Abramson Cancer Center

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Kim E. Nichols , MD

Degree and Institution
MD, Duke University School of Medicine

Faculty Title
Associate Professor, Pediatrics

Administrative Title
Director, Pediatric Hereditary Cancer Predisposition Program, Children's Hospital of Philadelphia

Department

Pediatrics, Children's Hospital of Philadelphia

Clinical Expertise

Dr. Nichols is a pediatric oncologist with clinical interests in cancer genetics and the treatment of children with lymphoma, EBV-related lymphoproliferative disorders, Langerhans cell histiocytosis and the hemophagocytic lymphohistiocytoses.

Research Expertise

Immunobiology with a focus on the development and activation of invariant natural killer T (iNKT) cells and neutrophils (polymorphonuclear cells; PMN).

Other Affiliations
Member, Histiocyte Society
Member, Macrophage Activation Subcommittee, Histiocyte Society
Member, Children's Oncology Group, Retinoblastoma Committee
Consultant, Histiocytosis Association of America
Member, Macrophage Activation Subcommittee, Histiocyte Society
Member, Clinical Immunology Society

Residency
Pediatrics, Children's Hospital, Boston

Fellowship
Hematology, Children's Hospital, Boston
Oncology, Dana-Farber Cancer Institute
Research Fellow, Massachusetts General Hospital

Board Certifications
American Board of Pediatrics
American Board of Pediatric Hematology/Oncology

Honors and Awards

• 2010, Foerderer Award, Children's Hospital of Philadelphia
• 2002, American Society of Hematology Junior Faculty Scholar Award
• 2001, McCabe Foundation Award, University of Pennsylvania School of Medicine
• 2001, MAPS Award, Children's Hospital of Philadelphia
• 2000, Mary L. Smith Award, University of Pennsylvania School of Medicine
• 2000, ACS IRG, University of Pennsylvania
• 1999, Artemis Fellowship Award, Nikolas Symposium on the Histiocytosis
• 1998, Lee Fellowship Award, Dana-Farber Cancer Institute
• 1995, Physician Scientist Award, National Institutes of Health
• 1989, Stead Research Fellowship, Duke University School of Medicine
• 1989, Alpha Omega Alpha, Duke University School of Medicine

Publications
Click here to see my publications

Contact Information

Researcher/Clinician:
Kim E. Nichols, MD

Children's Hospital of Philadelphia
Colket Translational Research Building, Room 3012
3501 Civic Center Boulevard
Philadelphia, PA 19104

Office Phone: (267) 425-3000
Fax: (215) 590-3770

Assistant:
Linda Yarbrough
Office Phone: (215) 590-2821
Appointment Phone: (215) 590-3025
Fax: (215) 590-3770
yarbrough@email.chop.edu

Description of Research:

Our laboratory is interested in the study of immune cells and their roles in maintaining health and mediating disease. In particular, we are examining how specific signaling molecules regulate the development and activation of invariant natural killer T (iNKT) cells and neutrophils (PMN). We use tissue culture systems and mice deficient in the expression of these signaling proteins, or animals expressing mutant proteins, to dissect their functions within these lineages. Our studies are relevant to the understanding of normal immune resopnses as well as the development and treatment of inflammatory diseases, immunodeficiency and cancer. Within this theme of innate immune cell biology/signal transduction, the lab has three major areas of research investigation:

• Study of Signaling Lymphocytic Activation Molecule [SLAM]-associated protein (SAP), a cytoplasmic adaptor that regulates numerous aspects of the normal immune response.
  We were among the first to demonstrate that mutations in the gene encoding SAP cause X-linked lymphoproliferative disease (XLP), an often life-threatening primary immunodeficiency marked by increased susceptibility to Epstein Barr virus infection, development of lymphoma and humoral immune defects. Since this initial observation, our lab has been interested in understanding how loss of SAP function impairs antiviral and antitumor immunity. Recently, we observed that expression of SAP is critical for the development of invariant natural killer T (NKT) cells, an innate-type lymphocyte sublineage that protects against infections and certain cancers, mediates graft tolerance and protects against autoimmune disease. Ongoing studies aim to dissect how SAP regulates NKT cell ontogeny and to determine whether SAP plays a role in mature NKT cell activation.
• Mechanisms controlling NKT cell cytotoxic responses.
  Many studies implicate NKT cells as potent mediators of antitumor immune surveillance. Existing data suggest that the protective properties of NKT cells may be due to their production of pro-inflammatory cytokines that then activate other cytotoxic effectors, such as natural killer (NK) cells and CD8+ T cells. Our data reveal that in addition to producing pro-inflammatory cytokines, NKT cells exhibit direct cytolytic responses towards tumor target cells. In our in vitro tumor model system, NKT cell-mediated killing of targets is T cell receptor-dependent and requires tumor cell CD1-dependent antigen presentation. Based on these findings, we are now further characterizing the molecular events that control NKT cell killing and lytic synapse formation and determining whether NKT cells traffic to and directly kill tumor cells in vivo. Collectively, these studies will define how NKT cells destroy malignant cells and suggest ways to manipulate their cytolytic functions to enhance the treatment of patients with malignancy and specific types of infection.
  
• Regulation of PMN functions by the Src homology 2 domain containing Leukocyte Phosphoprotein of 76 kD (SLP-76) and its associated partner proteins.
  PMN are among the first cells to respond to invading pathogens. While their antibacterial properties are critical for host protection, the aberrant activation of PMN leads to tissue destruction and contibrutes to organ damage in autoimmune disease. To better understand PMN functions and to develop novel therapies for these and related diseases, we are examining the mechanisms that govern PMN activation. Previously, we demonstrated that the adaptor molecule SLP-76 is critical for promoting in vitro PMN degranulation and production of reactive oxygen intermediates. Furthermore, loss of SLP-76, or mutation of its N-terminal domain, protects against leukocyte infiltration and development of joint destruction normally evident in a live animal model of serum-induced arthritis. These are the first data to demonstrate a role for SLP-76 in PMN activation and suggest that further elucidation of the SLP-76-dependent biochemical pathways may provide important insights into PMN biology.
  

  Rotation projects are available in all areas.