Computational Genomics

Research Description

Precision oncology facilitates individualized treatment decisions on the basis of patient and tumor specific factors for an increasing proportion of cancer patients. Despite growing evidence that inter-patient variation affects treatment responses after radiotherapy, patients receiving these treatments continue to be treated with the same or similar doses. We seek to develop an information capability at the forefront of personalized radiotherapy treatments. We achieve this through the assembly of experimental scaffolds that span the translational research spectrum and help us understand tumor complexity and predict clinical outcomes.

Briefly, we conduct large-scale projects that capture the diversity of our patients and provide a rich substrate for computational and mathematical models of cancer’s propensity to resist our treatments. Three large-scale projects have been completed or are currently in progress including: 1) The X-ray Target Discovery and Development (XTD²) project, which profiled 533 cancer cell line survival  comprising 26 cancer types to ionizing radiation. This project represented the largest profiling effort of cancer cell line survival after irradiation ever conducted. 2) The Pan-cancer Radiogenomic Atlas is a gene variant profiling project that interrogated >1000 common and rare genetic variants for response to ionizing radiation in immortalized human cells (non-cancer cells). Current work is building on the unary profiling methodology to study the interaction between varied gene variants, thus building toward greater complexity. 3) The 10,000 Avatar Project was inaugurated by our group in 2019. This will be the largest patient-derived xenograft (PDX) mouse experiment conducted to date by any group. ~10,000 mice engrafted with ~500 genetically annotated PDXs will be irradiated using a singular experimental platform. This work will correlate genetic and other omic (e.g. transcriptomic, metabolomic, et cetera) alterations with the likelihood of response to radiotherapy and matched recurrent tumors.

Concurrent with the large-scale biological profiling approaches described above, we have developed a clinomic dataset that integrates clinical information (e.g. demographics, treatments, outcomes) and patient avatar models (patient-derived xenografts) with omic outputs for individual patients. The latter include radiomics (embedded quantitative data derived from imaging modalities like computed tomography), genomics (genetic information derived from the patient’s tumor or germline), transcriptomics (gene expression), and others. Using this information, we seek to design and implement tools that can augment the physician’s ability to estimate the probability of treatment failures and modulate failure by individualized treatment recommendations.

For lab information and more, see Mohamed Abazeed's, MD,PhD, faculty profile.

Publications

See Dr. Abazeed's publications in PubMed.

Contact

Contact the Abazeed Lab at 312-503-2195. You may also contact Dr. Abazeed directly via email.

Post-doctoral Fellows

Priyanka Gopal, Rohan Bareja

Students

Alexandru Buhimschi

Technical Staff

Titas Bera, Dylan Schellenberg, Trung Hoang

Research Description

I am interested in understanding the key drivers of cancer and identifying novel therapeutic drug combinations to prevent cancer development and chemotherapy resistance. To achieve these goals, our lab is using and developing genomic and epigenomic mapping, editing and imaging approach to understand genome regulation in normal and malignant settings. We integrate experimental approaches with large-scale computational data analysis to verify our experimental observations and come up with new testable hypotheses.  Our laboratory is utilizing and also developing cutting-edge functional genomics strategies and developing novel CRISPR based manipulation tools to understand dynamic gene regulation and 3D genome organization in normal and malignant settings. These efforts are based on our previous expertise in genome-wide approaches and development of novel technologies for cancer research. Our lab has developed particular expertise in utilizing and developing CRISPR based technologies.

For more information, see Dr. Adli's faculty profile or the Adli lab website.

Publications

See Dr. Adli's publications in PubMed.

 

Contact Us

Dr. Adli

Research Description

Translation is the mechanism by which proteins are made from the information stored in the genetic code. This process is achieved with the help of RNA molecules such as ribosomal RNA (rRNA), transfer RNA (tRNA) and messenger RNA (mRNA). While translation is a tightly regulated process, global perturbations in protein synthesis are observed in stress conditions, cancer and aging, highlighting the regulatory mechanisms of translation as potential targets in cancer and age-related disorders. One poorly characterized layer of translation regulation is the epitranscriptome, defined as the set of more than 140 ribonucleotide modifications that alter the biochemical properties and function of all classes of RNA, including rRNA, tRNA and mRNA. While the distribution and function for most ribonucleotide modifications are undefined, the enzymes responsible for depositing RNA modifications are dynamic and sensitive to metabolic alterations, potentially regulating the temporal response to stress or the onset of human diseases such as cancer.

Our group investigates the mechanisms by which RNA modifications regulate protein synthesis and how these mechanisms affect cell fate decisions such as cell proliferation, survival and differentiation in cancer and stress conditions. By integrating RNA biology, transcriptomics and cell biology, we aim to uncover novel mechanisms of gene expression regulation and generate new tools that can be harnessed to develop anti-cancer therapies.

For more information, see Dr. Arango's faculty profile and laboratory website.

Current Projects

• Mechanisms and regulation of RNA acetylation in cancer cells
• Regulation of stress response by RNA modifications
• Targeting RNA-modifying enzymes and RNA modifications for therapeutic purposes

Publications

See Dr. Arango's publications.

Contact

Contact Dr. Arango at 312-503-0732.

