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Raul A. Dela Cadena, MDRaul A. Dela Cadena, MD

 

Assistant Dean, Recruitment and Retention

Professor, Physiology

Professor, Sol Sherry Thrombosis Research Center

Telephone:  215-707- 3595

Fax:  215-707-3597

Email: cadena@temple.edu

 

Department of Physiology

Sol Sherry Thrombosis Research Center

 

Educational Background:

 

MD, LaSalle School of Medicine, Mexico City, MX, 1984

 

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Research Interests:

 

My research interest is related to coagulation and inflammation and I have selected to study Rheumatoid Arthritis (RA) since it is an autoimmune disease that affects more than 2 million adults in the United States and is associated with activation of monocytes and neutrophils as well as with components of the coagulation and fibrinolytic systems. The onset of the disease (RA) generally occurs between 30-55 years of age, being more prominent in women. The pathophysiology of RA is comprised of several events initially characterized by infiltration of the periarticular space by neutrophils, lymphocytes and monocytes resulting in severe inflammation at the synovial lining. Biologic therapy for rheumatoid arthritis (RA) targets specific molecules that mediate and sustain the clinical manifestations of this complex illness. Compared with the general population, patients with RA die prematurely, in part due to associated cardiovascular disease.  Even though the mechanisms by which premature atherosclerosis develops in RA is unknown, chronic inflammation may play a major role.

 

Over a decade of research in my laboratory including work with cell lines, an animal model of erosive arthritis, patients afflicted with RA has allowed my laboratory to propose a pro-inflammatory axis comprised of three molecules that we believe play a major role in the pathophysiology or RA. The three molecules are thrombospondin-1 (TSP1), transforming growth factor beta (TGFß) and connective tissue growth factor (CTGF). The TSP1/TGFß/CTGF axis may contribute in the pro-inflammatory and pro-atherogenic state in patients affected with RA. In fact, increased TSP1 plasma levels are found in patients of RA. TGFß is activated by TSP1 through a non-enzymatic mechanism and is constitutively overexpressed by synovial fibroblasts from RA patients. Activation of TGFß pathway in synovial fibroblasts and other cells including neutrophils leads to downstream upregulation of CTGF. Overexpression of CTGF is associated with angiogenesis, fibrosis, atherosclerotic blood vessels and erosive arthritis lesions. Recent RA therapies emphasize the need for aggressive control of the activity of the disease to prevent premature atherosclerosis in RA patients. The complexity and heterogeneity of RA as judged by response to a wide spectrum of treatments mandates the elucidation of unknown pro-inflammatory pathways playing a major role in this disease. The TSP1/TGFβ/CTFG axis represents one of these pro-inflammatory pathways that may result in the development of promising therapeutic strategies to prevent chronic inflammation and thus premature atherosclerosis in RA.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24286015. Del Carpio-Cano FE, Dela Cadena RA, Sawaya BE, HIV and Bone Disease: A Perspective of the Role of microRNAs in Bone Biology upon HIV Infection. J Osteoporos 2013:(571418)2013

23861957. Garcia AE, Rico MC, Liverani E, DeLa Cadena RA, Bray PF, Kunapuli SP, Erosive arthritis and hepatic granuloma formation induced by peptidoglycan polysaccharide in rats is aggravated by prasugrel treatment. PLoS One 8:7(e69093)2013

22080699. Viera E, Colón D, Alonso Y, Armas J, Rico MC, Diaz R, Pagan A, Del Carpio-Cano F, DeLa Cadena RA, Improving patient provider communication for Latinos at Temple University Hospital and Temple University School of Medicine. J Health Care Poor Underserved 22:4(1144-50)2011 Nov

22028806. Garcia AE, Mada SR, Rico MC, Dela Cadena RA, Kunapuli SP, Clopidogrel, a P2Y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritis. PLoS One 6:10(e26035)2011

21889790. Rico MC, Rough JJ, Manns JM, Del Carpio-Cano F, Safadi FF, Kunapuli SP, DeLa Cadena RA, Assembly of the prothrombinase complex on the surface of human foreskin fibroblasts: Implications for connective tissue growth factor. Thromb Res 129:6(801-6)2012 Jun

21302290. Arosarena OA, Del Carpio-Cano FE, Dela Cadena RA, Rico MC, Nwodim E, Safadi FF, Comparison of bone morphogenetic protein-2 and osteoactivin for mesenchymal cell differentiation: effects of bolus and continuous administration. J Cell Physiol 226:11(2943-52)2011 Nov

19485899. Rico MC, Rough JJ, Del Carpio-Cano FE, Kunapuli SP, DeLa Cadena RA, The axis of thrombospondin-1, transforming growth factor beta and connective tissue growth factor: an emerging therapeutic target in rheumatoid arthritis. Curr Vasc Pharmacol 8:3(338-43)2010 May

