Inflammation and Pathogenesis T32 Training Grant

PROGRAM OVERVIEW

    The Inflammation and Pathogenesis (I&P) research training grant is an NIH-supported project consisting of 34 faculty mentors from 8 departments of the University of Louisville Health Sciences Center. These faculty mentors are dedicated to and highly invested in the training of future scientist leaders.

   The I&P training program supports a total of four Ph.D. students for a period of two years following their entry into Ph.D. candidacy and fellowship nomination.Information about current trainees may be found below.

   The major objective of this pre-doctoral training program is to prepare the next generation of basic and translational scientists with cross-disciplinary expertise in inflammation and pathogenesis to establish a pipeline of influential investigators to maintain research excellence in the United States of America.

This objective will be accomplished by-  

  1. Promoting excellence and diversity in trainees with interest in basic immunology, inflammation, and pathogenesis.
  2. Establishing robust conceptual framework through a combination of didactic coursework, and student led discussion programs. This includes training in effective oral and written communication, grant development, and the responsible conduct of research.
  3. Providing rigorous training in basic immunology, inflammation, and pathogenesis in a collegial yet intellectually challenging environment using state-of-the-art technologies and innovative approaches.
  4. Fostering professional development and scientific leadership through the use of academic and  / or industry career-oriented seminars and engagement opportunities.

   The foundation of the I&P research training program builds upon a richly collaborative environment across the basic science and clinical departments of the Schools of Medicine and Dentistry at the University of Louisville. The faculty mentors have cumulatively mentored over 95 pre-doctoral and 214 postdoctoral trainees over the past ten years, and are currently serving as mentors to 88 Ph.D. students and 92 postdoctoral fellows.

The Inflammation and Pathogenesis training program is supported by NIH-training grant T32 AI132146

CURRENT INFLAMMATION AND PATHOGENESIS TRAINEES

TraineeProject

 LaPointe

Autumn T. LaPointe

(2018-2020)

   My research is focused on determining the importance of noncapped viral RNAs during alphaviral infection, as well as the effects of modulating vRNA capping on viral pathogenesis. Previous work has shown that despite not being infectious, noncapped genomic RNAs are packaged into viral particles. My work so far has shown that reducing the presence of noncapped vRNA is detrimental to alphaviral infection and pathogenesis, resulting in decreased viral particle production and decreased inflammation in the brains of infected mice. I am currently working on better characterizing what the roles of noncapped alphaviral vRNA during infection may be and how they impact pathogenesis.

2nd Year Trainee in the Sokoloski Lab

 Skidmore

Andrew M. Skidmore

(2019-2021)

   My research focuses on the characterization of the mechanism of action of antiviral compounds and how their targets function during infection. I am currently utilizing previously developed compounds that inhibit the replication of Venezuelan Equine Encephalitis virus to characterize the target regions of the viral nonstructural proteins 2 and 4. These regions appear to be novel targets for antivirals against alphaviruses, as they have not been previously implicated in viral replication. In addition, the target regions show clade-specific diversity among alphaviruses, implying an importance in alphavirus evolution and pathogenesis.

1st Year Trainee in the Chung Lab

 

Ben Charpentier

(2020-2021)

Trainee under the Shirisb Barve and Scott Whittemore 

   

Alcohol induced pathogenic changes in the gut-liver-brain axis: relevance to neuroinflammation and neuronal injury

My project supported by the T32 will explore the direct role of the microbiome in the development of alcohol induced neuroinflammation as well as the combinatorial effects with ethanol consumption. Our work has determined that patients with alcohol use disorders have pathogenic changes in the gut microbiome characterized by a loss of butyrate producing bacteria. We have generated gut-humanized mice by subjecting conventional mice to fecal microbiota transplantation (FMT) from alcoholic hepatitis (AH) patients (or controls) from a well phenotyped cohort. Using this innovative mouse model that recapitulates several important clinical features associated with AH, we are examining the impact of alcohol on the gut-liver-brain axis and development of neuro-inflammation and injury.  Our initial findings have identified for the first-time functional changes in neurons in response to both FMT and ethanol consumption.  We will use the funding opportunity to investigate the ethanol-driven pathogenic mechanisms leading to neuro-inflammation and neuronal injury employing well-established animal models of chronic ethanol consumption. Our previous work has identified that phosphodiesterase 4B (PDE4B) is a critical mediator of ethanol induced neuroinflammation.  Through the use of PDE4B chimeric animals, paired with the FMT model, we will determine if neuro-pathogenesis is mediated through systemic inflammation or is directly affected by local (brain) PDE4B activation.  Through these experiments we expect to advance the field by determining the pathogenic role of gut microbial dysbiosis and consequent PDE4B expression in the development of ethanol induced neuroinflammation and injury.  

 

V "Trey" D. Landers III

(2019-2021)

   My research is focused on understanding the pathogenesis of alphaviruses and how the host inflammatory processes are dysregulated during infection. The specific virus models used causative agents of infectious arthritis. Recently, we have identified that the alphaviral capsid protein interacts with cellular transduction components to decrease PAMP and cytokine signaling pathways. My ongoing research is aimed at further characterizing this phenomenon to better understand alphaviral disease, and to develop novel therapeutic strategies.

1st Year Trainee in the Sokoloski Lab

PRIOR INFLAMMATION AND PATHOGENESIS TRAINEES

TraineeProject

 Morgan Duff

Morgan Duff

(2018-19)

Trainee in the Schmidt Lab

My project focuses on evaluating the influence of the gut microbiota on the immune response to Plasmodium infection in mice. Our lab has previously found that C57BL/6 mice from different venders exhibit either a resistant or susceptible phenotype when infected with Plasmodium, and that these phenotypes are reproducible in Germ Free mice following cecal transplants. My project thus far has focused primarily on identifying what aspect of the immune system is driving these differences and has found it seems to be differences in the humoral immune response. I am currently working to better define the mechanism that is driving these humoral immune differences.

