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VMI
 


Vascular Medicine Institute
University of Pittsburgh
BST E1240
200 Lothrop Street
Pittsburgh, PA 15261
Phone: 412-383-5853
Fax: 412-648-5980

Dennis C. Bruemmer, MD, PhD

 

Gladwin

 

Dennis Bruemmer, MD, PhD

Associate Professor of Medicine,
Division of Cardiology

1704 BST
200 Lothrop Street
Pittsburgh, PA 15261

Phone: 412-383-6030
Lab Phone: 412-383-6036
Email: bruemmer@pitt.edu

Assistant: Diane Margaria
margariad@upmc.edu | 412-383-6030


Bruemmer Lab

   

Bio

Dennis Bruemmer obtained his combined MD and PhD degrees from the University of Hamburg, Germany in 1998. Following his clinical residency training in Internal Medicine/Cardiology at the Charité/Rudolf-Virchow Hospital and the German Heart Institute at the Humboldt University in Berlin, Germany, he relocated to the United States in 2001 for a Research Fellowship in Molecular Biology at the University of California, Los Angeles. After completion of this research fellowship, Dr. Bruemmer joined the faculty at UCLA as Assistant Professor. In 2004, he was recruited to the University of Kentucky where he completed additional clinical subspecialty fellowship training in Endocrinology in 2009 and in Cardiovascular Medicine in 2015. Since 2004, Dr. Bruemmer had been a full-time faculty member and a clinician-investigator at the University of Kentucky. In 2009, he was promoted to Associate Professor and became the Associate Director of the Saha Cardiovascular Research Center. Since January 2016, Dr. Bruemmer is a faculty member of the Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute and the UPMC Heart and Vascular Institute.

Dr. Bruemmer’s research program has been supported by the National Institute of Health, the American Heart Association, and the American Diabetes Association. He has published over 75 peer-reviewed manuscripts. This research work has been cited in excess of 2300 times and published in Nature Chemical Biology, Science Translational Medicine, Nature Reviews in Cardiology, The Journal of Clinical Investigation, Circulation, Circulation Research, Journal of the American College of Cardiology, Diabetes and others. Dr. Bruemmer has been the recipient of multiple national and international investigator awards, including the Young Scholars Award of the American Society of Hypertension, the Young Investigator Award in Basic Sciences of the European Society of Cardiology, the Endocrine Society Young Investigator Award, the Merit Award for Young Investigators of the American Heart Association’s Council on Arteriosclerosis, Thrombosis, and Vascular Biology, a Career Development Award from the American Diabetes Association, andthe Irvine H. Page Award from the American Heart Association.


Research Interests

Dr. Bruemmer’s research interest is focused on basic investigation of mechanisms underlying vascular remodeling during atherosclerosis, aneurysm, and neointima formation. As detailed below, Dr. Bruemmer’s laboratory is currently focusing on the role of telomerase and telomere attrition in cardiovascular disease and diabetes. Specifically, he is interested to determine the mechanisms by which telomerase affects transcriptional programs during tissue remodeling. Over the past decade, Dr. Bruemmer’s laboratory has made the following observations:

1) Transcriptional Control of Vascular Remodeling by Nuclear Receptors

Dr. Bruemmer’s previous research identified novel mechanisms of gene expression during cardiovascular disease development. He characterized transcriptional programs by which the nuclear hormone receptors PPARg, LXRa/b, and NOR1 modulate cell proliferation and inflammatory responses during atherosclerosis and neointima formation (Bruemmer, et al. Circ Res 2003; Blaschke, et al. Circ Res 2004; Nomiyama, et al. JBC 2006; Gizard, et al. JBC 2011). The latter member of this family of transcription factors NOR1 had been of particular interest due to its important function to regulate myelopoiesis, monocyte adhesion, and macrophage inflammation (Nomiyama, et al. Circulation 2009; Zhao, et al. Circ Res 2010; Qing, et al. Stem Cells 2014). The analysis of the transcriptional mechanisms, by which these receptors modulate gene activation during disease formation led to the discovery of several novel target genes in vascular cells encoding proteins involved in the regulation of transcription, replication, the cell cycle, senescence and apoptosis, as well as cytokines and matrix proteins.

