Research into gene regulation using genomics approaches.
Labs in This Area
Mechanisms Underlying Glioblastoma Progression and Regulators of Asymmetric Cellular Division in Glioblastoma Stem Cells
Mechanisms Underlying Glioblastoma Progression
We investigate mechanisms of progression to glioblastoma (GBM), the highest grade astrocytoma, including genetics, hypoxia, and angiogenesis. Progression is characterized by tumor necrosis, severe hypoxia and microvascular hyperplasia, a type of angiogenesis. We propose that vaso-occlusion and intravascular thrombosis within a high grade glioma results in hypoxia, necrosis and hypoxia-induced microvascular hyperplasia in the tumor periphery, leading to neoplastic expansion outward. Since the pro-thrombotic protein tissue factor is upregulated in gliomas, we investigate mechanisms of increased expression and pro-coagulant effects.
In Silico Brain Tumor Research
We initiated an In Silico Center for Brain Tumor Research to investigate the molecular correlates of pathologic, radiologic and clinical features of gliomas using pre-existing databases, including as TCGA and Rembrandt. Using datasets and image analysis algorithms, we study whether elements of the tumor micro-environment, such as tumor necrosis, angiogenesis, inflammatory infiltrates and thrombosis, may correlate with gene expression subtypes in TCGA gliomas. We also have demonstrated the clinical relevance of TCGA subclasses within the lower grade gliomas using the Rembrandt dataset.
Regulators of Asymmetric Cellular Division in Glioblastoma Stem Cells
We study mechanisms that confer specialized biologic properties to glioma stem cells (GSC) in GBM. The Drosophila brain tumor (brat) gene normally regulates asymmetric cellular division and neural progenitor differentiation in the CNS of flies and, when mutated, leads to a massive brain containing only neuroblastic cells with tumor-like properties. We study the human homolog of Drosophila brat, Trim3, for its role in regulating asymmetric cell division and stem-like properties in GSCs. Trim3 may elicit its effects is through repression of c-Myc.
See Dr. Brat's publications in PubMed.
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 bioinformatics 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.
Genetic causes and pathogenic mechanism that underlie epilepsy
The primary goal of our research is to use gene discovery and molecular biology approaches to identify new treatments for epilepsy. We aim to 1) identify the genetic causes of epilepsy, 2) use stem cell models to understand how genetic mutations can cause epilepsy, 3) develop and test new therapeutics for this condition. Our work is based on the promise of precision medicine where knowledge of an individual’s genetic makeup shapes a personalized approach to care and management of epilepsy.
- Next generation sequencing in patients with epilepsy
- Alternative exon usage during neuronal development
- Identify the regulatory elements that control expression of known epilepsy genes
- Stem cell genetic models for studying the epigenetic basis of epilepsy
Please see Dr. Caraveo Piso's publications on 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
Structural and biochemical basis of chromatin folding and chromosome condensation
The folding of DNA within nuclei and chromosomes is one of the great mysteries of biology, impacts gene regulation and influences heredity. At the most basic level, DNA is wrapped around histones in the nucleosome to form an extended “beads-on-a-string” chromatin fiber. Chromosome conformation capture, involving chemical cross-linking of chromatin followed by restriction digestion, ligation and high-throughput DNA sequencing (Hi-C), detects further folding of the chromatin fiber. Hi-C has revealed “topologically associating domains” (TADs), regions of intra-chromosomal self-association that are interspersed with regions of little or no such self interaction, which are prevalent throughout metazoans. By applying Hi-C to the polytene chromosomes of Drosophila, I established that polytene bands are equivalent to TADs, connecting chromatin folding inferred from Hi-C with direct, physical observations from light microscopy. Furthermore, TADs are conserved between polytene and diploid cells identifying the polytene band-interband pattern as a general principle of interphase chromosome architecture. Chromatin between TADs exists in a fully extended state, whereas TADs, which are up to 30-foldmore condensed, reflect the next higher level of stable chromosome folding.
