Voth_S resized.jpgSarah Voth

Predoctoral Fellow and PhD Candidate, Year 4
Department of Physiology and Cell Biology
Center of Lung Biology
University of South Alabama College of Medicine

MENTOR
Troy Stevens, Ph.D.
Lenoire Locke Professor of Medicine
Chair, Department of Physiology and Cell Biology
Director, Center for Lung Biology

GUEST LECTURER
Department of Physician Assistant Studies

University of South Alabama Pat Capps Covey College of Allied Health Professions

PA 514 Introduction to Infectious Disease

  • Bacterial Pathogenesis
  • Normal Flora
  • Infectious Amyloids and Prions
  • Adaptive Immunity

PA 520 Clinical Medicine II – Pulmonology

  • Lung Mechanics
  • Acid-Base Balance

Medical Education
University of South Alabama College of Medicine

Microbiology and Immunology

  • M1 – Medical Microbiology Lab

Department of Biomedical Sciences
University of South Alabama

BMD 402 Medical Microbiology Lab

  • Infectious Amyloids and Prions

RESEARCH FOCUS
My research focuses on the complex host-pathogen interactions that modulate the function of host endothelial amyloids in the wake of nosocomial pneumonia.

CONTRIBUTIONS TO SCIENCE
Ventilator-associated pneumonia is a significant concern among the critically ill. Upon resolution of the primary infection and ICU discharge, < 50% of patients survive the first year. These survivors suffer secondary end-organ damage that may affect cardiovascular, renal, or neurocognitive function and contribute to increased rates of morbidity and mortality post-discharge. Our work has determined that bacterial infection of pulmonary microvascular endothelial cells elicits the release of amyloids that function as antimicrobial peptides. We have found that these endothelial-derived amyloids are potent, broad-spectrum antimicrobials. They are effective against Gram positive, Gram negative, and fungal pathogens. Endothelial amyloids exhibit marked bacteriostatic and bactericidal activity in a time-dependent manner. Antimicrobicity is amyloid-dependent and can be enriched through the depletion of tau. Intriguingly, these endothelial amyloids are self-replicating and can be propagated in cell culture indicating that they are a form of antimicrobial prion. In fact, to our knowledge they are the only amyloid prion that functions as an immune effector. We have also found them to be cytoprotective and some evidence points to their ability to prime the innate memory of pulmonary microvascular endothelium. Further, we have identified that the nosocomial pathogen Pseudomonas aeruginosa is able to circumvent this endothelial innate defense mechanism. P. aeruginosa utilizes a Type III Secretion system to inject a soluble, promiscuous nucleotidyl cyclase effector, Exoenzyme Y, into host endothelial cells. Exoenzyme Y intoxication abolishes the functional antimicrobial phenotype of endothelial amyloid prions and promotes a purely pathologic, cytotoxic phenotype. The production and release of endothelial tau oligomers appears to modulate the switch from antimicrobial prion to cytotoxic prion. These self-replicating cytotoxic prions also suppress learning and memory in mice while promoting an exaggerated fear response. Moreover, the immunodepletion of tau oligomers abrogates cytotoxicity and rescues the antimicrobial properties of Exoenzyme Y infection-derived endothelial amyloids.

POSITIONS AND SERVICE
2016 - present    Graduate Research Assistant; Physiology and Cell Biology, Center for Lung Biology
                             University of South Alabama College of Medicine, Mobile, AL

2018 - present    President of Basic Medical Science Student Organization
                              University of South Alabama College of Medicine, Mobile, AL

2018 - present    Member of Graduate Executive Committee
                              University of South Alabama College of Medicine, Mobile, AL

2018 - present    Member of Continuous Quality Improvement Committee
                              University of South Alabama College of Medicine, Mobile, AL

HONORS
2017     Young Investigator Award, The Grover Conference, American Thoracic Society, Assembly on Pulmonary Microcirculation
             Outstanding Research Related to the Pulmonary Circulation

2017     Oral Presentation, The Grover Conference, American Thoracic Society

2017     2nd Place Graduate Student Presentations, University of South Alabama College of Medicine Research Forum, 2017

2018     Abstract Scholarship - American Thoracic Society International Conference

2018     Oral Presentations, American Thoracic Society International Conference

ACTIVE GRANT SUPPORT
NIH T32 Predoctoral Training Grant HL076125, 2016 – present

ORIGINAL PUBLICATIONS

  1. Petranka J, Hopey M, Jennings B, Baird S, and Boone S. Breeding habitat segregation of wood frogs and American toads: the role of interspecific tadpole predation and adult choice. Copeia 1994:691–697.
  2. Lin M, Balczon R, Pittet J-F, Wagner B, Moser S, Morrow K, Voth S, Francis M, Leavesley S, and Stevens T. Nosocomial pneumonia elicits an endothelial proteinopathy, J. Resp. Crit. Care Med., 2018.
  3. Balczon R, Pittet J-F, Wagener B, Moser S, Voth S, Vorhees C, Williams M, Bridges J, Alvarez DF, Koloteva A, Xu Y, Zha X, Stevens T, and Lin M. Endothelium-derived neurotoxic amyloids impair learning and memory, submitted, 2018.
  4. Voth S, Gwin M, Francis M, Balczon R, Pittet J-F, Wagner B, Moser S, Zhou C, Piechocki S, Crawford M, and Stevens T. Pseudomonas aeruginosa Type III Secretion system effectors suppress the endothelial antimicrobial response following acute infection, in preparation, 2018.
  5. Voth S, Piechocki S, Francis M, Stevens T. Lung endothelial amyloids function as self-propagating antimicrobial peptides, in preparation, 2018.

