Microbiology
Research into bacteriology, parasitology, and virology
All Labs In This Area
Cytomegalovirus latency and reactivation
Research Description
Cytomegalovirus (CMV) is a herpes virus that infects the majority of adults and is able to establish a lifelong latent infection. Reactivation of the virus is frequently observed in transplant recipients and is associated with serious morbidity and occasionally with mortality. CMV infection can be transmitted from the mother to the fetus during pregnancy and can be associated with severe congenital abnormalities or death of the fetus. Our lab studies the molecular mechanism by which CMV establishes latent infection and reactivates from latency. These studies may suggest strategies for developing drugs that prevent reactivation and its associated sequelae.
Reactivation from latency:
Mice latently infected with murine CMV are used in transplants to investigate the hypothesis that reactivation is triggered by the allogeneic response to the transplanted organ. The inflammatory cytokine TNF and the transcription factor NFkB are particular targets of investigation. Transplanted organs are analyzed for RNA expression and activation of transcription factors known to be involved in regulating viral gene expression. Transgenic and knock-out mice are used to identify cellular genes involved in reactivation of the virus. Gene therapy vectors and pharmacological agents are used to investigate new potential therapeutic agents.
Molecular mechanism of latency:
The mechanism by which CMV is able to hide in a quiescent state in latently infected cells and avoid elimination by the host immune response is unknown. Studies to investigate potential epigenetic mechanisms of transcriptional silencing, including DNA methylation and histone modifications are being explored to investigate viral latency.
For more information, see Dr. Abecassis's faculty profile.
Publications
See Dr. Abecassis's publications on PubMed.
Contact Info
The Structural Basis of Protein Functions
Research Description
The interactions of proteins with other biological molecules are central features of all biological processes. A molecular understanding of these interactions requires a knowledge of both the three dimensional structures and the biological functions of the molecules involved. Because the most generally applicable method of determining three dimensional structures of biological macromolecules is X-ray crystallography, this technique is central to how we approach biological questions.
A major focus of the lab is in structural genomics. The genome sequencing projects are producing a vast database of sequence information and provide a list of the proteins and their sequences that are used by that organism. The next logical step is to ask what these proteins look like and how they work. This requires developing methods for high throughput structure determination and applying those methods to determine the structures of a large number of target proteins.
A second focus is utilization of the results of the structural genomics effort to expand our understanding of biology. The existence of large databases of protein sequences and structures, combined with the lack of functional characterization of many of those proteins, has reversed the historic pathway leading from function to structure and sequence. Now we need to utilize the sequence and structure information available for proteins to suggest possible functions. The existence of large families of proteins with conserved sequences and structures that are represented in a wide range of organisms but are functionally uncharacterized highlights fundamental areas of biology that are unexplored. Therefore, we are selecting particularly interesting proteins from our structural genomics efforts for further studies of their biological functions.
In addition to providing a library of the most biologically important protein structures, the international structural genomics initiatives provide important information for studies of enzyme mechanisms and the structural basis for catalysis, nucleic acid-protein interactions, protein-protein interactions, and allosteric regulation of protein function. Because the majority of the proteins that have been targeted for structure determination are from bacterial pathogens, the resulting library of structures additionally provide useful starting points for structure guided drug discovery of novel antimicrobials.
For more information, see Dr. Anderson's faculty profile.
Publications
Please see Dr. Anderson's publications in PubMed.
Contact
Pathogenesis of Legionella pneumophila and Stenotrophomonas maltophilia
Research Description
L. pneumophila, the agent of Legionnaires' disease, is a classic environmental, opportunistic pathogen. The aim of our research is to characterize the bacterial genes and gene products that promote the occurrence of Legionnaires' disease.
S. maltophilia is an environmental gram-negative bacterium that is being increasingly associated with an array of human infections, including most notably pneumonia. The emergence of S. maltophilia as a significant health concern is due in part to its marked antibiotic resistance. Our lab has developed murine models of lung infection and is currently identifying virulence factors produced by this important new pathogen.
We employ a multi-faceted approach toward understanding the pathogenesis and natural history of bacterial infectious disease, with the hope that basic insights will lead to new methods of disease prevention, diagnosis, or treatment.
