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MariaPilar Alcaide Alonso, PhD


Overview

Research Interests The main focus of my laboratory is to study the molecular and cellular mechanisms involved in leukocyte recruitment from the blood stream into the tissues which is an essential component of the inflammatory response that requires interactions of leukocytes with the activated endothelium. I am particularly interested in studying the mechanisms regulating the recruitment of T cell subtypes, which are critical in the immune response to infection and play a dominant role in inflammatory chronic diseases. My PhD training was in immunology, and how T cells and macrophages were targeted by the protozoan parasite T. cruzi to evade the immune response and persist in the infected host. My postdoctoral training was in vascular biology where I studied the mechanisms regulating immune cell trafficking across the vascular endothelium. In the past three years as an independent investigator at the Molecular Cardiology Research Institute (MCRI), where I was recruited to bring in expertise in immunology and inflammation, I combined my expertise in vascular immunology with the field of cardiac remodeling and heart failure. Very recent emerging evidence supports the important role of inflammation in the pathophysiology of Heart Failure (HF), a progressive syndrome generally caused by a decline in left ventricular function that increases LV pressure and activates LV hypertrophy (LVH) and fibrosis, a process known as cardiac remodeling. Despite the extensive research focusing on the mechanisms regulating cardiac remodeling in heart failure, the mechanisms regulating inflammation and how they may affect cardiac remodeling are largely unexplored. As an independent investigator within the MCRI my laboratory focuses in two main lines of investigation: Studying the mechanisms that regulate T cell subset recruitment to sites of inflammation and combining vascular immunology and cardiac physiology approaches to study the role of T cell immune responses in heart failure as well as the mechanisms triggering T cell recruitment into the heart in response to pressure overload.
Training + Education Universidad Autonoma of Madrid, Spain; Harvard Medical School
Gender Female
Accepted Insurances View Accepted Insurances at Tufts MC + Floating Hospital

Honors + Awards

1999-2003 Fellowship award from the Spanish Ministry of Science and Education

2002 Short-term travel internship award, Spanish Ministry of Science and Education

2003 PhD, cum laude, Department of Molecular Biology, University Autonoma of Madrid, Madrid, Spain

2004-2006 Fulbright award. Post-doctoral Grant at Harvard University , Boston, MA

2004 Alcaide et al, Int Immunol, 2004, 16 (10): 1365. Selected article of the month by the journal International Immunology

2007 Alcaide et al, Jour Exp Med, 2007, 204:431. Selected by the journal Cell, as Leading Edge Research

2008 Alcaide et al, Blood, 2008, 112:2770. Selected by the journal Nature Immunology as Research Highlights

2009-2014, NIH Pathway to Independence award. Brigham and Women’s Hospital and Harvard University,Boston, MA

2013-2014, The Russo Family Charitable Foundation award. Tufts Sackler School of Biomedical Sciences and Tufts University School of Medicine, Boston, MA

2014, Abstract selected as Best of American Heart Association Specialty Conferences: “T Cell Mediated Immune Responses Regulate Cardiac Remodeling and Survival in Pressure Overload Induced Heart Failure”.

Publications + National Presentations

1. Goni O, Alcaide P and Fresno M. Immunosuppression during acute Trypanosoma cruzi infection: involvement of Ly6G(Gr1+)CD11b+ immature myeloid suppressor cells. Int Immunol, 2002, 14 (10): 1125- 1134.

2. Alcaide P and Fresno M. AgC10, a mucin from Trypanosoma cruzi, inhibits the proinflammatory activity of macrophages by inhibiting p38SAPK/MK2 and destabilizing TNF mRNA. Eur J Immunol, 2004, 34 (6):1695-704.

3. Alcaide P and Fresno M. AgC10, a membrane mucin from Trypanosoma cruzi, inhibits T cell activation leading to a decreased transcription of IL-2. Int Immunol. 2004, 16 (10):1365-75.

4. Kawakami A, Aikawa M, Alcaide P, Luscinskas FW, Libby P and Sacks FM. ApolipoproteinCIII in apoB lipoproteins enhances the adhesion of human monocytic cells to endothelial cells. Circulation, 2006,113 (5):691-700.

5. Harari OA, Alcaide P, Ahl D, Luscinskas FW and Liao JK. Absence of TRAM restricts Toll-like Receptor-4 signaling in vascular endothelial cells to the MyD88 pathway. Circ Res, 2006, 98 (9): 1134-40.

