UCLA Genomic Analysis Training Program: Faculty

The UCLA faculty Genomic Analysis and Interpretation Training Program are organized into six research areas. Trainees working with these faculty are, of course, not limited to these research areas. Neither are trainees limited to these faculty. Potential additional faculty are urged to contact the Training Program Directors.

Genomic Technologies

Laboratories at UCLA are on the forefront of developing many of the technologies that will be used in future genomic research. These technologies range from microarrays to positron imaging. Students trained by faculty in this area are expected to gain insight into potential applications of the latest technologies, to apply them to solve problems in genetics, and to develop novel technologies themselves.

Arnold Berk studies molecular interactions that regulate transcription in mammalian cells, in particular transcription factors encoded by oncogenes and tumor suppressors and the regulation of cell replication. He studies proteins expressed early during infection by DNA viruses because these proteins interact with key host cell regulatory proteins such as p53, the Retinoblastoma protein family, the mediator of transcription complex, and chromatin modifying complexes. He also studies inactivation of the p53 tumor suppressor by adenovirus E1B. His work can explain how all p53 molecules are inactivated when only ~1% are modified by SUMO1. He applies "ChIP on chip" methodology to discover how the adenovirus small e1a protein forces contact-inhibited human cells to proliferate: small e1a directly re-localizes major chromatin-modifying complexes on a global genomic scale. He also works in the area of gene therapy: he engineered an adenovirus-Epstein-Barr virus hybrid vector that introduces stable episomes into infected cells in tissues of intact animals. [website]

James Liao's research integrates molecular biology and cDNA chips to investigate molecular recognition, signal amplification, and biological regulation. He is exploring the metabolic genomes of both microbes and humans, with emphasis on expression profiling and operon prediction. [website]

Stanley Nelson, as director of UCLA's microarray core, is developing new cDNA microarray and genotyping technologies, exploring a linkage strategy known as genomic mismatch scanning, and identifying SNPs (single nucleotide polymorphisms) by informatics means. He has applied microarrays to gene expression studies in cancer and in common complex traits such as attention deficit hyperactivity disorder and autism. His former students Dan Geschwind and Vivian Cheung have very successful academic careers. [website]

Jeanette Papp is the Director of the UCLA Genotyping and Sequencing Core Facility, and a member of the Bioinformatics Group in the Department of Human Genetics. In addition to overseeing data generation and analysis in her laboratory, Dr Papp's research interests include developing novel bioinformatic solutions for the management and analysis of all types of genetic data. [website]

Steve Young's research has demonstrated the in vivo importance of the post-translational modifications of isoprenylated proteins. Another focus of his laboratory has been gene-trapping in embryonic stem (ES) cells. Over the past five years Dr Young has led BayGenomics, an NHLBI-funded gene-trapping consortium involving investigators from UCSF and UCLA. BayGenomics uses gene-trapping techniques to randomly inactivate genes in mouse embryonic stem cells. One of the other goals of BayGenomics is to identify new genes that are relevant to cardiopulmonary development and disease. Dr Young has used BayGenomics ES cells to create knockout mice lacking several triglyceride biosynthetic enzymes. These knockouts permit identification of genes responsible for triglyceride synthesis in mammary epithelium, brown adipose tissue, skin, and cartilage. [website]

Model Organisms

Model organisms have been applied very successfully by participating faculty at UCLA in identifying genes contributing to heart disease and psychiatric disorders. Several disease predisposing genes have been cloned, and a unique resource of genome tagged mice is available for mapping new genes and testing their interactions. Because animal models are proving crucial to mapping genes for complex traits, students working with faculty in this area will be well positioned for future careers in either mouse or human genetics.

Esteban C. Dell'Angelica's laboratory conducts research aimed at understanding (1) the molecular basis for protein trafficking and organelle biogenesis within the endosomal/lysosomal system and (2) how defects in these processes can lead to human disease. Current efforts are focused on a small group of genes associated with schizophrenia or Hermansky-Pudlak syndrome (HPS), of which model mutant mice and flies have arisen through spontaneous mutations or created by targeted gene disruption. Studies using these mutant model organisms are complemented with biochemical and functional characterization of the gene products in vitro and in cultured cell lines. [website]

Katrina Dipple's research focuses on understanding the complexity of simple Mendelian disorders. Her laboratory investigates how genetic variation causes human disease and how single gene mutations are affected by the other genetic mutations and polymorphisms in the genome, using glycerol kinase deficiency as a model. Dr Dipple also studies the complexity and interconnectivity of metabolic genetic diseases. Her laboratory uses human and animal models in combination with molecular biology techniques and metabolic engineering concepts (including metabolic flux analysis, network component analysis, and mathematical modeling of protein functions) to unravel these complex interactions and networks. [website]

