Molecular phenotyping, single cell analysis, and metabolomics studies to characterize gene knockouts in iPSCs that will subsequently be differentiated into extra-embryonic cells. Identification of senescent cells in human pancreas. Laboratory management.
Associate research scientist with strong background in cell and molecular biology. Vast experience working with genetic of microorganisms in six different countries. Master’s in biotechnology and PhD in molecular microbiology with six years of experience as a postdoctoral associate in three different laboratories.
In the Robson lab I have been involved in a varied of projects such as the Molecular Phenotypes of Null Alleles in Cells (MorPhiC) with the aim to knockout (KO) 250 protein-coding genes in human induced pluripotent stem cells (iPSCs) that will subsequently be differentiated into two cell lineages, the extra-embryonic and the neuroectodermal, where cells will then be comprehensively phenotyped. And the KAPP-Sen Tissue Mapping Center which aims to address SenNet goals in the framework of healthy human Kidney, Adipose tissues, Pancreas, and Placenta. In addition, I am also laboratory manager taking care of the set up and organization of the lab, assuring the Good Laboratory Practice as well as generating several Standard Operating Procedures.
As an Associate Research Scientist & Program Manager for The Cube Initiative at the Jackson Laboratory, I oversee the wetlab portion of large-scale mouse projects. I am interested in the mechanisms of metabolic and cardiovascular diseases and how to use the mouse to model these diseases. The Cube Initiative is an ambitious project in a proof of concept phase currently studying Type 2 Diabetes. Here we are performing ATAC seq, RNA seq, Isoform seq, single cell RNA seq, single nucleus ATAC seq, metabolomics, proteomics, as well as in-depth metabolic phenotyping in mouse models predicted to display varied phenotypic manifestations of T2D.
I also have deep knowledge of CRISPR/Cas9 gene manipulations and mouse model generation. With my experience in Genetic Engineering Technologies, I worked with collaborators to design new mouse models. I have carried this knowledge into my personal research where I am creating new models for T2D as well as cardiovascular diseases. The new models will be used to test genetic drivers of disease predicted from multiple human data sets.
My research group studies mouse models with vestibular (inner ear) defects that may provide insights into balance disorders in humans. I am focusing on mutations that affect the structure and function of the otolithic end organs, small inner-ear structures that act as linear acceleration and gravity receptors. We have identified and characterized genes that are defective in head-tilt (het), head-slant (hslt), and neuromutagenesis facility (nmf) 333 mutant mice, each of which encodes an NADPH oxidase component. Thus, we've hypothesized that a previously unknown inner ear NADPH oxidase complex is necessary for proper development and function of the vestibular system.
I am also studying a mouse model that exhibits sex reversal, craniofacial defects and shortening of the limbs characteristic of some forms of human dwarfism. We have narrowed the genetic defect to a region on mouse Chromosome 7 and are analyzing that region of the genome with the goal of better understanding dwarfism and certain skeletal malformation syndromes in humans.
A mouse's genetics are reflected in its phenotype, its measurable characteristics including appearance, behavior and physiology. We work on the Mouse Phenome Project, an international collaborative effort seeking to comprehensively characterize a large set of commonly used and genetically diverse strains of mice and other reference populations. All the data are collected and disseminated from the Mouse Phenome Database (MPD) and include data relevant to addiction, atherosclerosis, blood disorders, cancer susceptibility, neurological and behavioral disorders, sensory function defects, hypertension, osteoporosis, obesity and other research areas. MPD also contains extensive genotypic data, which allows for genotype-phenotype association predictions and facilitates efforts to identify and determine the function of genes participating in normal and disease pathways.
I have used my formal training in molecular genetics in a variety of research areas: plant biology, immunology, dermatology and currently mouse behavior. I have been able to dissect the regulation of genes, identify genes underlying traits, map Quantitative Trait Loci (QTL), and identify modifier genes within different inbred populations. Currently I am using integrative functional genomics in the online software www.GeneWeaver.org, developed by Chesler et al., to bring together different types of data across numerous species and to utilize this convergent evidence to elucidate and validate the roles of genes in disease. I am also curating the addiction and alcoholism literature for the database, identifying relevant large-scale genomic studies and making these often incomputable data, computable.
