Leslie J. Krueger, Ph.D., FACMG

Chief, Molecular Genetics, Cellular and Tissue Transplantation Research Program
Director, Structural & Functional Genomics Laboratory

Contact

Nemours Biomedical Research
Administration and Research Building
Room 331
1600 Rockland Road
Wilmington, DE 19899

Phone: 302-651-5778
Fax: 302-651-6888
E-mail: lkrueger@nemours.org

Education

B.S.: Rutgers - The State University of New Jersey
M.S., Ph.D.: Johns Hopkins University
Postdoctoral: National Heart, Lung and Blood Institute
Postdoctoral: Rockefeller University

Research Interests

The main investigative goal of the Molecular Genetics, Cellular and Tissue Transplantation Laboratory is to identify and intervene in the mechanisms that result in increased morbidity and mortality in patients suffering from posttransplant disorders (PTLD).

Research: While transplantation is a life saving, curative and sustaining procedure, a small population of these children faces complications related to the lifelong requirement for immunomodulation. Using sophisticated genetic and proteomic technologies, we provide in concert with Stephen P. Dunn, M.D., Chief, Section of General Pediatric Surgery and Section of Solid Organ Transplantation and his staff, direct investigation into the complex mechanisms unique to the transplant population. We are focused on a drug that affects an evolutionarily conserved, universal metabolic pathway, the mTOR pathway. We are trying to extend the use of the drug from an immunosuppressant to an anti-lymphomagenic drug for PTLD. Other interests include targeted intervention in oncogene function. Finally, because of the impact of surgery in transplantation, we have recently fostered an interest in bleeding and clotting disorders. Additional cancer projects examine the role of integrating global DNA microarray technology to the more sensitive, but limited, real-time PCR. These efforts are enhanced by a long-standing multi-institutional alliance between the Center for Applied Genomics (CAG), Christiana Care Health Systems through the auspices of Brian W. Little, M.D., Ph.D., Vice President for Academic Affairs and Research, the Delaware Biotechnology Institute (DBI) and with Nicholas Petrelli, M.D., Medical Director, Helen F. Graham Cancer Center.

Diagnostic: Our molecular diagnostic goal is to develop and initiate "homebrew" diagnostics that are available real time to the medical community. In the Structural and Functional Genomics Core the clinical service is expanding greatly as it progresses from a specialized service for the pediatric transplant community to a central and more general molecular diagnostic service of the hospital. Because our primary goal remains providing state-of-the-art research into the areas that enhance the positive benefits of liver transplantation, we have an extensive educational program that is both translational and basic in scope. These experiences include fellow, resident, postdoctoral and undergraduate projects and are central to our mission.

Current Projects

• Mechanism of and therapeutic intervention in EBV-associated Posttransplant lymphoma in the chemically immunosuppressed child.
• Molecular Medicine in the Pediatric Diagnostic Laboratory.
• Genetic Predisposition for imbalances in hemostasis (clotters and bleeders); testing a new paradigm for organ donation.
• Novel drugs in Breast Cancer intervention - the role of the evolutionarily conserved mTOR pathway in epithelial cancers.

Research Group

• Valerie Sampson, Ph.D. - Research Associate (Ph.D., The University of the West Indies, Trinidad). Examining the low-molecular weight induced disassociation of the c-Myc-Max heterodimer in the cancerous growth induced by myc dysregulation in breast epithelial and Epstein Barr virus associated lymphoma cells. Integrated studies of c-myc transcripts and protein both in vitro and in vivo by c-myc inhibition. Non-invasive imaging of human breast cancer xenografts using a non-invasive ultrasound imaging system for measurement of tumor growth, neovascularization and their treatment-induced inhibition. Cancerous growth will be measured against direct effects of transcriptional inhibition as well as alteration in c-myc downstream targets.
• Nancy Rong, MT, M.D. - Research Assistant (M.D., Hunan Medical University, China). Focusing on the use of molecular medicine e.g., real time MGB-TaqMan PCR, pyrosequencing, etc in the measurement of specific targets in complex mixtures of nucleic acids. Develops and implements new diagnostic testing as defined by the clinical needs of Alfred I. duPont Hospital for Children and the Nemours enterprise. Other areas quantitative analysis of virus, genetic predisposition, genetic disease allelic discrimination and immune function.

Selected Publications

Gomez-Curet I., Perkins R.S., Dunn S.P., Feidler K.L., and Krueger L.J. C-Myc Inhibition Negatively Impacts Lymphoma Growth. American Journal of Pediatric Surgery (requested submission).

