Human Genetics

Department of Human Genetics

Human Genetics
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Department of Human Genetics

Genomic Analysis and Interpretation

Genomic Analysis and Interpretation

Genomic Analysis and Interpretation

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Faculty in the Genomic Analysis Training Program are organized into six research areas. Trainees working with these faculty are, of course, neither limited to these research areas, nor are trainees limited to these faculty. Potential additional faculty are urged to contact the Training Program Directors.

Choose a research area below:

Genomic TechnologiesModel OrganismsDisease Gene MappingStatistical GenomicsBioinformaticsEthical and Community Issues

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.

Chongyuan Luo’s laboratory studies how gene regulatory mechanisms contribute to human diseases including neurodevelopmental disorders. They are developing and applying new genomic and genetic technologies to address long-standing questions in human diseases including the causal cell type(s) of diseases and the functions of non-coding genetic variants. They have developed high-throughput single-cell epigenomic and multi-omic technologies, and use these methods to study the gene regulatory diversity in the brain.

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. Learn more →

Matteo Pellegrini's laboratory develops computational tools to interpret genomic data. These tools permit both high and low-level modeling of transcriptional and epigenetic regulation and signal transduction. His systematic approach integrates data produced by the latest generation of high throughput sequencers, tiling and expression arrays, and mass spectrometers. Dr. Pellegrini helps organize and run the UCLA Bruins-In-Genomics (BIG) Summer Undergraduate Research program, an intensive summer research experience for undergraduates in genomics and bioinformatics and an excellent pipeline into our training program.

Yi Yin's laboratory focuses on developing and applying high-throughput single-cell sequencing technologies to study how the repair of DNA breaks causes error-free and mutational genome rearrangements, and to better understand effects from genomic contexts, genetic mutations and tissue-of-origin.

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.

Paul Barber integrates genetics, genomics, ecology, and oceanography to understand the evolution of marine biodiversity with the aim of promoting marine conservation. He does his research largely in the context of innovative education programs focused on increasing the participation of underrepresented minorities in science. Barber’s Diversity and Health Disparities Program synthesizes marine and environmental research in the context of health disparities and social justice in an effort to increase the success of underrepresented minority and underserved premedical students.

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. Learn more →

Leonid Kruglyak's lab conducts experiments in model organisms (currently, the yeast Saccharomyces cerevisiae and the nematode worm Caenorhabditis elegans), as well as computational analyses, aimed at understanding how changes at the level of DNA are shaped by molecular and evolutionary forces, and how these changes lead to all the observable differences among individuals within a species.

Jamie Lloyd-Smith's laboratory studies the ecology of infectious diseases in wildlife and human populations. He combines mathematical and computer models with field and laboratory data to understand how infectious diseases spread and evolve, and how to reduce their health impacts.

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. Learn more →

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. Learn more →

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. Learn more →

Medical Genetics

The investigators in this area are at the forefront of disease gene mapping and clinical genetics. 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 mentors will be extremely well-equipped in human genetics and genetic epidemiology.

Valerie A. Arboleda's laboratory is focused on understanding how pathogenic variants in the genes that control chromatin structure lead to rare genetic disorders.  We combine a wet-lab approach with a dry lab approach to characterize the effects of pathogenic mutations in a cell-type specific manner. In the lab, we experimentally test genetic variants in cell models using a variety of approaches that range from 1) using CRISPR-Cas9 technology to perform large-scale CRISPR screens and 2) testing patient-derived induced pluripotent stem cells to identify cell-type specific effects of these pathogenic mutations. Our lab leverages functional genomics analysis to characterize global changes to chromatin structure, accessibility and gene regulation due to pathogenic chromatin modifier mutations. Finally, we can leverage existing data sets from cell-type specific studies to help us interpret the effects of genetic mutations on global chromatin structure. Ultimately the functional characterization of these variants will allow us to better diagnose patients with rare genetic disorders and to better identify putative treatments for genetic disease. Learn more →

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. Learn more →

Elaine Hsiao, PhD, Associate Professor, Integrative Biology & Physiology. Her laboratory studies interactions between the microbiome, brain, and behavior and how such system interactions may influence the etiopathogenesis and manifestations of gastrointestinal and neurological diseases. In particular, they mine the human microbiota for microbial modulators of host neuroactive molecules, investigating the impact of microbiota-immune system interactions on neurodevelopment and examining the microbiome as an interface between gene-environment interactions in neurological diseases.

Su Yon Jung, PhD, Assistant Professor, School of Nursing. She is a molecular genetic cancer epidemiologist. Her long-term research interests are within the field of genome–environmental cancer epidemiology, especially by exploring the role of biochemical–behavioral risk factors and their interactions with genetic and epigenetic markers. She has completed numerous studies of racial disparity in cancer biomarkers, GWA/genomic pathway studies, and epigenetic studies, by focusing on innovative statistical genetics analyses.

Beate Ritz, MD, PhD, Professor, Epidemiology and Environmental Health Sciences. Her research focuses on the health effects of occupational and environmental toxins such as pesticides, ionizing radiation, and air pollution on chronic diseases. For the past decade, she has studied the effects of air pollution on adverse birth outcomes as well as asthma in children in southern California. She collaborates with neuroscientists, human geneticists, and clinicians at UCLA.