2) Osteopontin in Vascular Biology and Diabetes

Among the downstream target genes regulated by nuclear receptors, Dr. Bruemmer’s research has initially focused on Osteopontin and more recently on Telomerase. Dr. Bruemmer has demonstrated that Osteopontin is transcriptionally repressed by several nuclear receptors (Ogawa, et al. Circ Res 2005 and Nakamachi, et al. Diabetes 2007). Mechanistic experiments further discovered that Osteopontin deficiency protects from atherosclerosis, aneurysm formation, and diabetes development (Bruemmer, et al. JCI 2003 and Nomiyama, et al. JCI 2007). He has further characterized Osteopontin as chemoattractant for monocytes that mediates infiltration into the arterial wall and adipose tissue inflammation during atherosclerosis formation and insulin resistance, respectively. This research on Osteopontin has been cited in excess of 700 times and reproduced by various research groups in more than 20 independent manuscripts.

3) Telomerase in Vascular Biology and Diabetes

The observation that Telomerase is transcriptionally regulated by nuclear receptors has led to the inclusion of Telomerase into Dr. Bruemmer’s research program. Owing to its activity to maintain the stability of telomeres, DNA-protein complexes that protect the ends of chromosomes, telomerase is rate limiting for tissue renewal. In addition to this telomere maintenance function, mounting evidence suggests that telomerase exhibits a direct regulatory role in the activation of gene expression programs. While most adult cells display low basal telomerase expression, telomerase is inducible during tissue remodeling to support key cellular functions. Dr. Bruemmer has previously characterized the transcriptional mechanisms for telomerase expression in various vascular cell types and diseases, including atherosclerosis and neointima formation (Ogawa, et al. Circ Res 2006; Gizard, et al. Circ Res 2008; Gizard, et al. ATVB 2011). Based on these observations, his laboratory is currently investigating the significance of telomerase expression for vascular disease development. These studies have highlighted a previously unrecognized role of telomerase to support inflammatory and mitogenic signaling events during vascular remodeling (Findeisen, et al. ATVB 2011, Aono, et al. JACC: Basic to Translational Science 2016).


Publications

View a complete list of Dr. Bruemmer’s publications on Google Scholar or Pubmed.

Bruemmer D, Yin F, Liu J, Berger JP, Kiyono T, Chen J, Fleck E, Van Herle A, Forman BM, Law RE. Peroxisome Proliferator-activated Receptorg Inhibits Expression of Minichromosome Maintenance Proteins in Vascular Smooth Muscle Cells. Mol Endocrinol. 2003; 17:1005-18. PMID 12677008.

Bruemmer D, Yin F, Liu J, Berger JP, Sakai T, Blaschke F, Fleck E, Van Herle AJ, Forman BM, Law RE. Regulation of the growth arrest and DNA damage-inducible gene 45 (GADD45) by Peroxisome Proliferator-activated Receptorg in Vascular Smooth Muscle Cells. Circ Res. 2003; 93:38-47. PMID 12881480.

Bruemmer D, Collins AR, Noh G, Wang W, Territo M, Arias-Magallona S, Fishbein MC, Blaschke F, Kintscher U, Graf K, Law RE, Hsueh WA. Angiotensin II Accelerated Atherosclerosis is Attenuated in Osteopontin Deficient Mice. J Clin Invest. 2003; 112:1318-31. PMID 14597759. PMC228408.

Blaschke F, Leppaenen O, Takata Y, Caglayan E, Liu J, Fishbein MC, Kappert K, Nakayama K, Fleck E, Hsueh WA, Law RE, Bruemmer D. Liver X Receptor Agonists suppress Vascular Smooth Muscle Cell Proliferation and inhibit Neointima Formation in balloon-injured Rat Carotid Arteries. Circ Res. 2004, 95(12):e110-23. PMID 15539633.

Ogawa D, Stone JF, Takata Y, Blaschke F, Chu VH, Towler DA, Law RE, Hsueh WA, Bruemmer D. Liver X Receptor Agonists inhibit cytokine-induced Osteopontin Expression in Macrophages through Interference with Activator Protein-1 Signaling Pathways. Circ Res. 2005, 96:59-67. PMID 15790955.

Ogawa D, Nomiyama T, Nakamachi T, Heywood EB, Stone JF, Berger JP, Law RE, Bruemmer D. Activation of peroxisome proliferator-activated receptor gamma suppresses telomerase activity in vascular smooth muscle cells. Circ Res. 2006 Apr 14;98(7):e50-9. PMID 16556873.

Nomiyama T, Nakamachi T, Gizard F, Heywood EB, Jones KL, Ohkura N, Kawamori R, Conneely OM, Bruemmer D. The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle cell proliferation. J Biol Chem. 2006 Aug 31; 281(44):33467-76. PMID 16945922. PMC1829169.

Nakamachi T, Nomiyama T, Gizard F, Heywood EB, Jones KL, Zhao Y, Fuentes L, Takebayashi K, Aso Y, Staels B, Inukai T, Bruemmer D. PPARa Agonists suppress Osteopontin Expression in Macrophages and decrease Plasma Levels in Patients with Type 2 Diabetes. Diabetes 2007; 56:1662-1670. PMID 17360982.