18674744. Rico MC, Manns JM, Driban JB, Uknis AB, Kunapuli SP, Dela Cadena RA, Thrombospondin-1 and transforming growth factor beta are pro-inflammatory molecules in rheumatoid arthritis. Transl Res 152:2(95-8)2008 Aug

17219411. Rico MC, Castaneda JL, Manns JM, Uknis AB, Sainz IM, Safadi FF, Popoff SN, Dela Cadena RA, Amelioration of inflammation, angiogenesis and CTGF expression in an arthritis model by a TSP1-derived peptide treatment. J Cell Physiol 211:2(504-12)2007 May

16869004. Manns JM, Uknis AB, Rico MC, Agelan A, Castaneda J, Arango I, Barbe MF, Safadi FF, Popoff SN, DeLa Cadena RA, A peptide from thrombospondin 1 modulates experimental erosive arthritis by regulating connective tissue growth factor. Arthritis Rheum 54:8(2415-22)2006 Aug

16181989. Isordia-Salas I, Manns JM, Sainz I, Parekh H, DeLa Cadena RA, Thromsbospondin-1 binds to the heavy chain of elastase activated coagulation factor V (FVaHNE) and enhances thrombin generation on the surface of a promyelocytic cell line. Thromb Res 116:6(533-43)2005

16059911. Sainz IM, Isordia-Salas I, Castaneda JL, Agelan A, Liu B, DeLa Cadena RA, Pixley RA, Adam A, Sartor RB, Colman RW, Modulation of inflammation by kininogen deficiency in a rat model of inflammatory arthritis. Arthritis Rheum 52:8(2549-52)2005 Aug

15331420. Espinola RG, Uknis A, Sainz IM, Isordia-Salas I, Pixley R, DeLa Cadena R, Long W, Agelan A, Gaughan J, Adam A, Colman RW, A monoclonal antibody to high-molecular weight kininogen is therapeutic in a rodent model of reactive arthritis. Am J Pathol 165:3(969-76)2004 Sep

15001555. Sainz IM, Uknis AB, Isordia-Salas I, Dela Cadena RA, Pixley RA, Colman RW, Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan-polysaccharide (PG-PS)-induced arthritis. FASEB J 18:7(887-9)2004 May

11339503. Uknis AB, DeLa Cadena RA, Janardham R, Sartor RB, Whalley ET, Colman RW, Bradykinin receptor antagonists type 2 attenuate the inflammatory changes in peptidoglycan-induced acute arthritis in the Lewis rat. Inflamm Res 50:3(149-55)2001 Mar

11039850. Majluf-Cruz A, Manns JM, Uknis AB, Yang X, Colman RW, Harris RB, Frazier W, Lawler J, DeLa Cadena RA, Residues F16-G33 and A784-N823 within platelet thrombospondin-1 play a major role in binding human neutrophils: evaluation by two novel binding assays. J Lab Clin Med 136:4(292-302)2000 Oct

9926286. Colman RW, Sartor RB, Adam AA, DeLa Cadena RA, Stadnicki A, The plasma kallikrein-kinin system in sepsis, inflammatory arthritis, and enterocolitis. Clin Rev Allergy Immunol 16:4(365-84)1998 Winter

9798662. Kaplan R, DeLa Cadena RA, Mechanism of the coagulopathy associated with acute promyelocytic leukemia -clinical conference-. Am J Hematol 59:3(234-7)1998 Nov

9684796. DeLa Cadena RA, Majluf-Cruz A, Stadnicki A, Tropea M, Reda D, Agosti JM, Colman RW, Suffredini AF, Recombinant tumor necrosis factor receptor p75 fusion protein (TNFR:Fc) alters endotoxin-induced activation of the kinin, fibrinolytic, and coagulation systems in normal humans. Thromb Haemost 80:1(114-8)1998 Jul

9459346. DeLa Cadena RA, Kunapuli SP, Walz DA, Colman RW, Expression of thrombospondin 1 on the surface of activated platelets mediates their interaction with the heavy chains of human kininogens through Lys 244-Pro 254. Thromb Haemost 79:1(186-94)1998 Jan

9428707. Selim TE, Ghoneim HR, Uknis AB, Colman RW, DeLa Cadena RA, High-molecular-mass and low-molecular-mass kininogens block plasmin-induced platelet aggregation by forming a complex with kringle 5 of plasminogen/plasmin. Eur J Biochem 250:2(532-8)1997 Dec 1

9398817. Stadnicki A, Gonciarz M, Niewiarowski TJ, Hartleb J, Rudnicki M, Merrell NB, Dela Cadena RA, Colman RW, Activation of plasma contact and coagulation systems and neutrophils in the active phase of ulcerative colitis. Dig Dis Sci 42:11(2356-66)1997 Nov

9269768. Bradford HN, Dela Cadena RA, Kunapuli SP, Dong JF, Löpez JA, Colman RW, Human kininogens regulate thrombin binding to platelets through the glycoprotein Ib-IX-V complex. Blood 90:4(1508-15)1997 Aug 15

