Organelle Structure and Function
Research on the structure and function of the intracellular organelles.
Labs in This Area
Role of mitochondria and metabolic processes in cancer growth, cardiac disease and metabolic disorders
Our lab focuses on three major areas of research:
Role of proteins involved in cellular and systemic metabolism
TTP is a protein that binds to AU-rich regions in the 3’ UTR of mRNA molecules and causes their degradation. It has been studied extensively in the field of inflammation. We recently showed that it also plays a role in cellular iron conservation. We have also shown that TTP is a key mediator of cellular metabolic processes. Our studies have demonstrated that TTP regulates glucose, fatty acid and branched-chain amino acid metabolism in the liver and muscle tissue. We also have evidence that TTP directly regulates mitochondrial electron transport chain (ETC) by targeting specific proteins in the ETC complexes. Finally, recent studies demonstrated that TTP also regulates systemic metabolism by targeting FGF-21 expression. We have both TTP Floxed mice (for the generation of tissue specific TTP knockout mice) and TTP knockout mice in the background of TNF-alpha receptor 1/2 knockout mice (to reduce the inflammatory burden). Current studies include: 1) role of TTP in liver metabolism of fatty acids and glucose, 2) effects of TTP on mitochondrial proteins, 3) mechanism of TTP regulation of branched-chain amino acid levels and 4) role of TTP in cardiac metabolism.
Adult cardiomyocytes regenerate at a very low rate, but neonatal cardiomyocytes grow and replicate at a high rate. We have identified specific tandem zinc-finger (TZF) proteins that bind to mRNAs to regulate cardiac regeneration and cardiac development. Our studies suggest that these proteins may alter DNA repair in response to damage by regulating p53 and helicases. Current projects include: 1) identifying the mechanism by which TZF proteins regulate p53 and DNA damage, 2) characterization of the role of helicases in cellular proliferation and regeneration and 3) role of TZF proteins in cardiac development.
Characterization of cellular and mitochondrial iron regulation
Our lab has identified a novel mitochondrial protein, ATP-Binding Cassette-B8 (ABCB8), which plays a role in mitochondrial iron homeostasis and mitochondrial iron export. Mice with ABCB8 knocked out in the heart develop cardiomyopathy and mitochondrial iron accumulation. In addition, we have shown that a pathway involving mTOR and tristetraprolin, treatment with doxorubicin (an anticancer drug that also causes cardiomyopathy) and SIRT2 protein also impact cellular and/or mitochondrial iron regulation. Current studies in this area include: 1) further characterization of ABCB8 in iron homeostasis in other organs and disorders, 2) characterization of the mechanism for iron regulation by SIRT2, 3) identification of the mechanism by which mTOR is regulated by iron, 4) role of iron in viral infection, particularly HIV, 5) characterization of the effects of iron on mitochondrial dynamics and 6) identification of novel mitochondrial-specific iron chelators.
For more information, see Dr. Ardehali's faculty profile.
See Dr. Ardehali's publications in PubMed.
Circadian and metabolic gene networks in the development of diabetes and obesity
An epidemic of obesity and diabetes has continued to sweep through the industrialized world, already posing a risk to over one-third of the US population who are overweight or obese. Although both physical inactivity and overnutrition are tied to “diabesity,” recent evidence indicates that disruption of internal circadian clocks and sleep also play a role. The primary research focus in our laboratory is to apply genetic and biochemical approaches to understand the basic mechanisms through which the circadian clock regulates organismal metabolism. We anticipate that a better understanding of clock processes will lead to innovative therapeutics for a spectrum of diseases including diabetes, obesity, autoimmunity and cancer.
Studies of Clock Function in Beta Cell Failure and Metabolic Disease
Glucose homeostasis is a dynamic process subject to rhythmic variation throughout the day and night. Impaired glucose regulation leads to metabolic syndrome and diabetes mellitus, disorders that are also associated with sleep-wake disruption, although the molecular underpinnings of circadian glucose regulation have been unknown. Work from our laboratory first demonstrated an essential role of the intrinsic pancreatic clock in insulin secretion and diabetes mellitus and present efforts focus on dissecting the genomic and cell biologic link between clock function and beta cell failure (Nature, 2010, 2013).
Studies of Clock Regulation of Metabolic Epigenetics
In 2009 we first reported discovery that the circadian system plays a central role in metabolism through regulation of NAD+ biosynthesis (Science, 2009). NAD+ is a precursor of NADP+ and is required for macromolecule biosynthesis, in addition to functioning as an oxidoreductase carrier. NAD+ is also a required cofactor for the class III histone deacetylases (silencer of information regulators, SIRTs), nutrient-responsive epigenetic regulators Biochemical analyses show that SIRT1 deacetylates substrate proteins generating O-acetyl-ADP-ribose and nicotinamide, which is then regenerated to NAD+ by the enzyme nicotinamide phosphoribosyl transferase (NAMPT). We originally showed that CLOCK/BMAL1 directly control the transcription of Nampt and in turn control the activity of SIRT1—identifying a feedback loop composed of CLOCK/BMAL1-NAMPT/SIRT1. More recently, we have identified a role for the clock-NAD+ pathway in mitochondrial respiration (Science, 2013), and our present efforts include the analysis of clock-NAD+ regulation of cellular redox and epigenetic regulation, with the ultimate aim of applying such knowledge to studies of cell growth and stress response.
See Dr. Bass' publications in PubMed.
The Chandel Lab studies the mitochondria as a signaling organelle; using reactive oxygen species as the primary signal for metabolic adaptation, differentiation and proliferation.