Through experimental and computational improvements to the Hi-C method, I mapped chromatin interactions at sub-kilobase resolution, the highest resolution for a metazoan genome to-date. This allowed me to determine the locations of chromatin loops across the Drosophila genome. Loops were frequently located within domains of polycomb-repressed chromatin. Loop boundaries or “anchors” were frequently associated with the protein Polycomb, a subunit of Polycomb Repressive Complex 1 (PRC1). Promoters located at PRC1 loop anchors regulate some of the most important developmental genes and are less likely to be expressed than those not at PRC1 loop anchors. Although DNA looping has most commonly been associated with enhancer–promoter communication, these results indicate that loops are also associated with gene repression.
These advances have significantly furthered our understanding of nuclear organization, but DNA folding at the scale of tens-of-nanometers and beyond is still largely undetermined. Enhancers, cis-regulatory regions often located a distance from gene promoters, are important for tissue specific gene expression and malfunction in cancer. Enhancers are often found within TADs and intra-TAD chromatin folding influences proper gene regulation by modulating enhancer-promoter interactions. Disrupting TAD structure pathogenically rewires these interactions in human disease, so determining how TADs fold is of great interest. At the highest level of DNA folding, mitotic chromosomes are one of the most recognizable structures in cell biology, yet a detailed understanding of their internal structure has remained elusive. Faithful propagation of mitotic chromosomes underlies cellular heredity, so it is important to relate chromatin folding within interphase TADs to chromosome condensation during metaphase. My lab combines concepts and approaches from structural biology with methods and analytical tools from molecular biology and genomics to determine the structural basis of chromatin condensation within TADs and mitotic chromosomes. A combination of molecular biology, biochemistry, genomics and imaging will pave the way for a deeper understanding of chromatin structure as well as unravel principles.
Visit the Eagen Lab Website.
For more information, visit the faculty profile page of Kyle Eagen
View lab publications via PubMed.
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
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.
Dissecting the regulation of gene transcription and RNA translation underlying oncogenic processes.
Cancer happens through accumulated genetic mutations and epigenetic alternation in normal cells. With the advances of genomic technologies, we now can precisely characterize the genome-wide alternations of gene expression underlying oncogenic processes in a cost-effective and unbiased manner. My lab will use the combined experimental genomic technologies and computational modeling to examine the regulation of gene transcription and RNA translation during steps of oncogenesis. We aim at revealing novel cancer therapeutic targets and strategies for precision medicine and immunotherapy.
Currently, we are working on the following projects.
- Characterizing the transcriptional regulatory circuits mediating inflammation in the cancer microenvironment.
- Examining the genome-wide regulation of RNA translation in cancers.
- Defining the functional roles of non-canonical translation in lncRNAs, pseudogenes and 5’UTRs in cancers.
For lab information and more, see Dr. Ji's faculty profile.
See Dr. Ji's publications on PubMed.
Contact Dr. Ji at 312-503-2187.
The Lin lab studies the functional significance of human-based genomic and transcriptomic discoveries in cardiometabolic and kidney diseases.
Elucidating How Genotype Lease to Phenotype in Cardiometabolic and Renal Disease
Unbiased human-based discovery efforts, such as genome-wide and exome-wide association studies, have identified many genetic loci for complex, disease-relevant traits. These genetics studies have provided invaluable data implicating novel loci in disease development and progression, but require functional follow-up to elucidate the mechanistic underpinnings driving the associated findings. A focus of the lab is to interrogate, through experimental wet-bench approaches, the functional significance of novel loci for blood lipids levels and measurements of renal function in the hopes of gaining new insights into pathways relevant to cardiometabolic and renal disease, respectively.
In particular, we are studying the role of A1CF, a gene encoding the RNA-binding protein APOBEC1 complementation factor and recently implicated as a locus for (1) elevated plasma triglycerides (Liu et al., Nature Genetics 2017), (2) estimated glomerular filtration fraction in non-diabetic individuals (Pattaro et al., Nature Communications 2016) and (3) serum urate (Kottgen et al., Nature Genetics 2013). We have already discovered that A1CF's actions extend beyond its canonical role of facilitating the editing of APOB mRNA, and we are currently integrating studies using animal and human cellular models to investigate how A1CF contributes to these associated traits.
