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).


Most Recent Peer-Reviewed Publications

  1. REPLY TO CHIEN: Clarification of the effect of ligand on γδ-TCR repertoire selection
  2. Role of a selecting ligand in shaping the murine γδ-TCR repertoire
  3. Disruption of thrombocyte and T lymphocyte development by a mutation in ARPC1B
  4. HEB is required for the specification of fetal IL-17-producing γδ T cells
  5. Non-coding Transcription Instructs Chromatin Folding and Compartmentalization to Dictate Enhancer-Promoter Communication and T Cell Fate
  6. JUN is a key transcriptional regulator of the unfolded protein response in acute myeloid leukemia
  7. THEMIS-tery is solved
  8. Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing
  9. The homeoprotein Dlx5 drives murine T-cell lymphomagenesis by directly transactivating Notch and upregulating Akt signaling
  10. Multisystem anomalies in severe combined immunodeficiency with mutant BCL11B
  11. Rpl22 loss selectively impairs αβ T cell development by dysregulating endoplasmic reticulum stress signaling
  12. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects
  13. Ribosomal protein Rpl22 controls the dissemination of T-cell lymphoma
  14. Appl1 and Appl2 are Expendable for Mouse Development But Are Essential for HGF-Induced Akt Activation and Migration in Mouse Embryonic Fibroblasts
  15. The BRCA1-Δ11q alternative splice isoform bypasses germline mutations and promotes therapeutic resistance to PARP inhibition and cisplatin
  16. Control of Early T Cell Development by Notch and T Cell Receptor Signals
  17. Development of γδ T Cells, the Special-Force Soldiers of the Immune System
  18. Using the Zebrafish model to study T cell development
  19. Kri1l: a novel gene that links defective ribosome biogenesis to impaired hematopoiesis through excessive autophagy
  20. Development of γδ T cells, the special-force soldiers of the immune system