Historically, reactive oxygen species (ROS) have been thought to be cellular damaging agents, lacking a physiological function. Accumulation of ROS and oxidative damage have been linked to multiple pathologies, including neurodegenerative diseases, diabetes, cancer and premature aging. This guilt by association relationship left a picture of ROS as a necessary evil of oxidative metabolism, a product of an imperfect system. Yet few biological systems possess such flagrant imperfections, thanks to the persistent optimization of evolution. It appears that oxidative metabolism is no different. More and more evidence suggests that low levels of ROS are critical for healthy cellular function. This idea was first proposed in the mid-1990s when low levels of hydrogen peroxide (H2O2) were demonstrated to be important for cellular signaling. Although mitochondria were known to produce H2O2, NADPH oxidases (NOXs) were the subject of early study due to their well-described role as ‘dedicated H2O2 producers’ in phagocytes. We provided early evidence in the late 1990s that mitochondria release H2O2 to regulate the transcription factor hypoxia inducible factor 1 (HIF-1) (i.e. oxygen sensing). Subsequently, we showed that mitochondrial release of H2O2 can activate p53 and NF-κB. We have recently demonstrated that mitochondria-generated H2O2 can regulate other physiological processes including stem cell differentiation, adaptive immunity and replicative life span of mammalian cells. Furthermore, we have shown that cancer cells co-opt mitochondria-generated H2O2 to hyper-activate signaling resulting in tumor cell proliferation. There have been numerous reports from other laboratories in the past decade also highlighting the importance of mitochondrial H2O2-dependent signaling in metabolic adaptation, immunity, differentiation, autophagy and organismal longevity. We propose that mitochondrial release of H2O2 has evolved as a method of communication between mitochondrial function and other cellular processes to maintain homeostasis and promote adaptation to stress.
See Dr. Chandel's publications in PubMed.
Contact Dr. Chandel’s Lab at 312-503-1792
Cancer stem cell biology, cellular signaling and therapy responses in human brain tumors, in particular, glioblastoma (GBM)
Integrated genomic analysis by TCGA revealed tat GBMs can be classified into four clinically relevant subtypes, proneural (PN), neural, mesenchymal (Mes) and classical GBMs with each characterized by distinct gene expression signatures and genetic alterations. We reported that PN and Mes glioma stem cells (GSCs) subtypes also have distinct dysregulated signaling pathways. Our current research focuses on novel mechanisms/cellular signaling of GSC biology, tumorigenesis, progression, invasion/metastasis, angiogenesis and therapy responses of GSCs and GBMs.
1. MicroRNAs (miRs) and non-coding RNAs in GSCs and GBMs – miRs and other small non-coding RNAs act as transcription repressors or inducers of gene expression or functional modulators in all multicellular organisms. Dysregulated miRs/noncoding RNAs plays critical roles in cancer initiation, progression and responses to therapy. We study the mechanisms by which deregulated expression of miRs influence GBM malignant phenotypes through interaction with signaling pathways, that in turn, influence proneural (PN)- and mesenchymal (Mes)-associated gene expression in GSCs and GBM phenotypes. We study the molecular consequences and explore clinical applications of modulating miRs and signaling pathways in GBMs. We are establishing profiles of non-coding RNAs in these GSCs and study mechanisms and biological influences of these non-coding RNAs in regulating GSC biology and GBM phenotypes. In addition, we explore novel therapeutic approaches of delivery of tumor suppressive miRs into GSC brain xenografts in animals.
2. Autophagy in GBMs. (Macro)autophagy is an evolutionally conserved dynamic process whereby cells catabolize damaged proteins and organelles in a lysosome-dependent manner. Autophagy principally serves as an adaptive role to protect cells and tissues, including those associated with cancer. Autophagy in response to multiple stresses including therapeutic treatments such as radiation and chemotherapies provides a mechanism for tumor cell to survive and acquire resistance to therapies. Tumors can use autophagy to support and sustain their proliferation, survival, metabolism, invasiveness, metastasis and resistance to therapy. We study mechanisms by which phosphorylation, acetylation and ubiquitination of autophagy proteins regulate GSC and GBM phenotypes and autophagic response, which, in turn contributes to tumor cell survival, growth and resistance to therapy. We investigate whether disruption of these post-translational processes on autophagy proteins inhibits autophagy and enhances the efficacy of combination therapies for GBMs. We examine whether cross-talks between miRs, autophagy and oncogenic signaling pathways regulate GSC stemness and phenotypes.
3. Heterogeneity, epigenetic regulation, DNA damage and metabolic pathways in GSCs and GBMs. Intratumoral heterogeneity is a characteristic of GBMs and most of cancers. Phenotypic and functional heterogeneity arise among GBM cells within the same tumor as a consequence of genetic change, environmental differences and reversible changes in cell properties. Subtype mosaicism within the same tumor and spontaneous conversion of human PN to Mes tumors have been observed in clinical GBMs. We explore an emerging epigenetic marker with distinct functions such as DNA methylation together with genetic mapping of these markers to assess their contributions to GBM heterogeneity. In addition, compared with PN GSCs, DNA damage and glycolytic pathways are aberrant active in Mes GSCs. We investigate the mechanisms by which these pathways regulate GSC and GBM phenotypes and responses to therapies.
4. Oncogenic receptor tyrosine kinase (RTKs) signaling, small Rho GTPase regulators in GBM and GSCs: Small Rho GTPases such as Rac1 and Cdc42 modulate cancer cell migration, invasion, growth and survival. Recently, we described mechanisms by which EGFR and its mutant EGFRvIII and PDGFR alpha promote glioma growth and invasion by distinct mechanisms involving phosphorylation of Dock180, a Rac-specific guanidine nucleotide exchange factor (GEF) and DCBLD2, an orphan membrane receptor. We are currently investigating involvement of other modulators/GEFs and other Rho GTPases in modulating GSC and GBM phenotypes and responses to therapy.
View Dr. Cheng's complete list of publications in PubMed.
Shi-Yuan Cheng, PhD at 312-503-5314
Visit us on campus in the Lurie Building, Room 6-119, 303 E Superior Street, Chicago, Illinois 60611.
Structural and biochemical basis of chromatin folding and chromosome condensation
The folding of DNA within nuclei and chromosomes is one of the great mysteries of biology, impacts gene regulation and influences heredity. At the most basic level, DNA is wrapped around histones in the nucleosome to form an extended “beads-on-a-string” chromatin fiber. Chromosome conformation capture, involving chemical cross-linking of chromatin followed by restriction digestion, ligation and high-throughput DNA sequencing (Hi-C), detects further folding of the chromatin fiber. Hi-C has revealed “topologically associating domains” (TADs), regions of intra-chromosomal self-association that are interspersed with regions of little or no such self interaction, which are prevalent throughout metazoans. By applying Hi-C to the polytene chromosomes of Drosophila, I established that polytene bands are equivalent to TADs, connecting chromatin folding inferred from Hi-C with direct, physical observations from light microscopy. Furthermore, TADs are conserved between polytene and diploid cells identifying the polytene band-interband pattern as a general principle of interphase chromosome architecture. Chromatin between TADs exists in a fully extended state, whereas TADs, which are up to 30-foldmore condensed, reflect the next higher level of stable chromosome folding.
