We are attempting to harness the immune system to cure child leukemia and to use blood-derived stem cells to cure other life threatening childhood diseases.

My work has evaluated clinically driven issues related to hematopoietic cell transplantation. Clinical investigations have focused on age-related factors affecting graph-versus-host disease (GVHD), graft-failure and graft-versus-leukemia (GVL). Laboratory investigations have used pre-clinical models and the performance of correlative studies in humans to investigate the mechanisms of GVHD and GVL and to develop experimental approaches to modulate these phenomena.

Our laboratory has evaluated the hypothesis that manipulation of MHC class II antigen presentation can alter T cell responses to endogenous antigens. We have investigated the importance of two MHC class II antigen presenting cells in vivo, B cells and dendritic cells, for T cell priming responses to leukemia, and minor histocompatibility antigens (MiHC). We have also investigated whether inhibition of MHC class II antigen presentation by lysosomotropic agents such as chloroquine can inhibit T cell responses to MiHC and development of GVHD. We have translated these pre-clinical observations into clinical studies. More recent investigations are evaluating the activity of 4-aminoquinolines on immune stimulatory motifs of unmethylated CpG oligodeoxynucleotides and their role in GVHD and induction of responses against ALL.

We are also investigating approaches to increasing T cell responses to leukemia by immunization approaches focused on overcoming defects in antigen presentation of endogenous antigens that are either specific to the malignancy or over-expressed in the malignancy. We have focused on the ability of all cells to act as antigen presenting cells.

Grupp SA, Frangoul H, Wall D, Pulsipher MA, Levine JE, Schultz KR. Use of G-CSF in Matched Sibling Donor Pediatric Allogeneic Transplantation: A Consensus Statement from the Children's Oncology Group (COG) Transplant Discipline Committee and Pediatric Blood and Marrow Transplant Consortium (PBMTC) Executive Committee. Pediatr Blood Cancer. 2006 Apr;46(4):414-21.

Schultz KR, Miklos DB, Fowler D, Cooke K,  Shizuru J, Emmanuel E, Holler E, Ferrara J, Shulman H, Lee SJ, Martin P, Filipovich AH, Flowers MED, Weisdorf D, Couriel D, Lachenbruch PA, Mittleman B, Vogelsang GB15, Pavletic SZ Towards Biomarkers For Chronic Graft Versus Host Disease: NIH Consensus Development Project On Criteria For Clinical Trials In Chronic Graft-Versus-Host Disease: III Biomarker Working Group Report  Biol Blood Marrow Transplant 2006 Feb;12(2):126-137.

Jastaniah WA, Alessandri AJ, Reid GSD, Schultz KR HLA-DM expression is elevated in ETV6-AML1 translocation positive pediatric acute lymphoblastic leukemia Leukemia Res 2005 Sep 24.

Reid GS, She K, Terrett L, Food MR, Trudeau JD, Schultz KR. CpG stimulation of precursor B lineage acute lymphoblastic leukemia induces a distinct change in costimulatory molecule expression and shifts allogeneic T cells towards a Th1 response. Blood. 2005 105:3641-7.

Shier LR, Schultz KR, Imren S, Regan J, Issekutz A, Sadek I, Gilman A, Panzarella T, Eaves CJ, Couban S. Differential Effects of G-CSF on Marrow and Blood-Derived Hematopoietic and Immune Cell Populations in Healthy Human Donors. Biol Blood Marrow Transplantation St ;10(9):624-34,2004.
 
Schultz KR, Reid G. The Unique Biology and Characteristics of TEL-AML1 (ETV6-CBFA2) Acute Lymphoblastic Leukemia: Potential Therapeutic Approaches. ASCO Educational Book (In press), 2004.
 
Reid GSD, Terrett L, Allessandri A, Grubb S, Stork L, Seibel N, Gaynon P, Schultz KR. Altered Patterns of T Cell Cytokine Production Induced by Relapsed Pre-B ALL Cells/ :eil Res 2-3'27(12):1135-42.
 
Schultz KR, Su WN, Hsiao C-C, Jevon G, Bader S, Gilman AL. Chloroquine Prevention Of Murine MHC Disparate Acute Graft-Versus-Host Disease Correlates With Inhibition Of Spleenic Response To CpG Oligodeoxynucleotides And Alterations In T Cell Cytokine Production, Biol Blood Marrow Transplant 8(12):648-55, 2002.
  
Alessandri AJ, Reid GS, Bader SA, Massing BG, Sorensen PH, Schultz KR. ETV6 (TEL)-AML1 pre-B acute lymphoblastic leukaemia cells are associated with a distinct antigen-presenting phenotype. Br J Haematol. 116:266-72, 2002.
 
Reid G, Bharya S and Schultz KR. Phosphoinositide-dependent and -independent natural cell killing of pre-B acute lymphoblastic leukemia cells by IL-2 activated NK cells and NK-92ci Clin Exp Immunol. 129:265-271, 2002. 

Soudabeh Aslanian - Lab manager
Hiromi Shimizu - Lab technician
Dr. Hisaki Fujii - Postdoctoral fellow

Stanley Soto - PBMTC co-ordinator, Arcadia, California

Nita Takeuchi - Senior research associate
Lejla Gavranovic - Clinical research associate