Research into gene regulation using genomics approaches.
Labs in This Area
Analyzing high–throughput genomic data in the context of biological networks
I am a computational biologist with an interest in the development of methods for integrative, systems-level analysis of high-dimensional genomic and proteomic data. These methods incorporate bioinformatic information with experimental data to characterize the networks of interactions that lead to the emergence of complex phenotypes, particularly cancers.
For more information, visit the faculty profile of Rosemary Braun, PhD, MPH.
See Dr. Braun's publications in PubMed.
Studying molecular motors and cell motility
Movement is a fundamental characteristic of life. Cell movement is critical for normal embryogenesis, tissue formation, wound healing and defense against infection. It is also an important factor in diseases such as cancer metastasis and birth defects. Movement of components within cells is necessary for mitosis, hormone secretion, phagocytosis and endocytosis. Molecular motors that move along microfilaments (myosin) and microtubules (dynein) power these movements. Our goal is to understand how these motors produce movement and are regulated. We wish to define their involvement in intracellular, cellular, and tissue function and disease—with the long-term goal of developing therapies for the treatment of diseases caused by defects in these molecular motors.
Our work involves the manipulation of myosin and dynein function in the single celled eukaryote Dictyostelium, cultured mammalian cells and transgenic and knockout mice. Yeast two-hybrid screens to identify proteins that interact with or regulate myosin and dynein and characterization of gene expression are being used to define the pathways regulating myosin and dynein. To analyze the biological significance of myosin and dynein, we use confocal and digital microscopy of living cells, analysis of cell movement, vesicle transport and cell division. We employ biochemical techniques including heterologous expression, enzyme purification and characterization, and analysis of how phosphorylation state affects physiological function. We are pursuing signal transduction studies to understand the physiologically important pathways that regulate cell motility and biophysical studies such as in vitro motility assays to understand how these molecular motors function at the molecular level.
See Dr. Chisholm's publications on PubMed.
Contact Dr. Chisholm at 312-503-3209.
Translational Bioinformatics and Cancer Genomics
Research in our lab focuses on developing informatics solutions to solve problems in biology and medicine. Current projects are focused on two closely related areas: (A) mammalian gene regulation at isoform-level, and (B) isoform-level transcriptional networks in brain development and brain tumors. The overarching goal of his lab is to translate Big Data from multiple high dimensional (-omic) platforms (e.g., NextGen sequencing) to derive experimentally interpretable and testable discovery models towards genomics-based clinical decision support systems for personalized cancer therapy. Our group is developing bioassays that can rapidly identify biomarkers from human tissue and blood samples. Towards these goals, our group applies state-of-the-art statistically rigorous data-mining methods and NextGen sequencing based experimental procedures in a systems biology setting.
Our research program is interdisciplinary in nature with a complement of experimental investigation. The current projects of our laboratory are:
- Informatics platform for mammalian gene regulation at isoform-level
- Isoform-level transcriptional networks in brain development and brain tumors
- Molecular classification of cancers
Coupled with advances in high throughput technologies, our computational modeling work seeks to address key outstanding issues in mammalian genomics and cancer. We currently maintain online databases (e.g., MPromDb – Mammalian Promoter Database), programs for NextGen sequence analysis (e.g., IsoformEx, Isoform level gene expression estimation from RNA-seq data; TPD – Modeling Transcription Factor Binding Site Profiles from ChIP-Seq Data; NPEBseq: Differential Expression analysis based on RNA-seq data; and Data-mining methods for molecular stratification of cancers (e.g., PIGExClass – Platform-independent Isoform-level Expression based classification-system).
For more information, visit the faculty profile of Ramana Davuluri, PhD.
See Dr. Davuluri's publications in PubMed.
Research Assistant Professors:
Yingtao Bai; Hong-Jian Jin
Segun Jung; Majoh Kandpal
The Green Lab investigates the genetics and molecular biology of cholestatic liver diseases and fatty liver disorders. The major current focus is on the role of ER Stress and the Unfolded Protein Response (UPR) in the pathogenesis of these hepatic diseases.
