Research Activity

From Research to the Power to Cure

The Center for Translational Medicine at Thomas Jefferson University is primarily focused on bridging cutting-edge basic research with clinical medicine in order to more efficiently translate new discoveries at the bench to the realization of improved patient care.

Our center, which is at the forefront of academic medicine, creates a new culture of collaboration and cooperation, merging a world-class team of basic science investigators with Thomas Jefferson University and Hospital’s renowned physicians and clinical investigators.

The Center for Translational Medicine conducts broad and multi-focal research. Multiple labs are engaged in models of heart and vasculature disease. Our research focuses on the regulation and signaling of many molecules vital in the progression in heart muscle diseases utilizing novel genetically engineered mouse models or viral-mediated myocardial gene delivery. We also study cellular and molecular mechanisms of cardiovascular development in vertebrates.

Pulmonary research is another strength of the Center for Translational Medicine, fostered by collaboration with the Jane and Leonard Korman Respiratory Institute — Jefferson Health and National Jewish Health. Understanding the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD), and developing novel drugs for their treatment, is the focus of the Penn Lab and Deshpande lab. The Deshpande Lab also investigates the mechanisms by which lung function declines with aging. Fibrotic lung disease, and the role of obesity in asthma, are the focus of the Summer lab. The Chan lab explores novel means of manipulating Akt kinase activity as treatment for multiple lung diseases.

Targeting mechanisms affecting bone and cartilage metabolism, as a means of treating or preventing osteoporosis and osteoarthritis, is the focus of the Wang lab.

Finally, our Center is also leading research in viral vector development and small animal models of disease, Small Animal Physiology Core.

Our Current Areas of Interest

Mitochondria, Cellular Receptors, Kinases and Cell Adhesion Proteins

Diseases of the Vasculature Focus on the Role of Platelets, Proteases, Nuclear Receptors, and Reactive Oxygen Species Signaling in Human Diseases

Pulmonary Research

Skeletal Biology and Diseases

Obstruction and Bladder Disease

Funded Projects - Past & Present

Current Support

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.

Current Support

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.

Completed Support

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

Current Support

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”

Completed Support

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

Completed Support

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”

Current Support

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.

Current Support

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

Completed Support

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.

Current Support

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.

Completed Support

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”

Current Support

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”

Completed Support

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”

Current Support

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.

Completed Support

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.

Current Support

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”

CTM Seminar Series

2016

  • August 16, 2016 - Calvin Cotton PhD
    "Primary human nasal epithelial cell cultures:  Cellular model for personalized
    CFTR-directed therapeutics"
  • August 25, 2016 - Zhenguo Liu, MD, PhD
    "Hyperlipidemia, oxidized LDL, and bone marrow stem cells"
  • September 8, 2016 - Bernadette R. Gochuico, MD
    "Clinical Spectrum and Mechanisms of Hermansky-Pudlak Syndrome"
  • September 29, 2016 - Dale Tang, MD, PhD
    "Is c-Abl a new biotarget for asthma treatment?"
  • October 6, 2016 - Robert Krauss, PhD
    "Niche regulation of muscle stem cell quiescence"
  • October 20, 2016 - Kenneth Walsh, PhD
    "Metabolic and genetic risk factors that causally contribute to cardiovascular disease"
  • November 3, 2016  - Harpreet Singh, PhD
    "Mitochondrial Ion Channels: Roles and Function"
  • December 15, 2016 – Maria I. Ramirez, PhD
    "Genetic and Epigenetic Regulation of Lung Epithelial Cell Differentiation"

2017

  • March 2, 2017 – Thomas M. Vondriska, PhD
    "Epigenomics of cardiovascular disease: from chromatin fiber to human populations"
  • March 23, 2017 – Philip S. Tsao, PhD
    “Molecular and Biomechanical Mechanisms of Abdominal Aortic Aneurysm (AAA) Disease"
  • August 7, 2017 – Varda Shoshan-Barmatz, PhD
    “VDAC1 as a Target: Crossing the Aisle from Cancer to Neurodegeneration and Diabetes”
  • September 28, 2017 – Cherie A. Singer, PhD
    “miRNA-mediated gene silencing as a regulator of airway smooth muscle phenotype”
  • October 5, 2017 – David A. Wyler, MD
    “Recrudescence of stroke signs:  Does anesthetic technique matter? and is a cellular model feasible?”
  • October 26, 2017 – E. Dale Abel, MD, PhD
    “Unexpected Roles for Mitochondrial Dynamics”
  • November 6, 2017 - Kris DeMali, PhD
    “Linking E-cadherin mechanotransduction to cell metabolism”
  • November 30, 2017- Sandrine Pouvreau, PhD
    “Mitochondria and synaptic function: learning from the mossy fiber-CA3 synapse”

2018

  • March 15, 2018 – Maria I. Kontaridis, PhD
    “Using iPSCs to delineate the molecular mechanisms that cause cardiovascular and gastrointestinal difficulties in RASopathy patients”
  • April 5, 2018 – Robert E. Akins, Jr., PhD, FAACPDM, FAHA
    “Cell instructive materials to support vascular grafts:  effects of substrate   modulus on arterial cell and tissue function”
  • April 18, 2018 – Souheil Y. El-Chemaly, MD
    “Targeting the lymphatic/hyaluronan axis in acute lung allograft rejection”
  • May 10, 2018 – Maria I. Ramirez, PhD
    “Role of the long noncoding RNA NKX2-1-AS1 in lung tumor cells”     
  • May 17, 2018 – Shey-Shing Sheu, PhD
    “Defeating heart failure with energy: mechanisms of cardiac excitation-contraction-bioenergetics coupling”
  • May 24, 2018 – Tatyana Svitkina, PhD
    “New applications of push/pull forces generated by the actin cytoskeleton” 
  • May 31, 2018 – Jason Choi, PhD
    “Unraveling the cell-type specific effects in the development of LMNA cardiomyopathy” 
  • June 14, 2018 – Tonio Pera, PhD
    “GPCR biased agonism in airway smooth muscle”
  • June 18, 2018 – Mudit Tyagi, PhD
    “HIV latency, the major hurdle in HIV eradication; and the impact of cocaine on HIV gene expression and replication”
  • June 21, 2018 – Glenn Radice, PhD
    “Molecular control of mechanical forces during cardiac development and regeneration”
  •  July 26, 2018 – Saul Schaefer, MD
    “Cardiac specific deletion of the 18kDa translocator protein protects the murine heart from pressure overload heart failure”
  • September 11, 2018 – Arie Horowitz, DSc
    “Elucidating the pathophysiology and molecular mechanism of congenital hydrocephalus” 
  • November 13, 2018 – Robert P. Mecham, PhD
  • December 18, 2018  – Gang Liu, MD, PhD 
  • December 7, 2018 – Andrew P. Fontenot, MD