Microbiology

Our goal is to merge the fields of synthetic organic chemistry with virology. We develop new reactions (and re-appropriate old ones) to gain insight into how viruses infects new host cells. Additionally, we are working to develop new methods to probe protein-protein interactions through the use of small molecules.Viruses can rapidly evolve and new tools are required to meet this ever-changing threat. While vaccinations have tamed many historically deadly viral diseases, there are still rogue viruses for which no vaccination strategy is available. Dengue virus (DENV), the virus that is responsible for dengue fever, hemorrhagic fever, and shock syndrome, is one such pathogen. The WHO estimates that the mosquito-borne pathogen infects over 50 million people each year. With a rapid increase in severe, potentially fatal, disease forms, DENV poses a significant risk to the 2.5 billion people who live in DENV endemic regions.

Dr. Bonnie Hurwitz is an Assistant Professor of Biosystems Engineering at the University of Arizona and BIO5 Research Institute Fellow. She has worked as a computational biologist for nearly two decades on interdisciplinary projects in both industry and academia. Her research on the human/earth microbiome incorporates large-scale –omics datasets, high-throughput computing, and big data analytics towards research questions in “One Health”. In particular, Dr. Hurwitz is interested in the relationship between the environment, microbial communities, and their hosts. Dr. Hurwitz is well-cited for her work in computational biology in diverse areas from plant genomics to viral metagenomics with over 1200 citations

Melissa Herbst-Kralovetz, PhD is an Associate Professor in the Departments of Basic Medical Sciences and Obstetrics and Gynecology and is Director of the Women's Health Microbiome Initiative at the UA College of Medicine-Phoenix. The Herbst-Kralovetz research lab is broadly interested in understanding innate mucosal immune responses to resident bacteria, pathogens (e.g HSV-2), and microbial products at mucosal sites, including the female reproductive tract. The mucosa provides a major immune barrier (physical, biological, and chemical) to microbial insult and her lab is interested in studying the mucosal barrier function of the lower female reproductive tract and its role in host defense against infection and inflammation as well as maintaining mucosal homeostasis. Dr. Herbst-Kralovetz has a long-standing interest and background in studying infections/conditions that impact women’s health.

Felicia Goodrum earned her Ph.D. from Wake Forest University School of Medicine studying cell cycle restrictions to adenovirus replication. She trained as a postdoctoral fellow at Princeton University in the laboratory of Dr. Thomas Shenk studying human cytomegalovirus latency. Dr. Goodrum joined the faculty at the University of Arizona in 2006. Dr. Goodrum is the recipient of the Howard Temin Award from the National Cancer Institute, the Pew Scholar in Biomedical Sciences Award, and the Presidential Award for Early Career Scientists and Engineers.Dr. Goodrum's research focuses on the complex host-virus interactions that result in viral persistence. Progress in understanding latent programs of persistence have been impeded by the inherent complexity of the herpesviruses and that paucity of adequate model systems. Herpesviruses are extraordinary for their ability to coexist with their host by establishing life-long latent infections. Latency is defined as a reversibly quiescent state during which viral gene expression and replication is highly restricted. Her laboratory studies cytomegalovirus or CMV, one of eight human herpesviruses. CMV is remarkable in that it persists latently in 60-99% of the population, generally in the absence of disease in the immunocompetent host. Reactivation of CMV from latency poses life-threatening disease risks in immunocompromised individuals, particularly transplant patients. CMV infection is also the leading cause of infectious disease-related birth defects, affecting ~1% of live births in the US. Further, the health cost of the latent coexistence of CMV is just beginning to emerge in an association to age-related pathologies including vascular disease, immune dysfunction and frailty. The key to eradicating CMV lies in understanding latency in order to ultimately develop novel antiviral strategies targeting latently infected cells or to prevent reactivation. Our studies aim to define the molecular basis of persistence by defining viral and cellular determinants important to viral persistence and the mechanisms by which these determinants function in relevant cell models. In turn, our work will provide critical insights into how CMV assimilates into and impacts human biology.

Dr. Galgiani has focused his career on Arizona’s special problems with Valley Fever. His work has included studies of the impact of Valley Fever on the general population and on special groups such as organ transplant recipients and patients with AIDS. For 19 years, as part of the NIH-sponsored Mycoses Study Group, Dr. Galgiani has been the project director of a coccidioidomycosis clinical trials group. Through collaboration, this group has evaluated new therapies for Valley Fever more rapidly and with greater clarity than might otherwise have been possible by investigators working in isolation. Dr. Galgiani has also been involved with efforts to prevent Valley Fever through vaccination. His group discovered and patented a recombinant antigen which is the basis for a vaccine candidate suitable for further development and clinical trials. Most recently, he has become the project leader for developing a new drug, nikkomycin Z, for treating Valley Fever. With recent NIH and FDA grant awards, clinical trials with this drug were resumed in 2007. Dr. Galgiani is also Chief Medical Officer of Valley Fever Solutions, Inc, a start-up company founded to assist in the drug’s development. In 1996, the Arizona Board of Regents accepted Dr. Galgiani’s proposal to establish the Valley Fever Center for Excellence for the Arizona universities. Based at the University of Arizona, the Center is pledged to spread information about Valley Fever, help patients with the severest complications of this disease, and to encourage research into the biology and diseases of its etiologic agent. The Center maintains a website (www.VFCE.Arizona.edu) and answers inquiries from health care professionals located in Arizona, other parts of the United States, and even from other countries. The Valley Fever Corridor Project, begun in 2009, intends to facilitate communication among Arizona clinicians to also improve patient care. In 2011, The Valley Fever Center in Phoenix was announced as a partnership between St. Joseph’s Hospital and the UA College of Medicine in Phoenix. It began operation in June, 2012. Research is increasing into the environmental biology of the fungus within its desert soil habitat as well as how the fungus caused disease and the body’s immunity controls it. Since Arizona has the only medical schools situated directly within the endemic region for Valley Fever, it is quite appropriate that Arizona lead in solving this problem. As Director of the Center, Dr. Galgiani is working for its full implementation as a means of ensuring an institutional commitment to accomplish this goal. Keywords: Coccidioidomycosis, Valley Fever, antifungal drugs, vaccines, serologic tests,