Through experimental and computational improvements to the Hi-C method, I mapped chromatin interactions at sub-kilobase resolution, the highest resolution for a metazoan genome to-date. This allowed me to determine the locations of chromatin loops across the Drosophila genome. Loops were frequently located within domains of polycomb-repressed chromatin. Loop boundaries or “anchors” were frequently associated with the protein Polycomb, a subunit of Polycomb Repressive Complex 1 (PRC1). Promoters located at PRC1 loop anchors regulate some of the most important developmental genes and are less likely to be expressed than those not at PRC1 loop anchors. Although DNA looping has most commonly been associated with enhancer–promoter communication, these results indicate that loops are also associated with gene repression.
These advances have significantly furthered our understanding of nuclear organization, but DNA folding at the scale of tens-of-nanometers and beyond is still largely undetermined. Enhancers, cis-regulatory regions often located a distance from gene promoters, are important for tissue specific gene expression and malfunction in cancer. Enhancers are often found within TADs and intra-TAD chromatin folding influences proper gene regulation by modulating enhancer-promoter interactions. Disrupting TAD structure pathogenically rewires these interactions in human disease, so determining how TADs fold is of great interest. At the highest level of DNA folding, mitotic chromosomes are one of the most recognizable structures in cell biology, yet a detailed understanding of their internal structure has remained elusive. Faithful propagation of mitotic chromosomes underlies cellular heredity, so it is important to relate chromatin folding within interphase TADs to chromosome condensation during metaphase. My lab combines concepts and approaches from structural biology with methods and analytical tools from molecular biology and genomics to determine the structural basis of chromatin condensation within TADs and mitotic chromosomes. A combination of molecular biology, biochemistry, genomics and imaging will pave the way for a deeper understanding of chromatin structure as well as unravel principles.
Visit the Eagen Lab Website.
For more information, visit the faculty profile page of Kyle Eagen
View lab publications via PubMed.
Epigenetic control of centromere assembly and chromosome segregation.
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.
See Dr. Foltz's publications on PubMed.
Contact Dr. Foltz at 312-503-5684.
Studying the intermediate filament (IF) system in fibroblasts, epithelial cells and nerve cells through biochemical, morphological, immunological, cell physiological and molecular techniques.
We focus on the structure and function of cytoskeletal systems, particularly the intermediate filament (IF) system in fibroblasts, epithelial cells and nerve cells. IFs are composed of large families of proteins that vary in composition from one cell type to another, even among cells in the same tissue. Using a variety of techniques, we have demonstrated that IFs form elaborate networks that course throughout the cytoplasm and establish connections with both the nuclear and cell surfaces.
At the nuclear surface, they are linked either directly or indirectly with the nuclear lamins, which are chromatin-associated IF protein family members. At the level of the plasma membrane, IFs are involved as cytoskeletal linkages to the focal adhesion of fibroblasts and the desmosomes and hemidesmosomes of epithelial cells. Throughout the cytoplasm, we have shown that IFs are associated with the other cytoskeletal elements, such as microtubules and microfilaments.
Our approach to studying the IF system involves biochemical, morphological, immunological, cell physiological and molecular techniques. Our hypothesis is that the IF system forms a continuous network linking the nuclear and cell surfaces, functioning in such diverse activities as the establishment and maintenance of cell shape, organelle movements within the cytoplasm, nuclear positioning, nuclear-cytoplasmic interactions and signal transduction.
Since many human diseases have been linked to changes in cytoskeletal IF systems, we are also developing models to study the mechanisms involved in IF alterations in various diseases. One example is amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) in which we have been able to induce neurofibrillary tangles to form in single cultured nerve cells. These tangles are similar to those found in ALS neurons. Therefore, we are able to study the effects of neurofilament tangle formation in single cells. During the summer, researchers from this laboratory also conduct studies on the mechanisms of chromatin/nuclear envelope interactions in eggs of the surf clam at the Marine Biological Laboratory in Woods Hole.
See Dr. Goldman's publications on PubMed.
Contact Dr. Goldman at 312-503-4215.
The Green Lab investigates the genetics and molecular biology of cholestatic liver diseases and fatty liver disorders. The major current focus is on the role of ER Stress and the Unfolded Protein Response (UPR) in the pathogenesis of these hepatic diseases.
Dr. Green’s laboratory investigates the mechanisms of cholestatic liver injury and the molecular regulation of hepatocellular transport. Current studies are investigating the role of the UPR in the pathogenesis and regulation of hepatic organic anion transport and other liver-specific metabolic functions. We employ genetically modified mice and other in vivo and in vitro models of bile salt liver injury in order to better define the relevant pathways of liver injury and repair; and to identify proteins and genes in these pathways that may serve as therapeutic targets for cholestatic liver disorders.
The laboratory also investigates the mechanisms of liver injury in fatty liver disorders and the molecular regulation of hepatic metabolic pathways. The current focus of these studies includes investigations on the role of the UPR in the pathogenesis of non-alcoholic steatohepatitis and progressive fatty liver disease. We employ several genetically modified mice and other in vivo and in vitro models of fatty liver injury and lipotoxicity. Additional studies include the application of high-throughput techniques and murine Quantitative Trait Locus (QTL) analysis in order to identify novel regulators of the UPR in these disease models.
See Dr. Green's publications in PubMed.
For more information, please see Dr. Green's faculty profile.
Contact Dr. Green at 312-503-1812 or the Green Lab at 312-503-0089
Autophagy in metabolic regulation and pathogenesis of metabolic diseases
The research in my lab is centered on autophagy, a lysosomal degradation pathway essential for nutrient recycling, cellular maintenance and physiological function. Autophagy is induced by various stress conditions and allows cells to adapt to changing nutrient and energy demands through protein catabolism. Malfunction of autophagy is implicated in a variety of diseases such as cancer, neurodegeneration, infection and aging. Our interest focuses on the roles and mechanisms of autophagy in the metabolic regulation of mammals and in the pathogenesis of metabolic disorders in human, including obesity and type 2 diabetes. There are many open questions in this largely unexplored area; our research directions include studies of the functions of autophagy in exercise-induced metabolic benefits and investigation of the molecular mechanism of autophagy and its relationship to other lysosomal degradation pathways in the prevention of metabolic dysregulation.
