Medicine

Donata Vercelli, MD, is a Professor of Cellular and Molecular Medicine, the Associate Director of the Arizona Respiratory Center and the Director of the Arizona Center for the Biology of Complex Diseases. Her research work is at the cutting edge of the immunology and genetics of complex lung diseases. Her laboratory spans both human and animal models. After characterizing cellular and molecular events critical for the regulation of human IgE synthesis, she became interested in the mechanisms through which natural genetic variants modify susceptibility to complex diseases, particularly allergy and asthma. To this purpose, she developed innovative, unique mouse models in which distinct human haplotypes of asthma- and allergy-associated genes are carried by BAC transgenic mice and can be directly compared for their regulatory properties in vivo. The unexpected, essential mechanisms underpinning the involvement of Th2 cytokines in allergy and asthma revealed by this mouse model have been fully validated in human populations. Dr. Vercelli's work on the epigenetic regulation of Th2 cytokine expression in human neonatal T cells revealed novel facets of early life regulatory events and her continued interest in epigenetics has led to the first demonstration that neonatal DNA methylation signatures in innate immunoregulatory pathways predict asthma during childhood. Most recently, Dr. Vercelli has devised a highly innovative approach that combines epidemiologic, biochemical and mouse model studies to dissect the mechanisms underlying the asthma-protective and asthma-promoting effects of two distinct US farming environments (Amish and Hutterite). Such studies are likely to critically advance our knowledge about fundamental mechanisms of asthma pathogenesis.

Vercelli Lab Website

Dr. Vedantam’s research interests are broadly focused on pathogenic mechanisms leading to antibiotic-associated diarrhea, and include host-pathogen studies of the diarrheagenic agent Clostridium difficile. C. difficile infection is currently a leading healthcare-acquired disease in the USA, incurring over $3 billion in treatment and containment costs. Dr. Vedantam’s laboratory uses multiple genomic and proteomic approaches to study C. difficile pathogenesis, including, but not limited to, automated iTRAQ-based comparative proteomics, and genomic analyses. Her laboratory also offers hospital surveillance and typing services, and a genetic manipulation program for clostridial pathogens. These efforts have identified attractive targets for interventions aimed at eliminating C. difficile from the gut, and are a focus of translational research goals. Dr. Vedantam is also involved in multiple teaching efforts, and offers a highly popular, upper-division, laboratory-based course on bacterial pathogens. The strengths she brings to any research endeavor are based on her expertise in genetic, mechanistic and animal model studies. Keywords: Infectious Disease, healthcare-associated infections, bacterial pathogenesis

Mechanisms and pharmacology of acute and chronic models of pain; endogenous opioid systems; sensory neural systems; opioid tolerance; antinociceptive synergy between cannabinoids and opioids.

Dr. Trouard is an Associate Professor of Biomedical Engineering and Medical Imaging and a member of the Evelyn F. McKnight Brain Institute. His research involves the development and application of novel magnetic resonance imaging (MRI) techniques to understand human health and effectively treat disease. Dr. Trouard’s multidisciplinary work spans a range from basic studies of cell culture systems, to studies of preclinical animal models of disease, to clinical imaging in humans. Many aspects of this work are directed towards understanding and treatment of neurological disorders including Alzheimer's Disease, Niemann Pick Type C disease, Stroke and Cancer.

Dr. Cynthia Thomson, PhD, RD, is a Professor and Director of the Canyon Ranch Center for Prevention and Health Promotion in the Mel and Enid Zuckerman College of Public Health at the University of Arizona. Dr. Thomson holds joint appointments in the College of Agriculture and Life Sciences and the College of Medicine. Her research emphasis includes dietary intervention in breast and ovarian cancer survivors, as well as behavioral interventions for weight control and metabolic regulation. Dr. Thomson received her Ph.D. from the Interdisciplinary Program in Nutritional Sciences, University of Arizona and completed NCI-sponsored post-doctoral training at the University of Arizona Cancer Center with a focus on diet and cancer prevention.

