Dana Levasseur Ph.D. [Former faculty]

Ben Darbro M.D., Ph.D.

Current
Ben
Darbro
M.D., Ph.D.
Associate Professor, Director of the Shivanand R. Patil Cytogenetics and Molecular Laboratory
Pediatrics
Research area(s): 
Genetic Determinants of Intellectual Disability
Address
Research
Research Focus: 

My primary research interest is in the genetic determinants of intellectual disability (ID), formerly referred to as mental retardation (MR).  I specifically study the roles of copy number variation and somatic structural variation in the context of a “genomic mutational burden” hypothesis of ID.  This hypothesis is investigated using a combination of conventional cytogenetics methods (chromosome analysis and fluorescence in situ hybridization) and new molecular, high throughput, and high data volume, genomic technologies including single nucleotide polymorphism (SNP) arrays, gene expression microarrays, comparative genomic hybridization (CGH) arrays as well as custom targeted, whole exome, and whole genome massively parallel DNA sequencing.  We perform all our own bioinformatics and are actively engaged in the development of new analysis tools to better meet our needs and those of the scientific community.  Drosophila melanogaster and the well-established GAL4/UAS/RNAi system are used to evaluate candidate ID genes with the use of a validated olfaction learning technique (T-Maze).  Candidate genes are derived from our extensive clinical database of patients with ID that have already undergone diagnostic chromosomal microarray testing.

Albert J Erives PhD

Current
Albert
J
Erives
PhD
Associate Professor
Biology
Research area(s): 
Bioinformatics, Developmental Genetics, Evolutionary Genetics, Gene Expression and Regulation
Address
424A
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424
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Research
Research Focus: 

The Genetics of Eukaryotic Transcriptional Enhancers

Transcriptional enhancers are DNA sequences that specify inducible, spatiotemporal patterns of gene expression at most gene loci. Several complementary results from genomic studies have shown that the majority of functional sites in a genome correspond to transcriptional enhancer sequences, thus underscoring their importance for understanding basic physiology. However, while transcriptional enhancers represent a major class of regulatory DNAs in eukaryotic genomes, the entire set of sequences that are necessary and sufficient for constructing a complex eukaryotic enhancer are not yet known.

Our laboratory is focused on using molecular biology, genomics, bioinformatics, and transgenic model systems to understand enhancer biology. A major area of focus in our laboratory is the study of how different morphogen-concentration specific responses are encoded at different loci. We are also interested in understanding the sequence-function relationship well enough to understand the complex patterns of molecular evolution occurring at enhancer sequences.

M. Bento Soares PhD

Professor
Pediatrics

Dana Levasseur Ph.D.

Assistant Professor
Internal Medicine

John R Manak Ph.D.

Current
John
R
Manak
Ph.D.
Associate Professor
Biology
Research area(s): 
Genetic basis of human disease using high-throughput genomics methodologies, fruit fly models of human disease and cancer.
Address
459A
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Research
Research Focus: 

Research in my laboratory covers three different but not mutually exclusive areas: 1) high-throughput genomics technologies to identify the genetic basis of human disease, 2) fruit fly models to understand human diseases such as epilepsy and cancer, with an emphasis on chromatin structure, 3) genomic technology development to facilitate identification of important mutations in both humans and model organisms. 

For the first project, we are utilizing array-based comparative genomic hybridization (aCGH) to identify copy number variants associated with a number of diseases, including cleft lip and palate, spina bifida, and renal agenesis (all relatively common birth defects).  Using this approach, we identify genes whose copy number is altered in affected individuals, and we functionally validate these disease-associated genes in vertebrate animal models such as frogs and fish.  Additionally, we are using exome sequencing to explore the genetic basis of the aforementioned diseases.  This new genomics technology allows enrichment and high-throughput sequencing of the protein-coding exons in the human genome; since roughly 85% of the mutations causing Mendelian disorders are thought to reside in such exons, this strategy eliminates the need for costly whole-genome sequencing.  However, this type of analysis requires careful selection of pedigrees that show strong Mendelian inheritance patterns of the disease, which is turn suggest that high effect loci are at play in the disease process in these families. 