In humans, vision is paramount for quality of life, and the impairment of sight represents a highly incapacitating condition. Vision loss or dysfunction can be caused by obstruction of the light path to the neural retina or inability of the retina to detect and/or transmit light-triggered signals to the brain. Mouse models provide fundamental insights into the associated biological pathways and often display phenotypes that are similar to clinical manifestations of the corresponding disease in humans, providing an opportunity to decipher mechanisms of disease pathology as well as develop innovative therapies. The main objective of our research program is to identify, characterize,preserve and distribute mice with genetically caused ocular disorders. These well-characterized models are used to support and promote vision research with the ultimate goal of advancing the elucidation, treatment and cure of heritable eye diseases. We have recently characterized mutations that may provide models for retinal degeneration diseases, including retinitis pigmentosa, a group of eye diseases that lead to progressive vision loss and eventual blindness, and for human achromatopsia, a key feature of which is the absence of color discrimination. Our laboratory is also studying the genetic defects in models for glaucoma, cataracts and photoreceptor function loss.
My early research was in the area of chemical physics performing computational modeling of molecular collisions. My work in biological systems began with post-doctoral work in computational biophysics modeling DNA denaturation. My first work at the Jackson Laboratory, with Carol Bult in collaboration with the University of Maine, was in the development of GenoSIS, a visualization and analysis tool for genome data interpretation using geographic information science concepts and technology. As part of Mouse Genome Informatics I work in Judy Blake's Gene Ontology (GO) group at JAX in the development of computational methods and tools for statistical analysis and visualization. My current research involves the development of OncoCL, an ontology of cancer cell types, to provide a semantic framework for the integration of cancer-associated molecular data and the properties imparted by the corresponding disrupted cellular pathways with conventional pathology data associated with cancer progression.
I graduated from Emory University with a PhD in neuroscience in 2017, and shortly thereafter joined the Kaczorowski lab as a postdoctoral associate. I employ a genetically diverse mouse model of Alzheimer's disease to investigate how genetic variability mediates the effects of a high fat diet on Alzheimer's-associated pathogenesis. I use a variety of behavioral, molecular, and computational techniques to precisely identify gene candidates and molecular networks that predict whether an individual will be vulnerable or resistant to environmental risk factors. Ultimately, these studies should lead to novel therapeutic targets for more personalized treatment strategies for Alzheimer's disease.
My research interest is focused on investigating key regulatory genes/elements and pathways involved in cancer development from the perspective of genetic alterations. In particular, I am interested in identification of characteristic genetic change which explains phenotype or sensitivity to drugs in a subset of tumors. Moreover, by the integration of next-generation sequencing data with the use of in vivo/vitro patient-derived xenografts and cancer cells, I aim to reproduce and demonstrate their involvement in cancer development. These developed models not only help the better understanding of the mechanism underlie a subset of tumors but also helps the development of novel approaches toward the personalized treatment for patients.
My research focuses on germ cell tumors (GCTs), a tumor type that occurs in pediatric and young adults. My focus in GCTs is around the developmental origins of GCTs and identifying new diagnostic and therapeutic targets. Additionally, I have an interest in utilizing pluripotent stem cells to model disease.
I am a physician-scientist, that clinically cares for children and young adults with cancer and blood disorders at Connecticut Children's. I completed my fellowship in Pediatric Hematology-Oncology at the Mattel Children's Hospital at the University of California Los Angeles (UCLA). It was at UCLA that I started my research in GCTs, using stem cells to model to the cell of origin for GCTs, the primordial germ cell (PGC). I continue to use this model and others to evaluate how alternations in normal germ cell development lead to disease states, such as cancer. Additionally, as a physician-scientist, I mentor rotating pediatric hematology-oncology fellows. I also bring my knowledge of stem cells and mouse models to other projects in the Lau lab.
Investigates the molecular mechanisms underpinning regeneration and scarring in adult tissues using comparative biology approaches that combine mouse repair models with salamander-based tools for discovery.
Finding regenerative strategies capable of faithfully repairing tissues after surgery, disease or traumatic injury will have the potential to transform modern medicine and improve the lives of a limitless number of patients.
In dramatic contrast to the poor repair outcomes for humans and rodent models such as mice, salamanders are able to completely regenerate heart tissue, whole limbs and many other tissues following injury, at any life stage. This astounding capacity for repair provides a template on which to understand the process of natural regeneration and develop strategies to improve human repair.
Dr Godwin’s work explores the molecular signals from nerve and immune cells that underpin the resistance to scarring, and the activation of regeneration in salamanders. This work combines both comparative biology and immunomodulation to investigate the potential for regeneration in a range of genetic mouse models.
Dr Godwin holds a dual appointment at the Jackson Laboratory and MDI Biological laboratory.
