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Divisions & Programs Medical Education Residency & Fellowships Research Faculty ContactRESEARCH
Faculty members in the Division conduct basic, translational and clinical research in a number of areas within human and medical genetics. These include projects on autism, attention deficit/hyperactivity disorder (ADHD), behavioral/psychiatric disorders, ion channel disorders, congenital heart defects, genomics, genetic syndromes, hemochromatosis, breast cancer, and Prader-Willi syndrome.
Current projects include:
Maureen Bocian, M.D.
Professor
Dr. Bocian's research interests include dysmorphology, new syndrome identification, natural history of genetic syndromes, and
the variability and heterogeneity in genetics syndromes.
John Jay Gargus, M.D., Ph.D.
Professor
Dr. Gargus's interests include functional genomics, diseases of ion pumps and channels, complex polygenic neuropsychiatric disease,
and molecular pathophysiology of inborn errors in signal transduction.
There are two major research thrusts on-going in the Gargus lab. The first is broadly a functional genomics approach to ion pumps and channels as candidate genes in common complex polygenic disease, a field he recently covered in invited reviews (Gargus, 2006 "Ion channel functional candidate genes in multigenic neuropsychiatric disease". Biological Psychiatry, in press; Gargus, 2003 "Unraveling monogenic channelopathies and their implications for complex polygenic disease" Am J Hum Genet 72: 785-803). The other field is broadly the molecular pathophysiology of inborn errors in signal transduction via receptors, transporters and channels, a field also covered in an invited review (Gargus, 2005 "Receptor, Transporter and Ion Channel Diseases" In: Encyclopedia of Molecular Cell Biology and Molecular Medicine. R.A. Meyers, eds. Wiley-VCH Verlag BmbH, Weinheim). The approach to both areas places a heavy reliance upon functional biophysical studies and molecular pathophysiology in addition to more
traditional human molecular genetics.
Taosheng Huang, M.D., Ph.D.
Assistant Clinical Professor, Research Geneticist
Dr. Huang is the director of the cardiovascular genetics clinic. His clinical research is on the genetic
syndromes with cardiac malformations and metabolic disease. In addition, he is the associate director of the
Mitochondrial Medicine Molecular Diagnostic Lab.
For additional information on Dr. Huang, please
visit mitomap.bio.uci.edu/mitomed/staff.html
The primary interest of Dr. Huang's lab is to study the molecular basis of genetic syndromes and
apply discoveries from genetic syndromes to common diseases. For additional information on Dr. Huang's lab,
please visit www.ucihs.uci.edu/pediatrics/drhuang/.
His lab is currently focusing on the following areas:
1. To study the role of TBX3 in breast cancer. TBX3 is also a T-box transcription factor. Mutation of TBX3 causes Ulnar-Mammary syndrome characterized by hypoplasia and absence of the mammary gland. Oveexpression of TBX3 plays an important role in breast cancer. To study the role of TBX3 in breast cancer, we are working on an animal model, and analyzed TBX3 expression in human breast cancer tissue. By working with animal and breast cancer tissue, our research aims to optimize the clinical relevance of our work.
2. To identify the disease-causing gene associated with noncompaction of the ventricular myocardium (spongy heart), we are studying a family with balanced translocation with this condition, and are also performing a linkage study and search for mutations of the candidate gene with this disease.
3. The intracellular pathway to study TBX5. TBX5 is a T-box transcription factor. Mutations of TBX5 cause Holt-Oram syndrome characterized by congenital heart diseases and limb anomalies. By studying the intracellular network of TBX5, including the upstream transcription factor that controls TBX5 expression cofactor that interacts with TBX5 and downstream target whose genetic regulation is dependent on TBX5. We anticipate identifying many genes associated with congenital heart disease, a most common malformation in humans, and contribute significantly to the mobility and mortality in pediatric populations.
4. The Genetic basis of optic atrophy. We are performing linkage analysis and candidate gene mutation analysis to elucidate the genetic cause of this condition. The animal models will be used for stem cell therapy.
Virginia Kimonis, M.D.
Professor, Chief of Human Genetics Division
Please visit Dr. Kimonis's lab on the web at www.ucihs.uci.edu/pediatrics/drkimonis/index.shtml
Dr. Kimonis's laboratory focuses on the genetic causes of muscle disease.Virginia Kimonis is particularly interested in inherited muscle disorders that occur in
combination with diseases of bone. Families with a combination of muscle disease, Paget disease of bone, and dementia
(also known as IBMPFD) have been studied in the laboratory, and the gene for the disorder has been localized to
chromosome 9. By identifying the causal gene (VCP, CDC48 or p97) for this disorder, the researchers are now
identifying the key pathways and functions that are disrupted by the mutations they have found in the affected
families.
