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Elias El Haddad

Elias El Haddad, PhD

Professor of Medicine


Department: Medicine: Division of Infectious Diseases & HIV Medicine

Education

  • PhD in Microbiology & Immunology - McGill University (1997)
  • MSc in Microbiology & Immunology - American University of Beirut (1991)
  • BSc in Biology - American University of Beirut (1987)

Memberships / Professional Affiliations

  • American Association of Immunologists
  • American Association for the Advancement of Science
  • International AIDS Society
  • International Society for Vaccines

Elias El Haddad, PhD, is a professor in the Division of Infectious Diseases & HIV Medicine at Drexel University College of Medicine.

Research Overview

Dr. El Haddad is an immunologist and cell biologist by training. His research sits at the interface of four disciplines: human immunology, systems biology, infectious disease pathogenesis and vaccinology. Dr. El Haddad’s research portfolio combines basic science and applied clinical research aiming at developing vaccine adjuvants, improving vaccine efficacy, developing immunotherapies and identify digital biomarkers in personalized medicine. His research also emphasizes examining immune responses in special populations, such the elderly, aiming at developing efficacious vaccines to improve their immune response and reduce the burdens of many infectious diseases in this population.

Research Interests

Human immunology, systems biology, infectious disease pathogenesis and vaccinology

Research

Original Research

Dr. El Haddad’s research has led to the elucidation of important mechanisms and concepts in the field of immunology, vaccinology and infectious diseases.

He has identified Rab27a as the primary molecule important for degranulation of CD8+ cytotoxic T cells. The absence of this molecule rendered mice (ashen mice) and humans (Griscelli patients) susceptible to repeated infection. These findings were published in the Journal of Clinical Investigation.

Dr. El Haddad was a co-senior author of the seminal paper that identified PD-1 as an exhaustion marker on HIV-specific CD8+ T cells. This paper has received a great deal of attention nationally and internationally. The findings were published in Nature Medicine. PD-1 is now an important target for immunotherapy for cancer. Multiple clinical studies targeting PD-1 signaling in humans have shown very promising results. Treatment with anti-PD-1 antibodies has significantly extended the life span and improved the quality of life of many of people suffering from cancers.

Additionally, Dr. El Haddad's group has identified FOXO3a transcription factor as a marker for central memory CD4 survival in HIV elite controllers, who have the ability to naturally control HIV infection. He showed that the FOXO3a pathway plays a critical role in educating the immune response towards the generation of central memory T cells that can control the virus naturally. These findings were published in Nature Medicine and the Journal of Experimental Medicine.

Another major scientific finding was recently published in Nature Medicine. Dr. El Haddad’s team has shown for the first time that a novel subset of follicular helper T cells is defective during HIV infection, and that this subset can be used as target in the design of novel vaccines against HIV infection. The follicular helper T cells are now an active target for vaccine development.

Dr. El Haddad has advocated the use of systems biology approaches to study human diseases. He has used this approach to identify biomarkers and immune signatures for many vaccines and natural infections. Systems analysis allows us to measure multiplex and integrative immune parameters that give more superior information on the biology of the immune system than single-parameter analysis.

Current Research Interests

Identification of mechanisms associated with long-term survival and maintenance of memory T and B cells. The survival of memory T and B cells is key in the generation of host response to infections and vaccines. However, our understanding of the underlying mechanisms leading to prolonged survival of these cells is not fully understood. Dr. El Haddad's group is studying the role of FOXO3a activation, and the identity of its target molecules in memory T cell and B cell maintenance.

Study of follicular helper T cells interaction with B cells in health and disease.
The interaction of follicular helper T cells (Tfh) with germinal center B cells (GC) in B cell follicles of secondary lymphoid tissues is a tightly regulated process that culminates in the generation of long-lived memory B cells (MBCs) and plasma cells (PC). The premature loss of MBCs in many diseases, including HIV-1 infection, leads to the establishment of profound defects in global and polyclonal humoral immunity and the inability to elicit efficient responses to most vaccines. Dr. El Haddad's group will identify the mechanisms responsible for the impairment of Tfh cells during HIV infection, and determine the help program of Tfh cell function in order to identify molecules that can be targeted for vaccine development  

Identification of novel adjuvants in order to improve vaccine response in elderly individuals. Immunosenescence has been shown to be associated with immune defects. Dr. El Hadda's team has found that dendritic cells have altered functions in response to TLR ligands in aging populations. This altered response affected their ability to stimulate T cells. The team will identify the target molecules that are defective in innate immunity in the elderly, and reverse innate immune defects in vitro and an in vivo.