See Dr. He's publications on PubMed.
Contact Dr. He at 312-503-3094.
Seeking to understand the nature and function of a unique nuclear structure, the perinucleolar compartment (PNC), and its relationship with the malignant phenotype
Our studies seek to understand the nature and function of a unique nuclear structure, the perinucleolar compartment (PNC), and its relationship with the malignant phenotype. Our work looks to address the function of the PNC and its significance during malignant transformation in multiple ways.
- Determine the correlation between PNCs and cancer in tissues. In collaboration with Dr. Ann Thor at Evanston Hospital, Northwestern University, we have initiated detection of PNC in breast cancer tissues.
- Investigate the function of the PNC, its relationship with the nucleolus and rRNA synthesis. We are in the process of isolating and identifying additional proteins and RNAs in the PNC.
Identification of activities taking place in the PNC will shed light on the understanding of the function of this structure and its relationship to the nucleolus and the transformed phenotype.
For lab information and more, see Dr. Huang's faculty profile.
See Dr. Huang's publications on PubMed.
Contact Dr. Huang at 312-503-4269 or the lab at 312-503-4276.
Role of MDia1 in the pathogenesis of del(5q) myelodysplastic syndromes
Our lab is interested in how cytoskeletal signaling, motor proteins and adhesion systems are integrated with chemical signaling pathways to regulate cell behavior and tissue differentiation and disease. The Ji lab studies small G proteins and downstream actin regulatory effectors that participate in enucleation during red cell development.
At the level of the nucleus, the Ji laboratory studies genes involved in erythroid lineage commitment, chromatin condensation and enucleation towards understanding how congenital red cell disorders and leukemia develop.
For more information, visit the faculty profile of Peng Ji, MD, PhD.
See Dr. Ji's publications in PubMed.
Looking to describe and probe the role of nuclear organization in stem cell maintenance and differentiation
Our lab studies the relationship between form and function in the human nucleus, with the long term goal of describing the behavior of a dynamic system, the human genome, in stem cells and progenitors as they differentiate. We are specifically interested in inter- and intra-chromosomal associations as a function of lineage-restricted gene expression and linear gene arrangement. In addition, we investigate changes in genomic and nuclear organization in the context of human disease.
See Dr. Kosak's publications on PubMed.
Contact Dr. Kosak at 312-503-9582.
Regulation of Motor Neuron and Dopaminergic Neuron Function in Development and Disease
Postdoctoral fellow jobs and graduate student rotation projects are available.
Research DescriptionSpinal Motor Neurons and Spinal Muscular Atrophy (SMA)
SMA is characterized by the selective degeneration of spinal motor neurons. As the leading genetic cause of infant mortality, SMA affects one in every eight thousand live births. Our group is interested in studying mechanism regulating motor neuron development and function, as well as why motor neurons specifically degenerate in SMA. To address these questions, we use a combination of genetic, biochemical and cell biological approaches and utilize genetically modified mice, induced pluripotent stem (iPS) cells reprogrammed from fibroblasts and zebrafish as model systems. We focus on the regulation of mitochondrial functions in SMA pathogenesis. Based on our findings, we hope to develop new therapeutic strategies for treating SMA.
Dopaminergic Neurons and Parkinson's Disease
Dopaminergic neurons located in the ventral midbrain control movement, emotional behavior and reward mechanisms. Dysfunction of these neurons is implicated in Parkinson’s disease, drug addiction, depression and schizophrenia. Our group is interested in the genetic and epigenetic mechanisms regulating dopaminergic neuron functions in disease and aging conditions. We are particularly interested in how aging and mitochondrial oxidative stress contribute to dopaminergic neuron degeneration in Parkinson's disease through transcriptional and epigenetic regulations. We use mouse models, cultured neurons and iPS cells for these studies.
View Dr. Ma's publications at PubMed
Nimrod Miller, PhD, Postdoctoral Fellow
Han Shi, Graduate Student
Brittany Edens, Graduate Student
Kevin Park, Graduate Student
Monica Yang, Undergraduate Student
Aaron Zelikovich, Undergraduate Student
Our goal is to understand the integration of signaling and cytoskeletal dynamics on diverse developmental processes including centriole amplification, cell migration and cell polarity.
Centrioles are microtubule based structures with nine fold symmetry that are involved in both centrosome organization and aster formation during cell division. During the normal cell cycle centrioles duplicate once, generating a mother/daughter pair and in most post-mitotic vertebrate cells the mother centriole then goes on to form the basal body of a sensory cilium. Abnormalities in the duplication of centrioles (and centrosomes) are prevalent in many cancers suggesting a link between centriole duplication and cancer progression. We study what factors limit centriole duplication from a novel direction with the use of Xenopus motile ciliated cells. Ciliated cells are unique among vertebrate cells in that they generate hundreds of centrioles (basal bodies) therefore providing a great system for studying the regulation of centriole duplication. Understanding how nature has overcome the typically tight regulation of centriole duplication will lend insight into the molecular mechanisms of cancer progression.
Tissue development and homeostasis requires dramatic remodeling as new cells migrate into an epithelium. How migrating cells breakdown junctional barriers during development or during diseases processes such as metastasis is poorly understood at the molecular level. During the early development of Xenopus embryos, distinct cell types join the outer epithelium in a process called radial intercalation. We are interested in the molecular mechanisms that regulate both the migration of these cells as well as the tissue remodeling that occurs to accommodate them.
The ability of ciliated epithelia to generate directed fluid flow is an important aspect of diverse developmental and physiological processes including proper respiratory function. To achieve directed flow, ciliated cells must generate 100-200 cilia that are polarized along a common axis both within and between cells. My lab is currently working towards understanding the molecular mechanisms for how cell polarity is coordinated as well as how individual cilia interpret the cells polarity. We have determined that ciliated cells receive polarity cues via the non-canonical Wnt/Planar Cell Polarity (PCP) pathway, but the details of this are still poorly understood. Additionally, the PCP pathway is known to influence a cells cytoskeleton dynamics and a main goal is to understand how this influences the ability of individual cilia to coordinate their polarity.
