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Charlotte Cunningham-Rundles

  • PROFESSOR Medicine, Clinical Immunology
  • PROFESSOR Pediatrics
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Certifications

  • American Board of Internal Medicine

Training Areas

Education

  • MD, Columbia University

  • PhD, New York University
    Immunology

  • Residency, Internal Medicine
    Bellevue Hospital Center

Biography

    Dr. Cunningham-Rundles is the David S. Gottesman Professor of Immunology at the Mount Sinai School of Medicine in New York. She is a Professor of Medicine and Pediatrics, a member of the Immunology institute,  and directs the Immunodeficiency Clinic at Mount Sinai. She is  also the Program Director of the Allergy Immunology Fellowship training program. She received her MD from Columbia College of Physicians and Surgeons,  and her PhD from New York University School of Medicine. Dr. Cunningham-Rundles is an expert in the more than 150 Primary Immune Deficiency diseases, conditions that result from genetic defects of the immune system. Her research has been supported by US Public Health Service, the Food and Drug Administration, and the National Institutes of Health (NIH) Division of Allergy Immunology and Transplantation.

    Her contributions have been widely recognized, notably the Clinical Immunology Society President's Award, the Boyle Award Immune Deficiency Foundation award, the Abbott Award from the American Society for Microbiology,  and the American Academy Asthma, Allergy, and Immunology Research Award where she has been on the Board of Directors. She is a Past President of the Clinical Immunology Society. Dr. Cunningham-Rundles has served as Chair of Allergy Immunology and Transplantation Committee for the National Institutes of Health and has Chaired the Immunology Review Committee of the National Aeronautics and Space Administration. She served on the Medical Advisory Boards of the Immune Deficiency Foundation, and the Jeffrey Modell Foundation. Dr. Cunningham-Rundles has served on the FDA Blood Safety and Advisory Committee and is the principal investigator of the USIDNET, a research cooperative sponsored by the NIH. She is a member of the International Union of Immunology Sciences Expert Committee on Immune Deficiency.

    In the News
    Dr. Cunningham-Rundles discusses immune deficiency disorders in The Daily News feature The Daily Check Up.
    View the PDF



Awards

  • 2009 -
    Best Doctors
    New York Magazine

Research

Human immunodeficiency diseases; mechanisms and treatments

In this laboratory, the area of investigation is human immunodeficiency diseases and immuno-reconstitution. This work has been supported by research grants from the Food and Drug Administration and the NIH, Division of Allergy Immunology and Transplantation, Child Health and Human Development and USIDNet. We are investigating B, T cell and dendritic cell immunity in a primary immunodeficiency disease, common variable immunodeficiency (CVID.) A recent theme is the investigation of B cell memory in this and other immune defects; CD27+B cells, and especially isotype switched B memory cells are deficient, which is related to lack of normal vaccine responses. How the development of B cell memory relies upon triggering of Toll like Receptors is under investigation, using methylated oligonucleotides containing CpG motifs. TLR9 function is abnormal in this immune defect a factor that leads to poor B cell proliferation, loss of cytokine production, lack of cell adhesion and defective B cell memory responses; plasmacytoid dendritic cells are also unable to respond normally to these or other TLR ligands. We are also particularly interested in the role of specific mutations in the TACI gene, either producing or influencing the CVID phenotype, and the role of related TNF family members in the abnormal immunity in B cell defects. Further studies using gene arrays in the investigation of human B cell defects are ongoing. While the phenotype of this disease is hypogammaglobulinemia, T cell and antigen processing defects result in anergy, defective co-stimulation, accelerated apoptosis and deficient cytokine production. We previously found that some of these T cell defects could be reversed by the administration of IL-2, allowing an opportunity to explore some of the mechanisms by which this cytokine activates and regulates human T cell immunity. Since T cell receptor co-stimulation is abnormal in CVID, a deficiency of intracellular signaling pathways could explain defective proliferation, anergy, cytokine deficiency, and premature apoptosis. We have investigated in what way the CD28 signaling other co stimulatory pathways differ from normal T cells, analyzing early signaling events, membrane reorganization, up-regulation of Bcl-xL, and the effects of receptor triggering on transcription and stabilization of cytokine mRNA. In other studies we have found markedly deficient production of IL-12 by monocycle derived dendritic cells, a deficit that could further lead to anergy. We have also investigated ICOS gene and its ligand, in CVID subjects, since mutation of ICOS in humans can lead to the CVID phenotype.

Publications

.;.