Dr. Green’s laboratory investigates the mechanisms of cholestatic liver injury and the molecular regulation of hepatocellular transport. Current studies are investigating the role of the UPR in the pathogenesis and regulation of hepatic organic anion transport and other liver-specific metabolic functions. We employ genetically modified mice and other in vivo and in vitro models of bile salt liver injury in order to better define the relevant pathways of liver injury and repair; and to identify proteins and genes in these pathways that may serve as therapeutic targets for cholestatic liver disorders.
The laboratory also investigates the mechanisms of liver injury in fatty liver disorders, and the molecular regulation of hepatic metabolic pathways. The current focus of these studies includes investigations on the role of the UPR in the pathogenesis of non-alcoholic steatohepatitis and progressive fatty liver disease. We employ several genetically modified mice and other in vivo and in vitro models of fatty liver injury and lipotoxicity. Additional studies include the application of high-throughput techniques and murine Quantitative Trait Locus (QTL) analysis in order to identify novel regulators of the UPR in these disease models.
See Dr. Green's publications in PubMed.
For more information, please see Dr. Green's faculty profile.
Contact Dr. Green at 312-503-1812 or the Green Lab at 312-503-0089
David Hillburn, MD
Xiaoying Liu, PhD
Pathogenesis of Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae infections
Our laboratory investigates the pathogenesis of the gram-negative bacteria Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. We focus on virulence factors such as the type III secretion, an apparatus that injects toxins directly into host cells. A second interest is the use of genomic approaches for the identification of novel virulence determinants. Our studies utilize a broad range of techniques, including molecular and cellular assays as well as animal models and epidemiologic studies on human populations.
See Dr. Hauser's publications on PubMed.
Contact Dr. Hauser at 312-503-1044 or the lab at 312-503-1081.
Environmental, genetic and epigenetic risk factors for disease
Dr. Hou’s research interest lies in integrating traditional epidemiologic methods with the ever-advancing molecular techniques in multi-disciplinary research focusing on identifying key molecular markers and understanding their potential impact on disease etiology, detection, and prevention.
Dr. Hou’s major research efforts to date have focused on two areas: 1) identification of risk factors that may cause chronic diseases; and 2) identification of biomarkers that serve as indicators of an individual’s past exposure to disease risk factors and/or predict future disease risks and/or prognosis. The environmental/lifestyle risk factors that Dr. Hou has studied include air pollution, pesticides, overweight, physical inactivity, and reproductive factors in relation to chronic diseases. The biomarkers that Dr. Hou has investigated include genetic factors (i.e., polymorphisms, telomere length shortening, mitochondria DNA copy number variations) and epigenetic factors (i.e., DNA methylation, histone modifications, and microRNA profiling). Her over-arching research goal is to understand the biological mechanisms linking environmental risk factors with subclinical or clinical disease development to ultimately lead to development of effective strategies for prevention of chronic diseases.
In addition to being a PI of several NIH funded grants, Dr. Hou is the co-director and Co-PI of the Northwestern Consortium for Early Phase Cancer Prevention Trials of the Division of Cancer Prevention (DCP) Consortia, National Cancer Institute.
For more information visit the faculty profile of Lifang Hou, MD, PhD.
See Dr. Hou's publications in PubMed.
Regulation of Motor Neuron and Dopaminergic Neuron Function in Development and Disease
Postdoctoral fellow jobs and graduate student rotation projects are available.
Research DescriptionSpinal Motor Neurons and Spinal Muscular Atrophy (SMA)
SMA is characterized by the selective degeneration of spinal motor neurons. As the leading genetic cause of infant mortality, SMA affects one in every eight thousand live births. Our group is interested in studying mechanism regulating motor neuron development and function, as well as why motor neurons specifically degenerate in SMA. To address these questions, we use a combination of genetic, biochemical and cell biological approaches, and utilize genetically modified mice, induced pluripotent stem (iPS) cells reprogrammed from fibroblasts, and zebrafish as model systems. We focus on the regulation of mitochondrial functions in SMA pathogenesis. Based on our findings, we hope to develop new therapeutic strategies for treating SMA.
