DNA

Nancy C Horton

Professor
Professor, Chemistry and Biochemistry - Med
Professor, Chemistry and Biochemistry-Sci
Professor, Genetics - GIDP
Member of the Graduate Faculty
Professor, BIO5 Institute
Primary Department
Contact
(520) 626-3828

Work Summary

The Horton lab uses biophysical, biochemical, and molecular biology to study protein-DNA interactions and filament formation by enzymes. Current projects include the investigation of mechanisms of disease caused by the Human Parvovirus B19, and advantages of filament formation by enzymes such as the sequence specific DNA endonuclease SgrAI, and the important metabolic enzyme PFK.

Research Interest

The Horton lab uses a variety of biochemical and biophysical methods to investigate DNA binding proteins. Recent projects include the discovery of a novel mechanism of regulation of enzyme activity using filamentation. Filamentation, or self-association into polymers of varied lengths, by enzymes has only recently been appreciated as a widespread phenomenon, although the purpose of filamentation is not known in most cases. We discovered this phenomenon in 2010 in a sequence specific endonuclease, SgrAI, and have now determined its high resolution structure via cryo-electron microscopy. We have also performed a full kinetic analysis showing that filamentation greatly expedites the activation of the enzyme, and also allows for the sequestration of enzyme activity onto only a subset of available substrates. The other major project in the lab concerns the triggering of autoimmune diseases in genetically susceptible individuals. We study proteins from the human parvovirus B19, a virus which often precedes the development of autoimmune diseases like rheumatoid arthritis, autoimmune hepatitis, and lupus. We study how these proteins interact with cellular components to modulate the immune system into loss of self-tolerance.

David A Kudrna

Coordinator, Bac/Est Resource Center
Primary Department
Department Affiliations
Contact
(520) 626-9596

Work Summary

We are a plant genomics lab who specialize in whole genome sequencing and assembly; with analyses of structural variation, gene modeling and transcriptomes. Our work on major projects of rice, corn, barley, etc, allows us to share our technical expertise with other researchers.

Research Interest

We are a plant genomics lab who specialize in whole genome sequencing and assembly; with analyses of structural variation, gene modeling and transcriptomes. Our work on major projects of rice, corn, barley, etc, allows us to share our technical expertise with other researchers. Our research in plant and animal genomes, at the whole genome and transcriptome levels, will impact successful genetic selections toward the goal of feeding the 9 billion people toward the year 2050. Keywords: "Genome Sequencing", "PacBio", "Structural Genomics", "Plant Genetics", "DNA Extraction"

Rod A Wing

Director, Plant Genomics Institute
Bud Antle Endowed Chair For Excellence, Agriculture-Life Sciences
Professor, Plant Science
Professor, Ecology and Evolutionary Biology
Regents Professor
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-9595

Work Summary

Harnessing 15MY of natural variation in the genus Oryza (rice) to help solve the 10-billion people question: i.e. how do we feed our world without destroying our world.

Research Interest

Rod Wing, PhD, and his lab, The Arizona Genomics Institute, specialize in building what geneticists call a physical map of a genome- a crucial foundation of any genome sequencing effort. AGI has earned a reputation for providing extremely high-quality maps, as documented in previous sequencing efforts leading to the genome sequences of rice and corn. The genome sequence will allow scientists to locate and identify genes that can improve and strengthen crops and increase yield in order to help solve the Earth’s looming food crisis by creating new strains of the cereal crops that make up 60% of humankind’s diet. Keywords: Genome Biology, Genome Sequencing/Assembly/Annotation, Food Security, Rice

Casey E Romanoski

Associate Professor, Cellular and Molecular Medicine
Associate Professor, Clinical Translational Sciences
Associate Professor, Genetics - GIDP
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-7244

Work Summary

My laboratory aims to identify the genetic and environmental reasons that certain individuals are predisposed to develop complex diseases like heart disease. We use new technologies, experimental, and computational approaches to identify molecular patterns indicative of disease predisposition.

Research Interest

Our laboratory is both experimental and computational. We use next-generation sequencing technologies to measure genome-wide molecular phenotypes. By leveraging the interconnected relationships between DNA sequence, transcription factor binding, chromatin modification, and gene expression, we study how cells achieve context-appropriate expression patterns and signal responsiveness. Lab Website: www.romanoskilab.com Keywords: Genetics, Genomics, Vascular Biology, Bioinformatics

Walter Klimecki

Associate Professor, Veterinary Medicine
Assistant Professor, Medicine - (Research Scholar Track)
Associate Professor, Pharmacology and Toxicology
Associate Professor, Public Health
Associate Professor, Genetics - GIDP
Adjunct Associate Professor, Nursing
Associate Professor, BIO5 Institute
Contact
(520) 626-7470

Work Summary

Walter Klimecki's research program involves the balance between the particular DNA sequence “versions” of genes that we inherit from our ancestors, and the particular environmental exposures that we experience throughout our lives. The Klimecki lab studies diseases resulting from human exposure to arsenic, contributing to a better understanding of the inherited genetic differences between people that result in altered chemical processing of arsenic after it enters the body.