Using iPSC and Genome Editing Technologies to Study Human Diseases
Although rodent models have contributed greatly to our understanding of human diseases, the genomic and physiologic differences between rodent and human have presented challenges in translating bench-based findings into clinic. To circumvent this roadblock, our lab is using iPSC-derived organoid models to study the effects of DNA variants within the native human genomic context. Using CRISPR-based technology to introduce or correct mutations in human iPSCs, we are modeling the effects of disease-associated mutations on cellular phenotype.
RNA-centric Approach to Studying Kidney Disease
Building upon A1CF-related work and previous experience with long non-coding RNA, we are studying the role of transcriptome-level regulation in the context of kidney disease. We have discovered that A1CF is a novel regulator of alternative splicing in both the liver and kidney, and we are currently working on how A1CF's regulation of splicing may influence intracellular metabolism. We are also studying how human-specific long non-coding RNAs influence gene expression and cellular phenotypes.
See Dr. Lin'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
The Martin Lab investigates the role of the skeleton in the endocrine regulation of mineral metabolism and the cardiovascular complications of mineral and bone diseases.
Our research program focuses on the contribution of the skeleton to the mineral balance in the body. Bone produces a hormone, Fibroblast Growth Factor (FGF)-23, that participates in this balance. However in mineral metabolism disorders, such as in chronic kidney disease, the massive production of FGF23 is associated with negative outcomes and mortality. By understanding the mechanisms that control the production of FGF23, our goal is to develop new therapeutic strategies and improve outcomes in mineral metabolism disorders. To this goal, we perform basic and translational research using a combination of genetics, molecular biology, proteomics, histology and advanced imaging techniques.
A major focus of the lab is to investigate the transcriptional and post-translational regulation of FGF23 within the bone cells. In particular, we study the specific role of a known regulator of FGF23, Dentin Matrix Protein 1 (DMP1), on these regulations and on osteocyte biology in the context of diseases associated with FGF23 excess (chronic kidney disease, hypophosphatemic rickets …). A second focus is to investigate the mechanisms involved in negative outcomes associated with FGF23 excess, including bone mineralization defects, cardiac hypertrophy and cognitive defects. Our team works in collaboration with the Center for Translational Metabolism and Health and the Division of Cardiology at Northwestern, and with multiple additional collaborators and partnerships around the world.
The Martin Lab is sponsored by the National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the Northwestern Women’s Health Research Institute.
Contact Dr. Martin at 312-503-4160 or the Martin Lab at 312-503-4805, or by email.
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 and biochemical analysis 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-clinical 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 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 has 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 312-503-6188 or the lab at 312-503-4119.
Clinical Research Coordinator
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.
Molecular machinery for histone modifications in yeast, Drosophila and human cells
Chromosomal rearrangements resulting in alterations of gene expression are a major cause of hematological malignancies. Our goal is to advance the understanding of the biochemical and molecular mechanisms of rearrangement-based leukemia and to provide insights into how translocations affect cellular division by altering gene expression. Using mammalian model systems such as tissue culture and mouse genetics, we plan to explore the regulation of gene expression via the MLL gene and its translocation partners found in human leukemia. We are currently defining the molecular composition of the MLL complexes and how translocations alter its biochemical function and integrity, resulting in leukemic pathogenesis. We are also planning to define the mechanism of the targeting of the MLL complex and its histone methyltransferase activity to chromatin to determine its normal cellular functions and its mistargeting and dysregulation in leukemogenesis.
One fusion partner of MLL in acute myelogenous leukemia (AML) is the ELL protein. We show that human ELL functions as a transcription elongation factor. We have identified the Drosophila homolog of ELL and demonstrate it to be essential for development. Drosophila ELL associates with elongating RNA polymerase II in vivo on chromosomes and is a regulator of the Notch signaling pathway. This has suggested to us that human ELL might also participate in the same process.
View Dr. Shilatifard's publications on PubMed.
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
The main focus of the Laboratory for Molecular Cancer Biology is to unravel the mechanistic link between aging and cancer with a focus on the regulatory role of post-translational modifications directed by sirtuins.