6. Xie C, Alcaide P, Song K, Schneider D, Herrmann M, Preissner KT, Luscinskas FW and Chavakis T. Suppression of experimental autoimmune encephalomyelitis by the anti-inflammatory extracellular adherence protein (Eap) of Staphylococcus aureus. J Exp Med, 2007, 204 (2): 431-9.

7. Cai YH, Alvarez A, Alcaide P, Duramad P, Lim YC, Jarolim P, Lowe JB, Luscinskas FW and Lichtman AH. Abrogation of functional selectin-ligand expression reduces migration of pathogenic CD8+ T cells into heart. J Immunol, 2006, 176(11):6568-75.

8. Kawakami A, Aikawa M, Alcaide P, Luscinskas FW, Libby P and Sacks FM. Apolipoprotein CIII induces expression of vascular cell adhesion molecule-1 in vascular endothelial cells and increases adhesion of monocytic cells. Circulation. 2006, 114(7): 681-7.

9. Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R and Pittet MJ. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest. 2007, 117(1): 195-205.

10. Lou O, Alcaide P, Luscinskas FW and Muller WA. CD99 is a key mediator of the transendothelial migration of neutrophils. J Immunol. 2007, 178(2): 1136-43.

11. Alcaide P, Jones TG, Lord GM, Glimcher LH, Hallgren J, Arinobu Y, Akashi K, Paterson AM, Gurish MA and Luscinskas FW. Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue. J Exp Med. 2007, 204 (2): 431-9.

12. Alcaide P, King SL, Dimitroff CJ, Lim YC, Fuhlbrigge RC and Luscinskas FW. The 130-kDa glycoform of CD43 functions as an E-Selectin ligand for activated Th1 Cells in vitro and in delayed-type hypersensitivity reactions in vivo. J Invest Dermatol. 2007, 127(8):1964-72.

13. Sircar M, Bradfield PF, Aurrand-Lions M, Fish RJ, Alcaide P, Yang L, Newton G, Lamont D, Sehrawat S, Mayadas T, Liang TW, Parkos CA, Imhof BA and Luscinskas FW. Neutrophil transmigration under shear flow conditions in vitro is junctional adhesion molecule-C independent. J Immunol. 2007; 178 (9):5879-87.

14. Rabodzey A, Alcaide P, Luscinskas FW and Ladoux B. Mechanical forces induced by the transendothelial migration of human neutrophils. Biophys J. 2008; 95(3):1428-38. PMCID: PMC2479581.

15. Noma K, Rikitake Y, Oyama N, Yan G, Alcaide P, Liu PY, Wang H, Ahl D, Sawada N, Okamoto R, Hiroi Y, Shimizu K, Luscinskas FW, Sun J and Liao JK. ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. J Clin Invest. 2008; 118(5):1632-44. PMCID: PMC2293333

16. Alcaide P, Auerbach S and Luscinskas FW. Neutrophil Recruitment Under Shear Flow: It's All About Endothelial Cell Rings And Gaps. Microcirculation. 2008; 16 (1): 43-57. PMCID: PMC2726622.

17. Alcaide P, Newton G, Sehrawat S, Mayadas-Norton T, Vincent PA, Yacono P, Golan DE, Kowalcyk A. and Luscinskas FW. p120-catenin regulates leukocyte transmigration through an effect on VE-Cadherin phosphorylation. Blood. 2008 Oct 1;112(7):2770-9. PMCID: PMC2556612.

18. Kasorn A, Alcaide P, Jia Y, Subramanian KK, Sarraj B, Li Y, Loison F, Hattori H, Silberstein LE, Luscinskas WF and Luo HR. Focal Adhesion Kinase Regulates Pathogen-Killing Capability and Life Span of Neutrophils via Mediating Both Adhesion-Dependent and -Independent Cellular Signals. J Immunol 2009, 183 (2):1032-43. PMID: 19561112

19. Jones TG, Hallgren J, Humbles A, Burwell T, Finkelman FD, Alcaide P, Austen KF and Gurish MF. Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1drestricted NKT cells. J Immunol. 2009, 183(8):5251-60. PMCID: PMC2782612

20. Alcaide P, Lim YC, Luscinskas FW and Fresno M. Mucin AgC10 from Trypanosoma cruzi Interferes with L-Selectin Mediated Monocyte Adhesion. . Infect. Immun 2010, 78(3):1260-8. PMCID: PMC2825940.