For lab information and more, see Dr. Cianciotto’s faculty profile and lab website.
Publications
See Dr. Cianciotto's publications on PubMed.
Contact
Contact Dr. Cianciotto at 312-503-0385 or the lab at 312-503-1034.
Pathogenesis of human immunodeficiency virus (HIV)
Research Description
The D’Aquila laboratory studies the pathogenesis of human immunodeficiency virus (HIV) persistence/latency, and mechanisms of host “intrinsic” immune control of HIV replication. The long-term goal is to develop innovative strategies for a “functional cure” of HIV. We are developing novel interventions to induce sustained remissions after defined-duration antiretroviral therapy (ART). This includes bench-to-bedside research to characterize / leverage / increase APOBEC3 (A3) “intrinsic” immune defenses against HIV, diminish T cell activation-fueled HIV replication, and innovate strategies to minimize latency/persistence of HIV.
In papers published in recent years, the D’Aquila laboratory proved that APOBEC3G and F are active in producer and target cells against wild-type (Vif-positive) HIV-1 at higher physiological levels of expression. Evidence was published that higher levels of A3G protein and activity contribute to the multiple mechanisms of spontaneous control of HIV-1 without ART seen in rare “elite controllers”. The laboratory has also identified that limiting c-Myc-dependent effects of the host T cell activation process limits early HIV replication in a way that may augment current virus-specific ART agents.
For more information, please see Dr. D'Aquila's faculty profile.
Publications
See Dr. D’Aquila's publications in PubMed.
Contact
Phone 312/695-5085
Targets and functions of miRNAs encoded by the human herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV)
Research Description
Viruses commonly modify their cellular environment to optimize viral replication and persistence. Much has been learned about the intervention of viral proteins with cellular pathways. More recently, it has become clear that herpesviruses also encode large numbers of microRNAs (miRNAs). The modest amount of space miRNA precursors occupy in the viral genome, their lack of immunogenicity and their potential as regulators of gene expression make miRNAs ideal candidates for viral effectors.
The lab’s research focuses on identifying targets and functions of miRNAs encoded by the human herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV causes cancer in immuno-compromised individuals. The clinically most relevant KSHV-induced disease is Kaposi’s sarcoma (KS), a complex tumor driven by KSHV-infected endothelial cells. Due to the AIDS epidemic, KS has become the most common cancer in parts of Africa. KSHV also infects B lymphocytes and can consequently cause B cell lymphomas, including primary effusion lymphoma (PEL). KSHV constitutively expresses viral miRNAs from 12 precursors, suggesting a role of these miRNAs in viral replication and pathogenesis.
My lab is currently pursuing the comprehensive identification of mRNA targets of these miRNAs in primary effusion lymphoma cell lines and KSHV-infected endothelial cells. Our data suggest that, together, the KSHV miRNAs directly target hundreds of cellular mRNAs encoding proteins with roles in several different biological pathways. Our goal is to use this knowledge to characterize the most important functions of the KSHV miRNAs.
For lab information and more, see Dr. Gottwein's faculty profile and lab website.
Publications
See Dr. Gottwein's publications on PubMed.
Contact
Contact Dr. Gottwein at 312-503-3075 or the lab at 312-503-3076.
Lab Staff
Postdoctoral Fellows
Graduate Student
Samuel Harvey, Letonia Copeland-Hardin, Kylee Morrison
Technical Staff
Pathogenesis of Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae infections
Research Description
Our laboratory investigates the pathogenesis of the gram-negative bacteria Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. We focus on virulence factors such as the type III secretion, an apparatus that injects toxins directly into host cells. A second interest is the use of genomic approaches for the identification of novel virulence determinants. Our studies utilize a broad range of techniques, including molecular and cellular assays as well as animal models and epidemiologic studies on human populations.
For lab information and more, see Dr. Hauser's faculty profile and lab website.
Publications
See Dr. Hauser's publications on PubMed.
Contact
Contact Dr. Hauser at 312-503-1044 or the lab at 312-503-1081.
