Peter B. Bitterman, MD

Professor of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine

Peter B. Bitterman

Contact Info

bitte001@umn.edu

Office Phone 612-624-0999

Lab Phone 612-625-7615

Office Address:
PACC Medicine
350 VCRC
401 E River Rd
Minneapolis, MN 55455

Mailing Address:
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine
420 Delaware Street, SE, MMC 276 (Pulmonary) MMC 434 (Allergy)
Minneapolis, MN 55455

Administrative Assistant Name
PACCS

Administrative Phone
612-626-3773

Administrative Email
paccmed@umn.edu

Administrative Fax Number
612-625-2174

Medical School, Yale University, New Haven

Residency, University of Chicago Hospitals and Clinics

Fellowship, National Institutes of Health, Washington, D.C.

Bachelors Degree, Tufts University, Boston, MA

Summary

Peter Bitterman, MD graduated from Yale University Medical School in 1976. He completed his residency at the University of Chicago and a fellowship with the National Institutes of Health. He is currently associate director of the MD PhD program and professor in the Pulmonary and Critical Care Medicine Division. He has been elected to the American Society of Clinical Investigation and the Association of American Physicians; and is a recipient of the American Thoracic Society Recognition Award for Scientific Accomplishment. Bitterman served as Associate Editor for several scientific journals and is an inaugural member of the Center for Lung Science and Health at the University of Minnesota; a center dedicated to interdisciplinary research, education, and public outreach activities that promote lung health and improve the care of patients with lung disease.

Professional Associations

National

  • American Association of Physicians
  • American Society of Clinical Investigation
  • American Thoracic Society Recognition Award for Scientific Accomplishment

University of Minnesota

  • Vice Chair for Research, Department of Medicine
  • Associate Director, MSTP
  • Co-Chair, Genetic Mechanisms of Cancer Program, University of Minnesota Comprehensive Cancer Center

Research

Research Summary/Interests

Translational Control; Interstitial Lung Disease; Lung Repair and Regeneration; Cancer; Drug Discovery

Research Projects

RESEARCH PROGRAM: TRANSLATIONAL CONTROL OF GENE EXPRESSION IN IPF AND CANCER

We seek to understand how the protein synthesis apparatus regulates gene expression and cell function. We have discovered that pathological activation of translation initiation complex eIF4F imparts primary fibroblasts and epithelial cells with autonomy for growth and survival and is required for cancer cells to maintain a malignant phenotype. Our research program addresses 4 major questions:

What mechanisms govern which mRNA are selected for translation and how is it organized to mediate normal or pathological cell function? In collaboration with the Henke laboratory at Minnesota and the Larsson laboratory at the Karolinska in Stockholm, this line of investigation features genome-wide approaches in vitro and in vivo. Our goal is to decipher the rules governing the translational control step in gene expression.

Can we disable pathological feedback loops in IPF? In collaboration with the Henke laboratory, we are pursuing experiments to understand how fibrosis begins and how we can interrupt the process. These studies focus on the mechanisms by which a fibrotic lung extracellular matrix can corrupt mesenchymal progenitor cells and differentiated fibroblasts to become fibrogenic.

Is COPD on the causal pathway to cancer? We are addressing this question as part of a large multi-level OMICS study of COPD lung tissue from patients with and without lung cancer. This will be the first study to integrate data from the genome, transcriptome, translatome and proteome. It is led by the Wendt laboratory at Minnesota and the Yang laboratory at Mayo with collaborators from the Karolinska.

Can we correct pathological function of the protein synthesis apparatus with small organic molecules? Our laboratory is testing novel translational repressors as potential anticancer and antifibrotic agents in collaboration with the Wagner laboratory in the College of Pharmacy.

Our investigations feature a dynamic collaborative network of biochemists, cancer biologists, lung biologists and medicinal chemists. Graduate students and post-doctoral fellows interact with a diverse group of trainees as part of our NIH-sponsored training grant led by David Ingbar; joining a cohort spanning an educational continuum beginning with honors undergraduates satisfying their research requirement, MD and MD/PhD students and post-doctoral fellows.

Research Funding Grants

ACTIVE GRANT SUPPORT
Principle Investigator or Project Leader:

  • R01HL125236 11/01/2014 – 10/31/2019 
    NIH/NHLBI “Role of fibrotic extracellular matrix in generating the IPF fibroblast”. This grant is focused on IPF mesenchymal cell population-level studies and has 2 specific aims: 1) Genesis of the IPF fibroblast - Characterize the mechanisms by which MPCs acquire IPF phenotypic hallmarks on IPF lung ECM; 2) Disease progression - Dissect the molecular and cellular mechanisms of the IPF ECM-driven positive feedback loop that increases integrin and ECM gene expression and suppresses their negative regulator, miR29.
  • P01 HL091775 (PI Project 2; Henke P01 PI) 05/01/09-04/30/14 (NCE)
    NIH/NHLBI “Translational Control of the Fibrotic Fibroblast in IPF” 
    The purpose of this grant is to test the function of RNA regulatory elements in IPF that confer lung fibroblasts with pathological properties.
  • R25HL088728 05/01/2007- 4/30/2017
    NIH/NHLBI “Summer Research at the University of Minnesota Medical School”. 
    This grant has 3 goals: 1. Recruit a diverse, academically outstanding cohort of students from across the US and Puerto Rico to the University of Minnesota, 2. Provide student participants with a program faculty-mentored independent research opportunity, and 3. Develop an innovative research-training module devoted to recruiting and training a cohort of students committed to the pursuit of a combined MD-PhD degree.

