Basic Science Labs

Research Description

The Ben-Sahra lab seeks to identify novel connections between oncogenic and physiological signals and cellular metabolism. My previous studies revealed new connections between mTORC1 (mechanistic Target of Rapamycin Complex I) signaling and de novo nucleotide synthesis pathways.

Using isotopic tracing experiments and genetic approaches, my lab investigates whether the additional signaling pathways such as PI3K/Akt, RAF/Erk, Hippo/Yap or AMPK could regulate metabolic pathways that supply small metabolites to sustain nucleotide synthesis independently of mTORC1 signaling. Furthermore, we are also interested in understanding how cells can sense changes in nucleotide levels. In addition to nucleotide metabolism, we also study connections between signaling pathway and global cancer cell metabolism. I predict that there could be points of regulations which could give selective advantages to cancer cells to grow and proliferate. The initial discovery that cancer cells exhibit atypical metabolic characteristics can be traced to the pioneering work of Otto Warburg, over the first half of the twentieth century.

Deciphering the interplay between oncogenic processes and metabolic pathways that contribute to metabolic reprogramming in a given setting may serve as a critical factor in determining therapeutic targets that yield greatest drug efficacy with marginal harmful effect on normal cells. Our research will enable further progress in the exploitation of unusual metabolic features in cancer as a means of therapeutic intervention.

For lab information and more, see Dr. Ben-Sahra's faculty profile and lab website.

Publications

See Dr. Ben-Sahra's publications on PubMed.

Contact

Contact Dr. Ben-Sahra.

DNA and proteins are non-randomly localized within the nucleus of the cell.  The Brickner lab studies how cells control the position of genes within the nucleus, and how gene positioning affects gene expression.  When genes are activated or repressed, their position in the nucleus often changes.  The lab has identified DNA "zip codes" in the promoters of genes that control their positioning, transcription and, through an epigenetic mechanism, chromatin structure.

Selected Publications

• A conserved role for human Nup98 in altering chromatin structure and promoting epigenetic transcriptional memory. Light WH, Freaney J, Sood V, Thompson A, D'Urso A, Horvath CM, Brickner JH.  PLoS Biology. 2013 Mar 26;11(3):e1001524.
• Transcription factor binding to a DNA zip code controls interchromosomal clustering at the nuclear periphery.  Brickner DG, Ahmed S, Meldi L, Thompson A, Light W, Young M, Hickman TL, Chu F, Fabre E, Brickner JH.  Dev Cell. 2012 Jun 12;22(6):1234-46.
• Interaction of a DNA zip code with the nuclear pore complex promotes H2A.Z incorporation and INO1 transcriptional memory. Light WH, Brickner DG, Brand VR, Brickner JH.  Mol Cell. 2010 Oct 8;40(1):112-25.
• DNA zip codes control an ancient mechanism for gene targeting to the nuclear periphery. Ahmed S, Brickner DG, Light WH, Cajigas I, McDonough M, Froyshteter AB, Volpe T, Brickner JH. Nat Cell Biol. 2010 Feb;12(2):111-8.
• H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state. Brickner DG, Cajigas I, Fondufe-Mittendorf Y, Ahmed S, Lee PC, Widom J, Brickner JH. PLoS Biology. 2007 Apr;5(4):e81.

Selected Honors

• 2014 Soretta and Henry Shapiro Research Professor in Molecular Biology
• W.M. Keck Young Scholar in Medical Research
• Baldwin Award for Biomedical Research
• Helen Hay Whitney Postdoctoral Fellowship

Lab Staff

Leads

Jason Brickner, PhD, Donna Brickner, PhD

Graduate Students

Undergraduate Students

Rachel Tompson, Suzetti Ueno-DaSilva, Winny Liu

Contact Information

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

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.

Research Description

The Eichner lab studies transcriptional dependencies in cancer development, progression and resistance mechanisms. We endeavor to elucidate in vivo transcriptional dependencies at the intersection of epigenetics, signaling, and metabolism to reveal and harness therapeutically targetable transcriptional vulnerabilities in cancer.

