cincinnati Children's Hospital Medical Center
KAyutzey's picture
KAyutzey Katherine Yutzey Ph.D Cincinnati Children's Hospital Medical Center
Wzacharias's picture
Wzacharias William Zacharias MD PhD CIncinnati Children's Hospital
AAziady's picture
AAziady Assem Ziady Ph.D Cincinnati Children's Hospital Medical Center
AAzorn's picture
AAzorn Aaron Zom Ph.D Cincinnati Children's Hospital Medical Center
Publication: 
Author(s) Title Link
Gautam Bandyopadhyay, Heidie L. Huyck, Ravi S Misra, Soumyaroop Bhattacharya, Qian Wang, Jared Mereness, Jacquelyn Lillis, Jason R Myers, John Ashton, Timothy Bushnell, Matthew Cochran, Jeanne Holden-Wiltse, Philip Katzman, Gail Deutsch, Jeffrey Whitsett, Yan Xu, Thomas J. Mariani, Gloria S. Pryhuber Dissociation, Cellular Isolation and Initial Molecular Characterization of Neonatal and Pediatric Human Lung Tissues view
Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway Epithelium view
Regeneration of the Lung Alveolus by an Evolutionarily Conserved Epithelial Progenitor view
Sustained miRNA Delivery from an Injectable Hydrogel Promotes Cardiomyocyte Proliferation and Functional Regeneration after Ischaemic Injury view
Distinct Mesenchymal Lineages and Niches Promote Epithelial Self-Renewal and Myofibrogenesis in the Lung view
EMC3 Coordinates Surfactant Protein and Lipid Homeostasis Required for Respiration view
Minzhe Guo, Erik Bao, Jeffrey Whitsett SLICE: Determining Cell Differentiation and Lineage Based on Single Cell Entropy view
Yina Du1, Joseph A Kitzmiller1, Anusha Sridharan1, Anne K Perl1, James P Bridges1, Ravi S Misra4, Gloria S Pryhuber4, Thomas J Mariani4, Soumyaroop Bhattacharya4, Minzhe Guo1, S Steven Potter2, Phillip Dexheimer3, Bruce Aronow3, Alan H Jobe1, Jeffrey A Whitsett1, Yan Xu1,3 Lung Gene Expression Analysis (LGEA): An Integrative Web Portal for Comprehensive Gene Expression Data Analysis in Lung Development view

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