Center of Excellence on Aging Prof. Carlo Patrono, “G. d’Annunzio” University Foundation, [email protected] Abstract - The Center of Excellence on Aging (CEA) was established in 2002 with the aim of focusing multidisciplinary research efforts at the University of Chieti on the aging process. Three main areas are being investigated at CEA: cardiovascular disease, cancer and neurodegenerative disorders. Each area is targeted with aging-related research projects, by integrating basic and clinical research in a 13.500 m2 dedicated research Keywords
building (Ce.S.I.) built with a €28.5 million grant from MURST to the University of Chieti. Ce.S.I. has 4.400 m2 of basic research labs, 4.400 m2 of
clinical research space including a General Clinical Research Center (GCRC) with 30 beds and 4.700 m2 of centralized facilities and administrativeoffices. Ce.S.I. is endowed with €11 million worth of state-of-the-art instruments and special equipment, including core facilities [eg proteomics,
genomics]. Ce.S.I. is interfaced with the Institute of Advanced Biomedical Technology (ITAB) and with the University Hospital within the sameCampus. ITAB is a 5.000 m2 core facility co-funded by the University of Chieti and the European Union and devoted to basic and clinical research
on brain imaging. ITAB is endowed with €9 million high-end instrumentation for functional neuroimaging including core facilities such as EEG-fMRI, MEG, HDEEG, NIRS, EEG-TMS. Research space within Ce.S.I. has been allocated on a competitive basis to basic and clinical research
groups working at the University of Chieti, with the aim of focusing multidisciplinary research efforts on the aging process. Research labs withoutdepartmental boundaries allow cross-fertilization of research ideas and methodologies from different disciplines, and allow cost-containment through
Alzheimer’s & Parkinson’s Disease
space- and time-sharing of costly facilities. Co-localization of basic and clinical research in one dedicated building allows synergistic interactions
between the two, with the ultimate goal of developing and testing research-based diagnostic and treatment paradigms for the elderly. Major achievements: Approx 100 publications with Impact Factor ≥ 10; 8 Patents; 10 International Projects: FP5-EUCIP (European Cancer Immunome Database) 2000-2003 FP5-FIHBO (Functional Imaging of the Human Body) 2003-2005 FP6-IBSEN (Investigation in Brain Sciences and Educational Network) 2005-2007 NIH (Oxidative Damage, Platelet Activation, and Inflammation to Predict Morbility Disability and Mortality) 2005-2008 FP6-EICOSANOX (Eicosanoids and Nitric Oxide: Mediators of Cardiovascular, Cerebral & Neoplastic Diseases) 2005-2009 FP7-BRAINSYNCH (Large Scale Interactions in Brain Network and their Breakdown in Brain Disease) 2008-2011 FP7-EUCAAD (European Consortium for Anticancer Antibody Development) 2008-2012 FP7-MEGMRI (Hybrid MEG-MRI Imaging System) 2008-2012 FP7- IMI SUMMIT (Innovative Medicine Initiative, SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) 2010-2014 NIH (Human Connectome Project) 2010-2015
The Cardiovascular Area consists of 11 Research Units,
The Cancer Area consists of 6 Research Units, that study
The Neurodegenerative Disorders Area consists of 8
studying age-related disease mechanisms and determinants of
molecular mechanisms controlling cell proliferation,
vascular disease and its atherothrombotic complications.
aging and cell death in cancer. Other key fields of
conditions of the aging human brain. Basic studies include
research include: (a) the study of immunity to block the
characterization of brain networks and of the human mirror
1. Mechanisms of vascular disease and insulin resistance in
progression of cancer; (b) genetic and regulatory
system. Investigation on Neurodegenerative Disorders
mechanisms of tumor cell growth and metastasization; (c)
include in vitro and animal studies, as well as clinical
2. Role of eicosanoids and their pharmacologic modulation in
studies on identification of predictive parameters based on
models of cancer; (d) prognostic - predictive markers,
3. Platelet activation and inhibition in atherothrombosis.
including genetic mutations, for personalized tumor
neuroimaging, behavioral patterns in stroke, AD and other
therapy; (e) development of targeting antibodies as novel
About 60 PhD students and 20 post-docs are annually
cyclooxygenase-2. N Engl J Med 2001;345:433-42.
targeting biologically relevant signal molecules.
engaged in research projects of this area.
2.Patrono C, Patrignani P, García Rodríguez LA. Cyclooxygenase-selective
1.Migliazza A, et al. Nucleotide sequence, transcription map, and
inhibition of prostanoid formation: transducing biochemical selectivity into
mutation analysis of the 13q14 chromosomal region deleted in B-cell
clinical read-outs. J Clin Invest 2001;108:7-13.
endocannabinoid inactivation. PNAS USA 2002;99:10819-24.
chronic lymphocytic leukemia. Blood 2001;97:2098-104.