For the second project, we are studying the Drosophila homolog of the c-Myb proto-oncogene (which causes leukemia and lymphoma in birds and mammals).  In particular, we are exploring the role of Drosophila Myb (Dm-Myb) in modulating chromatin structure and controlling gene expression.  Our recent results demonstrate that the Myb protein is controlling gene expression through its interaction with other chromatin-modulating factors, and that Myb is regulating different targets in different cell types.  Most interestingly, in contrast to the dogma in the field, Myb is a potent repressor of large numbers of genes in certain specialized cell types.

Additionally, we are using the Drosophila system to model another human disease, myoclonic epilepsy.  We have shown for the first time that the same gene mutated in flies, mice and humans causes this form of epilepsy, and that the epileptic flies can be successfully treated with human anti-epileptic medications (Am J Hum Genet, 2011).  Intriguingly, the mutated gene is prickle, a gene that has been shown to be involved in establishing planar cell polarity.  A number of laboratories have worked on this gene over the course of many years with regard to its involvement in planar polarity; however, up until now the epileptic behavioral phenotype had been missed.        

For the third project, we are developing a novel mutation mapping technology (in collaboration with my colleague in the dept, Josep Comeron) in order to efficiently and cost-effectively map both human disease-causing mutations as well as mutations of interest in a variety of model organisms, including mice and flies.  Currently, our technology can correctly identify known SNPs with an accuracy of 99% and we are now using the technology to identify novel mutations in several human diseases.    

Faculty affiliations: 

Ana Llopart Ph.D.

Current
Ana
Llopart
Ph.D.
Associate Professor
Biology
Research area(s): 
Speciation Genetics, Molecular and Population Genomics
Address
Research
Research Focus: 

In our laboratory we seek to understand the evolution of the genetic barriers responsible for species being reproductively isolated from one another; ultimately the genetic basis of speciation. Today we know that these barriers often involve genic incompatibilities among alleles that function normally in their usual genetic background and produce perfectly fit genotypes, but generate hybrid dysfunction (i.e. sterility and inviability) when encounter alleles from other species. 

To gain insight into the evolution of these genetic barriers we study hybrids where incompatibilities become apparent. Our approaches use methodologies that combine classic genetics, modern genomics and population genetics, and an ideal biological system of two very closely related species of fruit flies, Drosophila yakuba and D. santomea, which produce abundant hybrids in nature.

One of our current areas of research is centered on studying the genetic basis of sterility of female hybrids between D. yakuba and D. santomea. Hybrid female sterility is a trait that has been a bit more neglected than that of their counterparts hybrid males. In this system, sterility involves at least one factor of recent evolution in D. yakuba that is placed in the cytoplasm of the hybrid embryo and that is incompatible with D. santomea genes. We are also interested in evaluating natural introgression, that is, the effective exchange of genes between species through rare hybridization in nature. Experiments in the laboratory can be very useful to detect genomic regions associated with isolating barriers, but they seldom capture the full complexity of nature. By identifying genes that are able to transgress species boundaries in the natural habitat we can built introgression landscapes, which allow us to gain valuable insights into the chromosomal location of genes either responsible for local adaptation or involved in hybrid dysfunction. Our third on-going project focuses on a very special type of genic incompatibilities, those between cis-regulatory sequences of genes and transcription factors. Independent evolution of these two interacting components involved in transcription regulation in different species usually leads to breakdown of gene expression in hybrids.

Faculty affiliations: 

Richard J Smith M.D.

Current
Richard
J
Smith
M.D.
Professor and Vice Chair
Otolaryngology
Research area(s): 
Human Genetics
Address
Research
Research Focus: 