Dopaminergic Neurons and Parkinson's Disease
Dopaminergic neurons located in the ventral midbrain control movement, emotional behavior and reward mechanisms. Dysfunction of these neurons is implicated in Parkinson’s disease, drug addiction, depression and schizophrenia. Our group is interested in the genetic and epigenetic mechanisms regulating dopaminergic neuron functions in disease and aging conditions. We are particularly interested in how aging and mitochondrial oxidative stress contribute to dopaminergic neuron degeneration in Parkinson's disease through transcriptional and epigenetic regulations. We use mouse models, cultured neurons and iPS cells for these studies.
View Dr. Ma's publications at PubMed
Nimrod Miller, PhD, Postdoctoral Fellow
Han Shi, Graduate Student
Brittany Edens, Graduate Student
Kevin Park, Graduate Student
Monica Yang, Undergraduate Student
Aaron Zelikovich, Undergraduate Student
Host-microbiota specificity, communication, and evolution
Microbial symbioses are prevalent in animal biology, and often, as in the case of humans, the animal host is born devoid of its natural symbionts and must acquire microbial partners from the environment. Pathogenic and beneficial bacteria share common mechanisms by which they colonize animal tissue. In spite of these parallels, relatively little work has been accorded to the beneficial associations, which are widespread, and critical to the lifecycles of both the bacterial and animal partners.
Our lab is studying the natural Vibrio-squid model to understand the processes that underlie host association in animal-associated bacteria. I discovered that a single gene is sufficient to shift the host range of Vibrio fischeri. In future research, we will combine genetic, genomic, microscopy, and evolutionary approaches to study the dynamics of host-symbiont relationships.
The binary association between bioluminescent V. fischeri bacteria and Euprymna scolopes squid provides a natural system in which to investigate the mechanistic basis by which animals and bacteria initiate mutually-beneficial relationships. Both organisms may be obtained directly by environmental collection, and cultured independently of each other. As such, this association provides a relatively simple, yet natural, system in which to study the specific colonization of animal hosts by beneficial bacteria. Related squids harbor V. fischeri symbionts, and are also amenable to experimentation. This system reflects features that are shared by many beneficial and pathogenic host-bacterial interactions, including:
- Aposymbiotic (uncolonized) juvenile hosts acquire the symbiont from the environment
- Productive association relies on specificity in a mucosal environment
- The bacteria colonize host epithelial tissue
- Both partners undergo dramatic cellular and developmental changes as a result of the interaction
- Host and symbiont form a chronic association that persists throughout the lifetime of the host
Using this system, we are asking how host specificity develops, how symbiont genomes evolve, and how symbiont genetics and genomics influence the earliest stages of the interaction with the squid host.
See Dr. Mandel's publications on PubMed.
Contact Dr. Mandel at 312-503-4138 or the lab at 312-503-2915.
Cellular stress response systems in malignancies
For lab information, publications, and more, see Dr. Mendillo’s faculty profile.
View Dr. Mendillo's publications at PubMed
Studying Molecular Mechanisms of Oncogenesis In Acute Leukemia
This is an exciting time for cancer biology especially with the advent of epigenetics and chromatin biology. New molecules with tumor suppressive or oncogenic roles are currently identified and characterized paving the way for new therapeutic ways but at the same time, posing new challenges for researchers. This area of cancer epigenetics is my personal and laboratory's focus. To study this perplexing biology we use patient samples and disease-relevant mouse models.
The Ntziachristos laboratory studies the mechanistic aspects of oncogenesis with an emphasis on transcriptional and epigenetic regulation of acute leukemia. Important questions are related to how oncogenes interact with each other and with epigenetic modulators to influence gene expression programs as well as how their function is related to tri- dimensional (3D) structure of the nucleus and other biological aspects of cancer cells, like metabolism. To address these questions we use high-throughput molecular and cell biology techniques like ChIP-Seq, RNA-Seq, 4C-Seq and HiC, fluorescent in situ hybridization, biochemical analysis e.t.c. in cell lines and primary cells of human origin and tissues of mouse models of disease. In addition to understanding cancer biology these finding help us design and test targeted therapies in preclinical models of leukemia.