See Dr. Mitchell's publications on PubMed.
Contact Dr. Mitchell at 312-503-9251.
Focusing on the emigration of leukocytes across vascular endothelial cells in the process of inflammation
Most diseases are due to or involve a significant component of inflammation. My lab studies the inflammatory response at the cellular and molecular level. We are focused on the process of diapedesis, the "point of no return" in inflammation where leukocytes squeeze between tightly apposed endothelial cells to enter the site of inflammation. We have identified and cloned several molecules that are critical to the process of diapedesis (PECAM (CD31), CD99, and VE-cadherin) and are studying how they regulate the inflammatory response using in vitro and in vivo models. We have recently described the Lateral Border Recycling Compartment, a novel para-junctional organelle that contains PECAM and CD99 and is critical for diapedesis to occur. We are currently investigating how this compartment regulates diapedesis in the hope of finding novel and highly specific targets for anti-inflammatory therapy.
The “holy grail” of therapy is to develop selective anti-inflammatory agents that block pathologic inflammation without interfering with the body’s ability to fight off infections or heal wounds. By understanding how endothelial cells at the site of inflammation regulate leukocyte diapedesis, we are hoping to do just that. We have identified several molecules critical for diapedesis in acute and chronic inflammatory settings that can be genetically deleted or actively blocked to markedly inhibit clinical symptoms (e.g. in a mouse model of multiple sclerosis) and tissue damage (e.g. in a mouse model of myocardial infarction) without impairing the normal growth, development, and health of these mice. Our inflammatory models include atherosclerosis, myocardial infarction, ischemia/reperfusion injury, stroke, dermatitis, multiple sclerosis, peritonitis, and rheumatoid arthritis. We are also using 4-dimensional intravital microscopy to view the inflammatory response in real time in living animals.
- What are the molecular mechanisms and signaling pathways that endothelial cells use to regulate the inflammatory response?
- How can we therapeutically treat inflammatory diseases without compromising the ability of the immune system to respond to new threats?
- Do circulating tumor cells use the same mechanisms as leukocytes to cross blood vessels when they metastasize?
We have a high-resolution Perkin Elmer ULTRAVIEW Vox System spinning disk laser confocal microscope in the upright configuration on an Olympus BX51WI fixed stage in my laboratory designed for intravital microscopy. We can image the ongoing inflammatory response and response to our drugs in real time in anesthetized mice with unprecedented temporal and spatial resolutions. We presently image inflammation in the cremaster muscle, intestine, and brain.
Of interest to History of Science buffs, we have the original Zeiss Ultrafot II microscope used to film the first movies of neutrophils ingesting bacteria. As you might expect from something built by Zeiss in the first half of the 20th century, the optics are still fantastic and we use it in our daily work.
Recently we made two major discoveries in endothelial cell inflammatory signaling: Identification of TRPC6 as the cation channel responsible for the endothelial cell calcium flux required for transmigration and description of the CD99 signaling pathway. Both had eluded discovery for decades.
- Watson, R.L., J. Buck, L.R. Levin, R.C. Winger, J. Wang, H. Arase, and W.A. Muller. 2015. Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration. J. Exp. Med. 212:1021-1041.
- Weber, E.W., F. Han, M. Tauseef, L. Birnbaumer, D. Mehta, and W.A. Muller. 2015. TRPC6 is the endothelial calcium channel that regulates leukocyte transendothelial migration during the inflammatory response. J Exp Med 212:1883-1899. PMID: 26392222
- AAAS Fellow, elected 2010
- Rous-Whipple Award, American Society for Investigative Pathology, 2013
- Ramzi Cotran Memorial Lecture, Brigham and Women’s Hospital, 2014
- Karl Landsteiner Lecture, Sanquin Research Center, Amsterdam, Netherlands, 2016
- Member, Faculty of 1000 Leukocyte Development Section
- American Society for Investigative Pathology (ASIP) Council
- ASIP Research and Science Policy Committee Chair
- North American Vascular Biology Organization (NAVBO) Secretary-Treasurer
NIH R01 HL046849-26 William A. Muller 08/01/91 – 05/31/20
The Roles of Endothelial PECAM and the LBRC in Leukocyte Transmigration
This study investigates how PECAM-1 and the LBRC regulate transmigration. We will investigate how PECAM ligation on endothelial cells activates TRPC6 to promote the calcium flux necessary for transmigration (Aim I). We will identify how endothelial IQGAP1 regulates transmigration by regulating targeted recycling of the LBRC (Aim II). We will identify how kinesin light chain 1 variant 1 facilitates movement of the LBRC during targeted recycling (Aim III). All of these Aims include mechanistic studies in vitro and validation studies in vivo using mouse models of ischemia/reperfusion injury in acute inflammation and myocardial infarction.
NIH R01 HL064774-16 William A. Muller 04/01/00 – 08/31/20
Beyond PECAM: Mechanisms of Transendothelial Migration
This study investigates the role of PECAM, CD99L2, and CD99 in transendothelial migration. Aim I will test the hypothesis that leukocytes control the molecular order of transmigration by polarizing PECAM on their leading edge and CD99 on the trailing edge during transmigration. Aim II will identify the signaling mechanisms by which CD99L2 regulates transmigration. Aim III will identify the signaling mechanisms by which CD99 regulates targeted recycling of the LBRC and transmigration downstream of Protein Kinase A. All Aims have in vitro mechanistic studies and in vivo validation studies using intravital microscopy in the cremaster muscle circulation and a murine model of ischemia/reperfusion injury in myocardial infarction.