Lab Staff
Postdoctoral Fellows
Jonathan Allen, Kelly Bachta, Andrew Morris, Timothy Turner
Graduate Students
Mallory Agard, Ami Joy Hughes, Nathan Pincus, Angelica Zhang
Technical Staff
Studying the posttranscriptional regulation of intronless viral messages
Research Description
We study the posttranscriptional regulation of intronless viral messages. Intronless messages must be efficiently processed in the absence of splicing. Therefore, intronless messages must uncouple RNA processing and export from the splicing process making a simpler model system. We are currently focused on the posttranscriptional regulatory element (PRE) of the Hepadnaviruses, including hepatitis B virus (HBV) and woodchuck hepatitis virus (WPRE). Our goal is to understand the novel mechanism of the stimulation of heterologous gene expression by the WPRE. Understanding WPRE function will allow the development of even more efficient gene expression for a variety of applications from gene therapy to large scale protein production.
Although much is known about the molecular biology of HIV, little is known about the details of interactions between the virus and cellular components such as the cytoskeleton. To gain insights into these processes we are combining the disciplines of virology and cell biology to develop the field of cellular virology. We are especially excited by new methods we have developed – such as time-lapse analysis and fluorescent tagging – that allow for HIV to be visualized in living cells.
For lab information and more, see Dr. Hope's faculty profile and lab website.
Publications
See Dr. Hope's publications on PubMed.
Contact
Contact Dr. Hope at 312-503-1360.
Lab Staff
Research Faculty
Postdoctoral Fellows
Shannon Allen, Ann Carias, Katarina Halavaty, Joao Mamede, Danijela Maric, Yanille Scott, Roslyn Taylor
Project Manager
Technical Staff
Edward Allen, Melanie Bollnow, Ashley Lin, Edgar Matias, Michael McRaven
Program Staff
Molecular Mechanisms Of Bladder Inflammation and Pelvic Pain
Research Description
Our laboratory employs state-of-the-art cell culture and animal models to pursue multi-disciplinary projects in bacterial pathogenesis and neuro-immune interactions in a crippling pain syndrome. A key to our success is the rich training environment resulting from the close collaboration between clinical and basic scientists.
Urinary tract infection (UTI) is both a major medical issue and a fascinating problem of bacterial pathogenesis. We investigate all aspects of host pathogen interactions, from the immediate biochemical signaling evoked in bladder cells, to the associated inflammation, to the development of adaptive immune responses. We recently identified a novel signaling response of bladder cells induced by binding of uropathogenic E. coli (UPEC) that mediates the mutually exclusive processes of epithelial cell apoptosis and bacterial invasion of bladder epithelial cells; how this occurs is an active area of study. We have also identified a candidate live-attenuated UTI vaccine based on a UPEC mutant. We find that the UPEC mutant vaccine induces protective responses 100-fold greater than wild type UPEC. We are now determining the mechanism of this enhanced response by testing the hypothesis that the UPEC mutant skews the normal immune response and thus generates a more effective immunity.
Although pelvic pain can result from acute infection, interstitial cystitis (IC) is a debilitating chronic pelvic pain syndrome of unknown origin that is often considered a chronic bladder inflammation. We utilize a herpesvirus to induce an IC-like condition in mice. Using this model, we have identified the mechanisms that result in both bladder pathophysiology and pelvic pain. Interestingly, while both pain and bladder damage require mast cell activation, pelvic pain results from the release of mast cell histamine, whereas bladder pathology is driven by mast cell release of tumor necrosis alpha (TNF). Current studies include the genetic basis of pain susceptibility, the spinal regulation of histamine and TNF release, and the viral basis of pain. In addition, we recently were awarded a prestigious NIH center grant to study pelvic pain syndromes. The center award will extend our bladder pelvic pain studies to prostate- and bowel-associated pelvic pain and determine the mechanisms of pelvic organ crosstalk and signal integration in the spinal cord in mice. Our center collaborators will examine cortical and cognitive changes in pelvic pain patients using a combination of functional MRI and behavioral tests and develop novel quality-of-life tests to characterize pelvic pain non-invasively within populations. Thus, this center will illuminate pelvic pain mechanisms in clinical, epidemiologic, and basic animal studies.