For lab information and more, see lab website.
See Dr. Ntziachristos's publications at PubMed.
Dr. Ntziachristos 312-503-5225 or Searle 6-523
Understanding the cortical component of motor neuron circuitry degeneration in ALS and other related disorders.
The Les Turner ALS Laboratory II at Northwestern
We are interested in the cellular and molecular mechanisms that are responsible for selective neuronal vulnerability and degeneration in motor neuron diseases. Our laboratory especially focuses on the corticospinal motor neurons (CSMN) which are unique in their ability to collect, integrate, translate and transmit cerebral cortex's input toward spinal cord targets. Their degeneration leads to numerous motor neuron diseases, including amyotrophic lateral sclerosis, hereditary spastic paraplegia, and primary lateral sclerosis.
Investigation of CSMN require their visualization, and cellular analysis. We therefore, generated reporter lines in which upper motor neurons are intrinsically labeled with eGFP expression. We also characterized progressive CSMN degeneration in various mouse models of motor neuron diseases, and continue to generate reporter lines of disease models, in which the upper motor neurons express eGFP.
The overall goal in our investigation, is to develop effective treatment strategies for ALS and other related motor neuron diseases. We appreciate the complexity of the disease and try to focus the problem from three different angles. In one set of studies, we try to reveal the intrinsic factors that could contribute to CSMN vulnerability by investigating the expression profile of more than 40,000 genes and their splice variations at different stages of the disease. In another set of studies, we try to understand the role of non-neuronal cells on motor neuron vulnerability and degeneration, using a triple transgenic mouse model, in which the cells that initiate innate immunity are genetically labeled with fluorescence in an ALS mouse model. These studies will not only reveal the genes that show alternative splice variations, but also inform us on the canonical pathway and networks that are altered with respect to disease initiation and progression.
Even though the above mentioned studies, which use pure populations of neurons and cells isolated by FACS mediated approaches, will reveal the potential mechanisms that are important for CSMN vulnerability, it is important to develop therapeutic interventions. One of the approach we develop is the AAV-mediated gene delivery directly into the CSMN via retrograde transduction. Currently, we are trying to improve CSMN transduction upon direct cortex injection.
Identification of compounds that support CSMN survival is an important component of pre-clinal testing. We develop both in vitro and in vivo compound screening and verification platforms that inform us on the efficiency of compounds for the improvement of CSMN survival.
In summary, we generate new tools and reagents to study the biology of CSMN, and to investigate both the intrinsic and extrinsic factors that contribute to their vulnerability and progressive degeneration. We develop compound screening and verification platforms to test their potency on CSMN , and we develop AAV-mediated gene delivery approaches. Our research will help understand the cellular basis of CSMN degeneration and will help develop novel therapeutic approaches.
View Dr. Ozdinler's full list of publications at PubMed
Hande Ozdinler, PhD at 312-503-2774
Pharmacogenomics research in minority patient populations
The Perera laboratory focuses on pharmacogenomics (using a patient's genome to predict drug response) in minority populations. Working in this translation research space requires both clinical expertise as well as the use of high-throughput basic science approaches. Our goal is to bring the benefits of precision medicine to all US populations.
The Perera lab recruited patient populations from around the world. The data collection includes genomic (DNA), transcriptomic (mRNA), pharmacokinetic and clinical data. We then integrate these different data sources to understand genetic drivers of drug response (e.g. genetic predictors of adverse events) as well as disease. By studying minority populations the lab has discovered genetic risk variants that may benefit the implementation of precision medicine in African Americans and others.
- Warfarin Bleeding Risk Association study
We recently discovered a genetic variant that predispose African Americans to bleeding complications while on anticoagulant drugs. These bleeds occurred even when the patient was within the therapeutic window for the medication. We hope that this new data will help to identify high risk individuals prior to therapy.