The Kimonis group is studying additional members of the original families and additional families with the
combination of muscle and bone disease and are looking at the relationship between the familial disorders and the
individuals' genetic makeup. They are also looking for other disorders that have various combinations of muscle,
bone and brain disease, which may be related to IBMPFD and result from mutations in genes that are part of the VCP
pathways.
Identifying the single gene responsible for IBMPFD could have implications in many disciplines, leading to
greater understanding of inclusion body myopathy, dementia and Paget disease of the bone. These findings may not only
make it possible to develop better clinical treatments for families with IBMPFD, but also for those with other
sporadic and hereditary diseases that share components of IBMPFD.
Kathryn Steinhaus French, M.S., CGC
Clinical Professor, Genetics Counselor
Dr. Steinhaus French conducts research directed toward developing universal standards for human pedigree nomenclature. Through her research with
co investigator, Robin Bennett, Ms. Steinhaus-French has documented the need for the development of standardized pedigree symbols. She has developed recommendations for standardized family pedigree nomenclature which were published in the American Journal of Human Genetics in March, 1995. In the future, she will attempt to incorporate these standardized symbols into graduate, medical, and nursing student curriculum, board examinations, medical publications, and
computer software programs.
Ann Walker, M.A., CGC
Adjunct Professor, Director of Genetic Counseling Program
Ann Walker's research explores factors affecting delivery and utilization of genetic services such as prenatal diagnosis or screening for genetic traits that may increase reproductive risk or predispose to disease. Among factors affecting access to services are public and professional knowledge of genetics and perceptions or beliefs about genetic evaluation and its utility. Research is aimed at determining if and how primary care professionals recognize potential risk for genetic disease or birth defects in their patients including psychosocial issues surrounding molecular (DNA) testing for genetic risk to develop conditions such as cancer. Alzheimer's disease or other adult-onset diseases are also being studied to find out how patients and families are affected by such testing. This type of screening has enormous commercial potential and will inevitably be introduced on a wide scale. To prevent harm, it is critical to devise ethical and humane protocols for using these technologies. The goal of these
investigations is to develop effective strategies for teaching new and practicing health professionals about the implications of advances in genetics and for helping them incorporate this knowledge into their practice.
Michael Zaragoza, M.D., Ph.D.
Assistant Clinical Professor
Dr. Zaragoza’s primary research and clinical interest is in the genetic causes of congenital heart disease and cardiomyopathy. His research is focused on examining mitochondrial dysfunction as the etiology of cardiac malformations and cardiomyopathies in an animal model and in patients. During the past two years, he has conducted molecular genetic studies on families with the human cardiomyopathy, isolated noncompaction of the ventricular myocardium (INVM). The major feature of noncompaction cardiomyopathy is loose, trabeculated myocardium, thought to arise from a block in a process in which myofibrils compact during cardiogenesis. In humans, several genes contribute to the etiology; however, for most patients, the genetic defect and underlying mechanisms are unknown. Results from the genetic studies of Dr. Zaragoza provide evidence for a new locus for INVM on chromosome 11.
Dr. Zaragoza more recently began investigating the role of mitochondria in cardiomyopathy in two mouse models, mice deficient in the adenine nucleotide translocator proteins (ANTs), nuclear-encoded inner mitochondrial membrane proteins involved in oxidative phosphorylation and in apoptosis. Mice deficient in Ant1 develop hypertrophic and dilated cardiomyopathies while mice deficient in Ant2 die at mid-gestation from ventricular hypoplasia and cardiac noncompaction. The pathophysiological and molecular mechanisms by which mitochondrial dysfunction leads to these cardiac abnormalities currently are being investigated.
Dr. Zaragoza also will direct a new outpatient Cardiogenetics Clinic at UCI planned for 2006. The clinic will specialize in the evaluation, diagnosis and care of children and adults with congenital heart disease, heart failure and cardiomyopathies including dilated cardiomyopathy, hypertrophic cardiomyopathy, noncompaction cardiomyopathy and mitochondrial cardiomyopathies. Detailed pedigree analysis and clinical genetic evaluations will be conducted to determine the hereditary nature of the condition (familial versus sporadic) and whether the cardiac condition is “isolated” or a feature of a genetic syndrome. At the Cardiogenetics Clinic, patients and families may be provided information about the hereditary nature of the condition through genetic counseling and be offered diagnostic methods including DNA testing. Family screening for cardiomyopathies also will be available to help facilitate the identification of at-risk, asymptomatic family members. The clinic aims are to learn more about the genetic
factors in heart failure, cardiomyopathy and congenital heart disease and to improve the medical care of families with these conditions.
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