Lab Staff

Postdoctoral Fellow

Sweta Raikundalia

Graduate Student

Kevin Vasquez

Undergraduate Student

Adam Suh

Research Description

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.

For more information, visit the faculty profile of Daniel Brat, MD, PhD or the Brat Lab website.

Publications

See Dr. Brat's publications in PubMed.

Contact

Email Dr. Brat

Research Description

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.

Current Projects

• 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

For more information, see Dr. Carvill's faculty profile or the Carvill Lab Website.

Publications

Please see Dr. Caraveo Piso's publications on PubMed.

Contact Information

Gemma L. Carvill, PhD

Twitter: @CarvillLab

Research Description

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.

For lab information and more, see Dr. Chisholm's faculty profile.

Publications

See Dr. Chisholm's publications on PubMed.

Contact

Contact Dr. Chisholm at 312-503-3209.

Research Description

We employ cutting-edge genomics approaches to identify the genetic basis of inherited and acquired immunological disorders and skin cancer.

As an example, we have recently identified the genes and mutations underlying cutaneous T cell lymphoma, an incurable non-Hodgkin lymphoma of skin-homing T cells. The genes are components of the DNA damage, chromatin modifying, NF-kB and the T cell receptor signaling pathways. We are currently employing a comprehensive approach using human tissues and animal models to investigate the functions of these genes. We are confident these studies will allow us to elucidate the pathophysiology of this cancer and lead to the identification of novel therapeutic targets.

Work in the lab is funded by National Cancer Institute, Dermatology Foundation, American Skin Association and American Cancer Society. For further information, please also see Dr. Choi's faculty profile.

Publications

See Dr. Choi's publications on PubMed.

Contact

Contact Dr. Choi.

Our research develops computational approaches to analyze data generated in the pathology lab. Our goal is to improve diagnostics, to advance clinical translation of computational pathology research, and to provide investigators with tools to generate new insights from complex data. To accomplish these goals we focus on:

1. Fundamental research in machine-learning and artificial intelligence
2. Development of software infrastructure for computational pathology
3. Generating annotated datasets for training and validation of computational pathology algorithms

We apply these techniques to a number of problems including:

1. Measuring immune response in cancer and development of immuno-oncology biomarkers
2. Prediction of clinical outcomes from genomic and digital pathology data
3. Classification of hematologic malignancies

My research program centers on uncovering mechanisms underlying neuropsychiatric manifestations of systemic lupus erythematosus (SLE) via basic and translational methodology. SLE is a chronic and multi-systemic autoimmune disease plaguing 1.5 million Americans. Among the many organ systems affected, symptoms associated with the nervous system (NP-SLE) may appear in up to 90% of SLE patients depending on the attribution model and be among the earliest signs of SLE. NP-SLE can manifest in seizures, strokes, movement disorders, mood disorder, anxiety disorder, acute confusional state, psychosis, acute encephalopathy and/or chronic neurocognitive dysfunction. Despite the devastating impact of NP-SLE on health-related quality-of-life, our understanding of causal mechanisms is limited.

 Microglia, the resident innate immune cell of the brain, have recently been implicated in NP-SLE. Studies show histological evidence of microglia activation in NP-SLE patients and mouse models of disease. Microglia display regional, functional, and disease-associated heterogeneity; in particular, a disease-associated microglia (DAM) subset was recently identified in Alzheimer’s disease and aging. DAM co-localize with amyloid-b plaques, are enriched for genes involved in lysosomal, lipid metabolism and phagocytic pathways and may play a protective role in the early stages of AD by reducing amyloid-b plaque burden. However, very few studies have examined microglial heterogeneity or contributions to NP-SLE. Our group is the first to show that expression of a shared NP-SLE transcriptional signature and DAM-associated genes correlates with the severity of hippocampal- and cerebellar-associated behavioral deficits in microglia isolated from two NP-SLE models prior to overt systemic disease. Further, our single-cell RNA-sequencing (scRNA-seq) data identify DAM NP-SLE-prone mice. However, DAM in NP-SLE are enriched for genes associated with antigen presentation but depleted for genes associated with phagocytosis, which is in contrast to DAM in AD that are critical for amyloid-b plaque-associated phagocytic functions. We also find that restricted expression of the DAM transcriptional program in NP-SLE DAM corresponds to improved behavioral outcomes in NP-SLE-prone mice following treatment with fingolimod, a sphingosine-1-phosphate receptor modulator that reduces microglia activation and improves blood brain barrier integrity. These discoveries mark the first to implicate DAM as a potentially pathogenic microglia subset in NP-SLE, which is in contrast to their proposed protective role in early AD development.

 We also find that increasing numbers of macrophages in the brain correlates with worsening severity of behavioral deficits early in life and an expanded brain macrophage subset in end-stage disease via scRNA-seq analysis that is detectable at two months of age. Since a worse prognosis is suggested when NP-SLE accompanies lupus nephritis and infiltrating macrophages contribute to organ-specific SLE pathogenesis, we hypothesize that macrophage-specific mechanisms underlying systemic disease are conserved in kidney and brain and detectable in circulating monocytes prior to extravasation into the affected end-organ.