He B, Santamaria R, Xu W, Cols M, Chen K, Puga I, Shan M, Xiong H, Bussel JB, Chiu A, Puel A, Reichenbach J, Marodi L, Döffinger R, Vasconcelos J, Issekutz A, Krause J, Davies G, Li X, Grimbacher B, Plebani A, Meffre E, Picard C, Cunningham-Rundles C, Casanova JL, Cerutti A. The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nature immunology 2010 Sep; 11(9).

Yu JE, De Ravin SS, Uzel G, Landers C, Targan S, Malech HL, Holland SM, Cao W, Harpaz N, Mayer L, Cunningham-Rundles C. High levels of Crohn's disease-associated anti-microbial antibodies are present and independent of colitis in chronic granulomatous disease. Clinical immunology (Orlando, Fla.) 2011 Jan; 138(1).

Ahn S, Cunningham-Rundles C. Role of B cells in common variable immune deficiency. Expert review of clinical immunology 2009 Sep; 5(5).

Agarwal S, Smereka P, Harpaz N, Cunningham-Rundles C, Mayer L. Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal disease. Inflammatory bowel diseases 2011 Jan; 17(1).

Cunningham-Rundles C. How I treat common variable immune deficiency. Blood 2010 Jul; 116(1).

Marron TU, Rohr K, Martinez-Gallo M, Yu J, Cunningham-Rundles C. TLR signaling and effector functions are intact in XLA neutrophils. Clinical immunology (Orlando, Fla.) 2010 Oct; 137(1).

Mc Guire PJ, Cunningham-Rundles C, Ochs H, Diaz GA. Oligoclonality, impaired class switch and B-cell memory responses in WHIM syndrome. Clinical immunology (Orlando, Fla.) 2010 Jun; 135(3).

Isnardi I, Ng YS, Menard L, Meyers G, Saadoun D, Srdanovic I, Samuels J, Berman J, Buckner JH, Cunningham-Rundles C, Meffre E. Complement receptor 2/CD21- human naive B cells contain mostly autoreactive unresponsive clones. Blood 2010 Jun; 115(24).

Ahn S, Cunningham-Rundles C. Role of B cells in common variable immune deficiency. Expert review of clinical immunology 2009 Sep; 5(5).

Ballow M, Notarangelo L, Grimbacher B, Cunningham-Rundles C, Stein M, Helbert M, Gathmann B, Kindle G, Knight AK, Ochs HD, Sullivan K, Franco JL. Immunodeficiencies. Clinical and experimental immunology 2009 Dec; 158 Suppl 1.

Notarangelo LD, Fischer A, Geha RS, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C, Etzioni A, Hammartröm L, Nonoyama S, Ochs HD, Puck J, Roifman C, Seger R, Wedgwood J. Primary immunodeficiencies: 2009 update. The Journal of allergy and clinical immunology 2009 Dec; 124(6).

Nakagawa Y, Iwatani K. Scanning thin-layer chromatography-liquid secondary ion mass spectrometry and its application for investigation of drug metabolites. Journal of chromatography 1991 Jan; 562(1-2).

Ardeniz O, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Clinical immunology (Orlando, Fla.) 2009 Nov; 133(2).

Cunningham-Rundles C. Lung disease, antibodies and other unresolved issues in immune globulin therapy for antibody deficiency. Clinical and experimental immunology 2009 Sep; 157 Suppl 1.

Wasserstrom H, Bussel J, Lim LC, Cunningham-Rundles C. Memory B cells and pneumococcal antibody after splenectomy. Journal of immunology (Baltimore, Md. : 1950) 2008 Sep; 181(5).

Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. British journal of haematology 2009 Jun; 145(6).

Chen K, Xu W, Wilson M, He B, Miller NW, Bengtén E, Edholm ES, Santini PA, Rath P, Chiu A, Cattalini M, Litzman J, B Bussel J, Huang B, Meini A, Riesbeck K, Cunningham-Rundles C, Plebani A, Cerutti A. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nature immunology 2009 Aug; 10(8).

Yu JE, Knight AK, Radigan L, Marron TU, Zhang L, Sanchez-Ramón S, Cunningham-Rundles C. Toll-like receptor 7 and 9 defects in common variable immunodeficiency. The Journal of allergy and clinical immunology 2009 Aug; 124(2).

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Below are financial relationships with industry reported by Dr. Cunningham-Rundles during 2013 and/or 2014. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Scientific Advisory Board:

  • Baxter; CSL Behring

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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