Dr. Garima Agrahari, PhD.

Author: Deborah Donahue

While at the Center she worked on Group A Streptococcus (GAS) is a spherical, gram-positive bacterium that is responsible for numerous diseases with diverse clinical manifestations specifically in humans. GAS likely plays a role in global health issues such as impetigo, pharyngitis, scarlet fever and life-threatening diseases such as necrotizing fasciitis, toxic shock, acute post-streptococcal glomerulonephritis, acute rheumatic fever and rheumatic heart disease. The pathogenesis of invasive GAS infections involves several stages e.g., adhesion to epithelial surfaces, colonization, transmigration of the bacteria through the epithelium and subepithelium, survival in blood, penetration through the endothelium, and invasion into deep tissue. To accomplish these steps, GAS possesses numerous genes encoding virulence factors, many of which need to be transcribed and/or repressed at specific stages of infection. The multiple gene activator (mga) system is one of the best-studied regulators that activate and inactivate genes rapidly in GAS under changing environmental conditions. The cluster of virulence (cov) intracellular responder (covR)/extracellular sensor (CovS) system (covRS) is a two-component sensor/responder gene regulatory system in GAS that regulates repression and depression of ~15% of the GAS genome. At several stages of dissemination of GAS, this microorganism must develop strategies to evade the host innate immune system, especially complement-mediated elimination of the microbe in order to survive. Our studies have implicated CovRS in regulating the opsonophagocytosis of GAS by the host complement system which is a part of innate immune system. Therefore, my primary focus of interest is to study the regulation of bacterial opsonophagocytosis by the CovRS regulatory system.…

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Dr. Julia Beck, PhD

Author: Deborah Donahue

While at Notre Dame her research focus was on plasminogen, the zymogen, that when converted into its active form, plasmin, is able to activate the fibrinolytic system resulting in the degradation of fibrin and extracellular matrices. Group AStreptococcus (GAS) is able to hijack this system leading to a more invasive infection. This process is mediated by proteins found on the surface of the bacteria. One such protein is PAM that binds specifically to one of the lysine binding sites within the kringle domains of plasminogen. My interests are to further understand the role of the lysine binding sites in PAM binding.…

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Plenary Talk

Author: Deborah Donahue

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Dr. Francis J. Castellino was presented with a certificate of appreciation for giving the plenary talk at the 1st Joint Meeting of the ISFP and PA Workshop.  The organizing committee presented him with the certificate on October 17, 2016 in Shizuoka, Japan.…

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Kristofor Glinton, PhD

Author: Deborah Donahue

Kristofor Glinton

Congratulations Dr. Kristofor Glinton on Achieving Your PhD

Dr. Glinton focused on the interactions between the host fibrinolytic system and virulence factors associated with Group A Streptococcus. The ability of these bacteria to recruit fibrinolytic activity has been indicated in heightened virulence. The underlying mechanisms of this process will be explored, particularly the role of surface expressed M proteins binding to human fibrinogen.…

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ISTH SSC Montpellier, France

Author: Deborah Donahue

The ISTH SSC meeting was held in Montpellier, France May 25-28, 2016, two members of the Center were there to present work at the Fibrinolysis session.

Deborah Donahue presented "Coagulopathy in a Rat Model of Traumatic Brain Injury" and Dr. Mark Walsh gave a talk titled "The Incidence of Fibrinolysis in Multiple Trauma Identified with the Cartridge Thromboelastography (TEG6s): A Spectrum of Fibrinolytic Phenotypes".…

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The Three Minute Thesis (3MTĀ®) Competition

Author: Deborah Donahue

Kristofor Glinton is a finalist in the 3MT® competition with a talk entitled “Group A Streptococcal Infection: Manipulation of Host Fibrinolytic System”.

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Left to right: Claire Bowen, Nicholas Myers, and Kristofor Glinton, the College of Science 3MT Finalists.

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Congratulations Dr. Chandrahas and Dr. Kunda on Achieving Your PhDs

Author: Deborah Donahue

Vishwanatha Chandrahas

Vishwanatha Chandrahas

While at the Keck Center, Vishwanatha studied Group A streptococcus (GAS).  GAS is a human specific pathogen which causes trivial infections e.g., sore throat and impetigo, as well lethal infections e.g., necrotizing fasciitis and rheumatic heart disease. In order to infect its host, GAS expresses several pathogenic proteins like streptokinase (SK) which is secreted to the surrounding environment and M or M-like proteins which are embedded on cell membrane. M or M-like proteins are used as a basis for serotyping GAS strains into >250 types. GAS uses these proteins to exploit functional host fibrinolytic system for their own advantage. M or M-like proteins (e.g. M1 and PAM, respectively) tightly bind human plasminogen (hPg) and fibrinogen. SK secreted by GAS non-proteolytically activates hPg to a broad spectrum serine protease, plasmin (hPm), localizing proteolytic activity of hPm to GAS surface. hPm can break tissue barriers and assists GAS to invade tissue barriers and disseminate into deeper tissues.…

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Agrahari receives Fellowship from the Midwest Affliate of the American Heart Association

Author: Deborah Donahue

Garima Agrahari

Ms. Garima Agrahari, graduate student in the laboratory of Dr. Francis J. Castelllino, is a recent recipient of a 2 year predoctoral fellowship from the Midwest Affiliate of the American Heart Association.  The title of her study is “Molecular mechanisms of antiphagocytic activity mediated by Plasminogen binding group A streptococcal M-like protein.”…

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