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Kim E. Nichols, MD

Attending Physician

Director, Pediatric Hereditary Cancer Predisposition Program

Associate Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

I'm director of the Pediatric Hereditary Cancer Predisposition Program at The Children's Hospital of Philadelphia. Our program was established in 2005 and is one of the few in the nation to provide specialty oncology care and genetic counseling to children with a predisposition to cancer. The program also houses the Beckwith-Wiedemann syndrome (BWS)/isolated hemihypertrophy team. This sub-group within the program works with families of children with BWS and isolated hemihypertrophy, diseases that genetically predispose children to cancer.

In the clinic, we help identify families and children at increased risk to develop neoplasms, educate and monitor for the development of certain cancers, and provide treatment. Since these conditions require specialized management, we work closely with clinical genetics, as well as orthopedics, gastroenterology, surgery, immunology and bone marrow transplantation to provide optimized and comprehensive care for our patients.

Having established a clinical framework in pediatric cancer predisposition, we are now developing research protocols to collect blood and other tissues from patients for use in future studies aiming to identify novel genetic causes of pediatric cancer. We are also working to establish the proper combination of surveillance measures to most effectively monitor children affected by specific conditions and are evaluating the psychological issues related to cancer genetic testing in children.

In the laboratory, my research focuses on identifying and understanding how specific genes protect against the development of cancers and infections. Individuals with defects in their immune system are more likely to get certain kinds of cancer, such as lymphoma. As we expand our knowledge of the genes involved in predisposition to lymphoma and virus infections, we will be able to identify and develop new therapies for these conditions.

My interest in immune and genetic issues is long standing. As a post doctoral fellow, I worked on identifying the gene for X-linked lymphoproliferative (XLP) syndrome. This extremely rare inherited immunodeficiency disorder is caused by a defect in the SH2D1A gene. XLP is associated with increased susceptibility to infection with Epstein-Barr virus (EBV), as well as development of non-Hodgkin's B-cell lymphomas and immune system abnormalities, such as lowered production of antibodies. When individuals with XLP are exposed to EBV, many develop an overactive, yet dysfunctional immune response that results in a life-threatening condition known as hemophagocytic lymphohistiocytosis. Because of the poor prognosis, an early diagnosis to patients and families is critical.

The SH2D1A gene produces a protein known as SAP that is expressed in and controls the functions of cancer- and virus-fighting types of white blood cells known as T lymphocytes and natural killer (NK) cells. Most recently, we observed that SAP is critical for promoting the development of natural killer T (NKT) cells, a rare lymphocyte lineage that protects from infections, cancers and prevents autoimmune diseases.

Our current research is focused on understanding how SAP regulates NKT cell development and establishing whether SAP plays a role in mature NKT cell activation. We are also interested in determining whether NKT cells contribute to the control of EBV infection in normal individuals and assessing if the lack of NKT cells contributes to the development of disease manifestations in patients with XLP. While our research is directed primarily at XLP, it is also relevant to the understanding and treatment of an emerging group of genetic disorders known as familial HLH, which shares many clinical and laboratory features with XLP.

As a result of our clinical and research efforts, the Hereditary Cancer Predisposition Program and my laboratory research group is poised to advance our understanding of the genetic basis of diseases that predispose to cancer and immunodeficiency.

 


 

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