For more information, visit Dr. Klumpp's faculty profile or lab website.
Publications
See Dr. Klumpp's publications in PubMed.
Lab Staff
Graduate Student
Lizath Aguiniga
Contact
Molecular biology of human papillomaviruses (HPV) and their association with cervical cancer
Research Description
Our efforts are divided into two main categories:
- An examination of how the viral oncoproteins E6 and E7 contribute to the development of malignancy
- Studies on the mechanisms controlling the viral life cycle in differentiating epithelia
More than 100 distinct types of human papillomavirus have been identified and approximately one-third specifically target squamous epithelial cells in the genital tract. Of these genital papillomaviruses, a subset including types 16,18 and 31 have been shown to be the etiological agents of most cervical cancers.
One of our goals is to understand why infection by specific HPV types contributes to the development of malignancy. For these studies we have examined the interaction of the oncoproteins E6 and E7 with cellular proteins. In particular, E6 binds the p53 protein and facilitates its degradation by a ubiquitin-mediated pathway. It also activates telomerase as well as associates with PDZ-domain containing proteins. The interactions of the E6 and E7 proteins with these cellular proteins are being examined at both the biochemical and genetic level.
In examining the papillomavirus life cycle, we have used organotypic tissue culture systems to faithfully reproduce the differentiation program of epithelial cells in the laboratory. Using this system, the viral life cycle has been duplicated. We are studying the mechanisms that regulate viral DNA replication, cell entry, immune evasion and gene expression. These studies should provide insight into viral pathogenesis as well as the mechanisms regulating epithelial differentiation.
For lab information and more, see Dr. Laimins's faculty profile and lab website.
Publications
See Dr. Laimins's publications on PubMed.
Contact
Contact Dr. Laimins at 312-503-0648 or the lab at 312-503-0650.
Lab Staff
Research Associates
Postdoctoral Fellows
Elona Gusho, Sreedhar Pujari, Xin Zhao
Graduate Students
Host-pathogen interactions during pneumonic plague; post-transcriptional gene regulation in Yersinia pestis and Yersinia pseudotuberculosis
Research Description
Yersinia pestis and Yersinia pseudotuberculosis are two bacterial pathogens that are very closely related, yet cause vastly different diseases in the mammalian host. Y. pestis is infamous for causing the devastating disease plague, while Y. pseudotuberculosis infection often results in a mild, self-limiting gastrointestinal illness. While genetically similar, the distinct mechanisms by which these two bacterial species interact with the host is of great interest to our group.
Shared amongst both pathogens is a protein called Hfq, which serves as a chaperone for small, non-coding regulatory RNAs (sRNAs). One set of projects in the lab centers on understanding the post-transcriptional regulatory networks controlled by Hfq and sRNAs in both Yersinia species, particularly as they relate to virulence. Our group is testing the hypothesis that the similarities and differences in sRNA gene content and expression between these species may explain how a relatively mild pathogen evolved into one of the most deadly known to mankind.
We are also interested in determining the mechanisms by which Y. pestis specifically causes primary pneumonic plague, a respiratory form of disease that Y. pseudotuberculosis does not produce. Therefore, another set of projects in the lab focuses on dissecting the mechanisms by which the Y. pestis virulence factor known as the plasminogen activator Pla, a bacterial cell surface-bound protease, controls the development of pneumonic plague. These include understanding the interaction of Y. pestis and Pla with the mammalian fibrinolytic and coagulation cascades, the identification of additional host substrates cleaved by Pla that lead to the development of a severe pneumonia, and the mechanisms by which Pla specifically induces an overwhelming inflammatory response in the lungs during infection.
For lab information and more, see Dr. Lathem's faculty profile.
Publications
See Dr. Lathem's publications on PubMed.
Contact
Contact Dr. Lathem at 312-503-2252 or the lab at 312-503-9738.
