Department of Medicine

University of Pittsburgh

Daniel J. Kass, MD

Assistant Professor of Medicine
UPMC Montefiore Hospital, NW628
3459 Fifth Avenue
Pittsburgh, PA 15213

Phone: 412-624-7225
Fax: 412-624-1670
Email:kassd2@upmc.edu
Assistant: Terri Heinrich
Assistant Email: heinrichta@upmc.edu

Bio

Daniel Kass received his MD from New York University School of Medicine. He completed residency in Internal Medicine and fellowship training in Pulmonary and Critical Care Medicine at Columbia University Medical Center. Dr. Kass trained in basic science research under Dr. Steven Greenberg. Dr. Kass was appointed to the faculty at Columbia in 2006 and is currently supported by grants from the National Heart, Lung, and Blood Institute as well as the Entelligence Scholars Program in Pulmonary Hypertension. Dr. Kass joined the faculty in the Division of Pulmonary, Allergy, and Critical Care Medicine at the University of Pittsburgh in July, 2010.

Clinical Interests

Dr. Kass practices at the Simmons Center for Interstitial Lung Disease with a particular interest in idiopathic pulmonary fibrosis (IPF).

Academic and Research Interests

The focus of Dr. Kass' lab is Idiopathic Pulmonary Fibrosis (IPF). It is a progressive, scarring of the alveolar parenchyma that ultimately leads to respiratory failure and death. Pathologically, this disease is characterized by the unremitting accumulation of fibroblasts. These are the cells responsible for the deposition of extracellular matrix in pulmonary fibrosis.
To gain insight into the pathogenesis of IPF, Dr. Kass' colleagues performed gene expression profiling of IPF lungs compared to normal controls. Dr. Kass has focused on the genes that exhibited increased expression in IPF under the rationale that genes that are highly expressed in IPF likely contribute to the development of pulmonary fibrosis. Specifically, the lab has focused on MetAP2 and Twist1.
Dr. Kass made the novel insight that the MetAP2 expression is necessary for fibroblast proliferation in vitro and that inhibition of MetAP2 with the drug fumagillin suppresses bleomycin-induced pulmonary fibrosis in mice by selectively decreasing the proliferation of fibroblasts in the lung.  Upcoming works include testing fumagillin in animal models of pulmonary hypertension.

The figure belows shows the selective reduction in the number of myofibroblasts from the lungs of animals injured with bleomycin and treated with fumagillin compared to the vehicle control:

Dr. Kass' lab currently studies Twist1, a transcription factor that has been implicated in resistance of tumors to chemotherapy and in promoting metastasis. Work performed by Dr. Robert Bridges in Dr. Greenberg's lab showed that Twist1 expression in fibroblasts is induced by pro-fibrotic growth factors and that  Twist1 expression is critical to prevent apoptosis in lung fibroblasts exposed to pro-apoptotic stimuli common to IPF lungs. Dr. Kass is currently characterizing a double transgenic mouse engineered to delete Twist1 specifically in fibroblasts.

The figure below shows how overexpression of Twist1 permits fibroblasts to resist pro-apoptotic stimuli that occur in IPF lungs (oxidative stress- 4HNE and endoplasmic reticulum stress - thapsigargin).

The ultimate goal of Dr. Kass' work is to develop novel therapeutic strategies to treat IPF.

Key Publications

Factor P, Mutlu GM, Chen L, Mohameed J, Akhmedov AT, Meng FJ, Jilling T, Lewis ER, Johnson MD, Xu A, Kass D, Martino JM, Bellmeyer A, Albazi JS, Emala C, Lee HT, Dobbs LG, Matalon S. Adenosine regulation of alveolar fluid clearance. Proc Natl Acad Sci USA. 2007 Mar 6;104(10):4083-8. Epub 2007 Feb 28.PMID: 17360481

Kass D, Bridges RS, Borczuk A, Greenberg S. Methionine aminopeptidase-2: A Selective Target in Myofibroblasts in Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2007 Aug;37(2):193-201. Epub 2007 Apr 19.PMID: 17446530

Bridges RS, Kass D, Loh K, Glackin C, Borczuk AC, Greenberg S. Gene Expression Profiling of Pulmonary Fibrosis Identifies Twist1 as an Anti-apoptotic Molecular “Rectifier” of Growth Factor Signaling. Am J Pathol. 2009 Dec;175(6):2351-61. Epub 2009 Nov 5.PMID: 19893041

PubMed Link