Co-investigator:

  • R01HL105406-A1 Chen (PI) 08/05/2011- 04/30/2015
    NIH/NHLBI “Molecular Mechanism of 4E-Binding Proteins on Heart Failure Development”
    The purpose of this grant is to study the role of the 4E-binding proteins on the development of congestive heart failure in a mouse model.
  • R01HL107612 Wendt (PI) 07/01/2011-4/30/2015
    NIH/NHLBI/NCI “Common Pathogenetic Mechanisms of Lung Cancer and COPD”
    The purpose of this grant is to identify common steps in the gene expression pathway of COPD and lung cancer by integrating gene sequence data, genome-wide transcriptional and translational profiling data and proteomic data from human tissue specimens.
  • 1P01 HL091775 05/01/09-04/30/14 (NCE)
    NIH/NHLBI Henke (PI) “Integrin-ECM Regulation 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.
  • P30 CA077598-11 Yee (PI); Bitterman (Co-Leader, Genetic Mechanisms of Cancer)
    NIH/NCI “Cancer Center Support Grant”
    The goal of this grant is infrastructure for cancer research, education and patient care for the citizens of the Minnesota and the surrounding region.
  • 5T32GM008244 7/1/1988 – 6/30/2015
    NIH/NIGMS “Medical Scientist Training Program”
    This award supports the University of Minnesota combined MDPhD Program, Shimizu (PI).

Publications

  • Kim Y, Von Weyman L, Larsson O, Fan D, Underwood J, Hecht S, Polunovsky VA, Bitterman PB. The eukaryotic initiation factor 4E binding protein family of translational repressors: Sentinels at a translational control checkpoint in lung tumor defense. Cancer Res. (accepted).
  • Fan D, Bitterman PB and Larsson O. 2009. Regulatory Element Identification in Subsets of Transcripts: Comparison and Integration of Current Computational Methods. RNA 15(8):1469-82.
  • Ghosh B, Benyumov AO, Ghosh P, Jia Y, Avdulov S, Dahlberg PS, Peterson M, Smith K, Polunovsky VA, Bitterman PB, Wagner CR. 2009. Nontoxic chemical interdiction of the epithelial-to-mesenchymal transition by targeting cap-dependent translation. ACS Chem Biol. May 15; 4(5):367-77.
  • Larsson O, D Diebold, D Fan, M Peterson, RS Nho, Bitterman PB and C A Henke. 2008. Fibrotic Myofibroblasts Manifest Genome-Wide Derangements of Translational Control. PLoS One, 16; 3(9), e3220.
  • Xia H, D Diebold, R Nho, D Perlman, J Kleidon, J Kahm, S Avdulov, M Peterson, J Nerva, Bitterman PB, Henke C. 2008. Pathological Integrin Signaling Enhances Proliferation of Primary Lung Fibroblasts from Patients with Idiopathic Pulmonary Fibrosis. J. Exp. Med., 205(7): 1659-72.
  • Vlasova I.A., Tahoe N.M., Fan D., Larsson O., Vasdewani J., Karypis G., Bitterman PB, Bohjanen PR. 2008. Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1. Mol Cell.; 29(2): 263-70.
  • Larsson O, S Li, OA Issaenko, S Avdulov, M Peterson, K Smith, Bitterman PB and VA Polunovsky. 2007. eIF4E-induced progression of primary HMECs along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors. Cancer Res., 67 (14): 1-11.
  • Larsson O, Perlman DM, Fan D, Reilly CS, Peterson M, Dahlgren C, Liang Z, Li S, Polunovsky VA, Wahlestedt C, Bitterman PB. 2006. Apoptosis resistance downstream of eIF4E: posttranscriptional activation of an anti-apoptotic transcript carrying a consensus hairpin structure. Nucleic Acids Res.34(16):4375-86.
  • Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman DM, Manivel JC, Sonenberg N, Yee D, Bitterman PB, Polunovsky VA. 2004. Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells. Cancer Cell Jun; 5 (6):553-63.
  • Li S, Perlman DM, Peterson MS, Burrichter D, Avdulov S, Polunovsky VA, Bitterman PB. 2004. Translation initiation factor 4E blocks endoplasmic reticulum-mediated apoptosis. J Biol Chem. May 14; 279(20):21312-7.
  • Li S, Sonenberg N, Gingras AC, Peterson M, Avdulov S, Polunovsky VA, Bitterman PB. 2002. Translational control of cell fate: availability of phosphorylation sites on translational repressor 4E-BP1 governs its proapoptotic potency. Mol Cell Biol. 22:2853-61.
  • Polunovsky VA, Gingras A-G, Sonenberg N, Peterson M, Tan A, Rubins JB, Manivel JC, Bitterman PB. Translational control of the antiapoptotic function of Ras. J. Biol. Chem. 2000; 275: 24776-24780
  • Tan A, Bitterman PB, Sonenberg N, Peterson M, Polunovsky, V. Inhibition of Myc-dependent apoptosis by eukaryotic translation initiation factor 4E requires cyclin D1. Oncogene 2000; 19:1437-1447.
  • Polunovsky VA, Rosenwald IB, Tan A, White J, Chiang L, Sonenberg N, Bitterman PB. Translational control of programmed cell death: eukaryotic translation initiation factor 4E blocks apoptosis in growth-factor-restricted fibroblasts with physiologically regulated or deregulated. Myc. Mol Cell Biol 1996; 16:6573-6581.

Clinical

Clinics

Center for Lung Science and Health

Board Certifications

  • Critical Care Medicine
  • Pulmonary Medicine

Clinical Interests

Critical Care; Interstitial Lung Disease; Pulmonary Fibrosis; Acute Respiratory Distress Syndrome; Cancer; Idiopathic Pulmonary Fibrosis

Hospital Privileges

University of Minnesota Medical Center, Fairview