• Project 1: LKB1 (STK11) is among the most frequently mutated genes in Non-Small Cell Lung Cancer (NSCLC), where it is inactivated in about 20 percent of cases. Leveraging immune-competent genetically engineered mouse models to answer key questions in vivo, our work has revealed key insights into the molecular mechanisms driving this disease. We have identified that transcription plays an important and previously underappreciated role in mediating LKB1 function. Future work will continue utilizing mechanistic understanding to explore novel in vivo transcriptional dependencies and therapeutic liabilities of LKB1 mutant tumors.
• Project 2: We have identified critical roles of the druggable epigenetic regulator Histone Deacetylase 3 (HDAC3) in lung tumors. We found that HDAC3 directly represses the secretory component of the cellular senescence program, the SASP, and restrains recruitment of T-cells into tumors in vivo. Future work will continue defining the molecular mechanisms mediating HDAC3’s contribution to tumorigenesis, and further explore epigenetic regulation of the senescence program.

For lab information, publications and more, see Dr. Eichner's faculty profile and laboratory website.

Publications

See Dr. Eichner's publications on PubMed.

Contact

Contact Dr. Eichner.

Research Description

My research program is focused on the important basic question of how chromosomes are segregated during cell division to ensure the complete and accurate inheritance of the genome. Chromosome instability is a hallmark of cancer and can drive tumorigenesis. Therefore, how centromere specification is controlled is a basic biological question with great therapeutic potential. Centromeres are specified by the incorporation of a histone variant CENP-A in a centromere specific nucleosome. The stable inheritance of this locus is controlled by an epigenetic pathway and does not depend on the underlying DNA sequence. My research program is using a combination of cell biology, biochemical purification and in vitro reconstitution of centromeric chromatin to discover the mechanisms of epigenetic inheritance and CENP-A function during mitosis. A key to understanding the epigenetic inheritance of centromeres is determining the process by which new CENP-A nucleosomes are deposited. Our lab is studying how activity of the CENP-A chromatin assembly factor HJURP is coupled to existing centromeres. Non-coding RNAs, as well as chromatin modifying enzymes have been implicated in the process and we are exploring how these factors contribute to specific assembly of the CENP-A nucleosomes. We have identified novel post translational modifications of the CENP-A amino-terminus and we are working to determine how these modifications contribute to genomic stability and accurate chromosome segregation. Our immediate goal is to determine the mechanism of epigenetic centromere inheritance, with a long-term goal of delineating the role of this process in tumorigenesis so as to translate our basic understanding of the enzymes and proteins involved in this process into therapeutic approaches for genomic instability in cancer.

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

Publications

See Dr. Foltz's publications on PubMed.

Contact

Contact Dr. Foltz at 312-503-5684.

Research Description

The Gao Laboratory is dedicated to translating complex human genome data into new insights of cancer and aging diseases. At Northwestern University Feinberg School of Medicine, we are experts in single-cell sequencing technologies and bioinformatics with a focus on developing and applying these methods to dissect the cellular and molecular mechanisms of human diseases. Explore our current projects below:

• Single cell mosaic mutation atlas of human organs: This involves developing novel computational methods to detect mosaic mutations from large scale human cell atlas datasets, investigating the functionality of mosaic mutations during human heart and brain aging processes.
• Delineating cellular mechanism of chronic heart transplant failure: This involves developing novel single cell third generation sequencing technologies to dissect the donor and host cell identities and their contributions to transplanted heart failure.
• Tracking tumor evolution and neovascular adaption of brain metastatic tumors: This involves applying novel single cell DNA and RNA sequencing technologies to deconvolute tumor evolution and dissect the ecological systems of human brain.
• Human tumor cell atlas project of rare cancer: This involves using high throughput single cell sequencing methods to analyze tumor cell populations and their interactions with stromal and immune cell subpopulations.

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

This laboratory is interested in cancer, neural development and reproduction-related structural mechanisms of how extracellular signals (e.g., growth factors, adhesion molecules and morphogens) are translated into intracellular signals by plasma membrane receptors. We use biophysical methods (crystallography, calorimetry, surface plasmon resonance, analytical ultracentrifugation, etc.) in combination with functional studies to define the physiological states and binding processes of these receptors and their complexes with ligands. Our research targets include receptor tyrosine kinases, Semaphorin and its receptors and leucine-rich-repeat-containing G-protein coupled-receptors.

For more information, visit the faculty profile of Xiaolin He, PhD.

Publications

See Dr. He's publications in PubMed.