John A Szivek, PhD, is a Professor of Orthopaedic Surgery at the University of Arizona, College of Medicine and the Director of the Orthopaedic Research Laboratory in the Arizona Arthritis Center. He holds the William and Sylvia Rubin, Chair of Orthopaedic Research and serves as the Chair of the Biomedical Engineering Graduate Interdisciplinary Program. Dr. Szivek is a member of the Physiological Sciences Graduate interdisciplinary Program as well as an adjunct faculty member of Materials Science and Engineering and Aerospace and Mechanical Engineering. He is internationally recognized for his research on the development of implantable measurements systems to characterize the effect of implants on tissue and on activity induced musculoskeletal tissue regeneration (specifically bone and cartilage). Recently he has utilized adult stem cells on 3D printed scaffolds to regenerate joint cartilage in efforts to develop techniques to help athletes and osteoarthritis patients. He has published over 180 research articles, several in collaboration with investigators from around the world, and authored 2 book chapters. As part of the sensor and transmitter systems developed in his lab, computer software programs for hand held devices (including tablets, hand held computers and smart phones) have been written to allow portable monitoring of tissue while it heals. He is a frequent presenter at national and international meetings, and has been an invited speaker at the Arizona Rheumatology Society; the Musculoskeletal Transplant Society Board meetings and the research forums at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in the University of Toronto. He has won more than 165 grants, specifically to provide support to undergraduate minority students, allowing them to do hands on research on a range of activity induced tissue engineering topics. He has trained graduate students with federal grant support and has had support through a number of regional and national foundations to train top tier undergraduates and medical students. Dr. Szivek believes it is essential to effectively train the next generation of bioengineering researchers, clinicians and clinician scientists, in cutting edge topics so that the progress that his lab has made in developing tissue regeneration approaches and sensor/transmitter systems used to design patient specific therapies will become widely utilized.

Magdalene So, PhD, is a Professor in the Immunobiology Department and Director of the Microbial Pathogenesis Program at the University of Arizona College of Medicine. Dr. So is recognized internationally for her research in the microbial pathogenesis. Her research focuses on two medically important bacterial pathogens: Neisseria gonorrhoeae, which causes over 100 million new cases of sexually transmitted infections each year worldwide, and Neisseria meiningitidis, which frequently causes meningitis epidemics in Subharan Africa. Her goal is to understand on how these two pathogens cause disease, with the aim of applying this information to developing new antibiotics for treating these infectious agents and improving current methods of vaccine development. Dr. So recently expanded her research to the commensal species in the Neisseria genus. These bacteria are normal inhabitants of the body and are closely related to the two pathogenic species; but unlike their pathogenic cousins they do not cause disease. Dr. So’s new research effort seeks to determine the differences in behavior of commensal and pathogen Neisseria. Dr. So’s research approach is multidisciplinary, involving concepts and techniques in biophysics, bioinformatics, cell biology, biochemistry and genetics. Collaborators from institutions around the world contribute to this effort. Dr. So has published over 100 peer-reviewed research papers in internationally renowned journals, and over 20 reviews and book chapters. She holds several patents as a result of her research. She is frequently invited to speak at universities and national and international meetings. She is a member of the American Academy of Microbiology, an elected body, and serves on the scientific boards of several research centers. Over the course of her career, Dr. So has trained over 44 postdoctoral fellows and graduate students. The majority of her trainees are internationally recognized researchers in their own right. Keywords: Infectious disease, microbiology