21. Koduru S, Kumar L, Ozcan E, Oyoshi M, Massaad M, Lebron S, Ramesh N, Kaku M, Fujiwara Y, Kremer L, King S, Fuhlbrigge R, Sage P, Carman C, Alcaide P, Luscinskas FW and Geha RS. CIP4 is essential for integrin dependent T cell trafficking. Proc Natl Acad Sci U S A. 2010 107(37):16252-6. PMCID: PMC2941295

22. Zhang J, Alcaide P, Liu L, Sun J, He A, Luscinskas FW and Shi GP. Regulation of endothelial cell adhesion molecule expression by mast cells, macrophages, and neutrophils. PLoS One 2011;6(1):e14525. PMCID: PMC3021513

23. Williams MR, Azcutia V, Newton G, Alcaide P and Luscinskas FW. Emerging mechanisms of neutrophil recruitment across endothelium. Trends Immunol. 2011, 461-9. PMID: 21839681; PMCID: PMC3185121.

24. Maganto-García E, Bu D, Tarrio ML, Alcaide P, Newton G, Griffin GK, Croce KJ, Luscinskas FW, Lichtman AH and Grabie N. Foxp3+ Inducible Regulatory T cells Suppress Endothelial Activation and Leukocyte Recruitment. J Immunol. 2011, 187(7):3521-9.PMID: 21873519; PMCID: PMC3217244.

25. Alcaide P, Maganto-Garcia E, Newton G, Travers R, Croce KJ, Bu DX, Luscinskas FW and Lichtman AH. Difference in Th1 and Th17 lymphocyte adhesion to endothelium. J Immunol. 2012, 188(3):1421- 30. PMID: 22219321; PMCID: PMC3262911.

26. Griffin GK, Newton G, Tarrio ML, Bu DX, Maganto-Garcia E, Azcutia V, Alcaide P, Grabie N, Luscinskas FW, Croce KJ and Lichtman AH. IL-17 and TNF-α Sustain Neutrophil Recruitment during Inflammation through Synergistic Effects on Endothelial Activation. J Immunol. 2012, 188(12): 6287-99. PMID: 22566565; PMCID: PMC3370121.

27. Alcaide P, Martinelli R, Williams MR, Adam A, Vincent PA and Luscinskas FW. p120-catenin prevents neutrophil transmigration independently of Rho A inhibition by impairing Src dependent VE-cadherin phosphorylation. Am J Physiol Cell Physiol. 2012, 303(4):C385-95. PMCID: PMC3422989

28. Bene NC, Alcaide P, Wortis HH, Jaffe IZ. Mineralocorticoid receptors in immune cells: Emerging role in cardiovascular disease. Steroids, 2014; 91C:38-45. PMCID: PMC4205205

29. Massaad MJ, Oyoshi MK, Kane J, Koduru S, Alcaide P, Nakamura F, Ramesh N, Luscinskas FW, Hartwig J, Geha RS.Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing. Mol Cell Biol. 2014; 34(23):4343-54. PMCID: PMC4248745.

30. Nevers T, Salvador AM, Grodecki-Pena A, Knapp A, Velazquez F, Aronovitz M, Kapur NK, Karas RH, Blanton RM and Alcaide P. Left ventricular T cell recruitment contributes to the pathogenesis of heart failure. In press, Circulation: Heart Failure.

All Publications

Biography

Dr. Alcaide received her PhD in Molecular Biology from Universidad Autonoma of Madrid, Spain, where she studied the immunological aspects of Trypanosoma cruzi infection, the protozoan parasite that causes Chagas disease. As a recipient of a Fulbright postdoctoral fellowship, Dr. Alcaide trained in Dr. F.W Luscinskas laboratory in the Brigham and Women’s hospital where she trained in vascular biology and studied the mechanisms regulating immune cell trafficking. After completion of her postdoctoral research training, Dr. Alcaide was appointed to Instructor of Pathology at Harvard Medical School and successfully competed for an NIH K99/R00 award while in Dr. Luscinskas lab and later joined the faculty at MCRI in September 2011 to establish her independent research program.

