The Hematologic Malignancies Research Program at the University of New Mexico Cancer Center is a highly interactive transdisciplinary program with 25 Program Members from 4 Departments in the UNM School of Medicine (Medicine, Molecular Genetics and Microbiology, Pathology, and Pediatrics), 2 Departments on the UNM Main Campus (Mathematics, and Physics and Astronomy), and Los Alamos and Sandia National Laboratories. Research conducted by program members spans from the most basic interdisciplinary research, to translational investigations using human tissues and animal model systems, to the design of cancer clinical trials. The goals of the program are to: 1) use comprehensive genomic technologies and model systems to study the transcriptional regulation of hematopoiesis and the gene expression patterns of normal and leukemic cells in order to discover novel underlying genetic lesions in leukemia that may serve as new therapeutic targets;2) functionally characterize, image, and model signaling and adhesion pathways in normal and leukemic cells in order to understand how unique genetic abnormalities perturb these pathways to promote leukemogenesis and to identify targets for therapeutic intervention;and 3) translate program science and discoveries to novel diagnostic and therapeutic strategies and clinical trials at the UNM Cancer Center and within the NCI Cooperative Groups. Program members have used sophisticated genomic and computational technologies to develop gene expression classifiers for outcome prediction in leukemia and discover novel therapeutic targets in this disease (JAK2 mutations, CRLF2 activation, Metnase) that are being translated to clinical trials. These and other targets are also being studied in pre-clinical murine xenograft models to define the biochemical consequences of how these mutations perturb signaling pathways and to develop and test novel therapeutics. The development of advanced live cell imaging and spatiotemporal modeling technologies in the program are supporting high profile studies of receptors and signaling pathways involved in leukemogenesis. Since 2005, the program's funding and intra- and inter-programmatic interactions have significantly increased. Program members hold 3 interdisciplinary, multi-investigator, programmatic grants (one of 10 NIH National Centers for Systems Biology {P50GM085273;PI: Oliver);an LLS Specialized Center for Research in Leukemia {7388-06;PI: Willman);and a NCI Strategic Partnerships Grant {U01CA114762;PI: Willman)) and launched the first NCI TARGET Project to identify new therapeutic targets in high-risk pediatric ALL. Program members and their collaborators at St. Jude Children's Hospital and in the Children's Oncology Group have been notified of the awarding of a NCI ARRA TARGET Grant and a NCI ARRA Grand Opportunities Grant to continue to translate their work to leukemia clinical trials. As of September 2009, program members held $9,967,007 in total annual direct funding (representing a 44% increase in funding since 2005) of which $9,131,453 was peer-reviewed;annual direct NCI funding to the program has increased 55% to $2,448,182. In 2008, program members published a total of 64 cancer-relevant publications, of which 41 were intra-programmatic and 19% were inter-programmatic.

Public Health Relevance

The Hematologic Malignancies Research Program integrates a team of transdisciplinary basic, translational, and clinical scientists who use highly sophisticated genomic, computational, imaging, and modeling approaches in human leukemia specimens and animal model systems to study how novel underlying genetic mutations in leukemia perturb gene expression and signaling and adhesion pathways to promote leukemogenesis. Discoveries are actively being translated to new diagnostic strategies and therapeutic modalities at the UNM Cancer Center and within the NCI Cooperative Oncology Groups.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
3P30CA118100-09S2
Application #
8723101
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
9
Fiscal Year
2013
Total Cost
$6,251
Indirect Cost
$2,111
Name
University of New Mexico Health Sciences Center
Department
Type
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Flook, Adam M; Yang, Jianquan; Miao, Yubin (2014) Substitution of the Lys linker with the ?-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated ?-melanocyte stimulating hormone peptides. J Med Chem 57:9010-8
Davies, Suzy; Holmes, Anna; Lomo, Lesley et al. (2014) High incidence of ErbB3, ErbB4, and MET expression in ovarian cancer. Int J Gynecol Pathol 33:402-10
Wu, Yang; Tapia, Phillip H; Jarvik, Jonathan et al. (2014) Real-time detection of protein trafficking with high-throughput flow cytometry (HTFC) and fluorogen-activating protein (FAP) base biosensor. Curr Protoc Cytom 67:Unit 9.43.
Morris, K T; Khan, H; Ahmad, A et al. (2014) G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration. Br J Cancer 110:1211-20
Vaughan, Roger A; Gannon, Nicholas P; Garcia-Smith, Randi et al. (2014) ?-alanine suppresses malignant breast epithelial cell aggressiveness through alterations in metabolism and cellular acidity in vitro. Mol Cancer 13:14
Lu, Jie; Hathaway, Helen J; Royce, Melanie E et al. (2014) Introduction of D-phenylalanine enhanced the receptor binding affinities of gonadotropin-releasing hormone peptides. Bioorg Med Chem Lett 24:725-30
Campen, Matthew J; Paffett, Michael L; Colombo, E Sage et al. (2014) Muscle RING finger-1 promotes a maladaptive phenotype in chronic hypoxia-induced right ventricular remodeling. PLoS One 9:e97084
Yang, Jianquan; Flook, Adam M; Feng, Changjian et al. (2014) Linker modification reduced the renal uptake of technetium-99m-labeled Arg-Ala-Asp-conjugated alpha-melanocyte stimulating hormone peptide. Bioorg Med Chem Lett 24:195-8
Hill, Jeff W; Thompson, Jeffrey F; Carter, Mark B et al. (2014) Identification of isoxsuprine hydrochloride as a neuroprotectant in ischemic stroke through cell-based high-throughput screening. PLoS One 9:e96761
Scaling, Allison L; Prossnitz, Eric R; Hathaway, Helen J (2014) GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast. Horm Cancer 5:146-60

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