David Wiest, PhD

David Wiest, PhD

Deputy Chief Scientific Officer


Co-Leader, Blood Cell Development and Function

Colorectal and SI Cancer TRDG Member

Leukemia and MDS TRDG Member

Lymphoma and CLL Cancer TRDG Member

Director, Cell Sorting Facility

Research Program

Schematic of role of TCR signaling in fate adoption
Model by which prolonged ERK signals promote adoption of distinct fates
Extraribosomal functions of Rpl22 and Rpl22-like1 (Like1)
Control of hematopoietic stem cell emergence by Rpl22/Like1 antagonism
Antagonistic regulation of RNA splicing by Rpl22 and Like1
Analysis of Bcl11b candidate from a leaky SCID patient


Education and Training

Educational Background

  • Postdoctoral training, Developmental Immunology, NIH, 1995
  • PhD, Immunology, Duke University, 1991
  • BS, Microbiology, Penn. State University, 1984

Honors & Awards

  • NCI Board of Scientific Counselors
  • Senior Research Excellence Award, Temple Translational Science Symposium
  • American Cancer Society Southeastern Pennsylvania Research Award
  • Bucks County Board of Associates Key to the Chapter Award
  • Elected to Henry Kunkel Society
  • Inspired Leadership Award
  • Member, Program Committee, American Association of Immunologists
  • Member Faculty of 1000, Leukocyte Development Section
  • Member, CMIB study section
  • Cancer Research Institute Fellow
  • Norman F. Conant Award for Excellence in Research
Research Profile

Research Program

Research Interests

T lymphocyte development and transformation

  • Molecular basis for specification of the two major T lymphocyte lineages, αβ and γδ
  • Regulatory functions of the ribosomal protein Rpl22 in hematopoiesis, lymphoid development, and leukemogenesis
  • Using zebrafish to identify disease-causing genes in immunodeficient humans

Lab Overview

T lymphocyte development and transformation

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 αβ or γδ) and subunits that are invariant proteins and serve to transmit signals (CD3γδε and ζ). 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 processes are corrupted during development of cancer. In doing so, we exploit the zebrafish and mouse models, as well as both normal and transformed human hematopoietic cells... Expand

Lab Staff

Alejandra Contreras, PhD

Postdoctoral Fellow

Room: R364

Robert Sertori, PhD

Postdoctoral Fellow

Room: R364

Paul Harvilla, BS

Graduate Student, University of the Sciences

Room: R364

Ninnka Tamot, BS

Graduate Student, University of the Sciences

Room: R364

Yong Zhang, MD, PhD

Research Assistant Professor

Room: R364

Dinesh Singh, PhD

Research Associate

Room: R364

Michele Rhodes, BS

Scientific Assistant

Room: R364

Selected Publications

Rao, S., Peri, S., Hoffman, J., Cai, K.Q., Harris, B., Rhodes, M., Connolly, D.C., Testa, J.R., and Wiest, D.L. 2019. Rpl22L1 overexpression confers 5-FU resistance in colorectal cancer. PLOS One 14:e0222392. PMC6776433

Fahl, S.P., Coffey, F., Kain, L., Zarin, P., Teyton, L., Zúñiga-Pflücker, J.C., Kappes, D.J., and Wiest, D.L. 2018.  Role of a selecting ligand in shaping the gd TCR repertoire. PNAS 115:1889-1894. PMC5828614

Fahl SP, Wiest DL. 2018. Reply to Chien: Clarification of the effect of ligand on γδ-TCR repertoire selection. PNAS 115:E3607-E3608. PMC5910880

Tyner, J.W., Tognon, C.E., Bottomly, D., Wilmot, B., Kurtz, S.E., Savage, S.L., Long, N., Schultz, A.R., Traer, E., Abel, M., Agarwal, A., Blucher, A., Borate, U., Bryant, J., Burke, R., Carlos, A., Carpenter, R., Carroll, J., Chang, B.H., Coblentz, C., d'Almeida, A., Cook, R., Danilov, A., Dao, K.T., Degnin, M., Devine, D., Dibb, J., Edwards, D.K. 5th, Eide, C.A., English, I., Glover, J., Henson, R., Ho, H., Jemal, A., Johnson, K., Johnson, R., Junio, B., Kaempf, A., Leonard, J., Lin, C., Liu, S.Q., Lo, P., Loriaux, M.M., Luty, S., Macey, T., MacManiman, J., Martinez, J., Mori, M., Nelson, D., Nichols, C., Peters, J., Ramsdill, J., Rofelty, A., Schuff, R., Searles, R., Segerdell, E., Smith, R.L., Spurgeon, S.E., Sweeney, T., Thapa, A., Visser, C., Wagner, J., Watanabe-Smith, K., Werth, K., Wolf, J., White, L., Yates, A., Zhang, H., Cogle, C.R., Collins, R.H., Connolly, D.C., Deininger, M.W., Drusbosky, L., Hourigan, C.S., Jordan, C.T., Kropf, P., Lin, T.L., Martinez, M.E., Medeiros, B.C., Pallapati, R.R., Pollyea, D.A., Swords, R.T., Watts, J.M., Weir, S.J., Wiest, D.L., Winters, R.M., McWeeney, S.K., Druker, B.J. 2018. Functional genomic landscape of acute myeloid leukaemia. Nature 562:526-531. PMC6280667