 Further, we are translating our findings to human disease by evaluating cerebrospinal fluid (CSF)-resident microglia-like cells and macrophages as well as circulating monocyte subsets from NP-SLE patients via scRNA-seq to interrogate the penetrance of causative mechanisms. Thus, we are interrogating microglial and macrophage heterogeneity to dissect cell subset-specific contributions to disease with the ultimate goal of identifying critical populations and/or pathways that may serve to improve diagnostic and/or therapeutic strategies in NP-SLE.

Publications

View lab publications via PubMed.

For more information, visit the faculty profile page of Carla Cuda, PhD.

Contact Us

Email Dr. Cuda

 

Research Description

My research lab focuses on translational, basic science projects that aim to identify the critical driving factors in the vascular pathology in diabetic retinopathy (DR). We have a special focus the pathogenesis of fibrovascular transition in DR, which is a devastating clinical stage. Very little is currently known about the drivers of fibrovascular pathology in the ischemic retina, which is a vision threatening end stage of many ischemic retinopathies.

We are taking a systems biology approach to this problem. While most researchers have focused on one isolated compartment, either the retinal neurons, glia or vessels, our approach takes all these players into account in order to construct a wholistic view of the ischemic retina and diabetic retinopathy. Using single- and bulk RNA seq, we have collected a large dataset from mouse and human diabetic tissue. We are looking for candidates who are interested in studying this disease in depth and who have an interest in bio-informatics, RNA-Seq and neurovascular interactions.

For more information, visit the faculty profile for Amani A. Fawzi, MD or the Fawzi lab website.

Publications

See Dr. Fawzi's publications on PubMed.

Contact

Dr. Fawzi

Research Description

Dr. Ruli Gao's laboratory at Northwestern University Feinberg School of Medicine harbors both single cell sequencing technologies and computational methodologies under one roof.  Dr. Ruli Gao has significant contribution in tumor evolution fields by developing and applying single cell sequencing technologies and bioinformatic algorithms (Nature Genetics, 2016; Cell, 2018; Nature Communications, 2017; Nature Biotechnology, 2021).  The ongoing research projects in Gao Lab include: 1) Construction of single cell mosaic mutation atlas of human organs by developing novel computational methods for analyzing large scale human cell atlas datasets, 2) Delineating cellular mechanism of chronic heart transplant failure by developing novel single cell third generation sequencing technologies to dissect the donor and host cell identities and their contributions to transplanted heart failure, 3) Tracking tumor evolution and neovascular adaption of brain metastatic tumors by applying novel single cell DNA and RNA sequencing technologies to deconvolute tumor evolution and dissect the ecological systems of human brain, and 4) Developing human tumor cell atlas of rare cancer types using high throughput single cell sequencing methods to analyze tumor and immune cell populations.

 

For more information, please see Dr. Gao's faculty profile.

Publications

See Dr. Gao's publications in PubMed.

Contact

Contact Dr. Gao at 312-503-3796.

 

Research Description

The Gate lab in Northwestern Neurology works at the interface of the immune system and neurodegenerative disease. The lab is focused on employing human genomics approaches to uncover novel biomarkers and therapeutic targets for neurodegeneration. Chief among our strategies is single cell RNA sequencing (scRNAseq) to identify transcriptional changes in human specimens. We also employ spatial transcriptomics, immunohistochemistry and cytometry approaches to validate genomic changes observed by scRNAseq. The Gate lab is focused primarily on neurodegenerative diseases of aging, including, but not limited to: Alzheimer’s disease, Parkinson’s disease and Amyotropic lateral sclerosis.

For lab information and more, see Dr. Gate's faculty profile.

Publications

See Dr. Gate's publications on PubMed.

Contact

Email David Gate, PhD 

Twitter: @DGateLab

 

Research Description

Dr. Gershon is a leading expert in the application of Item Response Theory (IRT) in individualized and large scale assessments. He has developed item banks and Computerized Adaptive Testing (CAT) for educational, clinical, and health applications - including cognitive, emotional, and motor applications. He is currently principal investigator on these projects with the NIH: NIH Toolbox for the Assessment of Neurological Function and Behavior, the NIH Roadmap Patient – Reporting Outcomes Measurement Information System (PROMIS) Technical Center, the National Institutes on Aging Genetic Norming project, and the National Children's Study: Vanguard Study(South ROC). He is also co-investigator and measurement development expert on numerous smaller projects including the NINDS sponsored project “Quality of Life Outcomes in Neurological Disorders” (Neuro-QOL), and the cancer-specific supplement to PROMIS.

For more information visit the faculty profile of Rich Gershon, PhD.

Publications

See Dr. Gershon's publications in PubMed.

Contact

Dr. Gershon

Research Description

For lab information and more, see Jeffrey Goldstein, MD,PhD, faculty profile.

