? Hematologic Malignancies Program The Hematologic Malignancies (HM) Program drives basic scientific discoveries and translates them into novel therapeutics for patients with myeloid and lymphoid neoplasms. Formed in 1994, the Program has two scientific aims: 1) Develop a mechanisms-based understanding of the genetic, cellular, and biochemical processes regulating malignant hematopoiesis; and 2) Translate basic scientific discoveries into more effective and less toxic therapies for hematologic malignancies. Areas of national expertise include molecular processes (epigenetic, transcriptional, translational, signaling) underlying malignant hematopoiesis; hematopoietic stem cell biology and transplantation; molecular therapeutics; and immune-based therapies. Annual average accrual to interventional clinical trials has more than doubled this funding period compared to the prior, with heavy emphasis on investigator-initiated trials. Program members are heavy users of Shared Resources (e.g. Transgenic and Chimeric Mouse, Flow Cytometry and Cell Sorting, Human Immunology, Biostatistics and Bioinformatics, and Genomic Analysis) and have wide-ranging collaborations with members of multiple other Programs. The Program is co-led by Dr. Edward Stadtmauer, an expert in clinical trials of novel therapeutics for hematologic malignancies and blood and marrow transplantation, and Dr. Nancy Speck, an internationally known basic scientist working in the area of hematopoietic stem cells and leukemia. The Program's 29 members come from seven departments in the Perelman School of Medicine. Investments by the ACC include an innovative Hematologic Malignancies Translational Center of Excellence (TCE) co-led by Dr. Stadtmauer, as well as an emerging Lymphoid Malignancy TCE co-led by Drs. Stephen Schuster and Megan Lim. These and other investments have galvanized an already successful Program by expanding resources for laboratory, tissue banking, and clinical research and providing pilot grant funding. Scientific accomplishments this funding period include studies garnering multiple FDA approvals (CAR T cell therapy for adults with relapsed and refractory B cell non-Hodgkin's lymphoma; gilteritinib for refractory acute myeloid leukemia with FLT3 mutations; and selinexor, a first-in-class oral nuclear transport inhibitor for `penta-refractory' multiple myeloma). Basic discoveries revealed novel tumor-cell intrinsic pathways such as the demonstration that kelch-like 6 (KLHL6) functions as an E3 ubiquitin ligase, and KLHL6 mutations in lymphoma increase NF-?B signaling. Weekly seminars, collaborative grants, weekly clinical working group meetings, and an annual research retreat facilitate member interactions. Currently, members have research funding totaling $16.2M (direct), of which $5.8M is peer-reviewed and $1.9M is from the NCI. There are 20 R01-equivalents held by our members. During the project period, members published 450 cancer relevant publications, of which 32% were intra- Programmatic, 25% were inter-Programmatic and 73% were multi-institutional. The Program enrolled 1,567 subjects onto interventional trials this project period, and 2,162 subjects onto non-interventional trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA016520-45
Application #
10088746
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
1997-01-15
Project End
2025-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
45
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Bengsch, Bertram; Ohtani, Takuya; Khan, Omar et al. (2018) Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells. Immunity 48:1029-1045.e5
Krump, Nathan A; Liu, Wei; You, Jianxin (2018) Mechanisms of persistence by small DNA tumor viruses. Curr Opin Virol 32:71-79
Bhagwat, Neha; Dulmage, Keely; Pletcher Jr, Charles H et al. (2018) An integrated flow cytometry-based platform for isolation and molecular characterization of circulating tumor single cells and clusters. Sci Rep 8:5035
Nair, Praful R; Alvey, Cory; Jin, Xiaoling et al. (2018) Filomicelles Deliver a Chemo-Differentiation Combination of Paclitaxel and Retinoic Acid That Durably Represses Carcinomas in Liver to Prolong Survival. Bioconjug Chem 29:914-927
Kasner, Margaret T; Mick, Rosemarie; Jeschke, Grace R et al. (2018) Sirolimus enhances remission induction in patients with high risk acute myeloid leukemia and mTORC1 target inhibition. Invest New Drugs 36:657-666
Raposo-Ferreira, Talita M M; Brisson, Becky K; Durham, Amy C et al. (2018) Characteristics of the Epithelial-Mesenchymal Transition in Primary and Paired Metastatic Canine Mammary Carcinomas. Vet Pathol 55:622-633
Huffman, Austin P; Richman, Lee P; Crisalli, Lisa et al. (2018) Pharmacodynamic Monitoring Predicts Outcomes of CCR5 Blockade as Graft-versus-Host Disease Prophylaxis. Biol Blood Marrow Transplant 24:594-599
Karakasheva, Tatiana A; Lin, Eric W; Tang, Qiaosi et al. (2018) IL-6 Mediates Cross-Talk between Tumor Cells and Activated Fibroblasts in the Tumor Microenvironment. Cancer Res 78:4957-4970
Yam, Clinton; Xu, Xiaowei; Davies, Michael A et al. (2018) A Multicenter Phase I Study Evaluating Dual PI3K and BRAF Inhibition with PX-866 and Vemurafenib in Patients with Advanced BRAF V600-Mutant Solid Tumors. Clin Cancer Res 24:22-32
Huang, Mo; Wang, Jingshu; Torre, Eduardo et al. (2018) SAVER: gene expression recovery for single-cell RNA sequencing. Nat Methods 15:539-542

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