Nomiyama T, Perez-Tilve D, Ogawa D, Gizard F, Zhao Y, Heywood EB, Jones KL, Kawamori R, Cassis LA, Tschoep M, Bruemmer D. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J Clin Invest. 2007; 117:2877-88. PMID 17823662. PMC1964510.

Gizard F, Nomiyama T, Zhao Y, Findeisen HM, Heywood EB, Jones KL, Staels B, Bruemmer D. The PPAR[alpha]/p16INK4a Pathway inhibits Vascular Smooth Muscle Cell Proliferation by repressing Cell-Cycle-dependent Telomerase Activation. Circ Res. 2008; 103: 1155-63. PMID 18818403. PMC2756491.

Nomiyama T, Zhao Y, Gizard F, Findeisen HM, Heywood EB, Jones KL, Conneely OM, Bruemmer D. Deficiency of the NR4A Orphan Nuclear Receptor NOR1 attenuates Neointima Formation Following Vascular Injury. Circulation 2009; 119: 577-86. PMID 19153266. PMC2748681.

Zhao Y, Bruemmer D. NR4A orphan nuclear receptors: transcriptional regulators of gene expression in metabolism and vascular biology. Arterioscler Thromb Vasc Biol. 2010 Aug;30(8):1535-4. PMID 20631354. PMC2907171.

Zhao Y, Howatt DA, Gizard F, Nomiyama T, Findeisen HM, Heywood EB, Jones KL, Conneely OM, Daugherty A, Bruemmer D. Deficiency of the NR4A Orphan Nuclear Receptor NOR1 Decreases Monocyte Adhesion and Reduces Atherosclerosis in Mice. Circ Res. 2010;107(4):501-11.    PMID 20558821. PMC2924939.  

Brown A, Reynolds LR, Bruemmer D. Intensive Glycemic Control and Cardiovascular Disease: Lessons from Recent Intervention Trials. Nat Rev Cardiol. 2010 Jul;7(7):369-75. PMID 20404853.

Gizard F, Heywood EB, Findeisen HM, Zhao Y, Jones KL, Cudejko C, Post GR, Staels B, Bruemmer D. Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages. Arterioscler Thromb Vasc Biol. 2011; 31:245. PMID 21106948. PMC3025413.

Findeisen HM, Gizard F, Zhao Y, Cohn D, Heywood EB, Jones KL, Lovett DH, Howatt DA, Daugherty A, Bruemmer D. Telomerase Deficiency in Bone Marrow-Derived Cells Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation. Arterioscler Thromb Vasc Biol. 2011; 31:253. PMID 21088250. PMC3025410.

Findeisen HM, Gizard F, Zhao Y, Heywood EB, Jones KL, Cohn D, Bruemmer D. Epigenetic Regulation of Vascular Smooth Muscle Cell Proliferation and Neointima Formation by Histone Deacetylase InhibitionArterioscler Thromb Vasc Biol 2011;31:851. PMID 21233448. PMC3074344.

Gizard F, Zhao Y, Findeisen HM, Qing H, Cohn D, Heywood EB, Jones KL, Nomiyama T, Bruemmer D. Transcriptional regulation of the S-Phase kinase-associated protein 2 by the NR4A orphan nuclear receptor NOR1 in vascular smooth muscle cells. J Biol Chem. 2011; 286(41):35485-93. PMID 21868379. PMC3195596.

Bruemmer D. Targeting angiogenesis as treatment for obesity. Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):161-2. PMID 22258895.

Kahles F, Findeisen HM, Bruemmer D. Osteopontin: A Novel Regulator at the Cross Roads of Inflammation, Obesity, and Diabetes. Molecular Metabolism 2014; 3:384-93. PMID 24944898. PMC4060362.

Qing H, Liu Y, Zhao Y, Aono J, Jones KL, Heywood EB, Howatt D, Binkley CM, Daugherty A, Liang L, Bruemmer D. Deficiency of the NR4A Orphan Nuclear Receptor NOR1 in Hematopoietic Stem Cells Accelerates Atherosclerosis by Increasing Progenitor Cell Proliferation. Stem Cells 2014;32:2419-29. PMID 24806827. PMC4138236.

Aono J, Ruiz-Rodriguez E, Qing H, Findeisen HM, Jones KL, Heywood EB, Bruemmer D. Telomerase Inhibition Suppresses Smooth Muscle Cell Proliferation and Neointima Formation Through Epigenetic Gene Silencing. J Am Coll Cardiol (Basic to Translational Science) 2016 (in press).

Pubmed link