Jerome Rotter, MD, Professor, Pediatrics and Human Genetics. He is the Director of the Institute for Translational Genomics and Population Sciences. He conducts large-scale genomic studies of common diseases using outbred American populations and has made major contributions to the understanding of juvenile diabetes, inflammatory bowel disease, and atherosclerosis. These studies have been conducted in collaboration with clinical, physiologic, and epidemiologic investigators, often in multi-site studies such as the IRAS (Insulin Resistance and Atherosclerosis) Family Study, the Mexican-American Hypertension – Insulin Resistance Study (PI), the Mexican-American Coronary Artery Disease (MACAD) Study (PI), the CHS (Cardiovascular Health Study), PARC (Pharmacogenetics of Cardiovascular Risk Factor) Study, ADAGES (African Decent and Glaucoma Evaluation Study) (MPI), and the MESA (Multi-Ethnic Study of Atherosclerosis) Family Study.

Mary Sehl, MD, PhD, Associate Clinical Professor, Computational Medicine and Human Genetics. A major focus of her research is in studying DNA methylation patterns associated with aging, and the acceleration of these patterns in disease states, including HIV and cancer. Another focus of her work is in developing mathematical models to study cancer cell population dynamics, and the development of user-friendly stochastic simulation software to accurately and efficiently study in silico models of tumor response to treatment.

Desmond Smith uses the tools of modern functional genomics to dissect the pathways that connect genotype and phenotype. In particular, he seeks to identify genetic mechanisms underlying complex neurobehavioral traits and their related disorders, such as obesity and addiction. He also develops new tools and technologies for the genetic analysis of mammalian cells. His mission is to study living matter at a genome-wide level and to develop new, highly specific therapeutic strategies for common diseases.

Marc Suchard is an expert in high-performance statistical computing through massive parallelization, with a focus on inference of stochastic processes in genomics, HIV, evolutionary medicine and the clinical application of statistics. His lab also focusses on the analysis of very large-scale electronic health records (EHRs) for treatment optimization. He has trained 15 MD/PhD and PhD students and four post-docs, five who already hold tenure and four in tenure-track positions.

Roel Ophoff’s laboratory focuses on the molecular basis of complex traits, in particular neuropsychiatric illnesses such as schizophrenia and bipolar disorder. His research centers on the study of genetic variation at the DNA level and the study of gene expression profiles and epigenetic variation that may be involved in disease susceptibility. Learn more →

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. Learn more →

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. Learn more →

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. Learn more →

Statistical Genomics

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. Learn more →

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. Learn more →

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. Learn more →

Kirk Lohmueller’s lab develops and implements statistical methods to study genetic variation in humans and other species. His research is focused on understanding natural selection, particularly the removal of deleterious mutations (i.e., negative selection). He also specializes in applying genetic variation data to the inference of population history and personal identification. Learn more →

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. Learn more →

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. Learn more →

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. Learn more →

Hua Zhou’s research interests include numerical optimization problems, particularly those arising from statistical analysis of high-dimensional data such as large-scale genomic data. He has developed penalization methods for association screening of genome-wide association (GWAS) and next generation sequencing (NGS) data, and a nonlinear dimension reduction approach for genotype aggregation and association mapping. Currently he is working on genome-wide QTL association mapping based on family designs, genotype imputation, transcriptomics data analysis based on RNA-seq technology, and statistical methods for analyzing microbiome data. Learn more →

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. Learn more →

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. Learn more →

Jason Ernst’s research focuses on developing and applying machine learning methods for the analysis of high-throughput experimental data to address problems in epigenomics and gene regulation. His research is often conducted in close collaboration with experimental groups. Learn more →

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. Learn more →

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. Learn more →

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. Learn more →

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. Learn more →

Xinshu (Grace) Xiao’s lab is primarily interested in understanding how the unexpectedly small number of genes in our cells leads to the extraordinary spectrum of phenotypic diversity. In particular, she focuses on RNA processing and regulation which have proved pivotal to human health and disease. She uses a combination of approaches in genomics, bioinformatics, molecular biology and systems biology. This work is made possible by the revolutionary high-throughput sequencing technologies that have transformed modern biology into an information-rich science. Learn more →

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.

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. Learn more →

Constance Hammen’s research focuses on mood disorders in adolescents and adults, mainly addressing risk factors for recurrent unipolar depressive disorder, with a secondary interest in course and outcomes in bipolar disorder. In recent years the key risk factors her lab has studied are stress, parental depression, family factors,
and interpersonal functioning. Recently she has also been exploring gene x environment interactions. All of these studies are longitudinal, and attempt to model the complex transactions between the person and the environment. Learn more →

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. Learn more →

Beate Ritz’s research focuses on the health effects of occupational and environmental toxins such as pesticides, ionizing radiation, and air pollution on chronic diseases including neurodegenerative disorders (Parkinson’s disease), cancers, and adverse birth outcomes and asthma. For the past decade, she has studied the effects of air pollution on adverse birth outcomes as well as asthma in children in southern California. In 2006, she received the Robert M Zweig Memorial award for outstanding achievement in air quality and medicine from the South Coast Air Quality Management District. She also spend the past 15 years investigating the long-term effects of pesticide exposures on Parkinson’s disease and cancers and is currently conducting a project to implement a Parkinson’s disease registry required by a new law in California. Learn more →

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