Though not obvious, the tissue microenvironment of tumors and visceral fat share many immunological similarities. Both visceral fat and tumors contain a remarkable diversity of immune cell types, and these cells play major roles in tissue homeostasis and malignancy, respectively. In general, we are interested in comparing and contrasting the cellular ecosystem of visceral fat and tumors to provide insights into processes driving the sequelae of obesity and cancer.
Prior to joining the Verhaak lab, Dr. Gujar performed his postdoctoral work in Kim laboratory at the Washington University School of Medicine, where he studied the role and mechanisms of abnormal signaling in brain tumor, glioblastoma. Previously, Dr. Gujar obtained his PhD from the University of Louisiana at Monroe after completing B. Pharm from India. His PhD thesis work examined the coordination between two key brain gluco-sensing areas in counter-regulatory responses to insulin-induced hypoglycemia.
I have always been fascinated by the genetic diversity of the genome, both in terms of its functional consequences, as well as its enormous power as a population genetics tool. My previous studies have focused on population genetics, history and phylogeographic patterns of humans and great apes, and the effects of Y-chromosomal genetic diversity on male in/sub-fertility. Over the years I have become increasingly interested in the diversity and evolution of complex regions and their potential association to phenotypes. Chromosome Y in particular, presents with unique challenges but at the same time offers unique opportunities, with obvious translational implications on male fertility, but also as a tool to investigate male-specific patterns of population structure and migration history.
I am currently utilising long-read sequencing technologies and chromatin interaction methods to interrogate previously poorly studied regions, with a longer term research goal of re-evaluating the evolution and structural diversity of known and novel complex genomic regions.
I am originally trained as a molecular biologist. I studied HIV pathogenesis, Herpes viruses and pseudotyped viruses in the context of viral replication and cancers of lymphoid cells. This background led me to study B-cell development and DNA repair systems. I have explored various areas in DNA damage and homologous recombination, and immuno- and chemotherapy development using diverse mouse models. I also have experience in scientific services/core facility management.
Although trained as a developmental biologist, I have been working since 2000 in the area of semantic data integration for biological knowledge. Sequencing of whole genomes and development of large-scale genomic technologies, coupled with traditional experimental biomedical research, has resulted in the generation of vast amounts of information about genes and how they function. My work in the Blake lab focuses on two aspects of making our knowledge about genes manageable and accessible to researchers. First, I am an ontology developer for The Gene Ontology Consortium, working to develop formal networks to describe how genes act and how they achieve their overall biological objective in a species-neutral context using modern ontology-development principles. Second, I manage biological data capture and representation, particular those data derived from studies of the laboratory mouse. My work is integrated into two major bioinformatics resources: Gene Ontology and Mouse Genome Informatics.
We are interested in generating next-generation mouse models and novel therapeutics. Our primary focus is to develop and validate novel tools/reagents for rapid generation of mouse models of human disease using CRISPR/Cas9 and Integrase systems, identify genetic modifiers, and to treat the underlying cause of the disease.
Development of state-of-the-art technologies is essential to precisely and rapidly generate and characterize mouse models of human disease. Since 2015 we have been utilizing advanced genetic engineering technology, including CRISPR/Cas9 and Bxb1 recombinases to uncover several major findings: a) Gene disruption in mouse embryonic stem cells or zygotes is a conventional genetics approach to identify gene function in vivo. However, because different gene disruption strategies use different mechanisms to disrupt genes, the strategies can result in diverse phenotypes in the resulting mouse model. To determine whether different gene disruption strategies affect the phenotype of resulting mutant mice, we characterized Rhbdf1 mouse mutant strains generated by three commonly used strategies—definitive-null, targeted knockout (KO)-first, and CRISPR/Cas9. we found that Rhbdf1 responds differently to distinct KO strategies, for example, by skipping exons and reinitiating translation to potentially yield gain-of-function alleles rather than the expected null or severe hypomorphic alleles. These findings have significant implications for the application of genome editing in both basic research and clinical practice, b) Mice have been excellent surrogates for studying immune system and, moreover, murine models of human disease have provided fundamental insights into the roles of human macrophages and neutrophils in innate immunity. The emergence of novel humanized mice and high-diversity mouse populations offers the research community innovative and powerful platforms for better understanding the mechanisms by which human innate immune cells drive pathogenicity. We have been developing advanced genetic engineering tools, including Bxb1 recombinase system, sophisticated profiling technologies, and nanoparticle (NP)-based-targeting strategies to understand how genetic differences underpin the variation in macrophage/neutrophil biology observed among humans.
