Current research of the Shen Laboratory at the Rutgers Cancer Institute of New Jersey focuses the mechanisms by which genomic instability is provoked during tumorigenesis. Using a BRCA2 interacting protein BCCIP and its associated protein network as the platform, we investigate the roles of mammalian homologous recombination (HR) in error-less DNA repair, replication fidelity, and precise mitotic cell division.
Postdoctoral positions are available immediately in the Division of Radiation Cancer Biology at the Department of Radiation Oncology, under the mentorship of Dr. Zhiyuan Shen. The postdoctoral appointees may participate in the studies of DNA repair and its influence on tumor response to treatment, the mechanism by which the BCCIP regulates ribosome biogenesis, the role of non-histone lysine methylation in cell fate determination after DNA damage, and the mechanisms involved in the recovery of acquired bone marrow failure.
Ideal candidates should have a recent PhD with trainings in cell & molecular biology and/or cancer biology or other relevant fields, with effective communication skills in oral and written English and competence in common computer applications and have a background in relevant research as evidenced by a publication record consistent with the career level. Must be competent in basic cell and molecular biology techniques, and basic bio-statistic tools. Prior experience with DNA repair, ribosome biology, RNA biology, microscopy, hematopoiesis, and computational genomics are desirable but not required.
Housed in the Rutgers Cancer Institute of New Jersey, the Shen lab is located at a vibrant and interdisciplinary basic/translational/clinical research facility in New Brunswick, NJ. The Shen Lab leverages a wide range of research approaches, including cell and molecular biology, biochemistry, animal models, and bioinformatics. Postdocs have abundant opportunities to interact with a vast research community offered by Rutgers campuses, and participate in various career trainings and activities. New Brunswick has a convenient access to major cultural centers such as New York city and Philadelphia.
Positions are available June 1st, 2021 until filled. For interested candidates, please send CV to: email@example.com
Genomic Instability Provoked by Replication Stress
A form of metaphase chromosome abnormalities is sister chromatid union/fusion (SCU), which can subsequently seen as anaphase bridges and contribute to a cancer genomic signature called Breakage-Fusion-Bridge (BFB). Our study found that a partial loss of BCCIP can cause excessive structural chromatid instability including SCU, indicating a mis-repair of collapsed replication forks (PLoS Genomic 2011). We are now interested in further understanding of how BCCIP and HR pathway suppress SCU and the subsequent BFB.
Mitosis and Genomic Instability
In addition to suppressing anaphase bridges and chromatid alterations that consequentially cause mitotic abnormalities, BCCIP can modulate microtubule and mitotic spindle structure directly. BCCIP deficient cells have fragmented spindle poles and dis-orientated spindles (Oncogene 2017). We are interested in how BCCIP ensures mitotic fidelity through the concurrent regulations of microtubule dynamics and the chromosome integrity at mitosis.
|BCCIP (red) localizes to the mother centriole during interphase||BCCIP (yellow) localizes to the spindle poles during metaphase|
|Normal cell has focused spindle poles & a parallel spindle orientation||BCCIP deficient cell has fragmented spindle poles & disorientated spindles|
Mouse Models of Tumorigenesis Driven by Genomic Instability
BCCIP represents a type of unique genes that have caretaker function in the maintenance of genomic integrity, and at the same time is required for cell proliferation. To understand the unique feature of this class of essential caretaker genes in tumorigenesis, we extensively use genetically engineered mouse models. Using a unique BCCIP conditional knockdown mouse model, Shen laboratory reported that a partial and transient deficiency of BCCIP is not only sufficient but also required for medulloblastoma development (Cancer Research 2013). Shen lab thus proposed the concept that a subset of caretaker tumor suppressor genes may function as Suppressors of Initiation but Required for tumor Progression (SIRP). This concept explains why cancer mutations are rarely detected for some of the cell-viability-essential tumor caretaker suppressors. It underscores the importance of non-mutational events in cancer development, and the confounding roles of this special class of tumor suppressors in tumorigenesis. An ongoing effort in the Shen laboratory is to use various mouse models to understand the role of SIRP type of genes in tissue development and tumorigenesis, including how cancers can by-pass the growth-suppression effect of SIRP defects during tumorigenesis.
Research in the Shen laboratory is supported by NIH and DoD Breast Cancer Research Program.