Wiest, D.L. 2018. Gadd45 stress sensors in suppression of leukemia. Oncotarget 28:34191-34192. PMC6188131

Isoda, T., Moore, A.J., He, Z., Chandra,V., Aida, M., Denholtz, M., van Hamburg, J.P., Fisch, K.M., Chang, A.N., Fahl, S., Wiest, D.L., Murre, C.  2017. Non-Coding RNA ThymoD Regulates Compartmentalization and Chromatin Folding to Orchestrate T Cell Fate. Cell 171:103-119. PMC5621651

Somech, R., Lev, A., Lee, Y.N., Simon, A.J., Barel, O., Schiby, G., Avivi, C., Barshack, I., Rhodes, M., Yin, J., Wang, M., Yang, Y., Rhodes, J., Marcus, N., Garty, B.-Z., Stein, J., Amariglio, N., Rechavi, G., Wiest, D.L*, and Zhang, Y*. 2017 Disruption of thrombocyte and T lymphocyte development by a mutation in ARPC1B. J. Immunol. 199:4036-4045. * - co-corresponding authors; PMC5726601

Wiest, D.L. 2017. Themis-tery is solved. Nat. Immunol., 18: 368-370. PubMed

Zhang, Y., O’Learly, M.N., Peri, S., Zha, J., Melov, S., Kappes, D.J., Feng, Q., Rhodes, J., Amieux, P.S., Morris, D.R., Kennedy, B.K., and Wiest, D.L. 2017. Ribosomal proteins Rpl22 and Rpl22l1 control morphogenesis by regulating pre-mRNA splicing. Cell Reports 18:545-556. PMC5234864

Fahl, S.P., Coffey, F., MacCormick, D, and Wiest, D.L. 2016. Control of T cell development by TCR signals. Encyclopedia of Immunology Vol. 1:234–241. PubMed

Fahl, S.P., Kappes, D.J., and Wiest, D.L. 2016. TCR signaling circuits in αβ/γδ T lineage choice. In, CRC Methods in Signal Transduction: T cell diversity and function. CRC Press. Editors: Jonathan Soboloff and Dietmar J. Kappes. PubMed

Punwani, D.*, Zhang, Y.*, Yu, J., Cowan, M.J., Kwan, A., Mendelsohn, B.A., Sunderam, U. Srinivasan, R., Brenner, S., Wiest, D.L.*, and Puck, J.M.* 2016. Bcl11b defect in human severe combined immunodeficiency with multisystem anomalies. NEJM 375:2165-2176. PMC5215776 *Contributed equally; Selected for preview; Nominated to F1000. PubMed

Rao, S., Cai, K.Q., Stadanlick, J.E., Greenberg-Kushnir, N., Solanki-Patel, N., Lee, S.-Y., Testa, J.R., and Wiest, D.L. 2016. Ribosomal protein Rpl22 controls the dissemination of T cell Lymphoma. Cancer Research 76:3387-3396. PMC4891229

Simon, A.J., Lev, A., Zhang, Y., Weiss, B., Rylova, A., Eyal, E., Kol, N., Barel, O., Cesarkas, K., Soudack, M., Greenberg-Kushnir, N., Rhodes, N., Wiest, D.L., Schiby, G., Barshack, I., Katz, S., Pras, E., Poran, H., Reznik-Wolf, H., Ribakovsky, E., Simon, C., Hazou, W., Sidi, Y., Lahad, A., Katzir, H., Glousker, G., Amariglio, N., Tzfati, Y., Selig, S., Rechavi, G., and Somech, R. 2016. Mutations in stn1 cause coats plus syndrome and are associated with genomic and telomere defects. J. Exp. Med. 213:1429-1440. PMC4986528

Solanki, N.R., Stadanlick, J.E., Zhang, Y., Duc, A.-C., Lee, S.-Y., Lauritsen, J.P.H., Zhang, Z., and Wiest, D.L. 2016. Rpl22 loss selectively impairs αβ T cell development by dysregulating ER stress signaling. J. Immunol. 197:2280-9. PMC5011012 Highlighted in “In This Issue”. PubMed... Expand

Additional Publications


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