Cancer Cell Biology and Signaling
Primary Faculty
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Maurizio Bocchetta, PhD • OTUD6B deubiquitinase My laboratory is interested in identifying Notch-independent targets of γ-secretase inhibitors (GSIs). GSIs have a very high toxicity towards adenocarcinoma of the lung (ACL) cells, which is poorly recapitulated by Notch genetic inhibition. A combination of hypothesis- and discovery-driven approaches has led to the identification of the deubiquitinase OTUD6B as an important regulator of growth and proliferation of ACL cells. Preliminary data suggest that OTUD6B may act through the regulation of MYC expression/activity. OTUD6B is a highly conserved gene in vertebrates, yet, very little is known concerning the function of this protein. Currently, my main goal is to clarify the network of post-translational modifications regulated by OTUD6B splicing isoforms on oncogenic proteins and on the translational initiation complex. This will lead to a better understanding of growth and proliferation of ACL cells, which may lead to innovative therapeutic strategies for adenocarcinoma of the lung, which is the major cause of cancer-related deaths in the U.S.A. and worldwide. |
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Mitchell F. Denning, PhD • Keratinocyte biology Our laboratory is interested in understanding the regulation of cell fate decisions (proliferation, differentiation, death) for keratinocytes and melanocytes within the normal epidermis, as well as how these processes become perturbed during ultraviolet radiation-induced skin carcinogenesis. We are focused on protein kinase C signaling pathways as key regulators of epidermal biology, and use a variety of molecular, biochemical and cell biological approaches to uncover novel signaling mechanisms. The cellular responses to ultraviolet radiation are complex, and we are interested in the multitude of biological effects elicited by UV radiation, including inflammation, cell cycle arrest, DNA damage repair and cell death. By understating both physiological and pathological regulatory mechanism in the epidermis, we are able to test novel preventive and therapeutic approaches to combat the approximately 4.5 million new cases of skin cancers diagnosed annually in the USA. |
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Sean W. Fanning, PhD • Breast Cancer Nuclear Receptors (NRs) are small molecule-activated transcription factors and key drivers of cancer pathology. Because NR genomic activities are highly dependent on the bindings of small molecules to reprogram the transcriptions, they are well ideal therapeutic targets for a diverse range of diseases. In fact, 16% of all FDA approved drugs target NRs. Our goal is to understand how small molecules influence NR structures, alter their genomic activities, and achieve breast cancer-specific therapeutic endpoints. These structures enable the rational design of improved therapeutic small molecules which will be used as anti-cancer agents to address the unmet therapeutic needs of breast cancer patients. Curriculum Vitae: Sean Fanning, PhD |
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Irida Kastrati, PhD • Breast cancer Nearly 75% of breast tumors express estrogen receptor (ER) and will be treated with endocrine therapy, such as tamoxifen or aromatase inhibitors. Despite endocrine therapy’s proven success, an estimated 30-50% of patients will experience recurrence and will eventually die of their disease. In ER+ breast cancer, more than 1/2 of recurrences and 2/3 of deaths occur after completing 5 years of adjuvant endocrine therapy, suggesting that a small population of cells evade endocrine therapy, persist for years to decades, and eventually give rise to a recurrent tumor. These recurrent tumors tend to be therapy resistant, metastatic and lethal. Thus, one way to prevent lethal recurrence is to eradicate this population of cells that persists despite endocrine therapy. In order to accomplish this, we propose to exploit a small molecule, dimethyl fumarate (DMF), as: (i) a new therapeutic strategy to directly target endocrine therapy persister cells, and (ii) a chemical tool to identify druggable vulnerabilities in persister cells. We believe this two-pronged approach will allow us to eradicate these cells and prevent lethal recurrences of ER+ disease. Biosketch: Irida Kastrati, PhD |
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Clodia Osipo, PhD • Breast cancer I am an experienced chemist and cancer biologist with over 25 years of training, expertise, and a love for science. My desire to eradicate cancer stem cells comes from personal experiences. My maternal aunt and a very good friend died from complications due to cancer. I feel a very strong commitment to finding a cure for cancer in order for more people to spend time with their families. Currently, the Osipo laboratory is focused on determining mechanisms responsible for drug resistance in breast cancer. The main focus is on the role of Notch signaling in cancer stem cells and how current standard of care increases canonical and non-canonical Notch-dependent cancer cells that are resistant and responsible for tumor recurrence. Collaborations are key to our success and include a team of basic scientists and clinicians including other Notch experts (Dr. Lucio Miele), medical oncologists (Dr. Kathy Albain), breast pathologists (Dr. Ping Tang), estrogen signaling (Dr. Suzanne Fuqua), and biostatisticians (Dr. Susan Hilsenbeck). Together, we strive to eradicate breast cancer. |
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Jiwang Zhang, MD, PhD - • Hematopoiesis Our laboratory is committed to understanding how the molecular signals that emerge from the bone marrow (BM) micro-environmental niche regulate normal hematopoiesis and how deregulation of such signaling is involved in the pathogenesis of hematopoietic disorders. Specifically, we have identified: 1) factors from |
Joint Faculty |
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Wei Qiu, PhD • Hepatocellular carcinoma Our laboratory is interested in understanding the molecular mechanisms involving hepatocellular carcinoma (HCC) and alcoholic liver disease (ALD). More specifically, we investigate molecular signaling pathways that drive or mediate the development of HCC and ALD. Using molecular and cell biology techniques, state-of-the art cell imaging, transgenic and knockout mouse models, and clinical samples, the goal is to advance our understanding of how HCC and ALD initiate and develop, which is critical for identifying more effective therapeutic strategies for the prevention and treatment of HCC and ALD. In addition, we are also interested in studying the resistance mechanisms of FDA-approved targeted therapies (sorafenib, cabozantinib, and immunotherapies) for HCC, which shall help to improve the efficacy of these drugs in treating HCC. |