Research Interest

Walter T. Klimecki, DVM, PhD, is an Associate Professor in the Department of Pharmacology and Toxicology in the College of Pharmacy at the University of Arizona. Dr. Klimecki holds joint appointments in the College of Medicine, the College of Public Health, and the Arizona Respiratory Center. He is a Full Member of the Southwest Environmental Health Sciences Center (SWEHSC) where, together with BIO5 director Martinez and BIO5 Statistics Consulting Service director Billheimer, he leads the Integrative Health Sciences (IHS) Center at SWEHSC. The IHS is a translational research support core at SWEHSC, focused on lowering the “activation energy” for translational research.Dr. Klimecki’s research focuses on the toxicology of metals in the environment, an issue particularly relevant in our mining-intensive state. His research work has encompassed a wide range of experimental approaches, from epidemiological studies of arsenic-exposed human populations, to laboratory models including cell culture and rodents. Using cutting edge genetics tools, Dr. Klimecki’s group recently published the first report of an association between human ancestry and response to environmental toxicants. In this provocative work, his group found that individuals whose genomes were comprised of DNA with its origins in the indigenous American populations processed ingested arsenic in a less harmful manner than did individuals whose genomes had their origins in Europe. Using laboratory models his group made ground-breaking discoveries of the impact of arsenic exposure on a process known as autophagy, in which cells digest parts of their own machinery in a sort of “cash for clunkers” arrangement. The ability of arsenic to perturb this process is only now being appreciated by the toxicology community, thanks to the work of the Klimecki Lab. Dr. Klimecki was recently elected as a Vice President-elect to the Metals Specialty Section of the Society of Toxicology, the preeminent scientific toxicology organization in the world. Dr. Klimecki’s research is highly collaborative: his grants and publications have included many BIO5 members, including BIO5 director Fernando Martinez, and BIO5 members Donata Vercelli, Dean Billheimer, and Marilyn Halonen.

Laurence Hurley

Associate Director, BIO5 Institute
Professor, Medicinal Chemistry-Pharmaceutical Sciences
Professor, Medicinal Chemistry-Pharmacology and Toxicology
Professor, Cancer Biology - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-5622

Work Summary

Laurence Hurley's long-time research interest is in molecular targeting of DNA, first by covalent binders (CC-1065 and psorospermin), then as compounds that target protein–DNA complexes (pluramycins and Et 743), and most recently as four-stranded DNA structures (G-quadruplexes and i-motifs). He was the first to show that targeting G-quadruplexes could inhibit telomerase (Sun et al. [1997] J. Med. Chem., 40, 2113) and that targeting G-quadruplexes in promoter complexes results in inhibition of transcription (Siddiqui-Jain et al. [2002] Proc. Natl. Acad. Sci. U.S.A., 99, 11593).

Research Interest

Laurence Hurley, PhD, embraces an overall objective to design and develop novel antitumor agents that will extend the productive lives of patients who have cancer. His research program in medicinal chemistry depends upon a structure-based approach to drug design that is intertwined with a clinical oncology program in cancer therapeutics directed by Professor Daniel Von Hoff at TGen at the Mayo Clinic in Scottsdale. Dr. Hurley directs a research group that consists of a team of graduate and postdoctoral students with expertise in structural and synthetic chemistry working alongside students in biochemistry and molecular biology. NMR and in vivo evaluations of novel agents are carried out in collaboration with other research groups in the Arizona Cancer Center. At present, they have a number of different groups of compounds that target a variety of intracellular receptors. These receptors include: (1) transcriptional regulatory elements, (2) those involved in cell signaling pathways, and (3) protein-DNA complexes, including transcriptional factor-DNA complexes.In close collaboration with Dr. Gary Flynn in Medicinal Chemistry, he has an ongoing program to target a number of important kinases, including aurora kinases A and B, p38, and B-raf. These studies involve structure-based approaches as well as virtual screening. Molecular modeling and synthetic medicinal chemistry are important tools.The protein–DNA complexes involved in transcriptional activation of promoter complexes using secondary DNA structures are also targets for drug design.

Michael F Hammer

Associate Director, Omics
Research Scientist, Arizona Research Labs
Research Scientist, Ecology and Evolutionary Biology
Research Scientist, Neurology
Research Scientist, BIO5 Institute
Contact
(520) 621-9828

Work Summary

Michael Hammer has headed a productive research lab in human evolutionary genetics. His lab were early adopters of next generation sequencing (NGS) technology successfully employed NGS methods to identify molecular lesions causing neurodevelopmental disorders in undiagnosed children. 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.

Research Interest

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.