Dunn S.P., Tsai A., Griffin G., Toth S., Casas-Melley A., Falkenstein K., Marando C.A., and Krueger L.J. (2005). Liver Transplantation as Definitive Treatment for a Factor V Leiden Neonate. J Pediatr 146(3):418.

Faruqi S.A., Krueger, L.J. (2004). Substrate Dependent Genomic Heterogeneity in Cancers of the Lung. Cancer Therapy 2:69-74.

Casas A. et al. (2002). Domino Transplant as Bridge to Definitive Life-donor Transplantation in a Neonate. J Pediat Transplantation 6(3):249-254.

Dunn S.P., Krueger L.J., Butani L., and Punnet H. (2001). Late Onset of Severe Graft versus Host Disease in a Pediatric Liver Transplant Recipient. Transplantation 71:1-3.

Faruqi S.A., Noumoff J.S., and Krueger L.J. (2000). Evidence of Somatic Pairing in an Adenocarcinoma of the Lung. Cytologia 53:353-358.

Dunn S.P., and Krueger L.J. (1999). Immunosuppression of Pediatric Liver Transplant Recipients: Minimizing the Risk of Posttransplant Lymphoproliferative Disorders. Transplantation and Immunology Letter.

Wydner K.L., Li M., Singer-Granick C., Sciorra L.J., and Krueger L.J. (1995). X Microchromosome with Additional X Chromosome Anomalies Found in Turner Syndrome. Am J Med Genet 56:141-146.

Carrington M., Krueger L.J., Hosclaw D.S., Iannuzzi M., Dean M., and Mann D. (1994). Cystic Fibrosis-Related Diabetes is Associated with HLA DQB1 Alleles Encoding Asp-57- Molecules. J Clin Immunol 14:353-358.

Fletcher J.E., Calvo P.A., Krueger L.J., and Rosenberg H. (1993). Phenotypes Associated with Malignant Hyperthermia in Swine Genotyped as Homozygous or Heterozygous for the Ryanodine Receptor Mutation. Br J Anesthesia 71:410-417.

Dean M., White M.B., Gerrard B., Krueger L.J., Baranov V., Kapronov N., Iannuzzi M., Sebastio G., Leppert M., and Amos J. (1992). Genetic Analysis of Ion Transport. Hematology and Blood Transfusions 35, 194-198.

Dean M., Gerrard B., Stewart C., Krueger L.J., Holsclaw D., Quittell L., Baranov V., Kapronov N., Leppert, M., Amos J., and White M. (1991). Cystic Fibrosis Mutations. Adv Exp Med Biol 290, 45-51.

White M.B., Krueger L.J., Holsclaw D.S., Gerrard B., Stewart C., Quittell L., Dolganov G., Baranov V., Ivaschenko T., Kapronov N., Sebastio G., Castiglione O., and Dean, M. (1991). Rare and Widely Distributed Frame-shift Mutations in the Cystic Fibrosis Gene in an African-American (CF444delA) in an Italian (CF 2522 InsC) and in a Soviet (CF3821delT). Genomics 10, 266-269.

Krueger L.J., Lerner A., Katz S.M., Mack R., Holsclaw D.S., and Lebenthal, E. (1991). Cystic Fibrosis and Diabetes Mellitus: Interactive or Idiopathic? J Pediatric Gastroenterology and Nutrition 13, 209-19.

Fletcher J.E., Michaux K., and Krueger L.J. (1990). Fatty Acid Uptake and Catecholamine-stimulated Phospholipid Metabolism in Immortalized Airway Cells Established From Cystic Fibrosis Primary Cultures, International J Biochemistry 21, 733-740.

Katz S.M., Krueger L.J., and Falkner B. (1988). Microscopic Nephrocalcinosis in Cystic Fibrosis. New Eng J Med 319, 263-266.

Krueger L.J., Andryuk P.J., and Borigini M.J. (1986). Nucleic Acid Hybridization in Plasma: Method forthe Quantitation of Poly (I) Poly (C12,U) in Plasma of Cancer Patients. J Biol Response Modifiers 5, 539-7.

Krueger L.J., Benbow R.M., Caryk T.M., and Anderson W.F. (1978). Quantitative Synthesis of Full-size Globin Genes: Dependence on Templates. Biochem Biophys Res Commun 60-66.

Krueger L.J., Weiss G.B., Merrick W.C., Lloyd M.A., and Anderson W.F. (1976). Reverse Transcriptase:Cycling on Natural and Synthetic RNA Templates. Nature 260, 363-365.

Boyer S.H., Siggers D.C., and Krueger L.J. (1973). A Caveat to Protein Replacement Therapy for Genetic Disease. Lancet 2, 654-659.