Head and Neck Cancer Molecular Biology Laboratory

Director: Remco A. Spanjaard, PhD
Location: Housman Building, Boston University School of Medicine, 715 Albany Street R903
Boston, MA 02118

Laboratory:

Head and Neck Cancer Molecular Biology Laboratory is located in the Housman Building, Boston University School of Medicine, R903 and is part of the Cancer Research Center. It consists of 600 sq. ft. and is equipped with a refrigerator, fume hood, table top centrifuges, freezers (-20 C), water baths, microcentrifuges, microwave, PCR machine, veritcal/horizontal gel electrophoresis equipment, an automated luminometer and a spectrophotometer.

Major Shared Resources:

Approximately 1,000 sq. ft. of core laboratory space is shared by all members of the Cancer Research Center for large pieces of equipment. Core equipment and facilities on the floor include scintillation and gamma counters, AB 7500 Fast Real-Time PCR machine, ultracentrifuges, bacteriologic incubators, lyophelizers, freezers (-80 C, -135 C), tissue culture hoods, CO2 injection system incubator, fully equipped dark room with a fluorescence microscope coupled to digital imaging technology, and a cold room (4 C). BUSM also maintains oligonucleotide and DNA sequencing facilities, and a confocal microscope on a fee-for-service basis. In addition, a state-of-the-art mass spectrometry and Genomics Core facility, which provides Affymatrix microarray reader and custom array spotting services, are located in the same building or very close by.

Projects:

1. Novel mechanism of control of nuclear receptor signaling.
PI: Remco A. Spanjaard. Collaborator: Dr. Jeffrey R. Patton, University of South Carolina School of Medicine
The nuclear receptor (NR) superfamily is involved in a wide variety of normal physiological responses, such as development, proliferation, metabolism and homeostasis, but they are also implicated in cancers. We are particularly interested in the role of a newly-identified RNA coactivator of NR signaling called SRA. Our research wants to establish the molecular mechanism by which chemical modification of SRA by two enzymes called Pus1p and Pus3p regulate NR activity, and thereby malignant growth ushc as breast cancer. See also #2.

2. A novel strategy to target estrogen receptor signaling.
PI: Remco A. Spanjaard.
Estrogen receptors (ERs) play a critical role in early stage breast cancers that depend on estrogen for their growth. Our work suggests that blocking of the Pus1p/Pus3p-dependent modification of SRA may be a novel strategy to inhibit ER-signaling and thereby ER-dependent growth of ER+ breast cancer cells. In future work we will develop a new class of RNA inhibitors and test their effects on breast cancer cell growth, invasiveness and survival.

3. Identification and characterization of new tumor markers in head and neck squamous cell carcinoma (HNSCC).
PI: Remco A. Spanjaard.
We applied DNA microarray technology to identify novel HNSCC-associated genes (biomarkers). We found many new candidates, but we are particularly interested in two metalloproteinases, MMP11 and MMP12, in HNSCC. Preliminary research suggests that these proteins, which are known to play roles in carcinogenesis, may serve as novel prognostic factors in HNSCC. In the future, they may also become novel pharmacologic targets for small drug inhibitors.

4. Role of tumor suppressor EI24/PIG8 in chemotherapy resistance

PI: Remco A. Spanjaard. Collaborator: Dr. Douglas V. Faller, BUSM

P53, the cellular “gatekeeper’, controls processes related to repair and programmed cell death (apoptosis) in response to DNA damaging agents through regulation of specific genes such as EI24//PIG8. We and others have shown that EI24/PIG8 is a pro-apoptotic protein that may have an unexplored role as a tumor suppressor and functions to preventing tumor spreading. New evidence  suggests that loss of EI24/PIG8 results in increased resistance to chemotherapy in breast cancer cells due to interference with the p53-controlled apoptotic machinery. This work can lead to a new prognostic indicator of chemotherapy resistance based on the EI24 status of the tumor.

5. TROY, a novel diagnostic marker and therapeutic target in melanoma.

PI: Remco A. Spanjaard. Collaborators: Drs. Joyce Wong and Scott Schauss, BU School of Engeneering

We recently identified a novel cell surface receptor, an orphan member of the tumor necrosis factor receptor superfamily named TROY, as a highly specific marker for melanoma. Moreover, TROY activity may also be important for growth of melanoma cells. We will establish whether TROY can be used to develop a blood test for melanoma, and we also plan to identify small molecules that bind TROY, and which can potentially interfere with its signaling as a new therapeutic avenue.