For more information, visit the faculty profile of William A Muller, MD, PhD
View Dr. Muller's publications at PubMed
Research Assistant Professors
- David Sullivan, PhD firstname.lastname@example.org
- Annette Gonzalez, PhD email@example.com
- Tao Fu, PhD firstname.lastname@example.org
- Ayush Batra, MD email@example.com
- Neil Nadkarni, MD firstname.lastname@example.org
- Prarthana Dalal (MD/PhD) PrarthanaDalal@u.northwestern.edu
- Nakisha Rutledge Rutledge2012@u.northwestern.edu
- Margarette Clevenger MargaretteClevenger2021@u.northwestern.edu
- Clifford Carpenter, PhD email@example.com
Office: Ward Building, Room 3-126
303 East Chicago Avenue
Chicago, IL 60611-3008
Phone: (312) 503-0436
Fax: (312) 503-8249
Lab: Ward Building 3-070 and 3-031
Lab Phone: (312) 503-5200
Lab Fax: (312) 503-2630
Studying Molecular Mechanisms of Oncogenesis In Acute Leukemia
This is an exciting time for cancer biology especially with the advent of epigenetics and chromatin biology. New molecules with tumor suppressive or oncogenic roles are currently identified and characterized paving the way for new therapeutic ways but at the same time, posing new challenges for researchers. This area of cancer epigenetics is my personal and laboratory's focus. To study this perplexing biology we use patient samples and disease-relevant mouse models.
The Ntziachristos laboratory studies the mechanistic aspects of oncogenesis with an emphasis on transcriptional and epigenetic regulation of acute leukemia. Important questions are related to how oncogenes interact with each other and with epigenetic modulators to influence gene expression programs as well as how their function is related to tri- dimensional (3D) structure of the nucleus and other biological aspects of cancer cells, like metabolism. To address these questions we use high-throughput molecular and cell biology techniques like ChIP-Seq, RNA-Seq, 4C-Seq and HiC, fluorescent in situ hybridization and biochemical analysis in cell lines and primary cells of human origin and tissues of mouse models of disease. In addition to understanding cancer biology these finding help us design and test targeted therapies in preclinical models of leukemia.
For lab information and more, see lab website.
See Dr. Ntziachristos's publications at PubMed.
Dr. Ntziachristos 312-503-5225 or Searle 6-523
Investigating intracellular calcium signaling
Research in the laboratory of Murali Prakriya, PhD, is focused on the molecular and cellular mechanisms of intracellular calcium (Ca2+) signaling. Ca2+ is one of the most ubiquitous intracellular signaling messengers, mediating many essential functions including gene expression, chemotaxis and neurotransmitter release. Cellular Ca2+ signals generally arise from the opening of Ca2+ permeable ion channels, a diverse family of membrane proteins. We are studying Ca2+ signals arising from the opening of a Ca2+ channel sub-type known as the store-operated Ca2+ channel (SOC). SOCs are found in the plasma membranes of virtually all mammalian cells and are activated through a decrease in the calcium concentration ([Ca2+]) in the endoplasmic reticulum (ER), a vast membranous network within the cell that serves as a reservoir for stored calcium. SOC activity is stimulated by a variety of signals such as hormones, neurotransmitters and growth factors whose binding to receptors generates IP3 to cause ER Ca2+ store depletion.
The best-studied SOC is a sub-type known as the Ca2+ release activated Ca2+ (CRAC) channel. CRAC channels are widely expressed in immune cells and generate Ca2+ signals important for gene expression, proliferation and the secretion of inflammatory mediators. Loss of CRAC channel function due to mutations in CRAC channel genes leads to a devastating immunodeficiency syndrome in humans. A major effort in our lab is to understand the molecular mechanisms of CRAC channel function.
Despite the fact that SOCs are found in practically all cells, their properties and functions outside the immune system remain largely unexplored. In order to fill this gap, we have begun investigation of SOC properties and their functions in two major organ systems: in the brain and the lung.
- Neural stem cells (NSCs) express SOCs; robust Ca2+ signals arise from their activation, indicating that SOCs are a major route of Ca2+ entry in NSCs
- CRAC channels serve as a major route of Ca2+ entry in lung epithelial cells; CRAC channel activation leads to robust activation of NFAT and the production of proinflammatory cytokines
See Dr. Prakriya's publications on PubMed.
Contact Dr. Prakriya at 312-503-7030.
Looking to further define the molecular interactions and physiological functions of transcriptional activators and co-activators involved in the nuclear control of the respiratory apparatus
Our long-term objectives are to further define the molecular interactions and physiological functions of transcriptional activators and co-activators involved in the nuclear control of the respiratory apparatus. Current work in the lab combines molecular and biochemical approaches with the development of cellular and transgenic models to understand in vivo regulatory pathways and mechanisms.
For lab information see Dr. Scarpulla's faculty profile.
See Dr. Scarpulla's publications on PubMed
Contact Dr. Scarpulla at 312-503-2946.
Oxygen sensing in embryonic development, tissue responses to hypoxia and tumor angiogenesis.
Our lab is interested in the molecular mechanisms of oxygen sensing and the importance of this process for embryonic development, tissue responses to hypoxia and tumor angiogenesis. We are testing the hypothesis that the mitochondria play a central role in detecting cellular oxygenation and signal the onset of hypoxia by releasing reactive oxygen species (ROS). These signals trigger downstream signal transduction pathways responsible for the transcriptional and post-translational responses of the cell. Transcriptional activation of genes by Hypoxia-Inducible Factor-1 confers protection against more severe hypoxia by augmenting the expression of glycolytic enzymes, membrane glucose transporters and other genes that tend to augment tissue oxygen supply by increasing the release of vascular growth factors such as VEGF, erythropoietin and vasoactive molecules that augment local blood flow. Current experiments are aimed at improving our understanding of how oxygen interacts with the mitochondrial electron transport chain to amplify ROS production and clarifying the targets that they act on to stabilize HIF and activate transcription.
In specific tissues, oxygen sensing is essential for normal function, but it can also contribute to disease pathogenesis. For example, during mammalian development, the lung tissue is hypoxic and blood flow is restricted in the pulmonary circulation in order to prevent escape of oxygen from the pulmonary capillaries to amniotic fluid. At birth, inflation of the lung with air causes an increase in lung oxygen levels, which triggers relaxation of pulmonary arteries. In Persistent Pulmonary Hypertension of the Newborn, failure of the pulmonary circulation to dilate results in elevated pulmonary arterial pressures and significant lung gas exchange dysfunction. We are testing the hypothesis that pulmonary vascular cells sense O2 at the mitochondria and that ROS released from those organelles trigger an increase in cytosolic calcium, which causes smooth muscle cell contraction. In adult patients with hypoxic lung disease, similar activation of hypoxic vasoconstriction can lead to chronic pulmonary hypertension, which can progress to right heart failure. A fuller understanding of the mechanisms of oxygen sensing in health and disease may lead to insights into therapeutic inhibition of this response in disease states.