In the Media

Publications

Selected Recent Publications
See all of Dr. El Haddad's publications in PubMed

"Human Monocyte Subsets Are Transcriptionally and Functionally Altered in Aging in Response to Pattern Recognition Receptor Agonists"
Metcalf TU, Wilkinson PA, Cameron MJ, Ghneim K, Chiang C, Wertheimer AM, Hiscott JB, Nikolich-Zugich J, Haddad EK
J Immunol. 2017 Jul 10

"A Novel Agonist of the TRIF Pathway Induces a Cellular State Refractory to Replication of Zika, Chikungunya, and Dengue Viruses"
Pryke KM, Abraham J, Sali TM, Gall BJ, Archer I, Liu A, Bambina S, Baird J, Gough M, Chakhtoura M, Haddad EK, Kirby IT, Nilsen A, Streblow DN, Hirsch AJ, Smith JL, DeFilippis VR
MBio. 2017 May 2;8(3)

"Delayed differentiation of potent effector CD8+ T cells reducing viremia and reservoir seeding in acute HIV infection"
Takata H, Buranapraditkun S, Kessing C, Fletcher JL, Muir R, Tardif V, Cartwright P, Vandergeeten C, Bakeman W, Nichols CN, Pinyakorn S, Hansasuta P, Kroon E, Chalermchai T, O'Connell R, Kim J, Phanuphak N, Robb ML, Michael NL, Chomont N, Haddad EK, Ananworanich J, Trautmann, RV254/SEARCH010 and the RV304/SEARCH013 Study Groups
Sci Transl Med. 2017 Feb 15;9(377)

"Circulating CXCR5+CXCR3+PD-1lo Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth"
Martin-Gayo E, Cronin J, Hickman T, Ouyang Z, Lindqvist M, Kolb KE, Schulze Zur Wiesch J, Cubas R, Porichis F, Shalek AK, van Lunzen J, Haddad EK, Walker BD, Kaufmann DE, Lichterfeld M, Yu XG
JCI Insight. 2017 Jan 26;2(2)

"Altered Memory Circulating T Follicular Helper-B cell Interaction in Early Acute HIV Infection"
Roshell Muir, Talibah Metcalf, Virginie Tardif, Hiroshi Takata, Nittaya Phanuphak,    Eugene Kroon, Donn J Colby, Rapee Trichavaroj, Victor Valcour, Merlin L Robb, Jintanat Ananworanich, Lydie Trautmann, and Elias K Haddad, on behalf of the RV254/SEARCH010 and RV304/SEARCH 013 Study Groups
PLoS Pathog. 2016 Jul 27;12(7)

"HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses"
Zhang Y, El-Far M, Dupuy FP, Abdel-Hakeem MS, He Z, Procopio FA, Shi Y, Haddad EK, Ancuta P, Sekaly RP, Said EA
Sci Rep. 2016 Jul 7;6:29447. doi: 10.1038/srep29447

"An age-related population of human memory T cells masquerade as naïve T cells and respond to persistent infections in humans"
Vesna Pulko, John S. Davies, Carmine Martinez , Marion C. Lanteri, Michael P. Busch, Michael S. Diamond, Kenneth Knox, Erin S. Busch, Peter A. Sims, Shripad Sinari, Dean Billheimer, Elias K. Haddad, Kristy O. Murray, Anne M. Wertheimer and Janko Nikolich-Žugich
Nat Immunol. 2016 Aug;17(8):966-75

"A Numerically Subdominant CD8 T Cell Response to Matrix Protein of Respiratory Syncytial Virus Controls Infection with Limited Immunopathology"
Liu J, Haddad EK, Marceau J, Morabito KM, Rao SS, Filali-Mouhim A, Sekaly RP, Graham BS
PLoS Pathog. 2016 Mar 4;12(3)

"Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function"
Manuzak JA, Hensley-McBain T, Zevin AS, Miller C, Cubas R, Agricola B, Gile J, Richert-Spuhler L, Patilea G, Estes JD, Langevin S, Reeves RK, Haddad EK, Klatt NR
J Immunol. 2016 Mar 1;196(5):2401-9

"Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection"
Richner JM, Gmyrek GB, Govero J, Tu Y, van der Windt GJ, Metcalf TU, Haddad EK, Textor J, Miller MJ, Diamond MS
PLoS Pathog. 2015 Jul 23;11(7) PMID: 26204259

"Reversible Reprogramming of follicular helper T cells during HIV infection"
R Cubas, J van Grevenynghe, S Wills, BH Santich, CM Buckner, F Procopio, Z He, T Metcalf, K Ghneim, M Locci, P Ancuta, JP Routy, L Trautmann, RA Koup, C Petrovas, S Migueles, M Connors, GD Tomaras, S Moir, S Crotty, EK Haddad
J Immunol. 2015 Dec 15;195(12):5625-36

"BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms"
Hatzi K, Nance JP, Kroenke MA, Bothwell M, Haddad EK, Melnick A, Crotty S
J Exp Med. 2015 Apr 6;212(4):539-53

Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors.
Metcalf TU, Cubas RA, Ghneim K, Cartwright MJ, Grevenynghe JV, Richner JM, Olagnier DP, Wilkinson PA, Cameron MJ, Park BS, Hiscott JB, Diamond MS, Wertheimer AM, Nikolich-Zugich J, Haddad EK
Aging Cell. 2015 Jun;14(3):421-32

"Immune activation alters cellular and humoral responses to yellow fever 17D vaccine"
Muyanja E, Ssemaganda A, Ngauv P, Cubas R, Perrin H, Srinivasan D, Canderan G, Lawson B, Kopycinski J, Graham AS, Rowe DK, Smith MJ, Isern S, Michael S, Silvestri G, Vanderford TH, Castro E, Pantaleo G, Singer J, Gillmour J, Kiwanuka N, Nanvubya A, Schmidt C, Birungi J, Cox J, Haddad EK, Kaleebu P, Fast P, Sekaly RP, Trautmann L
J Clin Invest. 2014 Jul 1;124(7):3147-58

"Myeloid Dendritic Cells Induce HIV-1 Latency in Non-proliferating CD4(+) T Cells"
Pantel A, Teixeira A, Haddad E, Wood EG, Steinman RM, Longhi MP. Direct Type I IFN but Not MDA5/TLR3 Activation of Dendritic Cells Is Required for Maturation and Metabolic Shift to Glycolysis after Poly IC Stimulation. PLoS Biol. 2014 Jan;12(1):e1001759. Evans VA, Kumar N, Filali A, Procopio FA, Yegorov O, Goulet JP, Saleh S, Haddad EK, da Fonseca Pereira C, Ellenberg PC, Sekaly RP, Cameron PU, Lewin SR
PLoS Pathog. 2013 Dec;9(12):e1003799

"Human Circulating PD-1(+)CXCR3(-)CXCR5(+) Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses"
Locci M, Havenar-Daughton C, Landais E, Wu J, Kroenke MA, Arlehamn CL, Su LF, Cubas R, Davis MM, Sette A, Haddad EK; International AIDS Vaccine Initiative Protocol C Principal Investigators, Poignard P, Crotty S
Immunity. 2013 Oct 17;39(4):758-69

"Systems Analysis of a RIG-I Agonist Inducing Broad Spectrum Inhibition of Virus Infectivity"
Goulet ML, Olagnier D, Xu Z, Paz S, Belgnaoui SM, Lafferty EI, Janelle V, Arguello M, Paquet M, Ghneim K, Richards S, Smith A, Wilkinson P, Cameron M, Kalinke U, Qureshi S, Lamarre A, Haddad EK, Sekaly RP, Peri S, Balachandran S, Lin R, Hiscott J
PLoS Pathog. 2013 Apr;9(4):e1003298

"Inadequate T follicular cell help impairs B cell immunity during HIV infection"
Cubas RA, Mudd JC, Savoye AL, Perreau M, van Grevenynghe J, Metcalf T, Connick E, Meditz A, Freeman GJ, Abesada-Terk G Jr, Jacobson JM, Brooks AD, Crotty S, Estes JD, Pantaleo G, Lederman MM, and Haddad EK
Nat Med. 2013 Apr;19(4):494-9

"Impaired T-cell responses to sphingosine-1-phosphate in HIV-1 infected lymph nodes"
Mudd JC, Murphy P, Manion M, Debernardo R, Hardacre J, Ammori J, Hardy GA, Harding CV, Mahabaleshwar GH, Jain MK, Jacobson JM, Brooks AD, Lewis S, Schacker TW, Anderson J, Haddad EK, Cubas RA, Rodriguez B, Sieg SF, Lederman MM
Blood. 2013 Apr 11;121(15):2914-22

"Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques"
Klatt NR, Canary LA, Sun X, Vinton CL, Funderburg NT, Morcock DR, Quiñones M, Deming CB, Perkins M, Hazuda DJ, Miller MD, Lederman MM, Segre JA, Lifson JD, Haddad EK, Estes JD, Brenchley JM
J Clin Invest. 2013 Feb 1;123(2):903-7

"Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production"
Perreau M, Savoye AL, De Crignis E, Corpataux JM, Cubas R, Haddad EK, De Leval L, Graziosi C, Pantaleo G
J Exp Med. 2013 Jan 14;210(1):143-56


Contact Information


Research Office

Division of Infectious Diseases & HIV Medicine
245 N. 15th Street
Philadelphia, PA 19102
Clinical Research Unit Phone: 267.507.6612
Office Phone: 215.762.3643