Sarah L. Price

(2019-2020)

Trainee in Lawrenz Lab

 My research focus is to identify a novel zinc acquisition system inYersinia pestis and study how the system is involved in plague pathogenesis. Previous work has revealed that Yersiniabactin, a well-established iron siderophore, plays a role in zinc acquisition as well. Currently, I have demonstrated that the Yersiniabactin system contributes to virulence independent of iron acquisition by using a novel hemochromatosis mouse model. Furthermore, I have shown that the Yersiniabactin system allows Y. pestisto better compete for zinc with the host zinc sequestration molecule calprotectin. Finally, I plan to use a variation of Tn-seq, called droplet Tn-seq, to identify genes required for growth in Zinc-limited conditions.


INFLAMMATION AND PATHOGENESIS TRAINING GRANT FACULTY

Drs. Nejat Egilmez and Rich Lamont serve as Directors of the T32 Training program overseeing an engaged and diverse cadre of faculty mentors and highly talented trainees.

Mentor NameTitleArea of Research
Yousef Abu KwaikProfessorManipulation and exploitation of the host cell biology by intracellular bacterial pathogens.
Juhi BagaitkarAssistant ProfessorTo understand the immunological consequences of apoptotic cell clearance during inflammation and infection.
Haribabu BodduluriProfessorChemokine receptors in inflammation, host response and cancer.
Donghoon ChungAssociate ProfessorRNA virus replication and antiviral discovery.
Donald R. DemuthProfessorMechanisms of oral bacterial pathogenesis.
Nejat K. EgilmezProfessorImmunity in tumor suppression and progression.
Jala R. VenkatakrishnaAssociate ProfessorRegulation of inflammation, gut microbiota and microbial metabolites in cancer development.
Henry J. KaplanProfessorOphthalmology research;  anterior chamber associated immune deviation, age related macular degeneration, stem cell plasticity.
Irina A. KirpichAssistant ProfessorGut-Liver interactions in alcoholic and nonalcoholic liver disease.
Michelle KosiewiczAssociate ProfessorImmune regulation / dysregulation in autoimmune and inflammatory diseases.
Ashok KumarProfessorMolecular and signaling mechanisms that regulate acquisition, maintenance of skeletal muscle mass.
Richard J. Lamont

Professor

PD/PI
Microbial community pathogenicity and innate immune responses to oral biofilms.
Matthew B. LawrenzAssociate ProfessorHost-pathogen interactions, identification of bacterial virulence factors, regulation of virulence factors in bacteria.
Bing LiAssociate ProfessorImmunoregulation of autoimmune diseases and cancer.
Shuang LiangAssistant ProfessorTherapeutic targets for periodontal diseases; prevention and cure of bone loss in periodontitis.
Igor S. LukashevichProfessorNovel vaccine technologies, molecular biology and pathogenesis of viral hemorrhagic fevers.
Nobuyuki MatobaAssociate ProfessorHIV microbicides; mucosal vaccines and immuno-therapeutics; plant-based protein expression.
Craig J. McClainProfessorPathophysiology of liver diseases (alcoholic; non-alcoholic; Hepatitic C (HCV); etc. and the role of pro-inflammatory cytokines, such as tumor necrosis factor in liver injury / transplantation.
Robert A. MitchellProfessorFunctional and mechanistic contributions of macrophage migration inhibitory factor family member-dependent tumor progression.
Kenneth PalmerProfessorDevelopment of vaccines and antiviral proteins to prevent and treat viral diseases that predispose people to cancer.
Jeffrey C. PetruskaAssociate ProfessorAnatomical and electrophysiological plasticity of neurons, focusing on peripheral nervous system and spinal cord.
Jan PotempaProfessorProteolytic enzymes of bacterial pathogens.
Mariusz Z. RatajczakProfessorHematopoietic stem / progenitor cell biology.  Regulation, renewal and differentiation of very small embryonic like (VSEL) stem cells.
David A. ScottProfessorTobacco-induced alterations to Porphyromonas gingivalis and innate-pathogen interactions.
Hui ShaoProfessorImmune regulation in ocular inflammation and autoimmunity.
Haval Shirwan

Professor

PD/PI
Autoimmunity, vaccinology, transplantation, and cancer immunology.
Kevin J. SokoloskiAssistant ProfessorMolecular regulation of positive-sense RNA viruses.
David P. StirlingAssistant ProfessorIntrinsic and extrinsic mechanisms of white matter degeneration in living tissue following trauma to nervous system.
Silvia M. UriarteAssociate ProfessorInteraction between neutrophils and pathogens that causes periodontitis.
Jonathan M. WarawaAssistant ProfessorImaging and pathogenesis of pulmonary bacterial pathogens using animal models.
Scott R. WhittemoreProfessorMolecular and cellular biological approaches to spinal cord repair: 1) stem cell re-myelination, 2) angiogenesis, 3) endoplasmic reticulum stress, 4) control of locomotor circuits, 5) dysbiosis/ SCI.
Kavitha YaddanapudiAssistant ProfessorNovel immune-based therapeutic strategies for the treatment of cancer.
Jun YanProfessorRegulation of autoreactive B cells and b-glucan-mediated tumor immunotherapy.
Huang-ge ZhangProfessorRegulation of leukocyte inflammatory function in autoimmune disease and cancer.