We are looking for a brilliant and self-motivated individuals to join our team to generate and validate humanized mouse models of cancer using novel gene-editing technologies. This position is ideally suited for an individual with a strong background in molecular biology (CRISPR/Cas9) and next-generation sequencing methods.
Exceptional candidates can show early independence through the JAX Scholars Program.
I am currently a postdoctoral associate in the laboratory of Dr. Roel Verhaak where my research has focused on brain tumor evolution and heterogeneity. To uncover the evolutionary trajectories that brain tumors take from initial diagnosis to disease recurrence, I co-led an international longitudinal brain tumor sequencing project. Computational analyses of these collected genomics data helped establish the order of somatic events throughout a tumor’s molecular life history and identified the most common evolutionary routes under selective therapeutic pressures. These findings were recently published in Nature, and I continue to be involved with projects that leverage this rich dataset. In a separate study, I have sought to deeply characterize the epigenetic heterogeneity that exists within brain tumors. To this end, I established a single-cell DNA methylation assay that enables genome-wide coverage of the epigenome and applied it to human brain tumor specimens.
The Mouse Genome Informatics consortium (MGI) integrates data from over 40 external resources with hand-curated data from published literature to provide an integrated data resource/website that facilitates the use of the mouse as a model for human disease and biology. My role in MGI is to co-direct, with Joel Richardson, the technical work behind theresource. This includes overseeing the hardware and software architecture and thesoftware/database development for both the back end, where data is loaded/integrated,and the front end website, where data is made available for public researchers. This worksupports most of the MGI programs, including the Mouse Genome Database (MGD) and the Gene Expression Database (GXD).
I model data generated by high-throughout omics technologies in order to explain variation in gene expression and alternative splicing under various conditions such as different cell types, biological sex or viral infection. The resulting models can be used to derive hypotheses about the processes that lead to disease and suggest novel therapeutic targets.
My research involves a multidisciplinary approach to investigate the neuroprotective/therapeutic potential of natural products such as lycopene, curcumin, probiotics in neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease (AD). For the last six years, my research is focused on understanding if and how altered gut microbiota influence cognitive functions and disease progression in mouse models of AD. Even though genetics plays an important role in etiology of AD, environmental factors such as gut microbiota also have a significant influence on AD. My previous research findings provide evidence that the enteric nervous system, in addition to the central nervous system is affected in AD, supporting the role of gut-brain axis in pathophysiology of AD. At O'Connell’s lab I am investigating the complex interactions between the host genetics, gut microbiota and AD.
Glaucoma causes blindness in more than 70 million people worldwide. A major causal risk factor for glaucoma is the elevation of intraocular pressure (IOP). An increased resistance to the drainage of aqueous humor (the clear fluid filling the front of the eye) from the anterior chamber of the eye causes IOP elevation. However, the molecular mechanisms underlying both IOP elevation and aqueous humor drainage remain unknown. My goal is to fill this gap in knowledge. Using novel genetic tools,modern techniques and a variety of mouse lines, I am presently determining the molecular mechanism of aqueous humor outflow through the Schlemm’s canal (SC), a critical component of the pressure-dependent conventional outflow pathway. We have developed novel techniques and tools to measure outflow and study the SC at a cellular level. Using these tools we have already recently discovered that the SC is a unique vessel that has both lymphatic and blood vessel like characteristics. We are currently exploiting this new finding to obtain information regarding the molecular mechanisms of IOP elevation that can be leveraged to design new therapeutic interventions to prevent glaucoma.
I was admitted to Xi'an Jiaotong University at the age of 15. And I received my B. S., and Ph.D. degrees from Xi'an Jiaotong University, China in 2004, and 2010, respectively. Before I worked in Blekinge Institute of Technology, Sweden and Zhengzhou University, China. I have published lots of journal and conference papers in the areas of machine learning, E-Health system and DNA computing.
At JAX, I engaged in multi-omic data analysis, including epigenetic pattern mining and algorithm development, and long-read DNA methylation detection research.
My research is focused on the study of epigenetic, transcriptional and splice-variant transcriptome changes in innate and adaptive immune cells in the context of aging and vaccination. The integrated genomic analysis is correlated with specific functional analyses involving the key innate and adaptive immune cell subsets and the magnitude of specific immune response of the vaccinated subjects. The overall goal is to determine the epigenetic factors and transcriptional alterations associated with immunosenescence, which is linked to a decline in the protective immunity including response to vaccination.