ABSTRACTS

  1. Voth S and Townsley M. Ultrastructural survey of organelles in pulmonary microvascular endothelium: Morphometric analysis of volume densities. University of South Alabama College of Medicine Research Forum. Mobile, AL; November 4th, 2016.
  2. Stevens R, Cioffi E, Voth S, and Balczon R. Chemical properties of endothelial cytotoxic amyloids. 44th Summer Medical Student Research Day. Mobile, AL; July 28th, 2017.
  3. Voth SB, Balczon R, Francis CM, Audia J, and Stevens Lung infection elicits endothelial amyloids with distinguishable antimicrobial and cytotoxic properties. Am. J. Respir. Crit. Care Med., 197: A7616, 2018.
  4. Voth SB, Lin M, Balczon R, Francis CM, Stevens T.Nosocomial lung infection induces a pulmonogenic prionopathy that disrupts the endothelial barrier of the brain.  J. Respir. Crit. Care Med., 197: A7615, 2018.
  5. Voth SB, Balczon R, Francis M, and Stevens T. Pseudomonas aeruginosa Exoenzyme Y intoxication reversibly converts antimicrobial endothelial amyloids into amyloid prions. Am. J. Respir. Crit. Care Med., 197: A7616, 2018. Abstract Scholarship Award
  6. Berrou M, Stevens R, Voth S, Williams C, Balczon R, Stevens T. Pseudomonas aeruginosa induced lung endothelial amyloid proteinopathy: Characteristics and inhibitors. J. Respir. Crit. Care Med., 197: A7615, 2018.
  7. Lee J, Voth SB, Balczon R, Stevens T. Cytotoxic amyloids inhibit carbonic anhydrase IX in pulmonary microvascular endothelial cells: A potential mechanism of acid dysregulation and cell death during infection. J. Respir. Crit. Care Med., 197: A7615, 2018.
  8. Lee J, White R, Voth SB, Balczon R, Stevens T. A dual effect of acidosis on pulmonary microvascular cell survival during infection: Acid post-conditioning for pneumonia? J. Respir. Crit. Care Med., 197: A7615, 2018.
  9. Piechocki S, Voth S, Francis M, Gwin M, and Stevens T. Endothelial amyloids are antimicrobial prions. (Abstract #33). 42nd Summer Medical Student Research Day. Mobile, AL; July 28th, 2018.
  10. Crawford M, Voth S, Gwin M, Francis CM, and Stevens T. Clinical ExoY-competent strain of pseudomonas aeruginosa suppresses innate immunity and promotes cytotoxic prion phenotype. 42nd Summer Medical Student Research Day. Mobile, AL; July 28th, 2018.
  11. Voth SB, Piechocki S, Gwin M, Francis CM, and Stevens T. Pulmonary Endothelium Generates Antimicrobial Prions as an Innate Defense Mechanism, American Thoracic Society International Conference 2019,
  12. Voth SB, Gwin S, Crawford M, Saleh LA, Francis CM, Pittet J-F, Wagener BM, Moser S, and Stevens T. Clinical Strains of ExoY-Competent Pseudomonas Elicit Cytotoxic Endothelial Amyloid Prions, American Thoracic Society International Conference 2019,
  13. Voth SB, Gwin S, Francis CM, and Stevens T. Attenuation of Beta Amyloid Release During Pseudomonas aeruginosa ExoY Intoxication Preserves Innate Antimicrobial Activity of Endothelial Amyloids, American Thoracic Society International Conference 2019,

SCHOLARLY LECTURES

  1. Research in Progress: “Pulmonary Endothelial Amyloid Response to Nosocomial Infection:
    Pathological or Functional?” May 29, 2017. University of South Alabama Center for Lung Biology, Mobile, Alabama.
  2. (INVITED) The Grover Conference. Sedalia, CO; 2017. Lung infection elicits endothelial amyloids with distinguishable antimicrobial and cytotoxic properties.
  3. Research in Progress: “Endothelial Amyloids: ExoY Do We Care?” May 1, 2018. University of South Alabama Center for Lung Biology, Mobile, Alabama.
  4. (INVITED) American Thoracic Society International Conference. San Diego, CA; 2018. Lung infection elicits endothelial amyloids with distinguishable antimicrobial and cytotoxic properties.
  5. (INVITED) American Thoracic Society International Conference. San Diego, CA; 2018. Nosocomial lung infection induces a pulmonogenic prionopathy that disrupts the endothelial barrier of the brain.

INTELLECTUAL PROPERTY

  1. Voth S., Morrow K., Balczon R., and Stevens T. United States Provisional Patent no. 50880-009P01US filed 9/7/2018. Entitled, Microbe-induced endothelial amyloid compositions as antimicrobials.

MEMBERSHIPS
American Association for the Advancement of Science

American Physiological Society

American Thoracic Society

American Society of Microbiology

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