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Dr. Daniel J. Powell Jr., Ph.D.
Imagine going to work each day and having an unlimited Erector set available to you; everyday you expand upon the foundation you laid the day before. Thus is the life of a scientist.
”You’re a what?!”
I’m a Tumor Immunologist.
“Really. So…you uh…”
I study the interaction between the immune system and cancer, and try to design novel ways to allow a patient’s own immune system to attack and eliminate their cancer.
My scientific career began in 1996 under the mentorship of Dr. Jay L. Rothstein, Ph.D. at Thomas Jefferson University in Philadelphia, PA focusing on the oncogenic induction and immunology of thyroid carcinoma in the RET/PTC3 mouse model system. I finished up my graduate work on Friday April 26th 2002, and headed south to the Washington D.C. area to begin my postdoctoral training in the Surgery Branch of the National Cancer Institute under the direction and guidance of Dr. Steven A. Rosenberg, M.D., Ph.D., beginning on Monday April 29th 2002. Five years later, I’m still at it….
The picture above shows multiple members of the Surgery Branch including Dr. Rosenberg (left, front) and myself (right, front) at the 2005 Tumor Immunology Conference in Keystone, Colorado.
Here is a brief collection of papers from the vault:
(Note: for pdfs that wont open readily, save a copy to your desktop and open that file)
"Administration of a CD25-Directed Immunotoxin, LMB-2, to Patients with Metastatic Melanoma Induces a Selective Partial Reduction in Regulatory T Cells In Vivo" Journal of Immunology Article; describes a clinical effort to selectively eliminate Treg cells in vivo using a CD25-directed immunotoxin.
"Structures of MART-1(26/27-35) Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition" Journal of MolecularBiology; describes the structural analysis and T cell recognition of the native MART-1:27-25 peptide/HLA-A2 complex.
"Inability to Mediate Prolonged Reduction of Regulatory T Cell After Transfer of Autologous CD25-depleted PBMC and Interleukin-2 After Lymphodepleting Chemotherapy" Journal of Immunotherapy Article; describes the adoptive transfer of CD25+ Treg cell-depleted PBMC and IL-2 to lymphodepleted patients with metastatic melanoma.
"Persistence of Tumor Infiltrating Lymphocytes in Adoptive Immunotherapy Correlates With Telomere Length" Journal of Immunotherapy Article; describes the association between the persistence of transferred TIL in vivo and their telomere length.
"Adoptive Transfer of Vaccine-Induced Peripheral Blood Mononuclear Cells to Patients with Metastatic Melanoma following Lymphodepletion" Journal of Immunology Article; describes our clinical effort to treat malignant melanoma through adoptive transfer of vaccine-induced T cells.
"Gene Transfer of Tumor-Reactive TCR Confers Both High Avidity and Tumor Reactivity to Nonreactive Peripheral Blood Mononuclear Cells and Tumor-Infiltrating Lymphocytes" Journal of Immunology Article; details the identification, cloning and transfer of high affinity, MART-1 antigen-reactive TCRs for gene therapy
"Adoptive immunotherapy for cancer: building on success" Nature Reviews Immunology Article is a "view from the front" review, summarizing the current status and options for improving adoptive immunotherapy for cancer.
"Selective Elimination of Human Regulatory T Lymphocytes In Vitro With the Recombinant Immunotoxin LMB-2" Journal of Immunotherapy Article; describes the use of a CD25-directed immunotoxin for the elimination of regulatory T cells in vitro.
"Large scale depletion of CD25+ regulatory T cells from patient leukapheresis samples" Journal of Immunotherapy Article; details a "brute force", immunomagnetic approach for eliminating regualtory T cells from patient peripheral blood samples.
"Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy" An article in Blood which revealed that tumor-specific T cells with a "less-differentiated" phenotype, including IL-7Ra expression, appear best capable of in vivo persistence after autologous infusion.
*** "Long Live T cells" by L.J.N. Cooper is a commentary on this Blood article"
*** "Immunotherapy: MEMORY" by N. McCarthy featured the Blood article as Highlighted Research in Nature Reviews Cancer
"Cutting Edge: Persistence of Transferred Lymphocyte Clonotypes Correlates with Cancer Regression in Patients Receiving Cell Transfer Therapy" in the Journal of Immunology reveals the correlation between transferred T cell persistence and tumor regression in patients recieving adoptive immunotherapy for melanoma
"Phenotypic and Functional Maturation of Tumor Antigen-Reactive CD8+ T Lymphocytes in Patients Undergoing Multiple Course Peptide Vaccination" in Journal of Immunotherapy was my first Surgery Branch manuscript, that described the impact of repetitive vaccination on antigen-specific T cell expansion, differentiation and function.
"A Thyroid Tumor-Specific Antigen Formed by the Fusion of Two Self Proteins" in the Journal of Immunology, reveals the immunogenic nature of the oncogenic RET/PTC3 chimeric protein
"Altered gene expression in immunogenic poorly differentiated thyroid carcinomas from RET/PTC3p53-/- mice" in Oncogene, proposes a hypothetical model of gene acquisition and loss during the development of human thyroid carcinoma
"The TRK-T1 fusion protein induces neoplastic transformation of thyroid epithelium" in Oncogene, demonstrates the oncogenic nature of the TRK-T1 fusion protein in a mouse model
"Metastatic Solid / Insular Papillary Thyroid Carcinomas in RET/PTC3 Transgenic Mice" in Cancer Research, describes the generation and phenotype of RET/PTC3 transgenic mice which develop thyroid hyperplasia and solid tumor variants of papillary carcinoma analogous to human disease
My magnum opus: "THE RET/PTC3 FUSION PROTEIN: AN IMMUNOGENIC ONCOPROTEIN IN THYROID CARCINOMA"
A Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy
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