Contact

Contact Dr. He at 312-503-8030 or the He Lab at 312-503-8029.

Research Description

The main focus for our Top Down Proteomics subgroup is to push the limits for whole proteome analysis of mammalian cells, striving for a future in which Top Down analysis rivals that of Bottom Up in the number of protein identifications per run. Recently, we have seen progress toward this very goal with the introduction of a separation platform specifically designed to minimize the most common problem in Top Down Proteomics, intact protein separations. This platform effectively reduces sample complexity and separates proteins depending on size, resulting in an opportunity for the scientist to select the optimal analysis method for the sample.

Our Natural Products subgroup is focused on the discovery and biosynthesis of novel natural products. Developments from this subgroup include the introduction of the PrISM platform, geared towards the identification of natural products synthesized by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) without prior knowledge of a gene sequence. This is made possible by our ability to detect a phosphopantetheinyl (Ppant) ejection marker ion for NRPS/PKS thiolation domains. We also work in collaboration with groups from other universities to provide mass spectrometry analysis of novel biochemical systems.

We also have a long-standing interest in histone analysis. Our Chromatin Oncobiology and DNA-Damage subgroup continues to dig deeper into the "histone code", a complex mixture of post-translational modifications that together determine a host of cellular processes. We are interested in visualizing dynamic histone PTM changes simultaneously on multiple sites. Through application of technology developed in our Top Down Proteomics subgroup, we are able to apply "Precision Proteomics" to histone analysis.

For more information, visit the Kelleher Lab Web Page or see Dr. Kelleher's faculty profile.

Publications

View lab publications via PubMed.

Contact

Contact the Kelleher Lab at 847-467-1086 or 847-467-4362.

Research Description

The Kelley lab utilizes an interdisciplinary approach that integrates nanoscience, bioanalytical science and engineering, focusing on high-throughput single-cell profiling and the application of new technology platforms of the characterization of pathways relevant to cancer progression and treatment.

Publications

View Dr. Kelley's faculty profile for recent publications.

Contact

Contact Dr. Kelley at shana.kelley@northwestern.edu or 847-467-4176.

Research Description

The Lauberth Lab is located in the department of Biochemistry and Molecular Genetics at Northwestern University Feinberg School of Medicine and is located in the Simpson Querrey Biomedical Research Center on Northwestern’s campus in downtown Chicago.

Our primary research focus is to make advances in basic and translational studies in the cancer epigenetics field. The laboratory utilizes a combination of approaches that include cutting-edge high-throughput NGS technologies, state of the art microscopy techniques, quantitative proteomics, biochemistry, and cell-based/genetic assays. We also employ powerful cell-free assays that fully reconstitute transcription on chromatin templates and are powerful in discerning direct (causal) effects of epigenetic and transcriptional regulatory mechanisms. Explore our current projects below.