Publications

See Dr. Goldstein's publications

Contact

Email Dr. Goldstein

 

Research Description

We are interested in understanding the control principles governing biological processes at various scales, from tissue morphogenesis in development to cell-fate decisions in single cells. In particular, individual cells within a genetically identical population constantly undergo fluctuations in their molecular state which may enable them to adopt new fates in response to stimuli. As opposed to hardwired responses encoded in the genome, this dynamic ability of cells to react, either alone or in concert with each other, to external and internal cues is broadly referred to as “plasticity”. Leveraging our unique interdisciplinary approach, we combine novel frameworks, both experimental (e.g. single-cell profiling, spatiotemporally-resolved lineage tracing, multiplexed single-molecule RNA imaging, optogenetics) and computational (stochastic modeling, statistical analysis of large datasets), to track and control state-to-fate mappings in the context of animal development and cancer progression. Working across multiple mammalian model systems (cell lines, developmental and tumor organoids, mouse models), we will ask how diverse non-genetic variabilities drive fate choices and self-organization in development and disease.

To learn more about specific projects, please visit our Lab Website.

 

Publications

See the Goyal Lab’s publications on the Goyal Lab Website.

Contact

Dr. Goyal.

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.  

Publications

See Dr. Green's publications in PubMed.

For more information, please see Dr. Green's faculty profile.

Contact

Contact Dr. Green at 312-503-1812 or the Green Lab at 312-503-0089

Research Description

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.

For lab information and more, see Dr. Hauser's faculty profile and lab website.

Publications

See Dr. Hauser's publications on PubMed.

Contact

Contact Dr. Hauser at 312-503-1044 or the lab at 312-503-1081.

Lab Staff

Postdoctoral Fellows

Kelly Bachta, Travis Kochan, Sumitra Mitra, Timothy Turner

Graduate Students

Bettina Cheung, Marine Lebrun Corbin, Nathan Pincus

Lab Manager

Shradha Rao

Technical Staff

Sophia Nozick

Research Description

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.

Publications

See Dr. Hou's publications in PubMed.

Contact

Dr. Hou

Research Description

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.

Current Projects

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.

Publications

See Dr. Ji's publications on PubMed.

Contact

Contact Dr. Ji at 312-503-2187.

Lab Staff

Postdoctoral Fellows

Qianru Li

Graduate Students

Emily Stroup, Sheng Wang

Research Description

For more information, visit the Faculty Profile of Jennie Lin or visit the Lin Lab Website

Publications

See Dr. Lin's publications in PubMed.

Contact

Email Dr. Lin

Phone 312-503-1892

Research Description

As a researcher in the Division of Infectious Diseases in Northwestern University, my work combines virology and evolutionary biology to study viral evolution and the interaction between viruses and the host during infection. My main interests are RNA viruses, molecular evolution, and genomics. The ultimate goal of my research is to understand the virus-host system and its evolutionary properties in order to develop the best treatments and prevention strategies for human viral infections. During my career, I have led published studies on the evolution of HIV-1 and contributed greatly to the field of RNA virus host-virus genetics. I utilize state-of-the-art sequencing technologies and a combination of evolutionary biology, bioinformatics, statistical modeling, complex data analysis, and phylogenetics to answer fundamental questions about viral population dynamics and viral interaction with the host. My lab has adapted and developed viral deep sequencing pipelines and host genomics techniques, including bulk and single cell transcriptomics, as well as innovative spatial transcriptomics pipelines, to study the virus-host system. I am the director of bioinformatics of the Northwestern University Center for Pathogen Genomics and Microbial Evolution (CPGME) and a faculty member of Northwestern’s Institute of Global Health, the Third Coast Center for AIDS Research (TC CFAR), and the Buehler Center for Health Policy and Economics.

My research projects expand from clinically relevant studies that examine viral infection dynamics at the human population level both in national and global health settings, to studies that intend to comprehend viral reservoirs, with special focus on the HIV-1 cure field, as well as intra-host viral evolution and virus-host interaction.

For lab information and more, see Dr. Lorenzo-Redondo's faculty profile.

Publications

See Dr. Lorenzo-Redondo's publications on PubMed.

Contact

Contact Dr. Lorenzo-Redondo 

 

Research Description

For more information visit Dr. Luo's faculty profile page

Contact

Email Dr. Luo

Phone 312-908-7914

Postdoctoral fellow jobs and graduate student rotation projects are available.

Research Description

Spinal 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.

For more information visit Dr. Ma's faculty profile and Dr. Ma's lab website within the Children's Hospital Research Center.

Publications

View Dr. Ma's publications at PubMed

Contact

Email Dr. Ma

Phone 773-755-6339

Lab Staff

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

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.

Publications

For more information view Dr. Martin's Faculty Profile or  view publications by PubMed

Contact Us

Contact Dr. Martin at 312-503-4160 or the Martin Lab at 312-503-4805, or by email.

Research Description

My laboratory studies genetic mechanisms responsible for inherited human diseases including heart failure, cardiomyopathy, muscular dystrophy, arrhythmias, aortic aneurysms. Working with individuals and families, we are defining the genetic mutations that cause these disorders. By establishing models for these disorders, we can now begin to develop and test new therapies, including genetic correction and gene editing.

For lab information and more, see Dr. McNally's faculty profile or visit the McNally Laboratory site.

Publications

See Dr. McNally's publications on PubMed.

Contact

Email Dr. McNally

Phone  312-503-5600

Research Description

The Meeks lab is investigating the epigenetics and genetic mutations associated with cancer biology. Specifically, he is studying how chromatin remodeling genes play a role in bladder cancer. In addition, he is investigating the “driver mutations found in bladder cancer. In the future, he hopes to develop novel systemic and intravesical therapies to improve survival of patients with bladder cancer.