The Alcaide lab is a vascular immunology research team that combines several immunology, vascular biology and cardiac physiology in vitro and in vivo approaches to study several aspects of recruitment of T lymphocytes in diverse inflammatory settings, with a particular focus in the heart in the context of heart failure. The over-arching goal in the lab is to better understand the processes that take place during T lymphocyte recruitment to the heart, both in the T lymphocytes and in the endothelial cells, and how those can potentially be targeted in therapeutically useful ways.

Why T lymphocytes? T cell recruitment into tissues is a hallmark of several chronic inflammatory processes. Among T cells, the subset of T helper type 17 (Th17) cells plays a major role in autoimmunity and chronic inflammation, and we found that its interactions with the vascular endothelium differ from other T cell subsets. The lab combines real time imaging videomicroscopy under flow conditions and two different mouse animal models of autoimmunity to study the specific mechanisms that regulate Th17 cell trafficking.

Why heart failure? Heart Failure (HF) is a leading cause of morbidity and mortality. This progressive syndrome is generally caused by a decline in left ventricular (LV) function that increases LV pressure and activates LV hypertrophy and fibrosis, a process known as cardiac remodeling. Chronic inflammation has been recently associated with the pathophysiology of HF. Our lab uses the mouse model of pressure overload induced HF to study the role of T cells and T cell subsets in HF, the mechanisms triggering T cell recruitment to the heart, and the ways infiltrated T cells impair cardiac function. In collaboration with cardiologists in the MCRI, our lab also studies the role of T cells in human non-ischemic HF.

The Alcaide lab is formed by scientists who are passionate about their research and have interests of applying their immunology and vascular biology knowledge to heart disease. Our lab emphasizes the importance of collaborative team work in a friendly and multicultural environment to achieve the lab’s main research goals.

Professional Memberships

American Society for Investigative Pathology
Ad Hoc Reviewer for: Journal of Biological Chemistry, Journal of Leukocyte Biology
American Heart Association
Women in Medicine Committee, Tufts Medical Center
Elected Chair, Work-life Balance Subcommittee, Women in Medicine, Tufts Medical Center
Scientific Meetings Travel Awards Committee, Tufts Medical Center
Early Career Committee, Basic Cardiovascular Sciences Council, American Heart Association
Tufts CTSI Pilot Studies Review Committee, Tufts University School of Medicine
Interviewer, MD/ PhD Program Admissions Committee, Tufts University School of Medicine
Admissions Committee Member, Immunology Graduate Program, Sackler School of Biomedical Sciences, Tufts University School of Medicine
Cardiac Contractility and Heart Failure (CCHF) NIH Study Section
Mentored Transition to Independence (MTI) NHLBI Study Section

Research Support

K99/ R00 HL094706 Alcaide Alonso (PI) 2/1/09-8/31/15
Title: “Endothelial regulation of IL17 producing T effector cell migration”
The goal of this study is to identify the migratory profile of Th17 cells and how they differ from Th1 cells in their recruitment during inflammation. This grant is currently in a one-year no-cost extension
Role: Principal Investigator

AHA Grant in Aid 13 GRNT14560068 Alcaide Alonso (PI) 1/1/13-12/31/15
Title: “Role of inflammation and leukocyte recruitment in heart failure”
The goal of this study is to characterize the inflammatory mechanisms involved in heart failure progression and how leukocyte recruitment into the heart contributes to heart failure.
Role: Principal Investigator

R01 HL HL123658 Alcaide Alonso (PI) 7/01/14-06/30/19
Title: “T cell mediated immune responses as a regulator of heart failure”
The goal of this study is to identify the role for T cell immune responses in heart failure as well as the mechanisms that regulate T cell infiltration into the heart in response to pressure overload induced heart failure.
Role: Principal Investigator

R01 HL123658-01S1
Title: “Exploring the role of CD43 as a regulator of T cell subset recruitment in heart failure”.
The goal of this study is to study the role of CD43 as a potential specific adhesion molecule that regulates Th17 cell recruitment to the heart in heart failure. This project is a diversity supplement, integral to the parent R01 grant, to support the training of a graduate student in my laboratory.
Role: Principal Investigator

Contact Information

Phone: 617-636-0619

Molecular Cardiology Research Institute
Tufts Medical Center
800 Washington Street, Box #080
Boston, MA 02111


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