Biotechnology

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.

David Harris, PhD, occupies research efforts directed at the application of (cord blood and adipose) stem cells to transplantation, regenerative medicine and tissue engineering. The difficulty in locating bone marrow donors for patients needing transplants, particularly for minority patients, led to the investigation of other potential sources of stem cells. One such source that has become a viable alternative to bone marrow is umbilical cord blood. Not only has the use of cord blood allowed more patients to go to transplant due to less restrictive matching requirements between donor and recipient, but cord blood transplants are associated with fewer post-transplant complications, such as a lower incidence and severity of graft-versus-host disease (GVHD). In 1989, he began work on the use of cord blood for transplantation, which led to the establishment of the first cord blood bank in the United States in 1992, which is currently the largest such establishment in existence. Work continues today using animal models for cord blood transplantation to explore such research areas as graft-versus-leukemia, GVHD, regenerative medicine and tissue engineering applications. However, studies performed in his lab examining the use of cord blood stem cells in regenerative medicine is now our major emphasis. Work in regenerative medicine has focused on several specific areas of interest. The first area is the use of stem cells in an ischemia/reperfusion injury model of myocardial infarction in a rat model, with positive results. Efforts are underway to understand the molecular mechanisms involved and to derive small molecule drugs in collaboration with Dr. M. Gaballa at Sun Health Research Institute. Secondly, Dr. Harris has been successful in deriving epithelial tissues in vitro that mimic corneal tissues, both morphologically and histologically. When transplanted in vivo in rabbits, the tissues are equivalent to cadaver corneas in terms of sight restoration and function. Dr. Harris and his team are currently developing a human-to-human eye model that will avoid some of the xenogeneic complications associated with the rabbit model, in conjunction with the Dept. of Ophthalmology.Third, they have successfully derived glial, astrocyte and oligodendrocyte cell types from cord blood stem cells in vitro. Currently, these cells are used to study pediatric HIV infection at the molecular level, but are also amenable to work in Parkinson’s and spinal cord injury models. Dr. Harris is now collaborating with Dr. Madhavan of Neurology to study Parkinson’s disease and with Dr. Rogers of Stanford Research Institute to study Alzheimer’s disease. Fourth, recent work has begun comparing various stem cells sources (cord blood, bone marrow and adipose tissue) for the capacity to be used in regenerative medicine. Finally, over the past year they have investigated the use of cord blood stem cells for epithelial wound healing, with the goal being the treatment of non-healing wounds and ulcers in diabetic and bed-ridden patients. It has been found that injections of bone marrow stem cells, both intravenously as well as in the wound margins, significantly reduce healing time as well as minimizing scar formation. Of interest, the age of the recipient plays a significant role in wound healing. Keywords: stem cells, regenerative medicine, biobanking

Michael Hammer is a Research Scientist in the Division of Biotechnology at the University of Arizona with appointments in the Department of Neurology, Ecology and Evolutionary Biology, Bio5, the School of Anthropology, the University of Arizona Cancer Center, and the Steele Children's Research Center. Currently Dr. Hammer is interested in the use of the latest DNA sequencing technology to infer the underlying genetic architecture of neurodevelopmental diseases. Since 1991 Dr. Hammer has directed of the University of Arizona Genetics Core (UAGC), a facility that provides training and molecular biology services to University and biotechnology communities at large. After receiving his Ph.D. in Genetics at the University of California at Berkeley in 1984, he performed post-doctoral research at Princeton and Harvard. Over the past two decades, Dr. Hammer has headed a productive research lab in human evolutionary genetics, resulting in over 100 published articles documenting the African origin of human diversity, interbreeding between modern humans and archaic forms of the genus Homo, and genome diversity in the great apes. His lab and the UAGC were early adopters of next generation sequencing (NGS) technology and the application of whole genome analysis in humans, and his lab has been a key player in the Gibbon and Baboon Genome Projects, as well as a consortium that has analyzed the genomes of over 100 Great Apes (GAPE Project). In the past 3 years, Dr. Hammer's research team has succesfully employed NGS methods to identify molecular lesions causing neurodevelopmental disorders in undiagnosed children. This has led to the publication of articles identifying pathogenic variants associated with early onset epileptic encephalopathies. His lab is also currently pursuing studies to identify modifier genes that alter the expression of major genes and how they contribute to phenotypic heterogeneity in Mendelian disorders.