In solid tumors, consumption of oxygen by highly metabolic tumor cells leads to hypoxia and threatens glucose supplies. Hypoxic tumor cells retain their oxygen sensing capacity and turn on expression of HIF-dependent genes, leading to tumor angiogenesis and increased blood supply, which permits further growth. We are currently exploring the hypothesis that the mitochondrial oxygen sensor is required for this response using pursuing genetic models. A better understanding of how tumor cells detect hypoxia could lead to the discovery of therapeutic approaches that would prevent detection of hypoxia and thereby prevent tumor progression.
For more information visit Dr. Schumacker's faculty profile page
View Dr. Schumacker's publications at PubMed
The Thorp laboratory studies how immune cells coordinate tissue repair and regeneration under low oxygen, such as after a heart attack.
The Edward Thorp Lab studies the crosstalk between immune cells and the cardiovascular system and, in particular, within tissues characterized by low oxygen tension or associated with dyslipidemia, such as during myocardial infarction. In vivo, the lab interrogates the function of innate immune cell phagocytes, including macrophages, as they interact with other resident parenchymal cells during tissue repair and regeneration. Within the phagocyte, the influence of hypoxia and inflammation on intercellular and intracellular signaling networks and phagocyte function are studied in molecular detail. Taken together, our approach seeks to discover and link basic molecular and physiological networks that causally regulate disease progression and in turn are amenable to strategies for the amelioration of cardiovascular disease.
View Dr. Thorp's publications at PubMed
Contact the Thorp lab at 312-503-3140.
Xin-Yi Yeap, MS
Lab Manager and Microsurgery
Mechanisms of poxvirus and herpesvirus infection; translational control of gene expression; virus trafficking
Research in our laboratory focuses on two aspects of DNA virus biology:
1) The role of the host translation system during infection by poxviruses. Members of the poxvirus family include Variola Virus (VarV), the causative agent of smallpox, and Vaccinia Virus (VacV), a close relative that was used as a vaccine against smallpox and which has become the laboratory prototype for poxvirus research. These large double-stranded DNA viruses exhibit an impressive level of self-sufficiency and encode many of the proteins required for transcription and replication of their DNA genomes. Indeed, unlike many other DNA viruses, poxviruses do not require access to the host nucleus and replicate exclusively in the cytoplasm of infected cells within compartments termed “viral factories”. However, like all viruses, they remain dependent on gaining access to host ribosomes in order to translate their mRNAs into proteins and must also counteract host antiviral responses aimed at crippling the translation system to prevent virus replication.
Our work focuses on the function of two eukaryotic translation initiation factor (eIF) complexes, eIF3 and eIF4F, that regulate ribosome recruitment to capped mRNAs and their role in VacV infection. We have found that VacV stimulates the assembly of eIF4F complexes and that this is important for both viral protein synthesis and control of host immune responses. Furthermore, we have found that eIF3 functionally communicates with eIF4F during translation initiation and that this plays an important role in VacV replication. We have also found that VacV redistributes key eIF4F subunits to specific regions within viral factories, a process that appears to involve the viral I3 protein.
We are currently exploring the compartmentalized replication of VacV as a means to better understand fundamental mechanisms of localized translational control and how this functions to regulate viral protein synthesis and host antiviral responses. We are also studying how the virus controls eIF4F activity by targeting upstream signaling pathways, with a particular emphasis on the metabolic sensor mammalian target of rapamycin (mTOR).
2) Microtubule regulation and function during herpes simplex virus infection. We are also interested in how herpes simplex virus type 1 (HSV-1) exploits host signaling pathways and specialized microtubule regulatory proteins, called +TIPs, to facilitate virus movement within the cell at various stages of the viral lifecycle.
See publications on PubMed.
Contact Dr. Walsh at 312-503-4292
Technical StaffHelen Astar
The Wu Laboratory seeks to understand molecular mechanisms regulating gene expression and their involvement in the pathogenesis of age-related diseases, including neurodegeneration and tumor metastasis.
RNA Processing and Neurodegeneration
Accumulating evidence supports that aberrant RNA processing represents a general pathogenic mechanism for neurodegeneration, including dementia and amyotrophic lateral sclerosis (ALS). A number of RNA binding proteins (RBPs) have been associated with neurodegenerative diseases, especially various proteinopathies. Recent studies have defined TDP-43 and FUS proteinopathies, a group of heterogeneous neurodegenerative disorders overlapping with dementia, including frontotemporal lobar degeneration (FTLD) and ALS. Several important questions drive our research: what is physiological function of these RBPs? What are the fundamental mechanisms by which genetic mutations in or aberrant regulation of these RBPs cause neural damage? What are the earliest detectable molecular and cellular events that reflect the neural damage in these devastating neurological diseases? How to reverse/repair the neural damage and slow down the progression of these devastating diseases.
To address these questions, we have established cellular and animal models for both TDP-43 and FUS proteinopathies (Li et al, 2010;Barmada et al, 2010; Chen et al, 2011; Fushimi et al, 2011). Using combined biochemical, biophysical, molecular biology and cell biology approaches, we have begun to examine the molecular pathogenic mechanisms underlying neurotoxicity induced by TDP-43 and FUS. Our recent work using atomic force microscopy (AFM), electron microscopy (EM) and (NMR) approaches has shown the biochemical, biophysical and structural similarities between TDP-43 and classical amyloid proteins (Guo et al, 2011; Xu et al, 2013; Bigio et al, 2013). Our study has defined a minimal amyloidogenic region at the carboxyl terminal domain of TDP-43 that is sufficient for amyloid fibril formation and neurotoxicity (Guo et al, 2011; Zhu et al, unpublished). Using cellular and animal models for FUS proteinopathy, we have begun to identify the earliest detectable cellular damage caused by mutations in and overexpression of the human FUS gene. Our data have provided new insights into pathogenic mechanisms underlying these proteinopathies and suggested candidate targets for developing therapeutic approaches.