Timothy Secomb, PhD, studies the microcirculation, a network of extremely small blood vessels that supply oxygen and nutrients to all parts of our tissues. The focus of work in his research group is the use of mathematical and computational approaches to study blood flow and mass transport in the microcirculation. Working in collaboration with experimentalists, the aim is to understand quantitatively the processes involved. Dr. Secomb examines the relationship between red blood cell mechanics and flow resistance in microvessels. Theoretical predictions agree well with observations in glass tubes, but resistance is higher living tissue. The major cause is the presence of a relatively thick macromolecular lining (endothelial surface layer) on the walls of microvessels. He also simulates oxygen exchange between networks of microvessels and surrounding tissues in skeletal muscle and tumors. In skeletal muscle, oxygen can be exchanged diffusively between arterioles and capillaries, and Dr. Secomb’s lab is studying the determinants of maximal oxygen consumption. In tumors, the relationship between network structure and occurrence of local hypoxic (radiation-resistant) regions is a source of curiosity. They are analyzing the delivery of chemotherapeutic drugs in tumor tissues, and developing improved models to describe the responses of tumor cells to chemotherapy and radiation. Models for the structural responses of microvessels to functional demands are being developed. Maintenance of a stable, functionally adequate distribution of vessel diameters can be achieved if each vessel responds to changes in wall shear stress, intravascular pressure and local metabolic conditions, and if mechanisms exist for information transfer upstream and downstream along flow pathways. Models for the active regulation of blood flow by changes in vascular tone are also being developed, taking into account vascular responses to wall shear stress, pressure and local metabolic state, and including effects of conducted responses along vessel walls. Another project in the group is the development of computer simulations for the dynamics of the left ventricle that can be run in real time and provide a tool for analysis of data derived from ultrasound echocardiography images.

My laboratory investigates the normal biology of the Epidermal Growth Factor Receptor (EGFR, and its family members, HER2 and ErbB3), as well as their role in transformation and metastasis. These oncogenes are a family of transmembrane tyrosine kinases that drive a wide-variety of cancers including HER2 positive and triple negative breast cancer, squamous cell lung cancer and glioblastoma. Our work focuses on kinase-independent activities of these receptors (such as modulation of calcium signaling and functions as transcriptional co-factors) and how the receptors are mis-regulated during cancer progression (by a loss of lysosomal degradation). These studies include investigations into receptor trafficking, nuclear translocation and protein-protein interactions that are unique to cancer survival and metastasis. We are currently focused on understanding how EGFR enters the retrotranslocation pathway that allows for it to traffic to the nucleus and directly affect gene transcription, as well as understanding how these events drive migration and survival. Based on these studies, we have developed peptide-based therapeutics for cancer that block protein-protein interactions that promote EGFR retrotranslocation. We are developing these peptide-based therapeutics for clinical applications through peptide stability studies including hydrocarbon stapling and mutational analyses. To promote the clinical translation of these discoveries, the biotech start-up company Arizona Cancer Therapeutics was founded in my lab at the Arizona Cancer Center. We are currently performing toxicity testing of our compounds with the goal of applying for approval from the FDA for clinical trials. These studies have been accomplished through the hard work and dedication of the over 50 undergraduate students, 2 MS and 11 PhD students who have studied in my lab since 2002.

Dr. Monika Schmelz is a Assistant Professor of Pathology and Member of the University of Arizona Lymphoma Consortium. Dr. Schmelz pursuing research on mechanisms for immune escape in aggressive lymphoma with poor survival rates. Dr. Schmelz received a 2 year award (2013-2015) from The Hope Foundation to study how tumor cells escape immunosurveillance, which is a hallmark of cancer, in aggressive diffuse large B-cell lymphoma (DLBCL) with poor patient outcome, and how immunosurveillance can be manipulated for therapeutic purposes. ( see also link: http://pathology.arizona.edu/news/dr-monika-schmelz-recipient-2013-swog-development-award). Dr. Schmelz also is pursuing biorepository science. She received a multi-million dollar award for hosting the Biorepository for a NCI funded clinical trial. ANCHOR is a multi-site phase III clinical trial entitled “Topical or Ablative Treatment in Preventing Anal Cancer in Patients with HIV and Anal High-Grade Squamous Intraepithelial Lesions”. 17,385 participants will be screened to identify and to enroll 5,058 eligible participants. An estimated 314,535 biospecimens over the duration of the clinical trial (8 years) will be collected and sent to Dr. Schmelz's lab. The biorepository is an extremely important factor for the outcome of this clinical trial, since correlative translational studies on biomarkers for early detection of anal cancer development in these specimens are planned by the NCI. Keywords: Cancer, Diffuse Large B-Cell Lymphoma (DLBCL), Therapeutic Biomarkers