In the United States, there are an estimated 72,570 new cases of bladder cancer each year. Dr. Meeks is conducting innovative research to increase our understanding of the biology of bladder cancer and to identify new therapies and technologies for bladder cancer in order to improve quality of life for our patients. In this podcast, Joshua Meeks, MD, PhD, shares how his team of scientists are involved in three active trials focused on genetic and epigenetic changes in bladder cancer, as well as immuno-oncology in bladder cancer. Listen here >>

Dr. Meeks is investigating the gender disparities in bladder cancer by dissecting the tumor and immune mechanisms of resistance to chemotherapy and immunotherapy. This research may translate into novel pathways and potential therapeutic targets to improve outcomes and reduce gender disparities in bladder cancer. In this video, Meeks shares details about his work. Watch here >>

Select Publications

Meghani K, Cooley LF, Choy B, Kocherginsky M, Swaminathan S, Munir SS, Svatek RS, Kuzel T, Meeks JJ. First-in-human Intravesical Delivery of Pembrolizumab Identifies Immune Activation in Bladder Cancer Unresponsive to Bacillus Calmette-Guérin. Eur Urol. 2022 Aug 22:S0302-2838(22)02553-2. 

Cooley LF, Glaser AP, Meeks JJ. Mutation signatures to Pan-Cancer Atlas: Investigation of the genomic landscape of muscle-invasive bladder cancer. Urol Oncol. 2022 Jul;40(7):279-286.

Folgosa Cooley L, Weiner AB, Meng X, Woldu SL, Meeks JJ, Lotan Y. Survival by T Stage for Patients with Localized Bladder Cancer: Implications for Future Screening Trials. Bladder Cancer. 2021 Jan; 7(1): 23-31.

Meeks JJ, Robertson AG. Immune Signatures Dominate Molecular Subtyping to Predict Response to Neoadjuvant Immunotherapy. European Urology. June 2020.

Robertson AG, Groeneveld CS, Jordan B, Lin X, McLaughlin KA, Das A, Fall LA, Fantini D, Taxter TJ, Mogil LS, Lindskrog SV, Dyrskjøt L, McConkey DJ, Svatek RS, de Reyniès A, Castro MAA, Meeks JJ. Identification of Differential Tumor Subtypes of T1 Bladder Cancer. European Urology. January 2020.

Fantini D, Glaser AP, Rimar KJ, Wang Y, Schipma M, Varghese N, Rademaker A, Behdad A, Yellapa A, Yu Y, Sze CC, Wang L, Zhao Z, Crawford SE, Hu D, Licht JD, Collings CK, Bartom E, Theodorescu D, Shilatifard A, Meeks JJ. A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer. Oncogene. April 2018.

Refer to PubMed for a full list of publications. 

For more information visit Meeks Lab

Research Description

The cellular stress response systems guard the proteome from diverse endogenous and environmental insults to maintain the fitness of the organism. Ironically, this pro-survival system can act to the detriment of the host to enable tumor cells accommodate to the myriad stresses associated with malignancy. Our long-term goals are to identify and characterize the systems that promote protein homeostasis, understand how these systems are co-opted and perturbed in malignancy, and ultimately identify means to manipulate them for therapeutic benefit. To accomplish these goals our group bridges biochemical, genetic and chemical biology approaches with systematic high-throughput and genomic methods.

For lab information, publications and more, see Dr. Mendillo’s faculty profile.

Publications

View Dr. Mendillo's publications at PubMed

Contact

Email Dr. Mendillo

Phone 312-503-5685

Research Description

David C. Mohr, PhD, is the Director of the Northwestern University Center for Behavioral Intervention Technologies (CBITs).   Dr. Mohr’s expertise is in the design, development, evaluation, and implementation of technology-assisted behavioral and psychological interventions. These technologies use mobile phones, tablets, computers, and sensors to support patient behaviors related to health, mental health, and wellness.  In the area of development, Dr. Mohr’s primary expertise is in designing applications that can be deployed to phones and desktop computers aimed at treating mental health disorders. While many of these have been relatively standard applications, he is also developing methods of harnessing sensor data from the phone to identify user states that are relevant to the treatment of depression.  A second area of development focuses on developing applications aimed at improving adherence to medications and medical regimens. These applications are being deployed in General Internal Medicine, Community Health Centers, and Psychiatry.  Finally, Dr. Mohr examines methods of implementing behavioral intervention technologies in the healthcare settings.  In general, behavioral intervention technologies are not effective in improving symptoms when delivered as standalone treatments. Dr. Mohr has developed and evaluated methods of providing low intensity coaching support to enhance the use and effectiveness of behavioral intervention technologies. These coaching models can use health professionals, lay people, and  peers. 

He is also interested in the relationship between stress, depression and inflammation, particularly in multiple sclerosis.

For more information visit the faculty profile of David Mohr, PhD.

Publications

See Dr. Mohr's publications in PubMed.