At the Jackson Laboratory for Genomic Medicine, I am involved in several projects that explore the genome-wide patterns of genetic and transcriptional alterations characterizing human cancers. In particular,I am interested in the identification of key regulatory genes and/or pathways as well as complex rearrangement profiles, which may explain tumor initiation and progression as well as provide valuable targets for the development of novel therapeutic approaches and prognostic biomarkers. At present, I am investigating critical genomic aberrations implicated in ovarian and breast cancer tumorigenesis. By exploiting next-generation sequencing technologies combined with in vitro cell culture models and in vivo patient-derived xenografts, I aim at a better understanding of the individuality of cancer genomes and at the development of novel approaches toward the personalized management of cancer patients.
In my position as a Study Director I interface directly with customers to assess customer needs and ensure accurate capture of project specifications in order to develop detailed project plans. I ensure that plans are successfully tracked and seamlessly executed by ensuring that staff understand and are compliant with all policies and procedures to ensure the most efficient operation, and provide customers with the highest quality scientific service.
I am uniquely positioned to develop and execute strategic innovation and improvement initiatives, with the objectives to increase capacity, expand product offerings, improve service quality and improve customer experience. I participate in research validation data analysis and support implementation of new techniques and processes.
I have been developing computational pipelines to analyze human blood cells transcriptomics data at the single cell resolution in different contexts including SLE, aging, and influenza vaccination. My main project focusses on understanding how the single cell RNA-seq data can help resolving the SLE transcriptional signatures described decades ago. This analysis allowed a more accurate classification of lupus patients based on specific cell types. This first direct comparison of childhood and adult SLE confirmed the presence of similar transcriptional patterns across age groups and enabled patient classification according to disease activity.
Currently, my research includes understanding how the immune system varies: 1) during aging at the steady state (lifespan project): aimed at analyzing blood transcriptomes from infants, children, young and older adults; and 2) after in vivo stimulation (e.g. influenza vaccination): aimed at analyzing the responsiveness to influenza vaccine in the groups indicated above.
My current research focuses are (1) to better understand the tumor microenvironment and heterogeneity of osteosarcoma using single cell RNA sequencing and spatial transcriptomic analyses, and (2) to investigate alternative splicing events in osteosarcoma using hybrid RNA sequencing. The goal is to identify new biomarkers predicting treatment response, metastasis and survival and new therapeutic target for new treatment development.
In my previous positions, I led the development of medium-throughput in vitro functional platform testing the somatic mutations and fusions identified from cancer patients using 2 cell models, Ba/F3 and MCF10A and tested over 1,600 mutations and fusions, including allelic series of oncogenes PIK3CA, EGFR and BRAF. In addition, I worked proteomic analysis of lung adenocarcinoma, Head and neck squamous cell carcinoma as well as pan-cancers under The Cancer Genome Atlas (TCGA) program.
I study cancer heterogeneity and its evolutionary aspects, mainly through analysis of somatic mutations in TCGA data. I have been comparing allele frequency distributions across different cancers and mutation callers in order to determine dependence of tumor heterogeneity on mutation calling, and its correlation to clinical data. Furthermore, I have been studying models of cancer evolution and their relevance to these results.
Kristen Onos, PhD is a Research Scientist in the Howell lab. She is focused on improving preclinical to clinical translation of mouse models of neurodegeneration and drug testing. Her primary interests revolve around how changes in bioenergetics influence vascular function and glial activation. She is also an active member of the MODEL-AD consortium and a strong advocate for open science.
My research involves the development of therapies for treating type 1 diabetes in a humanized version of the NOD mouse. Using NOD mice in which the mouse MHC class I has been replaced with a human variant linked to type 1 diabetes development, I am studying how several therapies can tolerize autoreactive CD8+ T cells selected on the human HLA. The first project revolves around using hematopoietic stem cell transplantation and induction of mixed chimerism to determine how protective MHC can tolerize autoreactive CD8+ T cells. A second project revolves around peptide-microsphere conjugates and how dosing pre-diabetic humanized-NOD mice with diabetogenic peptides can prevent diabetes development, and the mechanisms by which autoreactive CD8+ T cells are tolerized by these peptide-microsphere conjugates. A final side project/collaboration involves dissecting the mechanisms by which IFNϒ can act as an inhibitory cytokine for autoreactive CD8+ T cell expansion.