One of the fundamental observations in oncology is that increasing age is the strongest statistic variable that predicts for carcinogenesis. A fact that has emerged over the last several years is that aging is a complex process that appears to be regulated, at least in part, by several signaling protein families that have been identified in multiple species, including sirtuins, a relatively new gene family that was initially identified in S. cerevisiae and C. elegans. SIrtuins have been found to both increase life span and decrease spontaneous tumor development suggesting that they may regulate both processes. They appear to function as fidelity proteins and loss or decrease of function, which may occur during aging, creates a cell environment permissive for several age-related illnesses, including cancer. The significant role played by sirtuins can be explained by accumulating evidence establishing their pivotal role in regulating post-translational modifications (PTMs) in both histone and non-histone proteins involved in diverse cellular processes. Despite recent scientific interest in this field, there is still scarcity regarding the functional consequences of the role of these PTMs in cellular homeostasis. Our proposed studies take an integrative approach to current challenges in dissecting the functional role of sirtuin-directed PTMs in tumorigenesis which may bridge the gap between the observation that tumorigenesis increases with age and the limited information regarding the specific mechanisms underlying this phenomenon. By blending classic molecular/cellular biology, biochemistry and mouse genetics with large-scale proteomics, our ultimate research goal is to elucidate the function of sirtuins in maintaining cellular homeostasis which may provide novel mechanistic insights in different aspects of tumorigenesis.
See Dr. Vassilopoulos’ publications in Pubmed.
Contact Vassilopoulos Lab
You may contact the lab through the lab website: www.vassilopouloslab.com. Also, you may contact Dr. Athanassios Vassilopoulos directly at 312-503-0727 or via firstname.lastname@example.org.
Mohamed Ahmed, PhD
Yang Guo, MD, PhD
Mingming Zhang, PhD
Yijun Fan, BSc
Michael Bofu Li
Defining the molecular mechanisms of breast tumor initiation, progression, and metastasis, and identifying novel targets for therapeutic development.
Posttranslational modifications such as ubiquitination, methylation, ADP-ribosylation as well as phosphorylation orchestrate genome stability, cell division, hormone-initiated signal transduction, apoptosis and tumorigenesis. Posttranslational modifications act as critical molecular switches or fine-tune operators that determine the activation, deactivation or subcellular localization of functional proteins. Emerging evidence has drawn attention to the modulation of regulatory proteins in response to extrinsic/intrinsic signaling being executed simultaneously by multiple posttranslational modifications. Research interests in my laboratory seek to address how defects in the ubiquitin-proteasome system (E3 ligase/deubiquitinase), protein methyltransferase and poly (ADP-ribose) polymerase 1 (PARP1) would result in genomic instability, abnormal cell cycle or apoptosis, and aberrant signal transductions (e.g., ER, TGF-β, EGFR and Hippo) that predispose otherwise normal cells to become cancerous tumor cells. The ultimate objective is to integrate our basic research with clinical translational studies that would allow the development of new anti-cancer therapy thereby fully exploiting our knowledge of posttranslational modifications. To achieve our goals, we have developed a multidisciplinary approach that includes biochemical, cell biological, genetic, protein structural analyses as well as the use of animal models and analyses of clinical specimens.
- Regulation of XIAP Turnover Reveals a Role for USP11 in Promotion of Tumorigenesis.
- Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis.
- Regulation of KLF4 turnover reveals an unexpected tissue-specific role of pVHL in tumorigenesis.
- Posttranslational Modifications in Genome Stability, Carcinogenesis and Cancer Treatment
- Posttranslational Modifications in Oncogenic Signaling Network and Tumor Initiation/Invasion
- Posttranslational Modifications in Mitotic Regulation, Apoptosis and Tumorigenesis
See Dr. Wan's publications on PubMed.
Contact Dr. Wan at 312-503-2769.
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.
Contact Dr. Yu at 312-503-2980 or the Yu Lab at 312-503-3041.
Will Ka-Wing Fong
Research Assistant Professor
Jonathan Zhao, MD, MS
Research Associate Professor
Nathan Damaschke, PhD
Yongik Lee, PhD
Xiaodong Lu, PhD
Gang Zhen, PhD
Xiaoyan Zhu, PhD
Genetics and epigenetics of complex traits including risks for common diseases and drug response
For more information, visit Dr. Zhang's Faculty Profile page.