Contact

Dr. Mohr

Research Description

Intensive monitoring is a core function of an intensive care unit, and generates large amounts of data. In a neurologic unit, surveillance neuromonitoring is as important as vital signs and cardiac rhythm, yet there has been less clarity as to precisely what should be measured (biomarkers, imaging markers, serial examination scores) and its impact on complications and outcomes. We have established methods and models for the retrieval and analysis of data from the electronic health record for patients with stroke for a large registry that I have maintained over 10 years (Northwestern University Brain Attack Registry, NUBAR), which now includes >1,000 patients.

Research to improve patient outcomes is limited to endpoints we can reliably measure. Collaborating with Neuro-QOL, a platform for measuring Quality Of Life in neurological disorders, and the NIH Patient Reported Outcomes Measurement Information System (PROMIS) Statistical Center, we have shown web-based computer-adaptive testing by study staff, patients or family members are valid compared to the usual standard of a validated interview, have increased statistical power, and highlight aspects of HRQoL, such as cognitive function, that would otherwise be undetectable (supported by K23 HS023437). Further, these measures improve our statistical power to perform research that measurably improves patient-centered outcomes.

In a continuing project with Preventive Medicine faculty, we are using network analytic techniques to identify high-performing teams. Previous publications have established methods to identify which members of the health care team (e.g., physicians, pharmacists, nurses) interacted with the patient in the electronic health record. Then, a quantitative measure of the success of interactions is calculated on an outcome. In past research, likelihood to recommend scores were the outcome. Here, we used NUBAR’s recorded functional outcomes (e.g., independence, dependence, death), and established that the interactions of team members are an independent predictor of patient outcome after accounting for severity of injury. This research opens up new lines of research on how to design high-performing teams.

In short, the lab collaborates widely to leverage innovative techniques to improve treatments for patients with life-threatening neurologic injury.

Contact Information

Andrew Naidech, MD, MSPH, FANA

Professor of Neurology

Research Description

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 Dr. Ntziachristos's faculty profile and lab website.

Publications

See Dr. Ntziachristos's publications at PubMed.

Contact

Contact Dr. Ntziachristos at 312-503-5225 or Searle 6-523

Research Description

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.

For more information see the faculty profile of Pembe Hande Ozdinler, PhD or the Ozdinler Lab website.

Visit the Les Turner ALS Center

Publications

View Dr. Ozdinler's full list of publications at PubMed.

Contact

Email Hande Ozdinler, PhD 

Phone: 312-503-2774

Twitter: @DrOzdinler

Research Description

The Peek Lab is focused on understanding the interplay between hypoxic and circadian transcriptional pathways both at the genomic and nutrient signaling levels. Peek aims to uncover novel mechanisms linking circadian clocks to the control of metabolic function and disease, such as type 2 diabetes and cancer. The lab utilizes metabolic flux analyses, in vivo metabolic and behavior monitoring, and next-generation sequencing in their research.

For lab information and more, see Dr. Peek's faculty profile and lab website.

Publications

See Dr. Peek's publications on PubMed.

Contact

Contact Dr. Peek at 312-503-6973.

Lab Staff

Graduate Student

Kaitlyn Hung

Technical Staff

Adam Steffeck, Abhishek Thakkar

Research Description

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.

Recent Findings

• 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.
• 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.

Current Projects

• 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.
• eMERGE
  We are involved in analyzing the GWAS and sequencing data specifically for genomics variation affect key pharmacogenomics gene in African Americans.

For lab information and more, see Dr. Perera's faculty profile and lab website.

Publications

See Dr. Perera's publications on PubMed.

Contact

Contact Dr. Perera at 312-503-6188 or the lab at 312-503-4119.

Lab Staff

Lab Manager

Cristina Alarcon

Bioinformatics Analyst

Mrinal Mishra 

Postdoctoral Fellow

Guang Yang

Graduate Student

Carolina Clark

Dr. Schwulst is an Assistant Professor of Surgery and attending Trauma and Critical Care Surgeon at Northwestern University and Northwestern Memorial Hospital. His primary research interests are in traumatic brain injury and post-injury immune dysfunction.  To date, his research has centered on three facets of TBI and immune dysfunction: the role of constitutive microglial activation in the etiology and evolution of chronic neurodegeneration after TBI (the focus of his current R01 award); the role of macrophage heterogeneity in the direction of TBI-induced immune dysfunction (the focus of his prior NIH K08 award); and understanding common molecular pathways between TBI-associated neurodegeneration and chronic neurodegenerative diseases such as Alzheimer’s Disease (the focus of an upcoming  NIH R21).

 

Research Description

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.

Publications

See Dr. Seifert's publications on PubMed.

Contact

Contact Dr. Seifert at 312-503-9788 or the lab at 312-503-9786.

Lab Staff

Research Faculty

Elizabeth Stohl 

Postdoctoral Fellows

Linda I-Lin Hu, Jayaram Narayana, Ella Rotman

Graduate Students

Wendy Geslewitz

Technical Staff

Hannah Landstrom, Brian Sands, Shaohui Yin 

Research Description

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.

For lab information and more, see Dr. Shilatifard's faculty profile or visit the Shilatifard Laboratory site.

Publications

View Dr. Shilatifard's publications on PubMed.

Contact

Email Dr. Shilatifard

Phone 312-503-5223

Research Description

My laboratory conducts research on behavioral risk factors (obesity, poor quality diet, physical inactivity, tobacco use). We also develop cutting-edge technologies that support self-regulation and healthy behavior change. Finally, we create on-line learning tools to support skill mastery in evidence-based practice and team science.

