Subspecialty	Clinical and Laboratory Immunology - Pediatrics , Clinical and Laboratory Immunology-Allergy and Immunology
Clinical Interests	Internal Medicine
	Clinical Immunology
Languages	English
	Spanish
Gender	Female
E-mail	charlotte.cunningham-rundles@mssm.edu
Education and Training	MD, Columbia University
	Residency, Internal Medicine, Bellevue Hospital Center
	Fellowship, Clinical Immunology, New York University School of Medicine
Awards	2009 Best Doctors New York Magazine

Dr. Cunningham-Rundles is the Director of the Allergy Immunology and Immunology Training Program and Director of the Immunodeficiency Clinic, a referral service for children and adults with primary immunodeficiency disease. Her research work has been in the area of human immunodeficiency diseases, and immuno-reconstitution. She holds research grants from the US Public Health Service, Food and Drug administration and the NIH, Division of Allergy Immunology and Transplantation. She served on the National Institutes of Health, Allergy Immunology and Transplantation Review committee from 1993 to 1997, and was Chairperson of this committee from 1995 to 1997. She is a Fellow in the American Academy of Allergy, Asthma and Immunology, and a member of the American Association of Immunologists. She has served as President of the Clinical Immunology Society. She is current Co-Director of the USIDNet, an NIH funded Consortium that funds and promotes training in Primary Immune Deficiency. At Mount Sinai, Dr. Cunningham-Rundles supervises the Immuno-deficiency Clinic, held weekly, as well as an active treatment facility, the Clinical Immunology Infusion Service.

STRIDE

Education and Training	MD, Columbia University
	Residency, Internal Medicine, Bellevue Hospital Center
	Fellowship, Clinical Immunology, New York University School of Medicine

Subspecialty	Clinical and Laboratory Immunology - Pediatrics , Clinical and Laboratory Immunology-Allergy and Immunology
Clinical Interests	Internal Medicine
	Clinical Immunology
Languages	English
	Spanish

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.

Wasserstrom H, Bussel J, Lim LC, Cunningham-Rundles C. Memory B cells and pneumococcal antibody after splenectomy. J Immunol 2008 Sep 1; 181(5): 3684-3689.

Sanchez-Ramon S, Radigan L, Yu JE, Bard S, Cunningham-Rundles C. Memory B cells in common variable immunodeficiency: clinical associations and sex differences. Clin Immunol 2008 Sep; 128(3): 314-321.

Zhang L, Radigan L, Salzer U, Behrens TW, Grimbacher B, Diaz G, Bussel J, Cunningham-Rundles C. Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes. J Allergy Clin Immunol 2007 Nov; 120(5): 1178-1185.

Pan-Hammarstrom Q, Salzer U, Du L, Bjorkander J, Cunningham-Rundles C, Nelson DL, Bacchelli C, Gaspar HB, Offer S, Behrens TW, Grimbacher B, Hammarstrom L. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet 2007 Apr; 39(4).

Herve M, Isnardi I, Ng YS, Bussel JB, Ochs HD, Cunningham-Rundles C, Meffre E. CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance. Epub 2007 Jun 11. J Exp Med 2007 Jul 9; 204(7): 1583-1593.

Cunningham-Rundles C, Radigan L, Knight AK, Zhang L, Bauer L, Nakazawa A. TLR9 activation is defective in common variable immune deficiency. J Immunol 2006 Feb 1; 176(3): 1978-1987.

Cunningham-Rundles C, Ponda PP. Molecular defects in T- and B-cell primary immunodeficiency diseases [review]. Nat Rev Immunol 2005 Nov; 5(11): 880-892.

Cunningham-Rundles C, Sidi P, Estrella L, Doucette J. Identifying undiagnosed primary immunodeficiency diseases in minority subjects by using computer sorting of diagnosis codes. J Allergy Clin Immunol 2004 Apr; 113(4): 747-755.