Research Activity

Dean’s Transformational Science Award (PI)
06/2015 - 6/2017
“Development of Akt Kinase Directed Small Molecules Targeting a Novel Allosteric Regulatory Switch”

Goals: Re-constituting Akt "dephosphorylation-protection cage" in a bacteria expression system and to exploit structural and mechanistic insights into "dephosphorylation-protection cage" to enable rational design of superior small molecule regulators of Akt.

AHA, Grant-In-Aid (PI)
07/2014 - 06/2016
“Dephosphorylation Regulation by Akt Carboxy-Terminus and a Novel Lipid-Bridge for Selective Akt2 Activator Development”

Goals: Developing specific carboxyl-terminal-targeting peptides and peptidomimetics that will selectively protect Akt2 against dephosphorylation, using both cell-free and cell-based assays.

ALA, Biomedical Research (PI)
07/2014 - 06/2016
“Lung Pathology Therapies Based on Akt Dephosphorylation Regulation”

Goals: This grant focuses on characterizing how manipulating bridging interactions in the hydrophobic pocket of Akt can protect Akt against dephosphorylation and thereby increase Akt activity in lung alveolar cells.

NIH/NHLBI, R01 HL58506 (Co-I)
02/2013 - 01/2018
“G protein-coupled receptor signaling in airway smooth muscle”

Goals: Specific Aims focus on characterizing mechanisms the effector and regulatory feedback mechanisms of GPCR-mediated PKA activity in airway smooth muscle.

NIH, P01 HL114471-01 (Co-I)
07/2013 - 06/2018
“Novel Molecular Mechanisms promote GPCR-induced bronchodilation in asthma”, Project 4 “Function and Targeting of the Proton-Sensing GPCR OGR1 in ASM”

Goals: To characterize pH-, and novel small molecule ligand-, mediated regulation and function of OGR1 in airway smooth muscle.

NIH/NHLBI, R00 HL118163 (PI)
02/2016 – 01/2019
“Dusp4 in the pathogenesis of LMNA cardiomyopathy”

Dilated cardiomyopathy arising from mutations in the LMNA gene is a highly deadly disease with little understanding of the pathogenic mechanisms involved. We identified Dusp4 as a mediator of LMNA cardiomyopathy and this project aims to elucidate its role in the disease pathogenesis. As no specific treatment currently exists to treat LMNA cardiomyopathy, understanding the molecular mechanisms involved will lead to novel mechanism-based therapies to treat LMNA cardiomyopathy and perhaps, other forms of cardiomyopathy. The proposed aims will take a multidisciplinary approach, spanning molecular and biochemical analyses to in vivo mouse genetics and live animal studies, with the ultimate goal of rapidly translating the gained knowledge into new clinical practice.

NIH/NHLBI, F32 HL094037 (PI)
02/2010 – 01/2013
“Molecular and Cellular Pathogenesis of Emery-Dreifuss Muscular Dystrophy”

NIH/NIA, R01 AG041265 (PI)
07/2012 – 06/2017
“Molecular basis of age-dependent changes in airway smooth muscle functions”

NIH/NHLBI, R01 HL104119 (PI)
05/2013 – 04/2015
“Novel mechanisms of smooth muscle Beta2-receptor regulation relevant to asthma”

American Asthma Foundation, AAF 13-0063 (PI)
07/2013 – 06/2016
“Anti-mitogenic effect of bitter taste receptor agonists on airway smooth muscle”

NIH/NHLBI, K99/R00 HL87560 (PI)
12/2006 – 11/2012
“Molecular Mechanism of airway smooth muscle relaxation” 

University of Pennsylvania, O’Brien Urology Research Program (PI)
2007 - 2008
“Role of stretch in transcriptional regulation of desmin and Vimentin gene expression in smooth muscle”

University of Pennsylvania, ARRA funded O’Brien Urology Research Program (PI)
2009 - 2011
“Role of hypoxia in transcriptional regulation of desmin and Vimentin gene expression in smooth muscle”

NIH/NIAID, R01 AI110007 (PI)
 07/2014 – 06/2019
“Optimizing beta-adrenoceptor signaling bias in asthma”

Goals: Identify therapeutic and pathological signaling via the beta-2-adrenoceptor in models of asthma.

NIH/NHLBI, P01 HL114471
07/2013-06/2018
Project 4 "Function and Targeting of the Proton-Sensing GPCR OGR1 in ASM" (Penn, PI) of PO1 "Novel Molecular Mechanisms Promote GPCR-Induced Bronchodilation in Asthma" (Panettieri, PI)

Goals: Characterize OGR1 signaling, function, and regulation in human airway smooth muscle cells in vitro, ex vivo, and in vivo, elicited by reduced extracellular pH and novel ligands.

NIH/NHLBI, RO1 HL58506 (PI)
02/2013 – 01/2018
"G protein-coupled receptor signaling in airway smooth muscle"

Goals: Specific Aims focus on characterizing mechanisms the effector and regulatory feedback mechanisms of GPCR-mediated PKA activity in airway smooth muscle.