The focus of my work is bioinformatics, specifically, the design, implementation,management and evolution of community databases. I have been intimately involved in the Mouse Genome Informatics (MGI) program since 1992. MGI provides online access to high-quality, comprehensive, and up-to-date information about the laboratory mouse, to support its use as a model for understanding human health and disease. Together with Jim Kadin, I lead the software and database development teams that support a number of resources,including the Mouse Genome Database (MGD – HG000330), the Gene eXpression Database for mouse development (GXD – HD062499), the Mouse Tumor Database (MTB –CA089713), and the International Mouse Strain Resource (IMSR - LM009693). I am also PI of the MouseMine project (HG004834), which provides a fast, powerful new data warehouse for accessing MGI data.
Tumors are continually evolving collections of cells, characterized by a dynamic interplay among heterogeneous sub-clonal populations that expand and contract under innate and imposed selective pressures. My research couples deep learning imaging techniques with high-resolution molecular assays and matched clinical information to analyze tumors through a framework of evolution. We study the impact of treatment on the dynamics of the tumor ecosystem to elucidate resistance mechanisms and identify potential targets for intervention.
Focuses on creating and characterizing mouse models that accurately model human disease and therefore can be used to understand neurodegenerative disease and be used in the development of new therapies.
As the Associate Director of Genetic Resource Science Model Development and Bioinformatics, I oversee the group responsible for the selection and importation of new mouse strains into the Repository. We curate strain information and develop tools that enable the public to access the information in our extensive strain database.
I also work on creating and characterizing mouse models that accurately model human disease and can be used in understanding neurodegenerative disease and in the development of new therapies. Ongoing projects are listed below.
Alzheimer's disease is the most common cause of dementia. It is characterized by brain pathology including amyloid plaques composed of Abeta and intracellular tangles made up of hyperphosphorylated tau protein. Abeta is a cleavage product of the amyloid precursor protein (APP), and mutations in APP and its processing enzymes (including the presenilins, Bace) are thought to be one cause of familial AD. The Jackson Laboratory offers a variety of genetic models for AD research, including strains expressing APP and presenilin (PSEN1) mutations, strains expressing mutant APP in either a constitutive or inducible manner, strains expressing mutant tau (Mapt), strains with Presenilin mutations, strains with Apoe mutations, and strains with Bace mutations. These models develop Alzheimer's-related characteristics as they age.
Parkinson's disease is characterized by the loss of dopamine-producing cells in the substantia nigra. While the earliest and most obvious symptoms are movement disorders including tremor, rigidity, gait abnormalities and bradykinesia (slowness of movement), there are many other manifestations, including cognitive, emotional and sleep disorders. Accumulation of alpha-synuclein deposits in the brain lead to the formation of Lewy bodies, a diagnostic marker of PD. The Michael J. Fox Foundation for Parkinson’s Research (MJFF) supports our program to develop, characterize, and distribute genetically engineered mice and information useful for their selection and use.
Other model development projects
With funding from the Chordoma Foundation, we are developing and characterizing novels models of this rare form of skull and spine cancer.
With funding from the Dravet Syndrome Foundation, we have created a novel model of this form of early onset epilepsy. This model is currently being validated.
Variation in observable traits, such as disease susceptibility, is pervasive in the natural world. Recent advances in sequencing and computation are providing us with an unprecedented view of patterns of genetic variation within species. A major outstanding challenge is to identify and characterize the specific genetic variants affecting complex traits, and the mechanisms through which they do so.
I am a biologist and data scientist who uses single cell functional genomics to understand the genetic basis of complex traits. I utilize genetically diverse model organism populations together with the methodology of statistical and quantitative genetics to reveal novel mechanistic insights into the biology of complex traits. My background and interests include cancer, cardiovascular disease, diabetes, and obesity/metabolic disorders.
Comparative phenotype analysis and bioinformatics can be used to analyze congenital defects and pathological processes with the objective of discovering new molecular elements and pathways that contribute to disease states.
My research focuses on comparative phenotype analysis and bioinformatics. I develop systems to
integrate and analyze phenotypic information in the context of the genetics and genomics data of the
laboratory mouse within the Mouse Genome Informatics (MGI) project. I am primary developer of
the Mammalian Phenotype Ontology (MP), a controlled, structured vocabulary to annotate
phenotype data, enabling data integration, analysis and computational reasoning. My current
research projects include developing ontological relationships among other human and model
organism phenotype ontologies and database knowledge systems to develop comparative analysis
tools. These tools will be used to analyze congenital defects and pathological processes with the
objective of discovering new molecular elements and pathways that contribute to disease states.
