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Wei
Tong, PhD
Assistant Professor, Pediatrics, Hematology Division, CHOP
Cancer Biology Program
Address
316A Abramson Research Center
The Children’s Hospital of Philadelphia
3615 Civic Center Blvd.
Philadelphia, PA 19104-4318
Office tel.: 267-426-0930
E-mail: tongw@email.chop.edu
Education
University of Science and Technology of China: BS (Molecular
and cellular biology), 1994.
Albert Einstein College of Medicine: PhD (Developmental and
molecular biology), 2000.
Whitehead Institute at MIT (Postdoctoral, Cell Biology), 2006.
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Research
Interests
- Our laboratory is interested in studying molecular mechanisms involved in cytokine receptor signaling in hematopoiesis, hematopoietic stem cell development, and leukemogenesis.
Key words:Hematopoiesis, leukemia, stem cells, cytokine receptor, signaling
Description
of Research
Our lab focuses on molecular hematology-oncology with an emphasis
on studying signal transduction in normal blood cell development and hematological
malignancies. We use genetically-engineered mouse models, bone marrow transplantation,
tissue culture cells, gene transcriptional profiling, protein complex purification
and mass spectrometric identification, coupled with extensive usage of molecular,
cellular, and biochemical technologies.
Hundreds of billions of blood cells have to be replenished everyday. Cytokines and cytokine receptors play important roles in blood cell formation, a process known as
hematopoiesis. The amplitude and duration of cytokine receptor signaling is a highly
regulated process that is crucial for cytokine- governed hematopoiesis. Dysregulation
of these complex signaling networks can predispose to myeloproliferative diseases and
myeloid leukemia.
We previously identified the adaptor protein, Lnk, as a novel negative regulator of
cytokine receptor signaling. Lnk deficiency in mice results in an enhanced proliferative
capacity of hematopoietic stem cells (HSCs) and progenitor cells of multiple lineages.
Lnk loss-of-function leads to hyper-sensitivity to thrombopoietin (Tpo) and
erythropoietin (Epo), which regulate platelet and red blood cell formation,
respectively. Our results also implicate a new mechanism for rapidly downmodulating
cytokine signaling: Lnk negatively regulates cytokine receptor induced JAK2 activity
in a phosphorylation-dependent manner. We are interested in:
- Elucidating
molecular mechanisms of Lnk regulatory functions in cytokine
receptor signaling
- Understanding
both normal and oncogenic cytokine receptor signaling processes
that control hematopoietic stem and progenitor cell numbers
and development in vivo
- Undertaking
studies to identify novel signaling components in the receptor/JAK2
signaling complex that lead to oncogenic transformation,
as JAK2 is the central kinase governing many cytokine receptor
signaling, and has been found mutated in some patients with
myeloproliferative diseases
Selected
Publications
Tong, W., and H.F. Lodish. Lnk Inhibits Tpo-mpl
Signaling and Tpo-mediated Megakaryocytopoiesis. Journal
of Experimental Medicine 200(5):569-580, 2004
Tong, W., J. Zhang, and H.F. Lodish. Lnk inhibits
erythropoiesis and Epo-dependent JAK2 activation and downstream
signaling pathways. Blood 105(12):4604-12, 2005
Zhang, C-C, Kaba, M., Ge, G., Xie, K., Tong,
W., Hug, C., and Lodish, HF. Angiopoietin-like proteins stimulate
ex vivo expansion of hematopoietic stem cells. Nature
Medicine 12:240-245, 2006
Scott L., Tong, W., Levine R., Scott M., Beer
P., Stratton M., Futreal A., McMullin M., Harrison C., Erber
W., Warren A., Gilliland DG., Lodish HF, Green AR. 2007. Gain-of-function
mutations of JAK2 exon 12 in acquired isolated erythrocytosis.
New England Journal of Medicine 356(5):459-68.
Bersenev, A., Wu, C., Balcerek, J., and Tong,
W. 2008. Lnk Controls Hematopoietic Stem Cell Self-Renewal
and Quiescence through Direct Interactions with JAK2. Journal
of Clinical Investigation (In press).
Search PubMed for more articles
Lab
Rotation Projects:
Potential projects can be discussed with Dr. Tong.
- Lab Personnel
Alexey Bersenev, postdoctoral fellow
Xiaoyun Dong, postdoctoral fellow
Chao Wu, technician
Joanna Balcerek, technician
Jae-won Shin, graduate student
last updated 7/2008
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