Lab Staff
Postdoctoral Fellow
Graduate Student
Temporary Staff
Epstein-Barr virus (EBV) and herpes simplex virus (HSV) entry, replication, and pathogenesis
Research Description
Research in the Longnecker laboratory focuses on herpes simplex virus (HSV) and Epstein-Barr virus (EBV). These viruses typically cause self-limiting disease within the human population but both can be associated with serious complications. EBV is associated with variety of hematopoietic cancers such as African Burkitt lymphoma, Hodgkin Lymphoma and adult T-cell leukemia. EBV-associated lymphoproliferative disease occurs in individuals with congenital or acquired cellular immune deficiencies. The two notable epithelial diseases associated with EBV infection are nasopharyngeal cancer and oral hairy leukoplakia. Similar to EBV, HSV latent infections are very common in humans. HSV typically does not cause severe disease but is associated with localized mucocutaneous lesions, but in some cases can cause meningitis and encephalitis. The Longnecker laboratory focuses on several aspects of EBV and HSV replication and pathogenesis. First, the molecular basis EBV transformation and how it relates to cancer is being investigated. The laboratory is currently screening selective inhibitors that may be beneficial in EBV-associated cancers such as Hodgkin lymphoma, Burkitt lymphoma and proliferative disorders that occur in HIV/AIDS and transplant patients. Second, the laboratory is investigating herpesvirus latency in the human host and pathogenesis associated with infections in humans. In this regard, the laboratory is developing animal models for EBV and HSV infections. Finally, the laboratory is investigating the function of herpesvirus encoded proteins and the cellular receptors that are important for infection both using in vivo culture models as well as animal models. Ultimately, studies by the Longnecker laboratory may provide insight for the development of novel therapeutics for the treatment of herpesvirus infections in humans and better understanding of the herpesvirus life cycle in the human host
For lab information and more, see Dr. Longnecker's faculty profile.
Publications
See Dr. Longnecker's publications on PubMed.
Contact
Contact Dr. Longnecker at 312-503-0467 or the lab at 312-503-0468 or 312-503-9783.
Lab Staff
Research Faculty
Adjunct Faculty
Sarah Connolly, Michelle Swanson-Mungerson
Postdoctoral Fellows
Jia Chen, Kamonwan "Pear" Fish
Graduate Students
Rebecca Edwards, Daniel Giraldo, Seo Jin Park, Richard Sora, Jr.
Technical Staff
Sarah Kopp, Rachel Riccio, Samantha Schaller, Nanette Susmarski
Host-microbiota specificity, communication, and evolution
Research Description
Microbial symbioses are prevalent in animal biology, and often, as in the case of humans, the animal host is born devoid of its natural symbionts and must acquire microbial partners from the environment. Pathogenic and beneficial bacteria share common mechanisms by which they colonize animal tissue. In spite of these parallels, relatively little work has been accorded to the beneficial associations, which are widespread, and critical to the lifecycles of both the bacterial and animal partners.
Our lab is studying the natural Vibrio-squid model to understand the processes that underlie host association in animal-associated bacteria. I discovered that a single gene is sufficient to shift the host range of Vibrio fischeri. In future research, we will combine genetic, genomic, microscopy, and evolutionary approaches to study the dynamics of host-symbiont relationships.
The binary association between bioluminescent V. fischeri bacteria and Euprymna scolopes squid provides a natural system in which to investigate the mechanistic basis by which animals and bacteria initiate mutually-beneficial relationships. Both organisms may be obtained directly by environmental collection, and cultured independently of each other. As such, this association provides a relatively simple, yet natural, system in which to study the specific colonization of animal hosts by beneficial bacteria. Related squids harbor V. fischeri symbionts, and are also amenable to experimentation. This system reflects features that are shared by many beneficial and pathogenic host-bacterial interactions, including:
- Aposymbiotic (uncolonized) juvenile hosts acquire the symbiont from the environment
- Productive association relies on specificity in a mucosal environment
- The bacteria colonize host epithelial tissue
- Both partners undergo dramatic cellular and developmental changes as a result of the interaction
- Host and symbiont form a chronic association that persists throughout the lifetime of the host
Using this system, we are asking how host specificity develops, how symbiont genomes evolve, and how symbiont genetics and genomics influence the earliest stages of the interaction with the squid host.
For lab information and more, see Dr. Mandel's faculty profile and lab website.