NIH, R01 (PI)
07/2013 - 06/2018
“Inflammatory proteases and Diabetic Cardiomyopathy”

The research proposed in this application will delineate the role of inflammatory proteases in mediating alterations in insulin/insulin growth factor-1 receptor signaling and determine their involvement in the development of diabetic cardiomyopathy

AHA, 0730109N (PI)
01/2007 – 12/2010
“Role of Ubiquitin Proteasome System in Cardiac Myocytes Apoptosis Induced By Inflammatory Proteases”

The research proposed in this application aimed to delineate the role of ubiquitin proteasome system activation in cardiac myocyte death induced by inflammatory proteases.

NIH/NHLBI, 1R01HL122124 (Co-PI)
02/2014 - 1/2018
“Mitochondria-SR Tethering: Its Role in Cardiac Bioenergetics and Ca2+ Dynamics”

We will apply interdisciplinary approaches to test the hypothesis that mitochondria and sarcoplasmic reticulum tethering via Mfn2 family proteins creates a micro-domain of high Ca2+ between these two organelles during excitation-contraction coupling. Moreover, mitochondria Ca2+ uniporters are clustered in the region of inner mitochondrial membrane that is in proximity with SR. Losses of this juxtaposition decrease excitation-bioenergetics coupling efficiency that leads to energy deficiency and oxidative stress and subsequent heart failure.

NIH/NHLBI, 2R01HL093671 (PI)
07/2014 - 04/2018
“Ca2+ and ROS Crosstalk Signaling in Cardiac Mitochondria”

This project is to establish a unified theory to describe the mechanisms of crosstalk signaling between Ca2+ and reactive oxygen species (ROS) in cardiac muscle cells, and to translate these signaling pathways to the physiology and pathology of cardiac excitation, contraction, and energy metabolism.

NIH/NHLBI, 1R01HL114760 (Co-I),
08/2012 - 04/2017
“Mitochondrial Respiration and Superoxide Production in Healthy and Failing Heart”

There are three specific aims in this proposal:
1. Test the hypothesis that superoxide flash arises from the transient acceleration of mitochondrial respiration and is modulated by mitochondrial Ca2+, permeability transition pores and fission/fusion dynamics.

2. Test the hypothesis that pathological stress inhibits superoxide flash activity at an early stage of heart failure and prior to detection of overt signs of mitochondrial dysfunction.

3. Determine whether increased mitochondrial or cytosolic ROS contributes to oxidative stress during mitochondrial respiratory dysfunction.

NIH/NHLBI, R21 HL110371 (PI)
07/2011 – 06/2013
“ADP: A Master Regulator for Bioenergetics and Ca2+/ROS Signaling in Heart”

NIH/NHLBI, 5R01HL033333 (PI)
04/2006 – 09/2012, no-cost extension
“Mitochondrial Ca2+ Transport in Heart Cells”

NIH/NHLBI, RO1 HL105490 (PI)
07/2011 - 06/2016
“Adiponectin inhibits activation and injury of lung endothelium”

NIH, R21 AA023571 (PI)
06/2015 - 07/2017
“Alcohol –Induced Lung Lipid Changes Contribute to development of Acute Lung Injury”

NIH/NHLBI R21 HL112672 (Co-I)
04/2012 - 03/2014
“Adiponectin in acute lung injury”

NIH/NHLBI K08 HL077138 (PI)
04/2006 - 03/2011
“The Identification and Study of a Lung Mesenchymal Stem Cell”

NIH, R01 HL103869-01 (PI)
11/2010 - 11/2016, no cost extension
“Regulation of Endothelial Nitric Oxide Synthase mRNA Stability”

The main goal of this project is to elucidate the molecular mechanisms regulating endothelial nitric oxide synthase expression at post-transcriptional levels

AHA, Established Investigator Award (PI)
01/2016 - 12/2020
“Role of PCMT1 in Cardiac Ageing”

The main goal of this project is to elucidate the anti-aging effect of PCMT1 in the heart and its mechanism of action.

AHA, SDG 0630047N (PI)
01/2006 - 12/2009
“Post-transcriptional Regulation of Endothelial Nitric Oxide Synthase Expression”

The main goal of this project is to identify the proteins that regulate endothelial nitric oxide synthase expression at post-transcriptional levels.

NIH/NIAMS, R03 AR063289 (PI)
04/2013 - 03/2017, no cost extension
“Novel Regulation of PTH Receptor Functions in Bone”

NIH/NIAMS, R03 AR062705 (PI)
07/2013 - 06/2017, no cost extension
“Novel Mechanism of PTH Effects on Bone Metabolism”

DOD PR152096 (PI)
07/2016 - 12/2017
“Inhibition of Chondrocyte Hypertrophy of Osteoarthritis by Disruptor Peptide”