• The general transcription machinery functions as signal transducers: Through an exciting collaboration with Nullin Divecha’s group (University of Southampton), we discovered a new role of the basal transcription TFIID complex component, TAF3 in transducing nuclear phosphoinositide signals into gene expression changes that are required to build muscle tissue. This work was published in Molecular Cell.
• p53 mutant enhancer selection and regulation imparts transcriptional plasticity to cancer cells in response to chronic immune signaling: My lab has made important contributions in revealing mechanistic insights into how chronic immune signaling drives alterations in the cancer cell transcriptome. We have demonstrated a functional crosstalk between the second most frequently identified p53 mutant and the master proinflammatory regulator NFkB that shapes an active enhancer landscape to reprogram the cancer cell transcriptome in response to chronic TNFa signaling. These studies also revealed insights into mutant p53-dependent gene regulation by describing new ways in which mutant p53 is recruited to specific classes of enhancers through various binding partners since mutant p53 does not directly engage with DNA. This new mechanism underlying the tumor-promoting roles of mutant p53 was published in Nature Communications.
• Mutant p53 Co-Opts Chromatin Pathways at Enhancers to Drive Cancer Cell Growth: Our studies have advanced our understanding of cancer epigenetics by establishing an interplay between p53 mutants and chromatin regulators that leads to aberrant enhancer and gene activation in human cancer. Specifically, through global analyses, we demonstrated a requirement for mutant p53 in regulating the prominent histone mark, monomethylation of histone H3 lysine 4 (H3K4me1) that demarcates enhancer regions. This is an important finding that provides new mechanistic insights into how H3K4me1 levels are altered, which is a frequent event in various human cancers. Also, by implementing cell-based and our unique cell-free assays, we revealed mechanistic insights into the cooperativity between epigenetic regulators, MLL4 and the histone acetyltransferase p300 in promoting joint epigenetic aberrations that support enhanced transcriptional activation by mutant p53. These important findings were published in the Journal of Biological Chemistry.
• eRNAs regulate the expression of tumor promoting genes: Our recent research efforts have resulted in new insights into the functions of eRNAs, which is particularly significant since these findings are among the few studies to date that have identified roles for these noncoding transcripts. Through global profiling analyses, we identified eRNAs that are synthesized by various p53 mutants, and by depleting several of these eRNAs, we identified their direct roles in the regulation of tumor promoting gene expression. We also revealed that these eRNAs function through the chromatin recognition bromodomains (BDs) of the extra-terminal motif (BET) family member BRD4. We further characterized a mechanism in which eRNAs are required to increase BRD4 binding to acetylated histones and promote enhanced BRD4 and RNAPII recruitment at specific enhancers that, in turn augments enhancer and tumor promoting gene activation. We also extended the implications of our findings by revealing that the BDs of all BET family members and several non-BET family members also directly interact with eRNAs. These findings provide a previously unrecognized convergence between eRNAs and histone posttranslational modifications in regulating the binding of chromatin reader proteins and highlight a mechanism in which eRNAs play a direct role in gene regulation by modulating chromatin interactions and transcription functions of BRD4. A manuscript describing these findings has been published in Nature Structural & Molecular Biology (NSMB).

We have also published several reviews on enhancer regulation and function and the mechanisms underlying eRNA functions that you can find by viewing our publications.

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

Publications

View all of Dr. Lauberth's publications on PubMed.

Contact

Contact Dr. Lauberth at 312-503-4780.

Northwestern University Feinberg School of Medicine
Simpson Querrey 7-400B
303 E. Superior Street
Chicago, IL 60611

Research Description

Prion diseases belong to a class of fatal, infectious neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs), including the bovine spongiform encephalopathies (BSE or mad cow disease) in cattle and Creutzfeldt-Jakob disease (CJD) in human. It is generally accepted that the infectious agent of prion disease is a normal host protein (PrPC) that has adopted a pathogenic conformation that is infectious (PrPSc). Remarkably, there are several atypical yeast proteins capable of existing in multiple stable conformations, each of which is associated with distinct phenotypes. Intriguingly, some of the conformations are able to self-propagate and are “infectious.” They are thus referred to as yeast prions. Our laboratory is interested in study this fascinating prion phenomenon using yeast as a model organism. Yeast offers a powerful system that is amenable to biochemical, cell biological and genetic manipulations. We want to obtain information on the structural properties of yeast prions, their mutual interactions and their interactions with other cellular factors, particularly, with molecular chaperones. We have recently discovered that the yeast heat-shock transcription factor (HSF), a master regulator of molecular chaperones’ production, plays an important role in governing the de novo formation and “strain” determination of yeast prion [PSI+]. We are working toward to identify novel cellular factors that are HSF targets and important for yeast prion formation and inheritance. The function of HSF is evolutionally conserved from yeast to human. We hope that results from our yeast prion studies will provide valuable information on the complex etiology of the devastating prion diseases.

Our laboratory is also interested in investigating how common the prion phenomenon in biology is. We wish to identify potential prion proteins from yeast and other non-yeast model organisms through a combined approach of bioinformatics and genetic screenings. Our ultimate goal is to uncover the mechanisms governing the prion conformational switch and to understand the biological significance of the protein conformation based prion-like inheritance.

For more information, visit the faculty profile of Liming Li, PhD.

Publications

See Dr. Li's publications in PubMed.

Contact

Email Dr. Li.

Research Description

My long-term research interest is to decode the human genome. The recent research focus of my lab is on developing and applying computational and high-throughput experimental methods in epigenomics to understand the gene regulatory roles of non-coding genetic variants in different pathological conditions, including cancers and neurodegenerative diseases. Specifically, we focused on the computational method development for circulating cell-free DNA fragmentation and new biotechnology development for the joint profiling of multi-omics within the same single cells, which will eventually enable biomarker discovery for the early diagnosis and prognosis of many complex diseases.