Sabriya completed her PhD in 2016 at the Mayo Graduate School in Rochester, MN where she studied the genome-wide epigenetic mechanisms underlying cellular transitions of the Interstitial cells of Cajal in the gastrointestinal tract. During this time Sabriya became interested in understanding how the epigenomic landscape impacts chromatin organization. To pursue this, Sabriya joined the Imbalzano Lab at the University of Massachusetts Medical School where she explored the role of arginine methyl transferase Prmt5 in mediating higher order chromatin structure in preadipocytes prior to and during adipogenesis using methods like ChIP-Seq and Hi-C. For this work, Sabriya was awarded the Ruth L. Kirschstein NRSA Postdoctoral Fellowship from 2019-2021. After this, Sabriya joined the Lee Lab as an Associate Research Scientist where she is currently exploring how structural variants in humans affect genome organization and modulate transcription.
I have had a longstanding interest in using animal models to enhance our knowledge of basic human biological processes as well as disease states. Having recently joined the Burgess lab group as an Associate Research Scientist, I am looking forward to using my training to develop mouse models of human neuromuscular disorders and to use these models to elucidate both the cellular and molecular processes that contribute to disease as well as possible therapeutic strategies.
As Program Manager for the JAX Center for Precision Genetics (JCPG), I work with the lead researchers to help manage and coordinate the Center's various research projects. In addition, I compile and synthesize the efforts of JCPG scientists and communicate the results to internal and external collaborators, overseers, and the NIH.
Dementia is an outcome of several neurodegenerative diseases, with no treatments currently available. Microglia, the brain’s immune cells, are implicated in resilience and susceptibility to cognitive decline. The goal of my research is to define the interplay between transcriptomic and functional changes that impact behavior in genetically diverse mouse models of cognitive decline and, subsequently, to discover small molecules that intervene in memory loss.
I am interested in understanding how interactions between genes (epistasis) contribute to the genetic architecture of complex traits. My adviser, Greg Carter, previously developed an analytical method, called the Combined Analysis of Pleiotropy and Epistasis (CAPE), that combines information across multiple phenotypes to constrain possible epistatic models and thereby infer the direction of interaction between genetic variants. I have packaged the analytical pipeline into a freely available R package. CAPE has been used to infer directed epistatic networks in yeast, Drosophila, and mice, and I am currently working to adapt the method for use in human populations. This adaptation will include development of a new software package for detection and interpretation of epistatic interactions in medical genetics.
Supervises wet lab, building amplicon, genomic and metagenomic libraries using various approaches to sequence on variety of platforms (illumina as well as PacBio) to study the understanding of the relationship between the microbiome and metabolic diseases.
I have worked in the area of microbiology and molecular biology for over 15 years during which time I focused on the study of cell division and cytoskeletal regulation in prokaryotes. I have extensive experience in microbiology, biochemistry, molecular biology, protein interaction and purification, western blotting, immuno-blotting, microscopy [which includes immunofluorescence microscopy (single label and double label), epi-fluorescence, phase contrast, single molecule fluorescence microscopy, PALM FRAP]. I have an expertise in bacterial cell imaging and bacterial genetics research.
My current research is in the area of microbiome where I am primarily involved in managing several projects and supervises wet lab. As a result of my research experiences, I am aware of the importance of frequent communication among project members and of constructing a realistic research plan and timeline. I am also involved in making various types of amplicon as well as whole-genome shot gun libraries to sequence on different illumina platforms (MiSeq, NextSeq, HiSeq) and PacBio to study the relationship between microbiome and several diseases.
My research focuses on the regulation of gene expression during lung development and in disease. Recent research projects include measuring gene expression in the lungs of three strains of mice during development from embryonic day E9.5 to maturity at 8 weeks of age and developing a new technique to identify direct messenger RNA (mRNA) targets of microRNAs (miRNAs). I am using a new technique, referred to as RIP-SIR, to study miRNA regulated gene expression during the progression of pulmonary adenocarcinoma in two mouse models. In a related project, serum samples collected from these lung tumor-bearing mice were analyzed to identify expression profiles of circulating miRNAs that may indicate the presence of early stage pulmonary adenocarcinoma. A new project is expanding upon this work and using patient-derived xenograft (PDX) mice to answer basic questions about which miRNAs are secreted from tumors and enter the circulatory system. Finally, as a member of a collaborative group headed by Dr. Patricia Donahoe, I am investigating gene expression in the developing mouse diaphragm and determining how novel mutations identified by this group contribute to congenital diaphragmatic hernia, a condition that is often associated with a fatal respiratory phenotype.