8856173. Stadnicki A, DeLa Cadena RA, Sartor RB, Kettner CA, Colman RW, The contact system in experimental enterocolitis. Immunopharmacology 33:1-3(314-6)1996 Jun

8856155. DeLa Cadena RA, Majluf-Cruz A, Stadnicki A, Agosti JM, Colman RW, Suffredini AF, Activation of the contact and fibrinolytic systems after intravenous administration of endotoxin to normal human volunteers: correlation with the cytokine profile. Immunopharmacology 33:1-3(231-7)1996 Jun

8626672. Kunapuli SP, Bradford HN, Jameson BA, DeLa Cadena RA, Rick L, Wassell RP, Colman RW, Thrombin-induced platelet aggregation is inhibited by the heptapeptide Leu271-Ala277 of domain 3 in the heavy chain of high molecular weight kininogen. J Biol Chem 271:19(11228-35)1996 May 10

8796272. Colman RW, Bradford HN, Kunapuli SP, DeLa Cadena RA, Rick L, Jameson BA, Wassell RP, Leu271-Glu292 in kininogens blocks thrombin-induced aggregation. Immunopharmacology 32:1-3(80-1)1996 May

8625762. Stadnicki A, DeLa Cadena RA, Sartor RB, Bender D, Kettner CA, Rath HC, Adam A, Colman RW, Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in Lewis rat. Dig Dis Sci 41:5(912-20)1996 May

7717377. DeLa Cadena RA, Fletcher factor deficiency in a 9-year-old girl: mechanisms of the contact pathway of blood coagulation. Am J Hematol 48:4(273-7)1995 Apr

7896018. Dela Cadena RA, Stadnicki A, Uknis AB, Sartor RB, Kettner CA, Adam A, Colman RW, Inhibition of plasma kallikrein prevents peptidoglycan-induced arthritis in the Lewis rat. FASEB J 9:5(446-52)1995 Mar

8034694. Wachtfogel YT, DeLa Cadena RA, Kunapuli SP, Rick L, Miller M, Schultze RL, Altieri DC, Edgington TS, Colman RW, High molecular weight kininogen binds to Mac-1 on neutrophils by its heavy chain (domain 3) and its light chain (domain 5). J Biol Chem 269:30(19307-12)1994 Jul 29

7974360. DeLa Cadena RA, Wyshock EG, Kunapuli SP, Schultze RL, Miller M, Walz DA, Colman RW, Platelet thrombospondin interactions with human high and low molecular weight kininogens. Thromb Haemost 72:1(125-31)1994 Jul

7947259. Page JD, DeLa Cadena RA, Humphries JE, Colman RW, An autoantibody to human plasma prekallikrein blocks activation of the contact system. Br J Haematol 87:1(81-6)1994 May

8122183. Wachtfogel YT, DeLa Cadena RA, Colman RW, Structural biology, cellular interactions and pathophysiology of the contact system. Thromb Res 72:1(1-21)1993 Oct 1

7685203. DeLa Cadena RA, Suffredini AF, Page JD, Pixley RA, Kaufman N, Parrillo JE, Colman RW, Activation of the kallikrein-kinin system after endotoxin administration to normal human volunteers. Blood 81:12(3313-7)1993 Jun 15

8428925. Kunapuli SP, DeLa Cadena RA, Colman RW, Deletion mutagenesis of high molecular weight kininogen light chain. Identification of two anionic surface binding subdomains. J Biol Chem 268:4(2486-92)1993 Feb 5

1373271. Pixley RA, DeLa Cadena RA, Page JD, Kaufman N, Wyshock EG, Colman RW, Chang A, Taylor FB Jr, Activation of the contact system in lethal hypotensive bacteremia in a baboon model. Am J Pathol 140:4(897-906)1992 Apr

1631790. Kunapuli SP, DeLa Cadena RA, Colman RW, Bacterial expression of biologically active high molecular weight kininogen light chain. Thromb Haemost 67:4(428-33)1992 Apr 2

1309001. DeLa Cadena RA, Sartor RB, Adam A, Raymond B, Legris F, Colman RW, Role of kallikrein-kinin system in the pathogenesis of bacterial cell wall-induced inflammation and enterocolitis. Trans Assoc Am Physicians 105:(229-37)1992

1304876. DeLa Cadena RA, Colman RW, The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc-dependent binding to an anionic surface. Protein Sci 1:1(151-60)1992 Jan

1949192. DeLa Cadena RA, Colman RW, Structure and functions of human kininogens. Trends Pharmacol Sci 12:7(272-5)1991 Jul

1996642. DeLa Cadena RA, Laskin KJ, Pixley RA, Sartor RB, Schwab JH, Back N, Bedi GS, Fisher RS, Colman RW, Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation. Am J Physiol 260:2 Pt 1(G213-9)1991 Feb

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