For more information, visit the faculty profile of Bonnie Spring, PhD.

Publications

View Dr. Spring's publications at PubMed.

Contact

Email Dr. Spring

Phone 312-908-2293

Research Description

The goal of Dr. Stranger's research is to understand how genetic and genomic variation contributes to complex disease, and how that varies by sex. Her cancer research is motivated by the observation that nearly all common cancers exhibit some form of sexual dimorphism, for example in incidence, prognosis, tumor aggressiveness, or response to treatment. This dimorphism has been hypothesized to derive from differences between males and females in hormones, sex chromosomes, and environmental exposures; however the molecular basis of these disparities remains largely uninvestigated. Dr. Stranger's research group is investigating the molecular basis of sexual dimorphism within and across cancers by leveraging their expertise in statistical genetics and genomics to examine sexual dimorphism at the molecular systems genomics level in tumors, in the contribution of germline genetic variation to cancer risk, and in the genetic and genomic mechanisms contributing to sexual dimorphism in response to therapeutics. An understanding of this dimorphism is fundamental to precision medicine initiatives in cancer, and may lead to discovery of novel biomarkers, therapeutic targets, and improved outcomes. Thus the ultimate goal of her research is to translate this new knowledge into cancer healthcare.

For lab information and more, see Dr. Stranger's faculty profile.

Publications

See Dr. Stranger's publications on PubMed.

Contact

Contact Dr. Stranger at 312-503-2675.

Lab Staff

Postdoctoral Fellow

Banabithi Bose

Research Description

Dr. Walunas’s primary research interest is the development and application of novel informatics methods to understand the mechanisms of autoimmune disease. This includes EHR-based phenotyping methods to identify autoimmune disease pathways, identification of environmental, social and behavioral determinants of health in medical records, and use of EHRs to track and improve health outcomes for patients with autoimmune disease.

For more information, visit Dr. Walunas's faculty profile page.

Publications

View Dr. Walunas's program publications at PubMed.

Contact

Dr. Walunas Lab: 312-503-3397

Center for Health Information Partnerships: 312-503-8019

Program Staff

Meghan Gelecke
Program Assistant
312-503-8019

Research Description

The Eisenbarth-Williams lab focuses on defining the cellular and molecular mechanisms that regulate adaptive immunity and antibody responses. The development of these responses relies on the interactions between three immune cells – dendritic cells (DCs), T cells and B cells. In addition, epithelial cells of the lung and intestine are important players in coordinating the immune system. We study how these three cell immune types and epithelial cells communicate to shape different types of immune responses, some protective in the case of vaccination and some harmful in the case of allergy and alloimmunization. By utilizing human samples to guide our studies and mouse models to test new mechanistic paradigms, we have identified novel and unexpected cell subsets and molecular functions. The fundamental principles governing the interaction between DCs, T cells, B cells and the epithelial are the same across these seemingly disparate responses, yet specialization in the subset of each cell type, the specific niche for the interaction and the cellular signals exchanged between the cells dictates what type of immune response is generated. This knowledge can be harnessed to induce protective immune responses and subvert pathogenic ones.

For more information, visit the faculty profile of Dr. Williams.

Publications

View Dr. Williams publications at PubMed

Contact Us

Contact Dr. Williams.

Research Description

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.

Publications

View Dr. Winter's publications at PubMed

Contact Us

Contact Dr. Winter at  312-503-0535 or by email.

Research Description

The Yang laboratory is interested in the integrative analysis of large-scale, multi-dimensional genomic data to understand the initiation and progression of diseases. The research projects involve in the development of highly accurate and sensitive computational methods for analyzing large-scale genomic data, especially in the area of detecting and analyzing genetic variations and somatic mutations using next generation sequencing data. Current work in the lab is to explore the functional consequences of somatic alterations in cancer patients, to identify driver alterations, and to understand the genetic mechanisms of cancer progression and drug resistance by integrating multi-dimensional data from large-scale cancer studies such as The Cancer Genome Atlas (TCGA). Example projects span from technique-driven research that aims developing algorithms for a wide range of applications to hypothesis-driven investigation of specific biological problems where the main goal is the discovery and advancement of biological knowledge.

For more information visit Dr. Yang's lab website: https://ylab-hi.github.io/

Publications

Wang TY, Liu Q, Ren Y, Alam SK, Wang L, Zhu Z, Hoeppner LH, Dehm SM, Cao Q, Yang R. A pan-cancer transcriptome analysis of exitron splicing identifies novel cancer driver genes and neoepitopes. Molecular Cell. May 2021.

Ting-You Wang, Rendong Yang. ScanITD: Detecting internal tandem duplication with robust variant allele frequency estimation. GigaScience, Volume 9, Issue 8. August 2020. 

Yingming Li, Rendong Yang, Christine M. Henzler, Yeung Ho, Courtney Passow, Benjamin Auch, Suzanne Carreira, Daniel Nava Rodrigues, Claudia Bertan, Tae Hyun Hwang, David A. Quigley, Ha X. Dang, Colm Morrissey, Michael Fraser, Stephen R. Plymate, Christopher A. Maher, Felix Y. Feng, Johann S. de Bono, Scott M. Dehm; Diverse AR Gene Rearrangements Mediate Resistance to Androgen Receptor Inhibitors in Metastatic Prostate Cancer. Clin Cancer Res 15 April 2020. 