Robert Goldberg is a Distinguished Professor of Molecular, Cell, & Developmental Biology and a AAAS fellow. His research seeks to understand the genomic, epigenomic and developmental processes that lead to specialized cells in higher plants. Furthermore, plants provide unique advantages as model organisms and fertile ground for development of new genomic technology. Specific questions that he has addressed in his research include: how genes organized in the genome, what are the mechanisms that control the regulation of plant gene expression, what are the sequences that program plant gene expression during development, what are the genes that control the differentiation of specific plant cell types, and what events cause an undifferentiated cell to take on a specialized state. He is a member of the seed institute, a collaborative effort to understand the genes and processes required to "make a seed." [website]

Aldons (Jake) Lusis has studied many complex genetic diseases and associated traits, particularly those tied to atherosclerosis and its risk factors. It is now clear that these traits can be attacked by quantitative trait locus (QTL) mapping using inbred animal strains. Thus far, Dr Lusis and his colleagues have identified murine loci contributing to cholesterol metabolism, obesity, and arterial inflammation. The major challenge is to understand the action of these disease genes at the molecular level. Dr Lusis is a well-respected teacher and mentor at UCLA. His 17 former doctoral students hold research positions in industry and faculty appointments at several major research universities. He is currently mentoring one postdoctoral and nine predoctoral students. [website]

Julian A. Martinez-Agosto was recently appointed as a faculty member in Human Genetics. He is interested in the genetic basis of human development and malformation syndromes. His focus is on overgrowth and cancer predisposition genetic disorders. He uses the power of Drosophila melanogaster genetics to generate human disease models and performs genetic and small molecule screens to identify novel therapeutic targets. His laboratory also uses whole genome comparative analyses across species to gain insight into the evolution of molecular mechanisms required for stem cell formation and maintenance. [website]

Karen Reue has used naturally occurring mutations in mouse models to identify genes important in human metabolic diseases. With this approach, her group has discovered a novel gene known as lipin, which is associated with obesity and diabetes, and a second novel gene that protects against high cholesterol levels and atherosclerosis. She is currently working to elucidate the function of these genes and their potential role in human disease using a combination of cell and molecular biology, transgenic and knockout mouse models, and studies in human subjects. [website]

Desmond Smith is interested in understanding how the genome constructs the brain in both health and disease. He has developed technologies for genome-scale acquisition of expression patterns in the brain. These methods, voxelation and gene expression tomography, survey both the transcriptome and proteome and combine the mathematical concepts of biomedical imaging with the high-throughput analytic tools of genomics. He is also employing genetic mapping to identify loci influencing behavior in the mouse. His ultimate goal is to decode how the conceptual wiring diagram of the genome gives rise to the neuronal wiring diagram of the brain. Dr. Smith was named to the "Scientific American 50" in 2008. [website]

Robert Wayne applies molecular genetic techniques to questions in systematics, population genetics, sociobiology, and conservation. His recent work deals with mammalian species such as bobcats, coyotes, badgers, wolves, and foxes. He is particularly interested in exploiting the recently sequenced dog genome. [website]

Disease Gene Mapping

The investigators in this area are at the forefront of disease gene mapping efforts. Their studies run the gamut from major genes in rare Mendelian traits to modifier genes in common complex disorders, and from large pedigrees in genetic isolates to case/control samples from outbred populations. Students working with these training faculty will be extremely well equipped in human genetics and genetic epidemiology.

Anne Coleman's research focuses on the prevention, diagnosis, treatment, and societal impacts of agerelated glaucoma, cataracts, macular degeneration, and correctable visual impairment in children. She seeks to understand the interplay of genetic and behavioral determinants of these eye diseases. [website]

Isla Garraway focuses on translational research in urologic oncology. Using tissue samples from prostate surgery patients, his lab generated primary prostate epithelial, stromal, and stem/progenitor cell lines. In addition, they have extracted DNA and RNA from micro-dissected cancer and matched normal tissues. This extensive collection of human prostate material can be used in functional assays, as well as in gene expression arrays, SNP arrays, and next generation (single molecule) sequencing.

Daniel Geschwind holds the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics. In 2004 he received the Derek Denny-Brown Neurological Scholar Award from the American Neurological Association. His research addresses human neuropsychiatric diseases such as autism and neurodegenerative diseases and their relationship to the full range of normal human higher cognitive function. He uses tools from network analyses and systems biology to connect molecular pathways to nervous system function in health and disease. [website]

Michael Gorin holds the Harold and Pauline Price Chair in Ophthalmology at UCLA. His research interests include the molecular genetics of hereditary eye disorders, particularly age-related macular degeneration (AMD), retinitis pigmentosa, and Stargardt disease. He also investigates monogenic disorders such as hereditary retinal degenerations, glaucoma, cataracts, and ocular syndromes. Other basic research areas include genetic modifiers of disease and ocular toxicities of systemic medications. His applied research interests include bioinformatics in clinical ophthalmic practice and research. [website]