- Novel African-specific genetic polymorphisms predict the risk of venous thromboembolism
We discovered a new genetic variant associated with a 2.5 fold increase in risk of developing a blood clot. We went on to show that this SNP significantly affects the expression of a key protein in the coagulation cascade. View article on PubMed. Read press release.
- Common genetic variant is predictive of warfarin metabolism and gene expression in African Americans
We tested the association of a SNP, previously shown to effect gene expression CYP2C9, for association with warfarin drug clearance (pharmacokinetics). This SNP increased the expression of CYP2C9 (enzyme that metabolized warfarin), hence causing fast clearance of the drug. This African American-specific SNP may help to explain the higher warfarin dose required by African Americans in general. View article on PubMed.
- Genomics of Drug Metabolism
We are using African America primary hepatocytes to understand the genetic regulation of drug metabolizing enzymes that are involved in a majority of drug used in the US.
- Anticoagulant Pharmacogenomics
We are conducting several genetic association studies to understand both the genetic drivers and the biological mechanisms behind response and adverse effect to anticoagulant medications.
- Pharmacogenomics of Inflammatory Bowel disease
We are investigating the genetic predictors of primary non-response to biologic therapies used in inflammatory bowel disease. Studies have implication for other autoimmune disorders that target the same pathways.
We are involved in analyzing the GWAS and sequencing data specifically for genomics variation affect key pharmacogenomics gene in African Americans.
See Dr. Perera's publications on PubMed.
Contact Dr. Perera at 312-503-6118 or the lab at 312-503-4119.
Bacterial pathogenesis, DNA recombination mechanisms, epithelial cell adherence
Our laboratory studies the pathogenesis of Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea. This gram-negative bacterium is an obligate human pathogen that has existed within human populations throughout recorded history. We are using a variety of molecular biological, genetic, cell biological and biochemical techniques to investigate the molecular mechanisms controlling gonococcal infection, define mechanisms and pathways of DNA recombination, replication and repair in this human specific pathogen, study the interactions between gonococci and human cells, tissues and the innate immune system, and determine how the pilus functions to help mediate genetic transfer and pathogenesis. Our goal is to discover new mechanisms important for the continued existence of this microbe in the human population to further our understanding of how infectious agents have evolved to specifically infect humans.
For lab information and more, see Dr. Seifert's faculty profile.
See Dr. Seifert's publications on PubMed.
Contact Dr. Seifert at 312-503-9788 or the lab at 312-503-9786.
Defining and targeting the oncogenome of Glioblastoma.
Our research program is aimed at understanding the genetic program that underlies the pathogenesis of Glioblastoma multiforme (GBM), the most prevalent and malignant form of brain cancer. Applying a combination of cell/molecular biology, oncogenomic and mouse engineering approaches, we are dedicated to systematically characterize novel gliomagenic oncogenes and tumor suppressors. We will functionally delineate and validate these pathways using cell culture and animal models, and develop novel nanotechnological approaches to target these aberrations in established tumors.
View Dr. Stegh's full list of publications at PubMed
Alexander Stegh, MD, PhD, at 312-503-2879
Timothy L. Sita (MSTP)
Andrea E. Calvert (DGP)
Carissa M. Ritner (DGP)
Research Technician/Lab Manager
Lisa M. Hurley
Research in our laboratory focuses on the mechanisms of fibrosis and inflammation/autoimmunity in human diseases.
Our research integrates genetic and genomic approaches with experimental studies using cell-based systems, organ cultures and animal models. In particular, we are studying regulation of fibroblast activation, mesenchymal cell differentiation, and the cross-talk between macrophages, monocytes and stromal cells, and the role of innate immune signaling, in aberrant tissue remodeling and wound healing.