Publications
See Dr. Mandel's publications on PubMed.
Contact
Contact Dr. Mandel at 312-503-4138 or the lab at 312-503-2915.
Lab Staff
Postdoctoral Fellows
Graduate Student
Technical Staff
Undergraduate Students
Temporary Staff
Elucidation of mechanisms of pathogenesis and immune regulation of autoimmune disease, allergy and tissue/organ transplantation
Research Description
The laboratory is interested in understanding the mechanisms underlying the pathogenesis and immunoregulation of T cell-mediated autoimmune diseases, allergic disease, and rejection of tissue and organ transplants. In particular, we are studying the therapeutic use of short-term administration of costimulatory molecule agonists/antagonists and specific immune tolerance induced by infusion of antigen-coupled apoptotic cells and PLG nanoparticles for the treatment of animal models of multiple sclerosis and type 1 diabetes, allergic airway disease, as well as using tolerance for specific prevention of rejection of allogeneic and xenogeneic tissue and organ transplants.
Promising Results in Early Trial of Novel MS Treatment: Listen to a Science Friday interview with Dr. Miller regarding the Phase 1 clinical trial in multiple sclerosis patients. Read the article in Science Translational Medicine Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis.
For lab information and more, see Dr. Miller's faculty profile.
Publications
See Dr. Miller's publications on PubMed.
Contact
Contact Dr. Miller at 312-503-7674 or the lab at 312-503-1449.
Lab Staff
Research Faculty
Joseph Podojil, Andrew Robinson
Postdoctoral Fellows
Igal Ifergan, Tobias Neef, Kyle O'Hagan, Haley Titus-Mitchell, Dan Xu
Technical Staff
Sara Beddow, Valerie Eaton, Lindsay Moore
Program Staff
Visiting Scholars
Microtubule regulation and function during infection by Human Immunodeficiency Virus (HIV)
Research Description
Our research focuses on infection by Human Immunodeficiency Virus type 1 (HIV-1), a retrovirus and causative agent of acquired immunodeficiency syndrome (AIDS). In addition to suppressing the immune system, rendering victims susceptible to opportunistic infections, HIV-1 can cross the blood-brain barrier and cause serious damage to the central nervous system, ultimately leading to HIV-associated dementia.
We are interested in how HIV-1 particles move within infected cells, including brain cell types such as microglia. Our work focuses on how the virus exploits host microtubules, the intracellular filaments that mediate cargo trafficking to different subcellular sites within the cell.
Our earlier work, employing a variety of screening approaches, identified a number of host proteins involved in cytoskeletal regulation and motor function as playing key roles in the early stages of HIV-1 infection. This includes Ezrin-Radixin-Moesin (ERM) proteins, which cross-link the actin and microtubule cytoskeletons. In exploring their role in HIV-1 infection, we identified the first biological function for the host protein, PDZD8, demonstrating that it binds ERMs to control microtubule stability. Furthermore, we uncovered that PDZD8 is a direct target for the HIV-1 protein, Gag.
Other work in our laboratory has shown that HIV-1 can induce the formation of highly stable microtubule subsets to facilitate early HIV-1 trafficking to the nucleus. We are interested in the role played in this process by proteins such as PDZD8, as well as a family of specialized microtubule regulatory proteins called +TIPs, which accumulate at the ends of dynamically growing microtubule filaments to control their growth and stability. We are also interested in the function of microtubule motors and cargo adaptor proteins in HIV-1 infection. In particular, we are exploring how Fasiculation and Elongation factor Zeta-1 (FEZ-1), a kinesin-1 adaptor protein that is highly expressed in neurons, functions to control HIV-1 infection. Our work employs a range of approaches, including biochemical characterization of protein-protein interactions as well as live imaging of fluorescently-labeled HIV-1 particles as they move within infected cells.
The ultimate goal of our work is to understand the molecular basis behind how microtubules, regulators of microtubule dynamics and microtubule motor proteins function to enable HIV-1 movement to and from the nucleus.
For lab information and more, see Dr. Naghavi's's faculty profile and lab website.
Publications
See Dr. Naghavi's publications at PubMed.