For lab information, visit the EpiFluid Lab site.

Publications

For publications, see Dr. Liu's faculty profile.

Contact

Email Dr. Liu or reach us by phone at 312-503-1699.

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 or reach us by phone at 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.

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.

Publications

Refer to PubMed for a full list of publications.

Contact

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 or reach us by phone at 312-503-5685.

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.

Research Description

The lab of Dr. Marcus Peter studies various forms of cell death including apoptosis, which is a fundamental process to regulate homeostasis of all tissues and to eliminate unwanted cells specifically in the immune system. 

Another interest lies in the study of RNA interference and based on toxic RNAs to development a novel form of cancer treatment. 

 

Publications

View lab publications via PubMed.

For more information, visit the faculty profile page of Marcus Peter, PhD or the laboratory's website.

Contact

Contact Dr. Peter at 312-503-1291 or the Peter Lab at 312-503-2883.

Research Description

Cell signaling is part of an intricate system of events activated by various stimuli that coordinate cell responses. Our laboratory is interested in unveiling pathways involved in cancer development in order to target them and control cancer progression. For over two decades, Dr. Platanias’ laboratory has identified several cellular cascades activated by IFN, ATRA and arsenic. Our research on Type I IFN found an essential role for SKAR protein in the regulation of mRNA translation of IFN-sensitive genes and induction of IFN-α biological responses. We also provided evidence for unique function of mTORC2 complex in inducing Type I IFN response. Our studies on arsenic signaling revealed a direct binding of this compound to a kinase called AMPK as a mechanism underlying its anti-leukemic activity. Other work included the activation of biological responses by BCR-ABL oncoprotein through the mTOR pathway. Dr. Platanias’ laboratory is also involved in testing new compounds in combination with approved therapies in order to identify synergy and improve the risk/benefit ratios of current therapeutic regimens for patients.

For more information, visit the faculty profile page of Leonidas Platanias, MD, PhD.

Publications

View lab publications via PubMed.

Contact

Contact Dr. Platanias at 312-908-5250 or the Platanias Lab at 312-503-4500.

Research Description

The Prindle lab is interested in understanding how molecular and cellular interactions give rise to collective behaviors in microbial communities. While bacteria are single celled organisms, we now understand that most bacteria on our planet reside in the context of structured multicellular communities known as biofilms. However, most bacterial research is still performed on domesticated lab strains in well-mixed conditions. We simply do not know enough about the biology and behavior of the most pervasive life form on our planet. It is our goal to discover and understand these behaviors so that we may apply our understanding to engineer biomolecular systems as solutions to challenging biomedical problems, such as antibiotic resistance. To do this, we also work on developing technologies that can characterize collective metabolic and electrochemical dynamics that emerge in the context of biofilms.

For more information, see Dr. Prindle's lab website.

Publications

See Dr. Prindle’s publications on PubMed.

Contact

Contact Dr. Prindle.

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 or call us at 312-503-5223.

Research Description

The Singer Lab focuses on determinants of resolution and repair of acute lung inflammation and injury. Our ultimate goal is to unravel the factors controlling resolution and repair and exploit those factors as therapies for acute respiratory distress syndrome (ARDS)—a devastating disorder responsible for the deaths of tens of thousands of people each year.

For more information, visit the Benjamin Singer Lab site or his faculty profile page.

Publications

View Dr. Singer's publications on PubMed.

Contact

Email Dr. Singer or contact us at 312-908-8163.

Research Description

Research aiming to understand how behavior arises has historically focused on the brain. However, the brain is not isolated from the rest of the body: peripheral organs like the gut produce a repertoire of unexplored signals that communicate with the brain and influence behavioral decisions. The focus of the lab is to identify novel peripheral organ signaling pathways and determine how they influence behaviors such as sleep and substance use disorder. Sleep is essential for life, and poor sleep quality represents a risk factor for metabolic and psychiatric disorders. While sleep duration has been extensively investigated, sleep depth, which is equally important because of its restorative functionovers, is understudied due to the challenges in measuring it. We have developed a behavioral setup that allows us to investigate how dietary manipulations and their effect on gut secretory signaling pathways affect sleep depth. Diet imbalances are also a strong predictor for substance use disorder and we have developed novel assays showing that dietary changes can alter psychostimulant preference. Our overarching goal is to provide crucial and missing molecular mechanistic understanding of how inter-organ signals shape essential and maladaptive behaviors, to enable novel preventive and therapeutic strategies.