Fibrosis is a non-specific response that occurs in reaction to any type of chronic or persistent tissue injury. While acute fibrogenesis is beneficial for rapidly restoring tissue homeostasis and regeneration, chronic or deregulated responses to injury lead to scar. Fibrosis is now one of the a leading causes of deaths worldwide. Therefore, an important goal is to define the cells, metabolic states, molecules and signaling pathways that regulate tissue repair, and how genetic and epigenetic modifications in these pathways result in chronic fibrosis. We focus on fibrotic diseases affecting the skin, lungs and heart.
We are investigating the molecular mechanisms that control activation of fibroblasts and myofibroblasts, and the role of innate immunity, toll-like receptors and related pattern recognition receptors, and the cross-talk among monocytes, macrophages, dendritic cells and adipocyte progenitor cells and mesenchymal stromal cells. In addition, studies are investigating the origins of activated stromal cells, using transgenic lineage tracing approaches. We focus on pathways implicated in large-scale genetic studies are candidates based on their association with scleroderma, pulmonary fibrosis and chronic inflammation.
We routinely employ molecular, cellular, biochemical and genetic approaches in our studies, along with omics approaches such as genomewide transcriptomics and GWAS, proteomics and candidate gene approaches. We make extensive use of human samples such as skin biopsies, lung tissue, explanted fibroblasts and blood cells, and animal models of disease. We are also developing organoid approaches to model fibrosis and repair in human skin. Many of our studies focus on the discovery of targeted therapies and of biomarkers for predicting disease severity, activity, and response to therapy in genetically diverse human populations.
View Dr. Varga's publications at PubMed
For more information visit Dr. Varga's faculty profile page
Contact Dr. Varga at 312-503-8003 or the Varga Lab at 312-503-0498
Swati Bhattacharyya, PhD
Research Assistant Professor
Roberta Goncalves-Marangoni, MD, PhD
Research Assistant Professor
Bo Shi, PhD
Research Assistant Professor
Computational immunology - Using genomic approaches to study rheumatic disease.
The goal of the Winter Lab of Functional Genomics is to apply genomic approaches to study rheumatic disease. Led by Dr. Deborah Winter, a computational immunologist, we employ the latest technologies for assays – such as RNA-seq, ChIP-seq, ATAC-seq, and single cell expression – to profile the transcriptional and epigenomic profiles of immune cells in health and disease. Our goal is to define the underlying regulatory networks and understanding how they respond to challenge, illness, and injury. We are particularly interested in the role of macrophages in diseases such as scleroderma, rheumatoid arthritis, and lupus. Previous research has addressed the impact of the tissue environment on resident macrophages and the role of microglia, CNS-resident macrophages, in brain development. Our research combines molecular and systems biology, biotechnology, clinical applications, and computer science. We use both mouse models and patient samples to help us understand and test different systems. We are committed to high standards of analysis and are continually updating and training in innovative computational techniques. We are currently recruiting highly motivated individuals to join the lab.
For more information, visit the faculty profile of Dr. Winter.
View Dr. Winter's publications at PubMed
Contact Dr. Winter at 312-503-0535 or by email.
The Yu laboratory focuses on understanding the genetic and epigenetic pathways to prostate cancer.
The Yu lab focuses on cancer genomics and translational cancer research. At the current stage, our primary research interest is to understand aberrant transcriptional and epigenetic regulation of prostate cancer and to translate such knowledge into clinical applications. We utilize high-throughput genomic techniques in combination with bioinformatics/statistical analysis to generate testable hypothesis. We then test these hypotheses using traditional molecular and/or cellular biological approaches and examine the functional relevance of these innovative regulatory pathways in vitro and in vivo using cell lines and mouse models. Based on the genetic and epigenetic underpinning of the disease, we pursue translational research to develop new biomarkers and novel therapeutics strategies for advanced prostate cancer.
View lab publications via PubMed.
For more information, visit the faculty profile page of Jindan Yu, MD/PhD.
Contact Dr. Yu at 312-503-2980 or the Yu Lab at 312-503-3041.
Will Ka-Wing Fong
Yeqing (Angela) Yang
Changsheng (Jonathan) Zhang
Genetics and epigenetics of complex traits including risks for common diseases and drug response
For more information, visit Dr. Zhang's Faculty Profile page.