Genetics

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.

The Gutenkunst group studies the function and evolution of the complex molecular networks that comprise life. To do so, they integrate computational population genomics, bioinformatics, and molecular evolution. They focus on developing new computational methods to extract biological insight from genomic data and applying those methods to understand population history and natural selection.

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.

Andrew Capaldi, PhD, researches the signaling pathways and transcription factors in a cell that are organized into circuits. They allow cells to process information and make decisions. For Dr. Capaldi, the work arises in understanding both how these circuits are built from their components, and how they function and malfunction. To address these questions, he is working to reverse engineer the circuitry that controls cell growth in budding yeast using a combination of genomic, proteomic and computational methods. http://capaldilab.mcb.arizona.edu

The control of gene expression is critical to nearly all aspects of cellular biology, from maintaining basic cell function and identity, to the ability of cells to respond to numerous signals that arise during processes such as development, exposure to pathogens or changes in the cellular environment. A key means by which all cells enact appropriate gene expression responses is to alter the function of messenger RNAs (mRNAs). mRNAs exist in different functional states, dependent upon the proteins bound to them. These states include translation (protein synthesis), repression (off state) and decay. The localization of an mRNAs can also affect its function, thus cells are offered an array of spatial and temporal mechanisms for gene expression control at the mRNA level. mRNAs can also cycle between these different functional states. For example, mRNAs exiting translation often accumulate in distinct mRNA-protein (mRNP) assemblies known as P-bodies and stress granules, from which they may ultimately return to translation again or possibly undergo mRNA decay. Dr Buchan (Ph.D, B.S.) and his lab are particularly interested in the study of P-bodies and stress granules. These conserved, mRNA-protein (mRNP) bodies contain important protein regulators of mRNA decay and translation, as well as signaling proteins, and thus affect gene expression control and cell signaling pathways. In addition, they strongly resemble other important mRNP granules that function in embryogenesis (maternal granules) and memory formation (neuronal transport granules). Finally, stress granules and P-bodies have numerous connections to disease, such as an involvement in RNA viral replication, elevated levels in certain cancer types, as well as the formation of aberrant stress granules in neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). The Buchan lab uses yeast and cell line models to study the assembly, disassembly and function of stress granules and P-bodies, and how aspects of stress granule and P-bodies contribute to ALS and forms of cancer

Michael Barker is an evolutionary biologist studying the origins of biological diversity, particularly how abrupt genomic changes such as polyploidy, chromosomal change, and hybridization have contributed to the evolution of plant diversity. Biologists have long been fascinated by these processes because they create unique opportunities for the evolution of ecological and phenotypic novelty with the potential for relatively rapid speciation. Although assessing the importance of these abrupt changes has historically been a difficult task, advances in genomics and bioinformatics have created new opportunities for addressing these longstanding questions. By integrating new computational and evolutionary genomic tools with traditional approaches such as molecular evolution, phylogenetics, mathematical modeling, and experimental work Barker's lab currently studies 1.) the contributions of recent and ancient polyploidy to eukaryotic diversity; 2.) the evolution of chromosome number and genome organization; and 3.) the impact of hybridization on speciation and novelty.

Lingling An, PhD, conducts research in the interdisciplinary boundaries of many fields such as statistical sciences, biological and medical sciences, genomics and genetics. Her statistical group's major research interests include development and application of statistical and computational methods for analysis of high-dimensional genomic/genetic, metagenomic/ metatranscriptomic, and epigenomic data. The overlying vision is to develop rigorous, timely and useful statistical and computational methodologies to help biologists/geneticists to ask, answer, and disseminate biologically interesting information in the quest to understand the ultimate function of DNA and gene network.