Cancer

Public Relevance Statement: Can you imagine having a mouthful of canker sores and cavities? Thousands of head and neck cancer patients suffer these consequences from radiation treatment. The Limesand lab works to prevent these side effects thereby improving patients' quality of life. Clinical Relevance: Radiation therapy for head and neck cancer causes adverse secondary side effects in the normal salivary gland including xerostomia, oral mucositis, malnutrition, and increase oral infections. Although improvements have been made in targeting radiation treatment to the tumor, the salivary glands are often in close proximity to the treatment site. The significant destruction of the oral cavity following radiation therapy results in diminished quality of life and in some cases interruptions in cancer treatment schedules. Research Interests: My research program has its foundation in radiation-induced gland dysfunction; mechanisms of damage, clinical prevention measures, and restoration therapies. Evidence suggests that salivary acinar function is compromised due to apoptosis induced by these treatments and temporary suppression of apoptotic events in salivary glands would have significant benefits to oral health. We utilize a number of techniques in my laboratory including: genetically engineered mouse models, real-time RT/PCR, immunoblotting, immunohistochemistry, primary cultures, siRNA transfections, irradiation, and procedures to quantitate salivary gland physiology. Current project areas: 1. Radiation-induced apoptosis 2. Mechanisms of preserving salivary gland function 3. Identifying the radiosensitivity of salivary gland progenitor cells 4. Restoration of salivary gland function 5. Role of autophagy in radiation-induced loss of function

Chengcheng Hu, Ph.D., is an Associate Professor, Public Health and Director, Biostatistics, Phoenix campus at the Mel and Enid Zuckerman College of Public Health, University of Arizona. He is also Director of the Biometry Core on the Chemoprevention of Skin Cancer Project at the University of Arizona Cancer Center. Hu has worked on multiple federal grants in a broad range of areas including cancer, occupational health, HIV/AIDS, and aging. In addition to extensive experience in collaborative research, he has conducted methodological research in the areas of survival analysis, longitudinal data, high-dimensional data, and measurement error. His current methodological interest, arising from studies of viral and human genetics and biomarkers, is to develop innovative methods to investigate the relationship between high-dimensional information and longitudinal outcomes or survival endpoints. Hu joined the UA Mel and Enid Zuckerman College of Public Health in 2008. Prior to this he was an assistant professor of Biostatistics at the Harvard School of Public Health from 2002 to 2008. While at Harvard, he also served as senior statistician in the Pediatric AIDS Clinical Trials Group (PACTG) and the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT). Hu received his Ph.D. and M.S. in Biostatistics from the University of Washington and a M.A. in Mathematics from the Johns Hopkins University.

Bernard Futscher, PhD, and his lab focus on the molecular origins of human cancer. More specifically, the lab group has 3 inter-related research objectives based on the underlying concept that developing an in-depth understanding of epigenetic mechanismsresponsible for governing cell fate will allow for the development of more effective strategies for the prevention, treatment, and cure of cancer. First, they wish to identify which epigenetic mechanisms participate in the transcriptional control of genes important to growth and differentiation. Second, they seek to determine how these epigenetic mechanisms, and therefore epigenetic homeostasis, become compromised during oncogenesis. Third, using a new and more complete understanding of epigenetic control of the genome, Dr. Futscher and his team are developing rational new therapeutic strategies that seek to repair these defects in the cancer cell and transcriptionally reprogram the malignant cancer cell to a benign state. To reach their objectives, a variety of in vitro models of cancer have been developed to address emerging hypotheses that are inferred from the literature in basic and clinical science as well as our own data. Results from these in vitro studies are then translated to the clinical situation to determine their meaning in the actual clinical face of the disease. Similarly, they attempt to take information obtained from the genome-wide assessment of clinical specimens in order to help guide our thinking and develop new hypotheses that can be tested experimentally in our in vitro models.

