Assistant Professor of Immunology; Head, NAD+ Immunology Laboratory
Assistant Professor of Immunology; Head, NAD+ Immunology Laboratory
Dr. Abdala Elkhal is Assistant Professor of Immunology and Head of the NAD+ Immunology Laboratory at HMRI. His research focuses on the role of NAD+ in immune regulation and its benefits in inflammation and diseases.
Dr. Elkhal received his PhD in cell biology and biochemistry from the University Rene Descartes Paris V, France, and completed his postdoctoral work at Boston Children’s Hospital/Harvard Medical School. From 2006 to 2020, Dr. Elkhal was a faculty member in the Departments of Medicine and Surgery at Harvard Medical School. In 2022, Dr. Elkhal joined HMRI as a lead investigator to study the role of nicotinamide adenine dinucleotide (NAD+) in immunity and inflammatory diseases, including cardiovascular diseases. Dr. Elkhal’s discoveries were the first to identify NAD+, a natural co-factor found in all living cells, as a major regulator of the immune system. Dr. Elkhal has shown that NAD+ regulates CD4+ T cell differentiation independently of major antigen presenting cells (APCs) and TCR-MHC crosstalk. His work has potential use and benefits in numerous inflammatory diseases including autoimmune, hemophilia, infectious disease, and transplantation.
Dr. Elkhal’s contributions to science:
A healthy immune system is essential for a superior quality of life. Evolution has allowed our immune system to develop complex strategies to protect us from many diseases/infections that often are life-threatening. However, our immune system can often become altered genetically and/or by our constantly changing environment, which results in dramatic consequences for our immune system and health. Indeed, alterations can result in different diseases including autoimmune diseases, allergies, immunodeficiencies, and cancer. Dr. Elkhal’s research program investigates these alterations that target the adaptive and/or innate immune system and aims to re-establish an adequate/balanced immune response. Dr. Elkhal’s lab uses a combination of animal disease models, genetics, cell biology, immunology, biochemistry, and imaging techniques to achieve their research goals.
For half of a century, scientists have made tremendous progress in understanding how our immune system communicates and provides protection. It is now well established that the adaptive immune response requires the entry of a pathogen (i.e., bacteria, virus) to trigger our immune response. This pathogen is captured by our innate immune cells, termed antigen presenting cells (APCs), which process the antigen into peptides and present it at their surface via MHC class molecule (MHC I or II) to a T cell receptor (TCR) of a lymphocyte (CD4+or CD8+ T cells). These discoveries allow us to better understand how our immune cells communicate to protect us against infection and lead to the development of vaccines. Currently, novel therapies are based on this model to develop chimeric antigen receptor-modified T (CAR-T) cell therapies to treat some blood cancers (B cell-lineage lymphoma and leukemia). Although these medical breakthroughs lead to the development of new therapies, alterations that target this pathway have been a limiting factor. Patients have been found to exhibit an alteration within the MHC or TCR molecules which affects APC-T cell communication altered or absent. Patients with primary immunodeficiencies (PIDs) are highly susceptible to infection and cannot mount a proper immune response to eliminate the pathogen. Moreover, an exaggerated T cell response has been shown to result in autoimmune diseases or atopic disorders.
Dr. Elkhal’s laboratory has shown that nicotinamide adenine dinucleotide (NAD+) can trigger an immune response in the absence of antigen, APCs, and MHC-TCR interaction. Dr. Elkhal’s team has demonstrated that NAD+ mediates this immune response via mast cells, which are mainly considered to play a role in allergic immune response. Moreover, Dr. Elkhal’s lab has shown that NAD+ was able to protect against autoimmune diseases and lethal infections. The lab is still investigating how NAD+regulates other immune cells and its application in other life-threatening diseases. Dr. Elkhal’s work has unraveled a novel pathway that does not require APCs and MHC-TCR interaction and is able to regulate immune cells including macrophages, dendritic cells, mast cells, CD4+and CD8+ T cells. This promising novel pathway will allow us to further understand how immune cells communicate and will help to develop novel therapeutic methods for diseases or inflammatory processes such as autoimmune diseases, infection, and hemophilia, and in the field of transplantation.
