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Manfred Boehm, M.D.

Laboratory of Cardiovascular Regenerative Medicine

Manfred Boehm, M.D.
Senior Investigator
Laboratory of Cardiovascular Regenerative Medicine


Building 10-CRC Room 5-3132
10 Center Dr
Bethesda, MD 20892
P: +1 301 435 7211
F: +1 301 451 7090
boehmm2@mail.nih.gov


Background

Manfred Boehm received his M.D. in 1993 from the University of Heidelberg, Germany and did his residency in internal medicine at the Franz-Volhard-Clinic in Berlin. Before arriving at the NHLBI, he was a research fellow at the Max Delbrück Center for Molecular Medicine, Berlin from 1996 to 1997, and the University of Michigan, Ann Arbor from 1997 to 1999. He joined the NHLBI as a research fellow in 1999 and has been an Investigator since 2003. Dr. Boehm received a Foundation for Advanced Education in the Sciences Award for Research Excellence from the NIH. Dr. Boehm has authored numerous original scientific articles, reviews, and book chapters. He serves on the editorial boards of Trends in Cardiovascular Medicine, ISRN Stem Cells, Atherosclerosis, and Journal of Molecular Medicine. Dr. Boehm holds two patents, has participated in cooperative research and development agreements with biotechnology companies and has several active clinical protocols.

Research Interests

Injury and remodeling of blood vessels occur as a direct result of cardiovascular disease, as in atherosclerosis or myocardial infarction, and also in response to therapeutic interventions, including stenting and vein graft bypasses. Dr. Boehm studies vascular injury and remodeling in order to understand the underlying molecular mechanisms and to develop new treatment methods. His laboratory develops animal models of disease and derives cellular models from patients with rare and even undiagnosed cardiovascular diseases.

To study the molecular mechanisms that support vascular remodeling, Dr. Boehm focuses on several signal transduction pathways, including TGFβ/SMAD, TNFα/RANTES/MCP-1, and Jak/Stat/HIF. His laboratory studies these pathways in mice developed to mimic different human cardiovascular diseases including models of wire injury, vein graft/transplantation, high-fat diet atherosclerosis, and myocardial infarction. To identify the origin of different cells that participate in vascular remodeling, his lab generates murine cell-lineage tracing models that label cells from specific developmental lineages (endothelial, smooth muscle, and monocyte/macrophage).

Dr. Boehm and his colleagues have delineated signaling mechanisms that mediate the complex interactions between local vascular and circulating immune cells during vascular wound repair. He has demonstrated that a cascade involving the cyclin-dependent kinase p21Cip1, Stat3, and SDF-1/CXCR4 regulates vascular proliferation and inflammatory mechanisms. He has also shown that the signaling molecule RANTES, a target of the transcription factor STAT3, regulates local T-cell recruitment to the site of injury.

Dr. Boehm’s laboratory develops patient-specific induced pluripotent stem (iPS) cells to establish cellular models to study vascular disease mechanisms. These cells are used for screening approaches, like RNA-seq, and can be modified for loss- and gain-of-function strategies to identify pathways and test candidate mechanisms. These same cells can then be used to test drugs or small molecules to interfere with the disease process. In the case that these drugs are already FDA-approved, treatment protocols are only a step away.

Dr. Boehm and his colleagues recently identified a novel disease, Arterial Calcification due to a Deficiency in CD73 (ACDC), and also diagnosed two very rare diseases (prolidase deficiency and adducted thumb-club foot syndrome) in patients seen at the NIH Clinical Center. Based on their work characterizing the ACDC disease mechanism, a clinical study has been initiated for treatment of these patients with an oral bisphosphonate. In addition, their work on STAT3 pathways as immune regulators in vascular remodeling has led them to a possible treatment for the related diseases of prolidase deficiency and hyper IgE syndrome.

More recently, as part of the National Human Genome Research Institute’s ClinSeq initiative to gather sequence data and cardiovascular measures from approximately 1,000 participants, Dr. Boehm has access to a subpopulation of patients with coronary artery disease that have a variant associated with aberrant Rantes signaling. In addition, people with CCR5Δ32 variants—better known for their resistance to a subtype of the HIV virus—have defective RANTES signaling. Given his work on this pathway, Dr. Boehm is interested in the differences these populations exhibit in their propensity to develop vascular disorders related to inflammation.

Selected Publications

NT5E mutations and arterial calcifications.
St Hilaire C, Ziegler SG, Markello TC, Brusco A, Groden C, Gill F, Carlson-Donohoe H, Lederman RJ, Chen MY, Yang D, Siegenthaler MP, Arduino C, Mancini C, Freudenthal B, Stanescu HC, Zdebik AA, Chaganti RK, Nussbaum RL, Kleta R, Gahl WA, Boehm M.
N. Engl. J. Med. 2011 Feb 3;364(5):432-42.
[Text Abstract on PubMed]

Perivascular T-cell infiltration leads to sustained pulmonary artery remodeling after endothelial cell damage.
Cuttica MJ, Langenickel T, Noguchi A, Machado RF, Gladwin MT, Boehm M.
Am. J. Respir. Cell Mol. Biol. 2011 Jul;45(1):62-71.
[Text Abstract on PubMed]

Major histocompatibility complex-I expression on embryonic stem cell-derived vascular progenitor cells is critical for syngeneic transplant survival.
Ma M, Ding S, Lundqvist A, San H, Fang F, Konoplyannikov M, Berry C, Beltran LE, Chen G, Kovacic JC, Boehm M.
Stem Cells. 2010 Sep;28(9):1465-75.
[Text Abstract on PubMed]

Stat3-dependent acute Rantes production in vascular smooth muscle cells modulates inflammation following arterial injury in mice.
Kovacic JC, Gupta R, Lee AC, Ma M, Fang F, Tolbert CN, Walts AD, Beltran LE, San H, Chen G, St Hilaire C, Boehm M.
J. Clin. Invest. 2010 Jan;120(1):303-14.
[Text Abstract on PubMed]

p21Cip1 modulates arterial wound repair through the stromal cell-derived factor-1/CXCR4 axis in mice.
Olive M, Mellad JA, Beltran LE, Ma M, Cimato T, Noguchi AC, San H, Childs R, Kovacic JC, Boehm M.
J. Clin. Invest. 2008 Jun;118(6):2050-61.
[Text Abstract on PubMed]

Manfred Boehm's Full List of Publications

DIR News
March 12, 2014
Researchers find reason why many vein grafts fail
January 29, 2014
Correlative super-resolution fluorescence and transmission electron microscopyExternal link Disclaimer
December 23, 2013
President Obama honors outstanding early-career scientists
November 25, 2013
AAAS council elects 388 new AAAS FellowsExternal link Disclaimer
November 21, 2013
A new multilayer-based x-ray grating

View all DIR News

Last Updated: April 30, 2013

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