Metastasis Clinical and Basic Research Center
In order to improve the understanding of metastatic cancer and thereby advance treatment options, the Metastasis Center has developed a basic and translational research component headed by a group of 12 principal investigators (PI’s). The scientists in this core group have varying interests in metastasis biology and detection, including the role of epigenetics, tumor microenvironment, target organ metastatic niches, transcriptional regulators, and signal transduction in metastatic progression. These PI’s have developed models in different cancers including breast, head and neck, melanoma, gastrointestinal, and prostate. A multidisciplinary team that includes investigators with ample experience also in imaging and technology development supports this group. The PIs will also work closely with surgeons and medical oncologists to determine the best way to bank and utilize bio-specimens gathered through surgical efforts in such a way that they further the research mission of the center.
Participating Research Faculty
Julio A. Aguirre-Ghiso, PhD, Associate Professor
The Aguirre-Ghiso lab is focused on understanding the biology of metastasis and in particular disseminated tumor cell (DTC) dormancy. This group explores how RTK, adhesion and stress signaling regulate the time to metastasis in HNSCC, breast, and prostate cancer models of DTC dormancy. Collectively this work is first to identify the mechanism behind a “dormancy signature” that can predict for prolonged metastasis-free periods in breast, HNSCC, and prostate cancer patients.
Emily Bernstein, PhD, Assistant Professor
The Bernstein laboratory studies the ways in which epigenetic mechanisms contribute to the biology of cancer. The focus is primarily on melanoma pathogenesis and how the chromatin template, including histone modifications, histone variants, and their dedicated chaperones, are altered during disease progression. Recently, we have identified a histone variant whose expression can inhibit metastasis of melanoma cells.
Ross Cagan, PhD, Professor
The Cagan laboratory uses a fruit fly to model thyroid, lung, breast, and colorectal tumors. Regarding metastasis, the laboratory explores mechanisms and develops novel therapeutics that act within the context of a whole animal.
Eduardo Farias, PhD, Assistant Professor
Dr. Farias’s research program focuses on breast cancer, retinol signaling, epigenetic reprogramming, tumor dormancy, and early tumor cell dissemination. Dr. Farias studies why therapies using retinoids are not effective against solid tumors, in particular breast cancer. His team discovered a pro-tumorigenic/metastatic function of one of the retinoic acid receptors (RARgamma) and the protective effect of the retinol binding protein 1 (CRBP1) in breast cancer. Dr. Farias also developed a mechanism to induce targeted epigenetic reprogramming by the interference of the PAH2 domain of the Sin3 co-repressor, which led to the development of small molecule inhibitors some of them with strong anti-metastatic effects in mouse xenografts.
Hanna Y. Irie MD, PhD, Assistant Professor
Dr. Irie’s lab-based research program focuses on identification of novel strategies to target treatment-resistant or metastatic breast cancers by integrating tumor genetic data with functional genomic approaches. Dr. Irie is also co-PI of the Breast Cancer Biospecimen Repository, which banks clinically annotated specimens from patients, including those who present with metastatic or treatment-refractory breast cancers with the goal of understanding what fuels the growth of these tumors and identifying novel targets for therapeutic inhibition. With these integrated approaches, we hope to enhance the efficacy of current therapies to prevent metastatic recurrences and to improve control of metastatic disease for better quality of life.
David Mullholand, PhD, Assistant Professor
The focus of this program is on using genetically engineered prostate cancer mouse models (mGEMS) and mouse and human orthotopic transplant models to determine the capacity for cancer initiating cell populations to promote soft tissue and bone metastasis, and the ability of drug resistant and quiescent cells to mobilize and become metastatic.
Andrew Sikora, MD, PhD, Assistant Professor
This team is focused on inflammation as a driver and therapeutic target in melanoma, head and neck cancer, and other tumors. We have published on the role of inducible nitric oxide synthase (iNOS) as a driver of aggressive tumor behavior and critical mediator of induction of myeloid-derived suppressor cells (MDSC), which contribute to tumor-mediated immunosuppression and metastasis.
Mihaela Skobe, PhD, Associate Professor
This team’s research is focused on understanding the role of microenvironment in cancer metastasis; specifically, the role of the lymphatic system in regional and distant spread. Current studies examine the role of lymphatic vasculature in progression of metastases, recurrence, and resistance to therapy. The overall goal is to develop better therapeutic approaches for the prevention and treatment of metastatic disease.
Bachir Taouli, MD, Professor
This team is focused on three areas: imaging detection of metastatic lesions in the liver, lymph nodes, peritoneal cavity, and bones using MRI and PET-MRI; use of functional imaging methods to predict and assess early response of metastases to new therapies; and the development of volumetric tools for assessment of metastatic tumor burden.
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