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

Shawn P. Fahl, PhD

Postdoctoral Fellow

Room: R364

Bryan Harris, BS

MD/PhD Student, Temple University

Room: R364

Michele Rhodes, BS

Scientific Assistant

Room: R364

Minshi Wang, PhD

Postdoctoral Fellow

Room: R364

Yong Zhang, MD, PhD

Research Associate

Room: R364

Selected Publications

Fahl SP, Coffey F, Kain L, Zarin P, Dunbrack RL, Jr., Teyton L, Zuniga-Pflucker JC, Kappes DJ, Wiest DL. Role of a selecting ligand in shaping the murine gammadelta-TCR repertoire. Proceedings of the National Academy of Sciences of the United States of America, 115(8):1889-94, 2018. PMC5828614

Fahl SP, Coffey F, Kain L, Zarin P, Dunbrack RL, Jr., Teyton L, Zuniga-Pflucker JC, Kappes DJ, Wiest DL. Role of a selecting ligand in shaping the murine gammadelta-TCR repertoire. Proc Natl Acad Sci U S A, 115(8):1889-94, 2018. PMC5828614

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. NIHMS838496

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. NIHMS836417

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 ab T cell development by dysregulating ER stress signaling. J. Immunol. 197:2280-9. NIHMS803835

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

Lee, S.-Y., Coffey, F., Fahl, S.P., Peri, S., Rhodes, M., Cai, K.Q., Carleton, M., Hedrick, S.M., Fehling, H.J., Zúñiga-Pflücker, J.C., Kappes, D.J., and Wiest, D.L. 2014. Non-canonical mode of ERK action controls alternative αβ and γδ T lineage fates. Immunity 41:934–946. PubMed

Coffey, F., Lee, S.-Y., Buus, T.B., Lauritsen, J.-P.H., Wong, G.W., Zúñiga-Pflücker, J.C., Kappes, D.J., and Wiest, D.L. 2014. The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification. J. Exp. Med. 211:329-43. PubMed

Zhang, Y., Duc, A.-C.E., Rao, S., Sun, X.-L., Bilbee, A.N., Rhodes, M., Li, Q., Kappes, D.J., Rhodes, J., and Wiest, D.L., 2013. Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs. Dev. Cell 24:411-425. PubMed

Rao, S., Lee, S.Y., Gutierrez, A., Perrigoue, J., Thapa, R.J., Tu, Z., Jeffers, J.R., Rhodes, M., Anderson, S., Oravecz, T., Hunger, S.P., Timakhov, R.A., Zhang, R., Balachandran, S., Zambetti, G., Testa, J.R., Look, A.T., and Wiest., D.L. 2012. Inactivation of the ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 120:3764-3773. PubMed

Roberts, J.L., Buckley, R.H., Liu, B., Pei, J., Lapidus, A., Peri, S., Wei, Q., Shin, J.,. Parrott, R.E., Dunbrack, R., Testa, J.R., Zhong, X.-P., and Wiest, D.L. 2012. CD45 deficient severe combined immunodeficiency caused by uniparental disomy. PNAS 109:10456-10461. PubMed

Lauritsen, J.P.H., Wong, G.W., Lee, S.Y., Lefebvre, J.M., Ciofani, M., Rhodes, M., Kappes, D.J., Zúñiga-Pflücker, J.C., and Wiest, D.L. 2009. Marked induction of the helix-loop-helix protein Id3 promotes the γδ T cell fate and renders their functional maturation Notch-independent. Immunity 31: 565-575. PubMed

Anderson, S.J., Lauritsen, J.P., Hartman, M.G., Foushee, A.M., Lefebvre, J.M., Shinton, S.A., Gerhardt, B., Hardy, R.R., Oravecz, T., and Wiest, D.L. 2007. Ablation of ribosomal protein L22 selectively impairs αβ T cell development by activation of a p53-dependent checkpoint. Immunity 26:759-772. PubMed

Additional Publications


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