3.Davì G, et al. Platelet activation in obese women: role of inflammation and
2.Sensi SL, et al. Modulation of mitochondrial function by endogenous
2.Di Pietro R, et al. Ionizing radiation sensitizes erythroleukemic cells
oxidant stress. JAMA 2002; 288:2008-14.
Zn2+ pools. PNAS USA 2003;100:6157-62.
but not normal erythroblasts to tumor necrosis factor-related apoptosis-
4.Rocca B, et al. Cyclooxygenase-2 expression is induced during human
3.Rossini PM, et al. Does cerebrovascular disease affect the coupling
inducing ligand (TRAIL)--mediated cytotoxicity by selective up-
megakaryopoiesis and characterizes newly formed platelets. PNAS USA
regulation of TRAIL-R1. Blood 2001;97:2596-603.
3.Nanni P, et al. Combined allogeneic tumor cell vaccination and
4.Caulo M, et al. Functional MRI study of diencephalic amnesia in
5.De Caterina R, Zampolli A. 5-lipoxygenase and inflammation: from asthma
systemic IL-12 prevents mammary carcinogenesis in HER-2/neu
Wernicke-Korsakoff syndrome. Brain 2005;128:1584-94.
to atherosclerosis. N Engl J Med 2004;350:4-7.
transgenic mice. J Exp Med 2001;194:1195-205.
5.Babiloni C, et al. Apolipoprotein E and alpha brain rhythms in mild
6.Landolfi R, et al. European Collaboration on Low-Dose Aspirin in
4.Di Carlo E, et al. The intriguing role of polymorphonuclear
cognitive impairment: a multicentric electroencephalogram study. Ann
Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in
neutrophils in antitumor reactions. Blood 2001;97:339-45. Neurol 2006;59:323-34.
polycythemia vera. N Engl J Med 2004; 350:114-24.
5.Buttitta F, et al. Human telomerase reverse transcriptase mRNA
6.Committeri G, et al. Neural bases of personal and extrapersonal neglect
7.Federici M, et al. G972R IRS-1 variant impairs insulin regulation of
expression assessed by real-time reverse transcription polymerase chain
in humans. Brain 2007;130:431-41.
endothelial nitric oxide synthase in cultured human endothelial cells.
reaction predicts chemosensitivity in patients with ovarian carcinoma. J
7.Del Boccio, et al. Cleavage of cystatin C is not associated with multiple
Circulation 2004;109:399-405. Clin Oncol 2003; 21:1320-5.
sclerosis. Ann Neurol 2007;62:201-204.
8.Patrono C, Garcia Rodriguez LA, Landolfi R, et al. Low-dose aspirin for the
6.Boss P, et al. IL-18 cDNA vaccination protects mice from
8.Mantini D, et al. Electrophysiological signatures of resting state
prevention of atherothrombosis. N Engl J Med 2005; 353:2373-83.
networks in the human brain. PNAS USA 2007;104:13170-5.
9.Kearney PM, et al. Do selective cyclo-oxygenase-2 inhibitors and traditional
9.Urgesi C, et al. Representation of body identity and body actions in
non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis?
7.Curcio C, et al. Nonredundant roles of antibody, cytokines, and
extrastriate body area and ventral premotor cortex. Nature Neurosci
Meta-analysis of randomised trials. BMJ 2006;332:1302-8.
perforin in the eradication of established Her-2/neu carcinomas. J Clin
10.Evangelista V, et al. De novo synthesis of cyclooxygenase-1 counteracts
10. Tosoni A, et al. Sensory-motor mechanisms in human parietal cortex
the suppression of platelet thromboxane biosynthesis by aspirin. Circ Res
underlie arbitrary visual decisions. Nature Neurosci 2008;11:1446-53.
pharmacological developments in antitumor activity and cardiotoxicity.
11. Dobrowolny G, et al. Skeletal muscle is a primary target of
11.Patrignani P, et al. Reduced thromboxane biosynthesis in carriers of toll-
Pharmacol Rev 2004;56:185-229.
SOD1G93A-mediated toxicity. Cell Metab 2008;8:425-36.
like receptor 4 polymorphisms in vivo. Blood 2006;107:3572-4.
9.Quaglino E, et al. Concordant morphologic and gene expression data
12. Durham WJ, et al. RyR1 S-nitrosylation underlies environmental heat
12.The ACTIVE Writing Group on behalf of the Active Investigators.
show that a vaccine halts HER-2/neu preneoplastic lesions. J Clin
stroke and sudden death in Y522S RyR1 knockin mice. Cell
Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in
the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of
10.Finazzi G, et al. Acute leukaemia in polycythemia vera: an analysis
13. Bonanni L, et al. EEG comparisons in early Alzheimer's disease,
Vascular Events (ACTIVE W): a randomised controlled trial. Lancet
of 1,638 patients enrolled in a prospective observational study. Blood
dementia with Lewy bodies and Parkinson's disease with dementia
patients with a 2-year follow-up. Brain 2008;131:690-705.