Dr. Elkhal’s current research focuses on studying the impact of NAD+ in cardiovascular diseases. Cardiovascular disease (CVD) is the leading cause of death in the United States and throughout the world. Among CVD, coronary heart disease (CAD) is the most common type of CVD, as well as cerebrovascular disease, including stroke and transient ischemic attack. One project investigates whether NAD+ can protect or ameliorate heart function following myocardial infarction. A second project aims to develop a novel way to promote coagulation and develop novel methods to treat hemophilia. Furthermore, NAD+ has been shown to decline with age, while the immune system has been shown to age as well in a process called immunosenescence. It is well established that aging is associated with many diseases and there are age-related diseases due to a chronic and sterile low-grade inflammation called inflammaging. Although we have shown distinct aspects of immunosenescence and inflammaging, its link with NAD+ remains unclear. Our third project will thus evaluate the role of NAD+ during the aging process and diseases that are age-associated.
Tullius SG, Biefer HR, Li S, Trachtenberg AJ, Edtinger K, Quante M, Krenzien F, Uehara H, Yang X, Kissick HT, Kuo WP, Ghiran I, de la Fuente MA, Arredouani MS, Camacho V, Tigges JC, Toxavidis V, El Fatimy R, Smith BD, Vasudevan A, ElKhal A. NAD+ protects against EAE by regulating CD4+ T-cell differentiation. Nature Communications. 2014 Oct 7;5:5101. doi: 10.1038/ncomms6101. PMID: 25290058.
Elkhal A, Rodriguez Cetina Biefer H, Heinbokel T, Uehara H, Quante M, Seyda M, Schuitenmaker JM, Krenzien F, Camacho V, de la Fuente MA, Ghiran I, Tullius SG. NAD(+) regulates Treg cell fate and promotes allograft survival via a systemic IL-10 production that is CD4(+) CD25(+) Foxp3(+) T cells independent. Scientific Reports. 2016 Mar 1;6:22325. doi: 10.1038/srep22325. PMID: 26928119.
Rodriguez Cetina Biefer H, Vasudevan A, Elkhal A. Aspects of Tryptophan and Nicotinamide Adenine Dinucleotide in Immunity: A New Twist in an Old Tale. International Journal of Tryptophan Research. 2017 Jun 14;10:1178646917713491. doi: 10.1177/1178646917713491. PMID: 28659716.
Rodriguez Cetina Biefer H, Heinbokel T, Uehara H, Camacho V, Minami K, Nian Y, Koduru S, El Fatimy R, Ghiran I, Trachtenberg AJ, de la Fuente MA, Azuma H, Akbari O, Tullius SG, Vasudevan A, Elkhal A. Mast cells regulate CD4+ T-cell differentiation in the absence of antigen presentation. Journal of Allergy and Clinical Immunology. 2018 Dec;142(6):1894-1908.e7. doi: 10.1016/j.jaci.2018.01.038. PMID: 29470999.
Iske J, El Fatimy R, Yeqi N, Eskandari S, Cetina Biefer RH, Vasudevan A and ElKhal A. NAD+ prevents septic shock by non-canonical inflammasome blockade and IL-10. bioRxiv preprint doi: https://www.biorxiv.org/content/10.1101/2020.03.29.013649v1
Biefer HRC, Elkhal A, Cesarovic N, Emmert MY. NAD+ the disregarded molecule in cardiac metabolism. European Heart Journal. 2020 Mar 1;41(9):983-986. doi: 10.1093/eurheartj/ehaa044. PMID: 32114630.
Iske J, Seyda M, Heinbokel T, Maenosono R, Minami K, Nian Y, Quante M, Falk CS, Azuma H, Martin F, Passos JF, Niemann CU, Tchkonia T, Kirkland JL, Elkhal A, Tullius SG. Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation. Nature Communications. 2020 Aug 27;11(1):4289. doi: 10.1038/s41467-020-18039-x. PMID: 32855397.
Seyda M, Elkhal A, Quante M, Falk CS, Tullius SG. T Cells Going Innate. Trends in Immunology. 2016 Aug;37(8):546-556. doi: 10.1016/j.it.2016.06.004. PMID: 27402226.
Oberhuber R, Heinbokel T, Cetina Biefer HR, Boenisch O, Hock K, Bronson RT, Wilhelm MJ, Iwakura Y, Edtinger K, Uehara H, Quante M, Voskuil F, Krenzien F, Slegtenhorst B, Abdi R, Pratschke J, Elkhal A, Tullius SG. CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A. Circulation. 2015 Jul 14;132(2):122-31. doi: 10.1161/CIRCULATIONAHA.114.014917. PMID: 25957225.