Ting-You Wang, Li Wang, Sk Kayum Alam, Luke H Hoeppner, Rendong Yang. ScanNeo: identifying indel-derived neoantigens using RNA-Seq data. Bioinformatics, Volume 35, Issue 20, 15 October 2019, Pages 4159–4161. 

See Dr. Yang's publications on PubMed.

Contact

Contact Dr. Yang.

Research Description

Mammalian skin and its appendages function as the outermost barrier of the body to protect inner organs from environmental hazards and keep essential fluid within. Our research program studies mechanisms that govern cell fate specification, stem cell maintenance and aging as well as initiation and progression of cancer. We use single-cell genomics and computational tools, live animal imaging and genetically engineered mouse models to study gene expression regulation mediated by transcription factors, epigenetic regulators and post-transcriptional mechanisms mediated by miRNAs and RNA binding proteins at the single-cell resolution in mammalian skin. 

Our research aims to address several fundamental questions in stem cell biology: how the developmental potential of embryonic progenitors and adult tissue stem cells is transmitted or restricted in their progenies at the molecular level when they go through critical transitions such as cell fate specification, self-renewal of stem cells as well as stress response, and how these regulatory mechanisms go awry in aging and diseases. Answers to these questions will help to manipulate skin stem cells for regenerative medicine and discover new treatment for human skin diseases.​

View all lab publications via PubMed.

For more information, visit the faculty profile page of Rui Yi, PhD or visit the Yi Laboratory website.

Contact Us

Email Dr. Yi

 

 

 

Research Description

 

The long-term goal of Dr. Yue’s group is to use a combination of high throughput genomics, computational modeling, and functional assays to study how genetic variants contribute to the pathogenesis of human cancer. In particular, he is interested to identify the mutations that can disrupt the function of non-coding regulatory elements such as enhancers and further contribute to the pathogenesis of cancer. He has been actively involved with several large NIH-funded consortia, including the ENCODE Project, the 4D Nucleome consortium, and Impact of Genomic Variation on Function Consortium (IGVF).  

Select Publications: 

1. Xu J, Fan S, Lyu H, Kobayashi M, Zhang B., Zhao Z, Hou Y, Wang X, Luan Y, Jia B, Stasiak L, Wong JH, Wang Q, Jin Q, Jin Q, Fu Y, Yang H, Hardison RC, Dovat S, Platanias LC, Diao Y, Yang Y, Yamada T, Viny AD, Levine RL, Claxon D, Broach JR, Zheng H, and Yue F. (2022) Subtype-specific 3D genome alteration in acute myeloid leukaemia. Nature; 611(7935):387-398.  doi: 10.1038/s41586-022-05365-x. PMID: 36289338.    
2. Wang X, Xu J, Zhang B, Hou Y, Song F, Lyu H, Yue F. (2021) Genome-wide detection of enhancer-hijacking events from chromatin interaction data in rearranged genomes. Nature Methods 18, 661–668 (2021). PMID: 34092790; PMCID: PMC8191102.  
3. Yang H, Luan Y, Liu T, Lee HJ, Fang L, Wang Y, Wang X, Zhang B, Jin Q, Ang KC, Xing X, Wang J, Xu J, Song F, Sriranga I, Khunsriraksakul C, Salameh T, Li D, Choudhary MNK, Topczewski J, Wang K, Gerhard GS, Hardison RC, Wang T, Cheng KC, Yue F. (2020) A map of cis-regulatory elements and 3D genome structures in zebrafish. Nature;588(7837):337-343. doi: 10.1038/s41586-020-2962-9. PMID: 33239788; PMCID: PMC8183574.  
4. Dixon JR, Xu J, Dileep V, Zhan Y, Song F, et al., Noble WS, Dekker J, Gilbert DM, Yue F. (2018) Integrative Detection and Analysis of Structural Variation in Cancer Genomes. Nat Genet; 50(10):1388-1398. PubMed PMID: 30202056. PubMed Central PMCID: PMC6301019

For more information, please see Dr. Yue's faculty profile or the Yue lab website.

Publications

 See Dr. Yue's publications on PubMed.

Contact

Contact Dr. Yue at 312-503-8248.

 

 

Dr. Zhang is particularly interested in using high throughput technologies (e.g., microarray, next generation sequencing) and systems biology approaches to study the genetics of complex traits or phenotypes such as the risks of common diseases (e.g., cancer and lung disease), individual drug response and gene expression. Dr. Zhang is also interested in building bioinformatic databases that aim to provide user friendly access to primary data from pharmacogenomic and genome-wide association studies (GWAS). An on-going research interest of Dr. Zhang’s is the mapping of expression quantitative trait loci (eQTLs) in sarcoidosis and sickle cell disease, as well as the impact of eQTL mapping on the prioritization of GWAS results form these complex diseases.

For more information, visit Dr. Zhang's Faculty Profile page.

Contact

Email Dr. Zhang

Phone 312-503-1040