13.Massaro M, et al. The omega-3 fatty acid docosahexaenoate attenuates
11.De Santo C, et al. Nitroaspirin corrects immune dysfunction in
14. Sensi SL, et al. Zinc in the physiology and pathology of the CNS.
endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and
tumor-bearing hosts and promotes tumor eradication by cancer
Nature Rev Neurosci 2009;10:780-91.
PKC epsilon inhibition. PNAS USA 2006;103:15184-9.
vaccination. PNAS USA 2005;102:4185-90.
15. Boncompagni S, et al. Characterization and temporal development of
14.Prontera C, et al. Homocysteine modulates the CD40/CD40L system. J Am
12.Chiaretti S, et al. ZAP-70 expression in acute lymphoblastic
cores in a mouse model of malignant hyperthermia. PNAS USA Coll Cardiol 2007;49:2182-90.
leukemia: association with the E2A/PBX1 rearrangement and the pre-B
15.Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J
16. Zatta P, et al. Alzheimer's disease, metal ions and metal homeostatic
therapy. Trends Pharmacol Sci 2009;30:346-55.
16.Santilli F, et al. Circulating endothelial progenitor cells and residual in vivo
13.Holmgren L, et al. A DNA vaccine targeting angiomotin inhibits
17. Lewis CM, et al. Learning sculpts the spontaneous activity of the
thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera
resting human brain. PNAS USA 2009;106:17558-63.
patients. Blood 2008; 112:1085-90.
18. De Pasquale F, et al. Temporal dynamics of spontaneous MEG
17.Antithrombotic Trialists' (ATT) Collaboration. Aspirin in the primary and
activity in brain networks. PNAS USA 2010;107:6040-5.
14.Chiodoni C, et al. Triggering CD40 on endothelial cells contributes
secondary prevention of vascular disease: collaborative meta-analysis of
19. Cirstea IC, et al. A restricted spectrum of NRAS mutations causes
to tumor growth. J Exp Med 2006;203:2441-50.
individual participant data from randomised trials. Lancet. 2009;373:1849-60.
Noonan syndrome. Nature Genet 2010;42:27-9.
15.Airoldi I, et al. Endogenous IL-12 triggers an antiangiogenic
18.Di Francesco L, et al. Induction of prostacyclin by steady laminar shear
20. Palty R, et al. NCLX is an essential component of mitochondrial
program in melanoma cells. PNAS USA 2007;104:3996-4001.
stress suppresses tumor necrosis factor-alpha biosynthesis via heme
Na+/Ca2+ exchange. PNAS USA 2010;107:436-41.
16.Bianchi F, et al. Survival prediction of stage I lung adenocarcinomas
oxygenase-1 in human endothelial cells. Circ Res 2009;104:506-13.
21. Thomas A, et al. Pathological gambling in Parkinson disease is
by expression of 10 genes. J Clin Invest 2007;117:3436-44.
19.Dragani A, et al. The contribution of cyclooxygenase-1 and -2 to persistent
17.Ugel S, et al. Autoimmune B-cell lymphopenia after successful
reduced by amantadine. Ann Neurol 2010 Mar 23. [Epub ahead of
thromboxane biosynthesis in aspirin-treated essential thrombocythemia:
adoptive therapy with telomerase-specific T lymphocytes. Blood
implications for antiplatelet therapy. Blood 2010;115:1054-61. Dr Francesca Santilli (University of Chieti) under the supervision of Professor Carlo Patrono
Scott VanAppledorn, MD Eastside Urology Associates, PS 11911 NE 132nd St. Ste #200 Kirkland, Washington 98034 (425) 899-5800 e-mail: [email protected] DOB: December 7, 1969 Place of birth: Ann Arbor, Michigan Personal: Married (Samantha) with three children (Alexandra, John, Andrew) Professional Interests: Laparoscopy, Robotic Surgery, Minimally Invasive Surgery Cu
UNIVERSITY OF LOUISVILLE’S TWENTIETH ANNUAL CARL A. WARNS, JR. LABOR AND EMPLOYMENT LAW INSTITUTE June 12-13, 2003 Proposed Amendment to the Americans With Disabilities Act Mark S. Dichter Morgan, Lewis & Bockius LLP 1701 Market Street Philadelphia, PA 19103-2921 (215) 963-5291 Sharon A. Lisitzky Morgan, Lewis & Bockius LLP 5300 Wachovia Financial Center 200 South