Philadelphia University + Thomas Jefferson University

Wiest, David

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David L. Wiest, PhD

Contact Dr. Wiest

333 Cottman Avenue
Fox Chase Cancer Center 333
Philadelphia, PA 19111

(215) 728-2966
(215) 728-2412 fax

Research and Clinical Interests

T lymphocytes recognize and destroy invading pathogens through an assembly of proteins called the T cell antigen receptor (TCR) complex. The TCR has protein subunits that are highly variable and responsible for target recognition (either alpha-beta or gamma-delta) and subunits that are invariant proteins and serve to transmit signals (CD3gamma, delta, epsilon and zeta). This critical protein assembly (the TCR) controls not only the behavior of mature T lymphocytes but also their development in the thymus. My laboratory seeks to understand how T cell development is controlled by the TCR and how these developmental process are corrupted during development of cancer. As indicated above, there are two types of TCR variable proteins, alpha-beta and gamma-delta. Utilization of these alpha-beta and gamma-delta pairs characterizes two distinct types of T lineages, alpha-beta and gamma-delta, respectively. These two T lineages are thought to arise from a single immature precursor in the thymus. We are attempting to identify the cellular factors that are essential for transmitting the signals that direct fate adoption (i.e., alpha-beta and gamma-delta). We are also interested in identifying the downstream molecular targets of those signals that are essential for development of these two different T cell types. We hypothesize that genes, which are essential for normal cell development, are also likely to regulate development of cancer. Indeed, we have recently identified such a gene, which encodes a component of a cellular machine used to synthesize all cellular proteins. This component, termed Rpl22, is not only essential for normal T cell development, but also may contribute to development of human T cell cancers termed T acute lymphoblastic leukemia (T-ALL).

Publications

Most Recent Peer-Reviewed Publications

  1. Non-coding Transcription Instructs Chromatin Folding and Compartmentalization to Dictate Enhancer-Promoter Communication and T Cell Fate
  2. Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing
  3. The homeoprotein Dlx5 drives murine T-cell lymphomagenesis by directly transactivating Notch and upregulating Akt signaling
  4. Multisystem anomalies in severe combined immunodeficiency with mutant BCL11B
  5. Rpl22 loss selectively impairs αβ T cell development by dysregulating endoplasmic reticulum stress signaling
  6. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects
  7. Ribosomal protein Rpl22 controls the dissemination of T-cell lymphoma
  8. Appl1 and Appl2 are Expendable for Mouse Development But Are Essential for HGF-Induced Akt Activation and Migration in Mouse Embryonic Fibroblasts
  9. The BRCA1-Δ11q alternative splice isoform bypasses germline mutations and promotes therapeutic resistance to PARP inhibition and cisplatin
  10. Development of γδ T Cells, the Special-Force Soldiers of the Immune System
  11. Using the Zebrafish model to study T cell development
  12. Kri1l: a novel gene that links defective ribosome biogenesis to impaired hematopoiesis through excessive autophagy
  13. Development of γδ T cells, the special-force soldiers of the immune system
  14. Using the zebrafish model to study T cell development
  15. Mutagenesis screen identifies agtpbp1 and eps15L1 as essential for T lymphocyte development in zebrafish
  16. Rpl22 loss impairs the development of B lymphocytes by activating a p53-dependent checkpoint
  17. Regulatory roles of Rpl22 in hematopoiesis: An old dog with new tricks
  18. Enforcement of γδ-lineage commitment by the pre-T-cell receptor in precursors with weak γδd-TCR signals
  19. The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification
  20. Fli-1 regulates the DN2 to DN3 thymocyte transition and promotes γδ T-cell commitment by enhancing TCR signal strength