A critical step in mammalian gene expression is the removal of introns by the process of pre-mRNA splicing. Alternative pre-mRNA splicing, the process of generating multiple mRNA transcripts from a single genetic locus by alternative selection of distinct splice sites, is one of most powerful mechanisms for genetic diversity and an excellent means for fine-tuning gene activity. Many genes critical for neuronal survival and function undergo extensive alternative splicing. Splicing defects play important roles in neurodegenerative disorders such as dementia and motor neuron diseases. For example, splicing mutations in the human tau gene and imbalance of tau splicing isoforms lead to frontotemporal lobar degeneration with tau-positive pathology (FTLD-tau). To understand mechanisms underlying FTLD-tau, we have set up a model system and developed a number of biochemical, molecular and cell biological assays to study alternative splicing of the human tau gene. Our work has led to the identification of a number of cis-elements and trans-acting RBPs controlling tau alternative splicing (Kar et al, 2006; Wu et al, 2006; Kar et al, 2011; Ray et al, 2011). Our experiments have begun to reveal previously unknown players in FTLD-tau and provided new candidate target genes for developing therapeutic strategy (Donahue et al, 2006; unpublished).
Molecular Mechanisms Regulating Axon Guidance, Cell Migration & Tumor Metastasis
Another line of our research focuses on the cellular and molecular mechanisms regulating cell migration and cancer metastasis. Previous studies from our group and others led to the discovery of Slit as a prototype of neuronal guidance cue. Our studies have shown that Slit interacts with Roundabout (Robo) and acts as a chemorepellent for axons and migrating neurons (Wu et al, 1999; Li et al, 1999;Yuasa-Kawada et al, 2009). Our work has demonstrated that Slit-Robo signaling modulates chemokines and inhibits migration of different types of cells, including cancer cells. The observation that Slit is frequently inactivated in a range of tumors suggests an important role of Slit in tumor suppression. We have established several assays and shown that Slit inhibits invasion and migration of cancer cells, including breast cancer, glioma and prostate cancer. We are using combined molecular and cell biology approaches to dissecting Slit-Robo signaling in neuronal guidance and tumor suppression. Our research has provided new insights into signal transduction pathways mediating Slit function. Enhancing or activating the endogenous mechanisms that restrict or suppress cancer invasion/metastasis will likely provide novel approaches to cancer metastasis.
View a full list of publications by Jane Wu at PubMed
Jane Wu, MD, PhD, at 312-503-0684
Molecular mechanisms of ribosome hibernation and antibiotic resistance
We broadly investigate the mechanisms used in bacterial cells to regulate antibiotic resistance and gene expression at the translational level. Our long-term goals are to address mechanistic questions about ribosome specialization and resistance evolution, in addition to developing aptamer-based diagnostic tools for bacterial pathogens.
Multidrug resistant ribosome
Macrolides, lincosamides and streptogramins (MLS) are structurally distinct and broad-spectrum antibiotics that inhibit protein biosynthesis by binding to the 50S large subunit of bacterial ribosome.The efficacy of MLS has rapidly eroded due to the widespread dissemination of the Erm RNA methyltransferases that catalyze the transfer of two methyl groups to a conserved adenine nucleotide (m26A2058) in the 23S rRNA of the 50S subunit. This dimethylation sterically hinders the binding of all MLS antibiotics that share the overlapping A2058, in addition to abrogating the MLS resistant bacteria from host immune recognition. Our studies seek to addresses several unresolved questions: How is the expression of erm regulated under antibiotic selection? How does Erm find its target? What are the consequences of ribosome methylation? How do the next-generation antibiotics recognize the methylated ribosome?
The bacterial 100S ribosome (dimer of 70S complexes) is important for pathogenesis, translational repression, starvation responses, and ribosome turnover. Our goal is to establish a mechanistic understanding of the biogenesis and function of the 100S ribosome in translational silencing and staphylococcal pathogenesis. This project focuses on the following unexplored questions: What factors control the constitutive production of the 100S ribosome in S. aureus? Why are only specific mRNAs translationally repressed during ribosome hibernation? How is hibernation beneficial to ribosome stability? How is ribosome turnover linked to successful host colonization? These questions will be addressed through a multi-disciplinary approach that spans genetics, molecular biophysics, biochemistry, and whole animal infection studies.
For lab information and more, see Dr. Yap's faculty profile.
See Dr. Yap's publications on PubMed.
Contact Dr. Yap.
The Zhao lab develops diagnostic markers and investigates pathogenic mechanisms of human diseases based on changes in cellular membranes.
Major research areas in the Zhao lab include:
- Apoptosis imaging technology development. Programmed cell death (apoptosis) plays a significant role in degenerative diseases. There is currently no clinical tool for assessing apoptosis in pathological conditions. Our research focuses on the development of optimal agents that combine sophisticated binding activities and favorable clearance kinetics for clinical translation.
- Assessing systemic toxicity in anticancer therapies. The outcome of chemotherapies hinges on the balance between tumor toxicity and patient tolerance. With the ability to noninvasively detect tissue apoptosis, we propose to assess anticancer therapies in a whole-body approach by monitoring tumor cell killing simultaneously with systemic tissue injury in response to chemotherapeutic agents. This is a transformative approach in oncology in terms of optimizing therapies on an individualized basis.
- Detecting myocardial injury in ischemic heart disease. Non-infarct myocardial injury in ischemic heart disease is of particular interest because this type of cardiac injury is not well understood in terms of its pathophysiological characteristics and its roles in long-term adverse cardiac events. Our research in this area focuses on the diagnosis of non-infarct myocardial injury, which in turn, will help address a significant gap in identifying patients at risk.
- Investigating the pathogenesis of antiphospholipid syndromes. The presence of circulating antibodies against phosphatidylethanolamine (PE) is positively correlated with clinical manifestations of antiphospholipid syndromes. However, the underlying pathogenic mechanism of anti-PE autoimmunity remains unknown. We have a major interest in investigating the cellular susceptibility to PE-binding agents, which in turn, will shed light on the potential pathogenic mechanism of aPE.
View publications by Ming Zhao in PubMed.
For more information, visit Dr. Zhao's Faculty Profile page
Contact Dr. Zhao at 312-503-3226.
Songwang Hou, PhD
Steven E. Johnson
Ke Ke, PhD
Kaixi Ren, MD