Stefano Guerra, MD, PhD, is a professor of Medicine, the Director of the Population Science Unit at the Asthma and Airway Disease Research Center, and a leading expert in the natural history and biomarkers of obstructive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). As principal investigator, he is engaged in the leadership and coordination of multiple studies that use bio-specimens and phenotypic information from independent epidemiological cohorts to characterize the natural history, profile the risk factors, and identify novel biomarkers of lung diseases.

Research in my laboratory over the last 30 years has focused on chronic heart failure (CHF), its pathophysiology and the development of new treatments for CHF. We have developed clinically relevant animal models of heart failure that allow us to explore the translational potential of new treatments. Our work initially examined the role of afterload reduction and neurohormal blockade. More recently we have been working with cell-based therapy for CHF using bioengineered scaffolds to prevent left ventricular (LV) remodeling and restore function in the damaged heart. Our most effective scaffold is a biodegradable vicryl mesh with embedded viable neonatal fibroblasts that secrete angiogenic growth factors. This patch increases myocardial blood flow, improves LV systolic function, and reverses LV remodeling if implanted at the time of an acute myocardial infarction. In CHF, this patch still improves myocardial blood flow but does not improve LV function or reverse LV remodeling. Thus, we have an effective delivery system for cell based therapy for CHF that increases myocardial blood flow and provides structural support for new cell growth. We are now focusing on seeding this patch with human inducible pluripotent stem cells in the cardiac lineage, the seeded cardiomyocytes align, communicate, contract in a spontaneous and rhythmic fashion. When implanted in rats with CHF, they improve LV function. We are exploring this patch seeded with human inducible cardiac pluripotent stem cells to treat patients with CHF. Keywords: induced pluripotent stem cells

Dr. Garcia is an authority on the genetic basis of inflammatory lung disease (with an emphasis on health disparities) and on the mechanistic basis of lung vascular permeability. Using bench-to-bedside approaches, his lab has explored novel methods to prevent vascular leak and to restore endothelial cell barrier function and vascular integrity. This expertise in lung inflammation and vascular permeability provides a natural linkage to interrogation of lung vascular contribution to the development of lung metastases. Leveraging their genomic expertise, in recent years, Dr. Garcia's lab has identified vascular genes whose products are key participants in inflammatory lung injury that also play a role in cancer development. They have developed lung endothelial inflammatory gene expression profiles as well as diagnostic gene signatures influenced by MYLK and NAMPT that impact lung and breast cancer prognosis. This work with NAMPT led to development of a therapeutic NAMPT neutralizing antibody that has shown promise in treating lung cancer, melanoma, and chronic lymphocytic leukemia. Finally, Dr. Garcia's lab is also interested in the untoward effect of thoracic radiation and has been examining strategies designed to attenuate radiation–induced pneumonits, fibrosis and vascular leak. These collaborative and highly translational cancer research efforts have bolstered the overall mission of the University of Arizona Cancer Center.

David Galbraith obtained undergraduate and graduate degrees in Biochemistry from the University of Cambridge, and postdoctoral training as a NATO Fellow at Stanford University. His first academic appointment was at the University of Nebraska Lincoln, and he became Professor of Plant Sciences at the University of Arizona in 1989. His research has focused on the development of instrumentation and methods for the analysis of biological cells, organs, and systems. He is internationally recognized as a pioneer in the development and use of flow cytometry and sorting in plants, developing widely-used methods for the analysis of genome size and cell cycle status, and for the production of somatic hybrids. He also was among the first to develop methods for the analysis of gene expression within specific cell types, using markers based on Fluorescent Protein expression for flow sorting these cells, and microarray platforms for analysis of their transcriptional activities and protein complements. Current interests include applications of highly parallel platforms for transcript and protein profiling of minimal sample sizes, and for analysis of genetic and epigenetic mechanisms that regulate gene expression during normal development and in diseased states, specifically pancreatic cancer. He is also funded to study factors involved in the regulation of bud dormancy in Vitis vinifera, and has interests in biodiversity and improvement of third-world agriculture. He has published more than 180 scholarly research articles, holds several patents, was elected a Fellow of the American Association for Advancement of Science in 2002, and serves on the editorial board of Cytometry Part A. He is widely sought as a speaker, having presented over 360 seminars in academic, industrial and conference settings. He was elected Secretary of the International Society for Advancement of Cytometry in 2016. Keywords: Plant and Animal Cellular Engineering; Biological Instrumentation; Flow Cytometry and Sorting