My research interests are focused on the establishment and characterization of genetic models of embryonic morphogenesis as a means to develop a more synthetic understanding of genome regulation and function, and thereby advance human health.
My research interests are focused on the establishment and characterization of genetic models of embryonic morphogenesis as a means to develop a more synthetic understanding of genome function, and thereby advance human health. As a member of the Knockout Mouse Phenotyping Program (KOMP2) and International Mouse Phenotyping Consortium (IMPC), I bring to bear a broad expertise in embryology and genetics in order to advance this collaborative effort in the functional annotation of the mouse genome.
Advancing a mechanistic understanding of craniofacial development represents my core research interest. Craniofacial morphogenesis demands coordinated outgrowth of multiple facial prominences that are initially spatially separated. How morphogenetic domains are organized to coordinate craniofacial development is an important question. While a number of genes and pathways important for palate development have been identified, a systems-level understanding of how the regulatory networks are integrated to achieve precise control of midfacial development remains a challenge. This knowledge gap hinders the identification of causal mutations associated with human craniofacial pathologies. I seek to define transcriptional landscapes underpinning the modularity of midfacial outgrowth and skeletal differentiation along the anterior-posterior axis of the upper jaw, a parameter critically influencing midfacial morphogenesis. I seek to leverage multi-omics approaches in conjunction with developmental and systems genetics, and 3D imaging to establish a multiscale model of mechanisms that coordinate midfacial morphogenesis. This research will ultimately define the mechanisms underlying tolerance to morphological variation separating normal craniofacial development from pathology, as well as opening new avenues to advance the diagnosis and treatment of an important class of human birth defects.
The human breast cancer microenvironment displays features of T helper 2 (Th2) immunity, which
promotes tumor development. We showed that breast cancer cell-derived thymic stromal lymphopoietin
(TSLP), by inducing OX40L expression on DCs, contributes to the Th2 immunity conducive to breast tumor
In order to reprogram the inflammatory pro-tumor Th2 (iTh2) into anti-tumor Th1 microenvironment, we
tested the impact of targeting the innate receptors on DCs to render the resistant to tumor environment.
We show that intratumoral delivery of β-glucan, a natural ligand for dectin-1 expressed on DCs, blocks the
generation of iTh2 cells leading to decreased IL-13 in the tumor microenvironment and prevents breast
cancer development. β-glucan exposed DCs expand CD8+ T cells, which produce higher IFNg, Granzyme A
and Granzyme B, accumulate in the tumors leading to enhanced tumor necrosis in vivo. Our data
demonstrate that exploiting pattern-recognition receptors on tumor-infiltrating DCs enables cancer
We are further exploring the ATACseq and RNAseq approach to understand the regulation of TSLP
production in breast tumor cells and how TSLP alters the infiltrating DCs. It can be novel molecular biology
approaches to decode tumor infiltrating DCs and T cells and define potential targets for immunotherapy.
My research focuses on comparative phenotype analysis and bioinformatics. I develop systems to integrate and analyze phenotypic information in the context of the genetics and genomics data of the laboratory mouse within the Mouse Genome Informatics (MGI) project. I am primary developer of the Mammalian Phenotype Ontology (MP), a controlled, structured vocabulary to annotate phenotype data, enabling data integration, analysis and computational reasoning. My current research projects include developing ontological relationships among other human and model organism phenotype ontologies and database knowledge systems to develop comparative analysis tools. These tools will be used to analyze congenital defects and pathological processes with the objective of discovering new molecular elements and pathways that contribute to disease states.
My first research program focuses on the regulation of the de novo ceramide biosynthesis pathway that determines cellular profiles of sphingolipid metabolites, i.e. sphingoid long-chain bases (LCBs) and ceramide (acylated LCB) species, which have been implicated in many neurological diseases. Using mouse models generated in The Jackson Laboratory or contributed to the mouse depository at The Jackson Laboratory, I have been working toward elucidating the potentially specific neural functions and pathological roles of different LCBs and ceramides, respectively, in two related projects.My second research program focuses on the transcription network controlling photoreceptor differentiation and how deregulation of this network causes photoreceptor degeneration. We adopted a genetic approach to identify novel regulators of this network by searching for genetic modifiers of rd7, a mutation of the transcription factor NR2E3 causing a retinopathy called Enhanced S-Cone Syndrome. We have found several modifiers that suppress rd7. Currently, we are trying to identify the underlying genes and assess their interactions with other genes’ encoding factors involved in photoreceptor differentiation.