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Serge Y. Fuchs
Assistant Professor of Cell Biology, Dept of Animal Biology,
School of Veteranary Medicine
Cancer Biology Program
Address
Room 316 Hill Pavilion
380 S University Avenue
Philadelphia, PA 19104-4539
Office tel.: 215 573-6949
Lab tel.: 215 573-6950
Fax: 215 746-2295
E-mail: syfuchs@vet.upenn.edu
EDUCATION
Yaroslavl State Medical School (Russia): MD, 1987.
All-Union Cancer Research Center, Academy of Medical Sciences
(Russia): PhD (Experimental Oncology), 1992.
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RESEARCH INTERESTS
- Aberrations of protein ubiquitination and degradation in cancer.
Key words: ubiquitin,
ligase, proteolysis, cancer, cytokine, signal transduction.

Search PubMed for articles
DESCRIPTION OF RESEARCH
Protein ubiquitination and degradation have emerged as important mechanisms in
regulating cell growth and survival that play a key role in cancer. The long-term
objective our laboratory is to identify the aberrations in ubiquitination of regulatory
proteins that contribute to cell transformation and tumor progression and determine the
usefulness of specific mediators of ubiquitination as potential targets for anti-cancer
therapy. Our current focus is on the disregulated proteolysis of cytokine and hormone
receptors in human malignant melanomas and breast cancers. For our studies, we employ
various approaches and methods of molecular and cellular biology, biochemistry and
mammalian genetics.
Main research areas:
- Proteolysis of the interferon alpha receptor. This receptor plays an
essential role in anti-tumorigenic, anti-viral and immunomodulatory effects of
Type I IFN, which are often used in therapy of cancers, chronic viral infections
and multiple sclerosis. We recently found that ligand-dependent down regulation of
this receptor depends on its phosphorylation and ubiquitination by the beta-Trcp/HOS
E3 ubiquitin ligase. This down regulation is accelerated in some human tumors including
malignant melanomas. We are determined to understand the molecular mechanisms of IFNalpha
receptor phosphorylation, ubiquitination, endocytosis and degradation as well as aberrations of
these processes in cancers and the role of IFN receptor stability in the anti-tumorigenic effects of
IFNalpha.
- Proteolysis of the prolactin receptor that mediate cellular responses to
hormone/cytokine prolactin, which is crucial for survival of human breast
epithelial cells. Whereas degradation of prolactin receptor also involves specific
phosphorylation, beta-Trcp-dependent ubiquitination and endocytosis, human breast
cancer cells gain advantage in prolactin signaling by inhibiting the phosphorylation
and degradation of its receptor. Investigation of the mechanisms of this inhibition
and the role of increased stability of prolactin receptor in pathogenesis of breast
cancer is currently underway.
- 3. Identification of novel substrates for beta-Trcp E3 ubiquitin ligase and
delineation of the mechanisms that regulate the activities of this ligase. Beta-Trcp
levels and activities are often up-regulated in human cancers to ensue rapid
proteolysis of proteins that negatively affect cell growth and survival (such as
IkappaB, Emi1, etc). Conversely, the inhibition of beta-Trcp impairs growth and
survival of human cancer cells. The ongoing delineation of the mechanisms regulating
beta-Trcp activities and identification of its substrates may pave the road to
targeting beta-Trcp for the therapeutic purposes.
RECENT PUBLICATIONS
Suresh Kumar K.G., Tang W., Ravindranath, A.R., Clark,
W.A., Croze, E. and Fuchs, S.Y. (2003). SCFHOS
ubiquitin ligase mediates the ligand-induced down regulation
of the interferon alpha receptor, EMBO J, 22, 5480-90.
2. Li, Y., Suresh Kumar, K.G., Tang, W., Spiegelman, V.S.
and Fuchs, S.Y. (2004). Negative regulation
of prolactin receptor stability and signaling mediated by
SCFβ-TrCP E3 ubiquitin ligase. Mol Cell Biol, 24,
4038-4048.
Suresh Kumar, K.G., Krolewski, J.J. and Fuchs, S.Y.
(2004). Phosphorylation and specific ubiquitin-acceptor sites
are required for ubiquitination and degradation of the IFNAR1
subunit of Type I interferon receptor. J Biol Chem.
279, 46614-46620.
Li, Y., Minkovsky, N., Suresh Kumar, K.G., Clevenger, C.V.,
Raghunath, P.N., Tomaszewski, J.E., Spiegelman, V.S., and
Fuchs, S.Y. (2006). Stabilization of prolactin
receptor in breast cancer cells. Oncogene. 25, 1896–902.
Noubissi, F., Elcheva, I., Bhatia, N., Shakoori, A., Ougolkov,
A., Liu, J., Minamoto, T., Ross, J., Fuchs, S.Y.,
and Spiegelman, V.S. (2006). CRD-BP mediates stabilization
of βTrCP1 and c-myc mRNA in response
to beta-catenin signaling. Nature. 441, 898-901.
Lab
ROTATION PROJECTS
Lab rotation projects are available in every main research
area.
- Personnel:
- • Serge Y. Fuchs, M.D., Ph.D. P.I.
• Jianghuai Liu, Ph.D., Postdoctoral Fellow
• Alex Plotnikov, Ph.D., Postdoctoral Fellow
• Wei-Chun HuangFu, Ph.D., Postdoctoral Fellow
• Gayathri Swaminathan, Ph.D., Postdoctoral Fellow
• Christopher J. Carbone, Ph.D., Postdoctoral Fellow
• Bentley Varghese, Graduate Student
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last updated 8/2007
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