Joel Cuello, PhD, focuses his research on applying engineering to put biological systems to work. His collaborative research projects, which have been sponsored by DOE, NASA and USDA, among others, are divided into two major thrusts: Bioprocess Engineering and Controlled-Environment Engineering.With bioprocess engineering, Dr. Cuello’s concentrations are on design and scale up of bioreactors for production of biofuels and biochemicals from algae, plant cells and organs. Also, he explores the optimization of algae and cell-culture productivity through biochemical and environmental strategies. Also, he attends to wastewater treatment using algae, microbial mat and hydroponics.In regard to controlled-environment engineering, Dr. Cuello’s concentrations -- for both Earth and Space applications -- are on design of novel lighting systems, including hybrid solar-electric lighting systems, light-emitting diode arrays, and water-cooled high-intensity discharge lamps. He complements this work with trying to design bioproduction systems, including a hybrid hydroponics-and-aquaculture system.

Dr. Minying Cai is currently a research professor in the Department of Chemistry and Biochemistry at the University of Arizona. She has been working in the Chemistry & Biochemistry department for more than 16 years and has more than 100 publications in the area of novel drug discovery for obesity, diabetes, cancer and pain. Dr. Cai received the Ph.D. at the University of Arizona in Biochemistry and Molecular Biophysics in 2004. Before that, she had been working in Shanghai Institute of Materia Medica; Shanghai Research Center of Biotechnology in Chinese Academy of Sciences. Dr. Cai has been working on peptide based drug discovery for more than 23 years, starting with discovery of developing anti-microbial peptide and insulin related peptide drug. Sixteen years ago, she started working on melanotropin and opioid related drug discovery. Dr. Cai's research in peptides involves highly multidisciplinary areas including chemistry and biochemistry; molecular pharmacology, molecular imaging, and cancer research, with expertise in molecular pharmacology, synthetic, organic and peptide methodology, chemical and biophysical analysis and evaluation, and in vitro and in vivo expression. Dr. Cai is currently working on several projects at the interface of chemistry, pharmacology and biology within the areas of: 1. Structure based drug design and synthesis of GPCR ligands, including developing selective hMCRs ligand; 2. Developing novel biophysics tools for molecular imaging; novel biomarker for high-throughput screening system. 3. Exploiting novel scaffold via computational chemistry for small molecule therapeutics for energy balance and cancer study; 4. Creating a nanostructured integrated platform for biodetection and imaging-guided therapy. Keywords: Drug Discovery, Melanoma Prevention, neurodegenerative diseases, Obesity and Diabetes, Melanocortin System

Research in the Bhattacharya lab focuses on molecular approaches to direct B cell differentiation to establish immunity to infectious disease, and stem cell differentiation for regenerative medicine. Current projects in the lab include: 1) Understanding the cellular basis of antibody-mediated immunity to variable viruses. After infection or vaccination, B cells that recognize the pathogen proliferate and undergo a massive level of expansion. Upon clearance of the infection a small fraction of the "best" B cells are retained to become memory B cells or long-lived plasma cells. Our recent work has established that memory B cells are excellent at recognizing not only the original pathogen, but also mutant escape variants of the pathogen. In contrast, long-lived plasma cells are highly specific only for the original pathogen. We are studying the transcription factors that regulate the memory B cell vs. long-lived plasma cell fate, and are studying mechanisms to alter this fate to provide effective immunity against mutable viruses such as influenza and Dengue. 2) Identifying molecular regulators of the duration of immunity. Most clinically used vaccines rely on the production of antibodies to confer immunity. The duration of immunity can vary greatly between different vaccines, yet the molecular basis of this remains unknown. Current efforts are focused on the identification of genes that regulate plasma cell lifespan and on the features of the vaccine that confer durable antibody immunity. 3) Engineering human pluripotent stem cells to generate antibody-mediated immunity. A small fraction of patients infected with HIV or dengue virus, or vaccinated against influenza develop remarkable antibodies that neutralize nearly all clinical isolates of these viruses. Yet it is unclear how to induce these types of antibodies in the broader population through standard vaccination. Using novel targeted nuclease technologies, we are engineering human embryonic stem cells to express these antibodies and differentiating them into transplantable long-lived plasma cells. The long-term goal of this project is to provide permanent immunity to recipients of these engineered plasma cells.