Contact
Contact Dr. Naghavi at 312-503-4294.
Lab Staff
Postdoctoral Fellows
Qingqing Chai, Viacheslav Malikov, Sahana Mitra, Eveline Santos da Silva, Christopher Traylen
Technical Staff
Role of bacterial protein toxins in the pathogenesis of Vibrio vulnificus and Vibrio cholerae
Research Description
My research focuses on the role of secreted protein toxins on bacterial pathogenesis. The toxins we study are members of the MARTX family and are produced by Vibrio cholerae, a pathogen important for the diarrheal disease cholera, and Vibrio vulnificus, a pathogen that causes septicemia and necrotizing fasciitis from seafood consumption as well as wound infections. Our group studies the mechanism of action of these toxins using a combination of cell biology, biochemistry, and structural biology. In addition, we investigate the role of these toxins in pathogenesis using animal and tissue culture models with focus on mechanisms of tissue damage and evasion of innate immune clearance.
For lab information and more, see Dr. Satchell's faculty profile and lab website.
Publications
See Dr. Satchell's publications on PubMed.
Contact
Contact Dr. Satchell at 312-503-2162 or the lab at 312-503-1503.
Lab Staff
Postdoctoral Fellows
Graduate Students
Technical Staff
Bacterial pathogenesis, DNA recombination mechanisms, epithelial cell adherence
Research Description
Our laboratory studies the pathogenesis of Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea. This gram-negative bacterium is an obligate human pathogen that has existed within human populations throughout recorded history. We are using a variety of molecular biological, genetic, cell biological and biochemical techniques to investigate the molecular mechanisms controlling gonococcal infection, define mechanisms and pathways of DNA recombination, replication and repair in this human specific pathogen, study the interactions between gonococci and human cells, tissues and the innate immune system, and determine how the pilus functions to help mediate genetic transfer and pathogenesis. Our goal is to discover new mechanisms important for the continued existence of this microbe in the human population to further our understanding of how infectious agents have evolved to specifically infect humans.
For lab information and more, see Dr. Seifert's faculty profile.
Publications
See Dr. Seifert's publications on PubMed.
Contact
Contact Dr. Seifert at 312-503-9788 or the lab at 312-503-9786.
Lab Staff
Research Faculty
Postdoctoral Fellow
Graduate Students
Cell and molecular biology of herpesvirus invasion of the nervous system
Research Description
We investigate the relationship between infection of the nervous system by herpesviruses and disease outcome. Some of the most traumatic diseases – including polio, rabies and encephalitis – result from infections of the nervous system. In contrast, herpesviruses are highly proficient at infecting the nervous system, yet normally do not cause neurological disease. This is achieved in part by self-imposed restrictions encoded within the viruses that limit viral reproduction and prevent dissemination into the brain. For the individual, this results in a relatively benign infection, yet the virus becomes a life-long occupant of the nervous system that will periodically reemerge at body surfaces to infect others. Unfortunately, this infectious cycle can go awry resulting in several forms of severe disease (i.e. keratitis and encephalitis).
We have pioneered methods to genetically manipulate herpesviruses and visualize individual viruses in living neurons. Using these methods, we are studying the mechanisms by which the virus achieves its stringently controlled infectious cycle. Current genetic manipulations are based on a full-length infectious clone of the herpesvirus genome. The clone was made as a bacterial artificial chromosome (BAC) in E. coli. Transfection of purified E. coli BAC plasmid into permissive eukaryotic cells is sufficient to initiate viral infection, allowing for immediate examination of viral mutant phenotypes in a variety of biological assays. For example, by fusing the green fluorescent protein (GFP) to a structural component of the viral capsid, individual viral particles can be tracked within the axons of living neurons during both entry and egress phases of the infectious cycle. Studies in culture can be complemented by examining the pathogenesis of mutant viruses in rodent models of infection.
Using these methods, we have discovered key aspects of cellular infection, viral assembly and intracellular transport. Looking forward, we are continuing to pursue our multidisplinary approach of combining neuroscience, cell biology, bacterial genetics and virology to better understand these important pathogens.
For lab information and more, see Dr. Smith's faculty profile.