Paivi Pajukanta has investigated the genetic background of several complex traits predisposing to coronary heart disease such as familial combined hyperlipidemia (FCHL), low HDL-cholesterol, and obesity. She is especially interested in combining molecular genetic approaches with new statistical and bioinformatics tools to identify and characterize DNA sequence variants contributing to common cardiovascular disorders. [website]

Jerome Rotter at Cedars-Sinai Medical Center conducts large-scale genetics studies of common diseases using outbred American populations. He has made major contributions to the understanding of juvenile diabetes, inflammatory bowel disease, and atherosclerosis. [website]

Eric Vilain conducts research on the genetics of human sexual development. Sexual development involves the interaction of a complex network of genes, most of them still unknown. In understanding this network, Dr Vilain employs bioinformatic tools, DNA sequencing, expression profiles, and evolutionary homology. [website]

Statistical Genetics

UCLA has one of the largest and most productive groups of statistical geneticists in the world. Trainees will be exposed to a rich environment fostering population genetics, statistical modeling, algorithm development, and genetic data analysis.

Rita Cantor is a statistical geneticist involved in multiple projects for mapping and identifying complex disease genes in humans. She exploits genome linkage scans, mouse/human synteny, and linkage disequilibrium patterns of SNPs and microsatellite markers in studying diseases as diverse as familial combined hyperlipidemia, lupus, autism, and Kawasaki disease. She has successfully mentored several graduate students and postdoctoral fellows in applying statistics to solve their own genetic research problems. [website]

Steve Horvath is developing and applying methods for allelic association tests and microarray data analysis. He and colleagues have introduced family based association tests that extend the standard transmission disequilibrium test (TDT). He collaborates with Stan Nelson on DNA microarrays and with David Seligson on tissue microarrays. He is currently mentoring three doctoral students. [website]

Kenneth Lange's interests include human genetics, population biology, computational statistics, and applied stochastic processes. He has worked on problems of linkage and radiation hybrid mapping, risk prediction in genetic counseling, genetic epidemiology, and forensic uses of DNA profiling. These areas tie in well with his activities in computational statistics and highlight his contributions to the computation of complex probabilities on human pedigrees. His computer programs Mendel and Fisher incorporate many of these algorithmic advances. In population biology, he has investigated models in population genetics, methods for the reconstruction evolutionary trees, stochastic versions of stable demographic theory, models for dispersal of insect species, and models for the growth of microorganisms. His former students, Neil Risch, Michael Boehnke, Daniel Weeks, Laura Lazzeroni, and Eric Sobel, are leading figures in statistical genetics. He is currently the Chair of the UCLA Department of Human Genetics. [website]

Bogdan Pasaniuc's research focuses on medical population genetics. His lab group develops computational and statistical methods for understanding the genetic architecture of common diseases. They are particularly interested in methods that leverage the genetic diversity across and within populations for large scale studies. More precisely, they develop approaches for analyzing large scale genomic studies such as genome-wide association studies or fine-mapping studies. [website]

Janet Sinsheimer works on Bayesian techniques for reconstructing evolutionary trees from molecular data. She has applied these phylogenetic methods to determining the rate of evolution of HIV, to the clinical identification of microbial pathogens, and to understanding the genes determining sex in mammals. She is also deeply involved in statistical genetics, both at the theoretical and practical levels. She is a co-developer of the gamete competition model and a statistical collaborator on studies of osteoporosis, osteoarthritis, attention deficit hyperactivity disorder, autism, and schizophrenia. She has six current doctoral students. [website]

Eric Sobel is Director of Bioinformatics in the UCLA Department of Human Genetics and an expert on the application of Markov chain Monte Carlo methods in human genetics. His computer program SimWalk - used worldwide for haplotyping and linkage analysis - makes it possible to extract the full genetic information found in the large pedigrees used in many disease gene studies. Dr Sobel is currently adapting SimWalk2 to detect genotyping errors and is collaborating on various genetic studies in the department. [website]

Bioinformatics

Bioinformatics at UCLA studies the structure in the avalanche of biological data, e.g., the multiple genomes and proteomes now available, using the analytic theory and practical tools of mathematics and computer science.