Janet L. Funk, MD, FACP, is a Professor of Medicine at the University of Arizona College of Medicine. Dr. Funk leads a federally-funded research team that is focused on identifying new treatments for chronic diseases that have strong inflammatory components, including metabolic bone diseases, such as arthritis, bone tumors and osteoporosis, and cardiovascular diseases, including diabetes. Recent studies have focused on the use of medicinal plants that have historically been used to treat inflammatory conditions, such as arthritis. By understanding whether and how these plants work in blocking inflammatory pathways in the body, we are striving to harness the power of nature and the wisdom of our ancestors to indentify new treatments for diseases that are common in our modern society. Discoveries we have made at the lab bench have allowed us to move forward into the clinics, building upon the old to discover the new.

Dr. Thomas Doetschman, PhD, Biochemistry & Biophysics, University of Connecticut, has been involved in cardiovascular research for over a decade through investigations into the cardiovascular roles of the three TGFβ ligands and FGF2 ligand isoforms in genetically engineered mice. These mice have determined that TGFβ2 plays major roles in heart and vascular development and for maintenance of valvular and large vessel integrity in the adult and that both the TGFβ1 and FGF2 are involved in adult heart disease.His work has also demonstrated roles of TGFβ in cancer and immunology. He found that a major function of TGFβ1 is to inhibit autoimmunity and to establish homeostatic balance between immune regulatory and inflammatory cells. He has shown that an imbalance in the latter is critical in the tumor suppressor function of TGFβ in the colon.Dr. Doetschman has also played an important role in the development of the mouse genetic engineering field. He has been responsible for the establishment of 3 mouse genetic engineering facilities, in Cincinnati OH, Singapore and the University of Arizona’s BIO5 Institute. Keywords: "Cancer", "Microbiome", "Mouse Genetic Engineering", "Connective Tissue Disorder"

Clara Curiel-Lewandroski, PhD, is the director of the Pigmented Lesion Clinic and Multidisciplinary Cutaneous Oncology Program, both part of the University of Arizona Cancer Center Skin Cancer Institute. She completed two research fellowships, the first in the Department of Dermatology at Harvard Medical School, and the second at the Ludwig Boltzman Institute and Immunobiology of the Skin at Miinster University in Germany. Dr. Curiel is certified by the American Board of Dermatology.Dr. Curiel-Lewandroski’s research focus is on melanoma chemoprevention, early detection of melanoma, cutaneous T cell lymphomas and skin cancer. She studied the extended use of non-steroidal anti-inflammatory drugs, particularly aspirin, and their ability to possibly decrease the risk of cutaneous medanoma (CM) development. CM is responsible for more than 77 percent of skin cancer deaths.

Samuel Campos, PhD, studies early events of Human Papillomavirus (HPV) infection. HPVs are small, non-enveloped DNA viruses that cause a variety of lesions ranging from benign waters to cervical cancers. Although over 100 types of HPVs have been identified, HPV16 is the most prevalent, and is alone responsible for more than 50% of cervical cancers in women worldwide. Dr. Campos and his lab study the mechanisms of HPV virus transmission at a cellular level, in hopes to discover new approaches for the prevention and treatment of HPV.HPV16 virions consist of an ~8kb circular dsDNA genome packaged into a ~60 nm protein capsid. The genome is condensed with cellular histones and exists in a chromatin-like state. The capsid is comprised of 72 pentamers of the major capsid protein L1 and up to 72 molecules of the minor capsid protein L2, localized along the inner capsid surface, within the central cavities beneath the L1 pentamers. Mature HPV16 virions exist in an oxidized state, with adjacent L1 pentamers crosslinked together by disulfide bonds to stabilize the capsid. In order to establish an infection, HPV16 virions must bind and penetrate host cells, ultimately delivering their genomes to the host cell nucleus to initiate early gene expression, cell cycle progression, and genome replication. Non-enveloped viruses are faced with the challenge of getting their genetic material across a cellular membrane and often overcome this by disrupting the endosomal or lysosomal membranes and translocating to the cellular cytoplasm during the course of intracellular virion trafficking. Keywords: virology, microbiology, virus-host interaction, HPV