Publications
See Dr. Smith's publications on PubMed.
Contact
Contact Dr. Smith at 312-503-3745 or the lab at 312-503-3744.
Lab Staff
Research Faculty
Postdoctoral Fellows
Graduate Students
The Sznajder Lab investigates the mechanisms of acute lung injury as related to aging, high CO2, low oxygen, lung cancer and influenza infection.
Seasonal influenza infection affects a significant proportion of the population in the US and worldwide and while most patients infected with influenza A virus (IAV) recover without sequelae, in many patients influenza virus infection may cause ARDS. Alveolar epithelial cells (AEC) are targets for IAV, and play an important role in mounting the initial host response. The Sznajder Lab hypothesizes that the alveolar epithelium plays an important effector role in protecting the lung from severe injury. Findings indicate that the degradation of PKCζ, which triggers the down-regulation of Na,K-ATPase, by the E3 ligase HOIL-1L decreases AEC death. HOIL-1L is a member of the Linear Ubiquitination Assembly Complex (LUBAC) and the lab studies whether LUBAC participates in the modulation of the inflammatory intensity in the lung epithelium during IAV infection. Also, they are investigating the mechanisms by which modest inhibition of the Na,K-ATPase, whether pharmacologic inhibition of the Na,K-ATPase by cardiotonic steroids such as ouabain are protective by inhibiting virus replication.
Studies suggest that signals from the injured lung during IAV infection disrupt skeletal muscle proteostasis and contribute to skeletal muscle dysfunction. The slower recovery of the skeletal muscle function in aged mice during IAV pneumonia is the consequence of diminished proteostatic reserve in cells responsible for regenerating the damaged skeletal muscle.
Hypercapnia (high pCO2) is observed in patients with lung diseases such as chronic obstructive pulmonary disease (COPD), broncho-pulmonary dysplasia and advanced neuromuscular diseases. The lab hypothesizes that hypercapnia promotes the ubiquitin-proteasome mediated muscle degradation and impairs the function of muscle satellite cells required for its regeneration.
Alveolar fluid reabsorption is effected by vectorial Na+ transport via apical Na+ channels and basolateral Na,K-ATPase of the alveolar epithelium. We and others have reported that β-adrenergic agonists upregulate the Na,K-ATPase in AEC by increasing the traffic and recruitment of Na,K-ATPase containing vesicles into the cell membrane, resulting in increased catalytic activity. Moreover, GPCR-mediated upregulation of the Na,K-ATPase resulted in increased alveolar fluid clearance in normal lungs and in rodent models of lung injury. We are investigating mechanisms of Na,K-ATPase regulation and active Na+ transport in lungs which will help with the design of new strategies to increase lung edema clearance.
Publications
View Dr. Sznajder's publications on PubMed
For more information visit the faculty profile of Jacob Sznajder, MD.
Contact
Contact Dr. Sznajder at 312-908-7737 or the Sznajder Lab at 312-503-1685.
Lab Staff
Laura Brion, PhD
Visiting Scholar
312-503-1685
Ermelinda Ceco, PhD
Postdoctoral Research Fellow
312-503-1685
Nina Censoplano, MD
Fellow, Pediatric Critical Care
312-503-1685
Laura A Dada, PhD
Research Associate Professor
312-503-5397
Jeremy Katzen, MD
Research Fellow
312-503-1685
Emilia Lecuona, PhD
Research Associate Professor
312-503-5397
Natalia Magnani, PhD
Postdoctoral Research Fellow
312-503-1685
Masahiko Shigemura, PhD
Postdoctoral Research Fellow
312-503-1685
Lynn C. Welch
Research Laboratory Manager
312-503-1685
Mechanisms of poxvirus and herpesvirus infection; translational control of gene expression; virus trafficking
Research Description
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.
For lab information and more, see Dr. Walsh's faculty profile and the lab website.
Publications
See publications on PubMed.
Contact
Contact Dr. Walsh at 312-503-4292
Lab Staff
Postdoctoral Fellows
Stephen DiGiuseppe, Sujata Jha, Vladimir Jovasevic, Nathan Meade, Dean Procter