My laboratory is studying the genetic basis of deafness and membranoproliferative glomerulonephritis type 2 (MPGN 2). Hereditary deafness is common. It affects 1:2,000 newborns and accounts for greater than 50% of severe-to-profound childhood deafness. It also affects the elderly. Nearly 50% of octogenarians have difficulty communicating without the use of amplification, and in many, the cause is genetic. Inherited hearing impairment can occur with other co-inherited clinical features to form a recognized phenotype (syndromic hearing loss) or appear in isolation (non-syndromic hearing loss). Non-syndromic hearing loss accounts for approximately 70% of genetic deafness. It is almost exclusively monogenic and is highly heterogeneous, with some estimates of the number of deafness-causing genes exceeding 100. We are studying both syndromic and non-syndromic types of deafness. Projects include gene localization by linkage analysis and homozygosity mapping, mutation screening and detection, a variety of functional studies, and hearing-related research on mouse mutants targeting specific genes by RNAi. Membranoproliferative glomerulonephritis type 2 is also called Dense Deposit Disease (MPGN II/DDD). It causes chronic renal dysfunction that leads to kidney failure and a retinal disease similar to age-related macular degeneration, which is the most common cause of blindness in the elderly. Deficiency of and mutations in complement Factor H (CFH) are associated with development of MPGN II/DDD. Changes in CFH are also associated with another renal disease, atypical hemolytic uremic syndrome, and with age-related macular degeneration. We are studying relationships between the alternative pathway of the complement cascade, the structure of the glomerular basement membrane, and MPGN II/DDD to better understanding the pathophysiology of this disease.

Faculty affiliations: 

Todd E Scheetz Ph.D.

Current
Todd
E
Scheetz
Ph.D.
Professor
Ophthalmology and Visual Sciences
Research area(s): 
Ophthalmology and Visual Sciences
Address
3185
MERF
3185
MERF
Research
Research Focus: 

Dr. Scheetz's research interests focus on bioinformatics, genomics, systems biology, and genetic analyses including genotype-phenotype correlation and genome-wide association studies. Much of his research is performed in collaboration with other faculty within the University of Iowa and other institutions. These collaborative projects include analysis of genomic integration patterns, analysis of expression, and identification of regulatory elements in the mammalian eye.

Faculty affiliations: 

Paul B McCray M.D.

Current
Paul
B
McCray
M.D.
Professor
Pediatrics
Research area(s): 
Human Genetics; Molecular and Biochemical Genetics
Address
6320
PBDB
6320
PBDB
Research
Research Focus: 

Dr. McCray has a long-standing interest in the pathogenesis and treatment of cystic fibrosis. His laboratory has two main areas of investigation: 1) innate mucosal immunity in the lung and how this is altered in disease states, and 2) gene transfer for the treatment of inherited diseases.

Studies of the anti-microbial properties of the airway surface liquid have stimulated interest in the anti-microbial proteins and peptides secreted by epithelia. Dr. McCray's lab is currently defining the tissue specific expression, regulation and anti-microbial activity of epithelial defensins and other proteins in model systems. These molecules may play a role in the innate mucosal immunity of the lung and other mucosal surfaces. A major effort is directed towards identifying novel host defense genes using genomics and large scale expression profiling.

Another area of investigation is the development of integrating viral vectors for the treatment of inherited diseases. Current projects include gene transfer to airway epithelia for cystic fibrosis and gene transfer to the hepatocytes for the treatment of hemophilia A. The focus of these studies is on the development and optimization of retrovirus-derived vectors. A long-term goal is to develop strategies with integrating vector systems that could be successfully used to treat genetic diseases.

Faculty affiliations: 

Bryant F McAllister Ph.D.

Current
Bryant
F
McAllister
Ph.D.
    Associate Professor
    Biology
    Research area(s): 
    Computational Genetics; Evolutionary Genetics
    Address
    Research
    Research Focus: 

    My research interests are in the field of evolutionary genetics, especially in processes occurring at or influenced by the genome. Active research projects in the lab are primarily concerned with using the fly species Drosophila americana to understand the factors influencing chromosomal change and the mechanisms involved in the differentiation of sex chromosomes. Changes in chromosomal arrangement are common, but their significance is unknown. We are currently examining a chromosomal rearrangement involving a centromeric fusion of the X chromosome and an autosome in D. americana. This derived arrangement exists as a polymorphism with the ancestral arrangement, showing a strong latitudinal cline in the central and eastern US. Population genetic analyses are used to examine the hypothesis that these alternative chromosomal arrangements coordinate adaptive genetic variation. Independently evolved pairs of sex chromosomes exhibit similar patterns of differentiation. The Y chromosome is genetically inert, and the X chromosome contains many active unique genes and often compensates for differences in dosage between genders. The X-4 centromeric fusion in D. americana provides a system for examining the earliest asymmetries between newly evolved sex chromosomes. We are testing models of sex chromosome evolution by examining patterns of sequence variation on this pair of neo-sex chromosomes.

    Faculty affiliations: 

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