Bentley A. Fane, PhD, is a Professor in the School of Plant Sciences, College of Agriculture and Life Sciences and holds a joint appointment in the Department of Immunobiology, Arizona College of Medicine. Dr. Fane has an international reputation for his research into virus structure, assembly and evolution. His research focuses on the viruses of the Microviridae, of which he is considered one of the leading experts. He has been instrumental in defining the biochemical and structural parameters that allow these viruses to replicate and produce progeny in as little as five minutes. The rapid lifecycle has facilitated in depth studies into how viruses evolved resistance mechanism to anti-viral proteins targeting particle assembly.He has published over 60 original research paper in leading scientific journals, including Nature, Molecular Cell, and Journal of Virology, in which his publications on the evolution of resistance mechanisms and kinetic traps have been selected by the journal editors as articles of “significant interest.” He is a frequent presenter at national and international meetings, and has been invited to State of the Art and plenary talks at give the American Society for Virology. He presently serves on the Editorial Boards of two leading virology journals: Virology and the Journal of Virology. At the University of Arizona, Dr. Fane has been actively involved in promoting undergraduate research has been honored with teaching awards on the department, college, and university levels. Keywords: Virus structure and assembly, Viral DNA translocation, Viral evolution

An overwhelming obesogenic environment, the backdrop to a globally-expanding western lifestyle, has led to a ‘diabesity’ pandemic that represents a costly and urgent global health crisis. The success of gastric bypass surgery and gut-derived diabetes/obesity treatments highlight the major role of the gastrointestinal (GI) tract in metabolic diseases. My research aims to better understand the complex intestinal signaling mechanisms involved in the regulation of energy and glucose homeostasis in physiological and pathophysiological states. My work to date has focused on elucidating how nutrients are sensed by the gut, and how changes in these mechanisms lead to a reduction in food intake and/or a reduction in endogenous hepatic glucose production via a gut-brain neuronal axis. More specifically, my work focused on alterations in intestinal detection of fats and carbohydrates and paracrine gut peptide signaling (CCK and GLP-1) during high-fat feeding, the influence of the gut microbiota on these pathways, and how these contribute to the development of obesity and diabetes. As such, I plan to continue to decipher this complex interaction between gut-sensing mechanisms and the gut microbiota, as a better understanding of these pathways are crucial for the development of successful, gut-targeted therapeutic options in the treatment of metabolic diseases. Given the rapid rise of obesity/diabetes in only several generations, obesity cannot be attributed to genomic alterations, but more likely results from a complex set of interactions between genetic risk factors and environmental changes. Importantly, studies suggest the development of adult phenotypes (obesity and diabetes) results from early, transient environmental interactions, coined ‘early life programming,’ which has been partly attributed to epigenetic changes. Gut microbiota development is also crucial during this time, and differing modes of development (i.e. maternal microbiota, type of delivery, breastfeeding vs. formula feeding, etc.) can lead to later metabolic dysfunctions. Therefore, using animals models prone to the development of obesity and/or diabetes from polygenetic inheritance and transgenerational, epigenetic, changes in gene activity, I am studying how varying environmental factors (diet, housing, exercise, pre/post-natal environment, etc.) result in differential effects on the gut microbiota, intestinal nutrient sensing, and whole body energy and glucose homeostasis. A better understanding of how early changes in the gut microbiota can impact the development of metabolic regulation, and vice versa, is vital for developing successful strategies to curb diabetes and obesity.

The Carini lab is focused on understanding how microbes help make Earth habitable for humans. This view leads us to diverse questions in both terrestrial and aquatic environments with the goal of understanding how microbial communities transform important nutrients, remove pollutants, affect soil fertility and influence aquatic productivity. By studying the growth of microbial cultures, their genome sequences and their environmental distributions, we design experiments that help uncover new and unusual biogeochemical cycles and provide hypothesis-based explanations for long standing geochemical observations. Keywords: Microbial ecology, environmental microbiology, microbiome, soil microbiology, microbial oceanography

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

Judith Brown, PhD, and her research interests include the molecular epidemiology of whitefly-transmitted geminiviruses (Begomoviruses, Family: Geminiviridae), the basis for virus-vector specificity and the transmission pathway, and the biotic and genetic variation between populations of the whitefly vector, B. tabaci, that influence the molecular epidemiology and evolution of begomoviruses. Keywords: Plant viral genomics, emergent virus phylodynamics, functional genomics of insect-pathogen interactions