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

Publications

See Dr. Titos Vivancos's publications on PubMed.

Contact

Contact Dr. Titos Vivancos or 312-503-2759. 

Research Description

Human Cancer Development: Understanding the Important Functions of Epigenetic Factor Mutations: Mutations and/or translocations within genes that encode for epigenetic factors, such as histone protein lysine methyltransferases (KMTs), lysine demethylases (KDMs), and DNA methyltransferases (DNMTs) are all common mechanisms involved in driving tumorigenesis (Cancer Cell. 2019, Feb 11; 35(2):168-176). We utilize state-of-the-art technologies that are designed to conduct epigenetic-related experiments, which allow us to directly uncover the underlying mechanisms of how mutations in epigenetic factors contribute to human cancer development (Nat Med. 2018, Jun; 24(6):758-769).

Novel Cancer Treatment Options: Targeting Dys-Regulated Epigenetic Factors: Misregulation of histone/DNA modifiers have emerged as a common therapeutic target option for treatments of different human diseases, including cancer. (Genes Dev. 2017, Oct 15; 31(20):2056-2066), Cancer Cell. 2014, Jan 13; 25(1):21-36, Sci Adv. 2015 Oct 9; 1(9):e1500463). Currently, several protein methyltransferases and demethylases have been identified, but their physiological significance has just begun to be elucidated. Our goal is to understand the relationship between dys-regulated epigenetic factors and cancer development through the use of these advanced technologies, such as CRISPR screening and experiments involving small inhibitor molecules. As a result, this could lead us to generate potential cancer treatment options by identifying the druggability of selected epigenetic factors, in order to develop a novel and more precise use of a drug that can be translational to clinical applications.

For lab information and more, see Dr. Wang’s faculty profile and lab website.

Publications

See Dr. Wang’s publications.

Contact

Contact Dr. Wang.

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).  

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.

Research Description

The Zhang laboratory is focused on two research directions: 1) determining role of tumor suppressors in development and cancer progression and 2) identifying immune components that control breast cancer metastasis.

The main focus of my research program is to study the roles of tumor suppressors in normal development and in breast and prostate cancer progression, focusing on maspin and an Ets transcription factor PDEF. Maspin is a unique member of the SERPIN family that plays roles in normal tissue development, tumor metastasis and angiogenesis. Genetic studies by my laboratory using maspin transgenic and knockout mice demonstrated an important role of maspin in normal mammary, prostate and embryonic development. Recently, we have identified several new properties of maspin. As a protein that is present on cell surface, maspin controls cell-ECM adhesion. This function is responsible for maspin-mediated suppression of tumor cell motility and invasion. We have also discovered that maspin is involved in the induction of tumor cell apoptosis through a mitochondrial death pathway. The long-term goals of these projects are to elucidate the molecular mechanisms by which maspin and PDEF control tumor metastasis and to identify their physiological functions in development. These analyses are not only important for basic biology and but also may lead to a therapy for cancer and other developmental diseases.

Another focus of research in Zhang lab is to identify immune components that control breast cancer metastasis. Chronic inflammation not only increases neoplastic transformation but also drives the inhibition of the immune response in a protective negative-feedback mechanism.  Suppressive immune cells are recruited to the sites of inflammation and function to inhibit both innate and adaptive immune responses, enabling tumor tolerance and unmitigated tumor progression. To study the interplay between tumor and immune cells, the Zhang lab has developed a unique animal model of breast cancer that reproduces different stages of breast cancer bone metastasis. Molecules that control tumor-immune cell interaction and immunosuppression have been identified. We are currently studying roles of these genes in tumor-driven evolution that control chronic inflammation and immunosuppression. We hypothesize that these key pro-inflammatory genes are upregulated during cancer progression, which function synergistically to recruit and activate suppressive MDSCs, TAMs and Tregs, inducing chronic inflammation and an immunosuppressive tumor microenvironment conducive to metastatic progression.

For more information visit Ming Zhang's faculty profile.

Publications

View publications by Ming Zhang in PubMed

Contact

Dr. Zhang

Phone 312-503-0449