Craig Henke, MD

Professor of Medicine
Contact Information 
 

Clinical Activities

Clinical activities and interests include: sub-specialty pulmonary clinic focusing on interstitial lung diseases and attending in the Medical Intensive Care Unit. 

Research Activities

The focus of my research program is pulmonary fibrosis. IPF is a progressive and lethal fibrotic lung disorder.  It is characterized by the replacement of the alveolar airspace with proliferating fibroblasts and their major connective tissue product: type 1 collagen.  We have obtained an NIH Program Project Grant to study the molecular pathways that regulate the pathologic behavior of the IPF fibroblast.

Selected Recent Publications

Xia H, Nho RS, Kahm J, Kleidon J, Henke C. FAK is upstream of PI-3-kinase/Akt in regulating fibroblast survival in response to contraction of type 1 collagen matrices via a beta1 integrin-viability signaling pathway. J Biol Chem  2004; 279(31):33024-33034.

Nho RS, Hong X, Kahm J, Kleidon J, Diebold D, Henke CA. Role of integrin-linked kinase in regulating phosphorylation of Akt and fibroblast survival in type 1 collagen matrices through a beta 1 integrin viability signaling pathway. J Biol Chem  2005; 280(28): 26630-26639.

Nho RS, Hong X, Diebold D, Kahm J, Kleidon J, White E, Henke CA. PTEN regulates fibroblast elimination during collagen matrix contraction.  J Biol Chem  2006; 281(44):33291-33301.

Xia H, Nho RS, Kahm J, Kleidon J, Henke CA. Polymerized collagen inhibits fibroblast proliferation via a mechanism involving the formation of a Beta 1 integrin-protein phosphatase 2A-tuberous sclerosis complex 2 complex that suppresses S6K1 activity. J Biol Chem 2008, 283(29):20350-60 .   

Xia H, Diebold D, Nho RS, Perlman D, Kleidon J, Kahm J, Avdulov S, Peterson M, Nerva J, Bitterman P, Henke C.  Pathological integrin signaling enhances proliferation of primary lung fibroblasts from patients with idiopathic pulmonary fibrosis.  J Exp Med, 2008; 205(7):1659-72.

Larsson O, Diebold D, Fan D, Peterson M, Nho RS, Bitterman PB, Henke CA.  Fibrotic myofibroblasts manifest genome-wide derangements of translational control.  PLoS ONE, 2008; 3(9):e3220.

Active Grant Support 

NIH/NHLBI R21 RHL096567A            7/1/2009 – 6/30/2011
Henke (MPI)

Role of FoxO3a in Regulating the IPF Fibroblast Phenotype

The objective of this proposal is to examine the role of the FoxO3a transcriptional activator in regulating the IPF fibroblast phenotype.  The hypothesis is that the aberrantly-activated PI3K/Akt signal pathway in IPF fibroblasts suppresses FoxO3a expression/function, which down-regulates the cell cycle inhibitor p27 and the apoptosis-inducing protein Bim.  This confers IPF fibroblasts with a hyper-proliferative and apoptotic-resistant phenotype.

PO1 HL 091775  (MPI-Henke)                             4/1/2009-3/31/2014
NIH/NHLBI

IPF Fibroblast Phenotype

The objective of this P01 is to provide direct mechanistic insight into the molecular processes that make an IPF fibroblast abnormal by uncovering those components of the myofibroblast cellular machinery that result in unrelenting fibrosis in IPF, and in proper tissue healing under normal circumstances.

PO1 (MPI-Henke)                                              4/1/2009 – 3/31/2014
NIH/NHLBI

IPF Fibroblast Phenotype
Project 1: Integrin-ECM Regulation of Fibroblast Proliferation
Role: Project Leader of Project 1 – 3.6 Calendar months

The objective of Project 1 is to examine the role of the PI3k/Akt-PTEN axis in conferring IPF lung fibroblasts with the ability to circumvent the negative proliferative properties of polymerized type I collagen.

PO1 Core A (PI Henke)                                          4/1/2009 – 3/31/2014
NIH/NHLBI

Administrative Core

RO1 HL089228-01A2     (Henke-MPI)                            4/1/2009 – 3/31/2014
NIH

Integrin-Collagen Interaction and Control of Fibroblast Proliferation

The objective of this proposal is to define the role of integrin in regulating PTEN function in response to fibroblast interaction with polymerized type I collagen.

Recent Grant Support

RO1 HL 074882  (PI Henke)                                    7/4//2005-5/31/2009
NIH/NHLBI

Extracellular Matrix Regulation of Fibroblast Viability

The objective of this grant is to investigate the role of the beta1 integrin PI3K/Akt signal pathway in regulating the viability of normal fibroblasts in contractile collagen matrices.