Michael Alfaro studies the factors that govern the evolutionary dynamics of organismal diversification. In particular he is interested in why are some groups morphologically diverse, whether there are general laws or themes that can be used to explain the uneven distribution of diversity in physiological traits across lineages and whether morphological diversity always signal mechanical, functional, or ecological diversity. His research approach is interdisciplinary and quantitative and crosses traditional boundaries among evolutionary morphology, molecular phylogenetics, and theoretical evolution. [website]

David Eisenberg and his colleagues in the UCLA DOE Laboratory of Structural Biology and Molecular Medicine are assessing sequence and folding patterns that contribute to heat stability in proteins of extreme thermophiles. The DOE Lab plans to determine the 3D crystallographic structure and function of as many members as possible of the proteome of the thermophilic microbe, Pyrobaculum aerophilum. Over the past decade, Eisenberg's interests have increasingly focused on structural genomics and computational biology. Following a thread of discovery from his earlier work on sequence families and assignment of protein sequences to 3D folds, he is now concentrating on assigning genome sequences to biological functions. His new methods depend on correlated inheritance of proteins in species; correlated fusion of domains into single protein chains; and correlated mRNA expression patterns. Dr Eisenberg is a member of the US National Academy of Science and the Howard Hughes Medical Institute. He has mentored over 100 students, many who have gone on to significant careers in genomics. [website]

Eleazar Eskin's research interests are in the relationship between genetic variation and disease in humans at the intersection of genetics, genomics and bioinformatics. His laboratory takes advantage of recently available human variation reference sets such as the HapMap to improve computational approaches for gene mapping. Other projects in Dr Eskin's laboratory include developing methods for discovering the genetic basis of complex traits in model organisms, understanding the genetics of gene expression patterns and predicting the molecular function of variation to better understand the role of variation in disease. [website]

James Lake's laboratory centers on research in genomics and evolution of early life forms. The lab is analyzing sequence information with the goal of understanding the origins of eukaryotes from prokaryotes and the separation of the deuterostome (vertebrate and echinoderms, for example) from the protostome (fruit flies and clams, for example). His lab is also working on the comparative analysis of syntenic blocks common to the genomes of closely related organisms, such as those found in humans and mice. This aids in the identification of gene boundaries, open reading frames, and the interpretation of gene organization. [website]

Chris Lee's laboratory carries out genome-wide analyses of raw sequence data. The lab uses bioinformatics methods and data mining tools to search for single-nucleotide polymorphisms and alternative splicing sites. It applies similar techniques to proteome databases to annotate, predict, analyze, and validate protein structural and functional features, activities, and interactions. [website]

Matteo Pellegrini's lab is interested in the development of computational approaches to interpret genomic data. These methodologies allow them to develop large-scale models of transcriptional and epigenetic regulation as well as signal transduction. Their approach is to build models that integrate varied data that sheds light on these phenomena. This data is produced using the latest generation of high throughput sequencers, tiling and expression arrays along with mass spectrometry. This research focuses on the development of both low and high-level analyses. For instance, they are developing suites of tools for the analysis of high-throughput sequencing data, as well as tools that combine multiple data types to infer transcriptional regulatory mechanisms. [website]

Marc Suchard is helping to develop the nascent field of evolutionary medicine. This field harnesses the power of methods and theory from evolutionary biology to advance our understanding of human disease processes. Just as phylogenetic approaches have stimulated the field of evolution at large, they posses the potential to revolutionize evolutionary medicine, particularly in the study of rapidly evolving pathogens. To bridge the gap between phylogenetics and human-pathogen biology, Dr Suchard's interests focus on the development of novel reconstruction methods drawing heavily on statistical, mathematical and computation techniques. Some of his current projects involve jointly estimating alignments and phylogenies from molecular sequence data and mapping recombination hot-spots in the HIV genome. [website]

Xia Yang's research group focuses on investigating the causal genes and molecular networks underpinning the metabolically connected common complex disorders including coronary artery disease, type 2 diabetes, and obesity. Her research involves highly integrative systems biology approaches that leverage genetic, transcriptional, epigenomic, and phenotypic data from individual tissues in human and rodent populations, to derive key causal genes and tissue-specific gene networks that are perturbed by genetic and environmental risk factors of the common metabolic disorders. [website]

Ethical and Community Issues

UCLA has taken a leading role in studying the ethical and social issues that must be an integral part of the current revolution in genetics. For example, the UCLA Center for Society and Genetics seeks to provide direction for the co-evolution of science and humanity by promoting innovative and socially relevant research and education.

Christina Palmer's research focuses on understanding the personal and social impact of genetic information. She is the PI of a multi-institutional, multidisciplinary NIDCD-funded project assessing the role of Connexin 26 genetic testing as an adjunct to newborn deafness, as well as a multi-institutional, multidisciplinary NHGRIfunded project assessing the impact of genetic testing on deaf adults and the deaf community. [website]

Wayne Grody investigates the molecular genetics of metabolic and heritable neoplastic diseases. He is also director of UCLA's Diagnostic Molecular Pathology Laboratory, which has been studying the effectiveness of large-scale population screening for mutations causing cystic fibrosis, thrombotic disorders, and breast and colon cancer. [website]