Biography
Hall received a B.S. degree in Microbiology (1989) and an M.S. degree in Molecular Biology (1999) from the University of Alabama in Huntsville. She earned her Ph.D. in Pharmacology (2004) from Case Western Reserve University. Following her Ph.D. degree she completed a 1-year post-doctoral fellowship at NIDDK and a 2-year post-doctoral fellowship at the University of New Mexico.
Personal Statement
Staphylococcus aureus bacteria commonly colonize a large percentage of the population. Historically known as an agent of nosocomial infection (hospital-acquired) in patients with predisposing health conditions, recent years have witnessed a dramatic rise in S. aureus infections in apparently healthy individuals in the community setting (community-acquired). Further complicating this problem, S. aureus has acquired resistance genes which protect the bacterium from frequently utilized methicillin-type antibiotics. These strains, known as methicillin-resistant Staphylococcus aureus (MRSA), are seen in both hospital-acquired (HA-MRSA) and community-acquired (CA-MRSA) infections. MRSA is frequently highlighted in the press due to its impact on both public health and on the added financial burden to patient care.
The rise in CA-MRSA infections is due to changes in virulence of strains causing the infections, but previously unidentified defects in immune defense mechanisms of otherwise healthy individuals may also contribute. In this regard, our lab is interested in understanding how our immune system defends us against invasive infection by S. aureus, particularly by CA-MRSA, and how we can enhance protection. S. aureus utilizes a peptide-pheromone based communication system, called quorum-sensing, to switch from an adherent colonizing phenotype to a virulent phenotype capable of causing invasive infection. The peptide pheromones responsible for signaling this change in virulence are referred to as autoinducing peptides or AIPs. We are currently pursuing a vaccine designed to produce a neutralizing antibody response to the AIPs, thus blocking virulence. Also, we have found that female mice are much more resistant to infection, and specifically to a S. aureus secreted toxin known as alpha-hemolysin (Hla). This resistance depends on estrogen, as ovariectomized female mice are no longer protected. We are currently addressing the molecular mechanism by which female mice demonstrate resistance to Hla and infection. This information will provide insight into the role of sex in the innate immune response to S. aureus and Hla and possibly provide clues to the identification of therapeutics to increase host defense.
Areas of Specialty
Staphylococcus aureus host-pathogen interactions #1
Animal models of Staphylococcus aureus infection #2
Education
PhD, Case Western Reserve University, 2004 (Pharmacology)
MS, University of Alabama in Huntsville, 1999 (Molecular Biology)
BS, University of Alabama in Huntsville, 1989 (Microbiology)
Key Publications
Journal Article
Triplett, Kathleen, D Pokhrel, Srijana, Castleman, Moriah, J Daly, Seth, M Elmore, Bradley, O Alexander, Joyner, J Sharma, Gee, Herbert, Guy, Campen, Matthew, J Hathaway, Helen, J Prossnitz, Eric, Hall, Pamela, R Accepted GPER activation protects against epithelial barrier disruption by Staphylococcus aureus ?-toxin Scientific Reports
Journal Article
Castleman, M, J Pokhrel, S, Triplett, K, D Kusewitt, D, F Elmore, B, O Joyner, J, A Femling, J, K Sharma, G, Hathaway, H, J Prossnitz, E, R Hall, Pamela, R 2018 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by ?-Hemolysin. Journal of immunology (Baltimore, Md. : 1950)
Journal Article
Joyner, J, A Daly, Seth, Peabody, J, Triplett, K, D Pokhrel, S, Elmore, B, O Adebanjo, D, Peabody, D, S Chackerian, B, Hall, Pamela, R 2020 Vaccination with VLPs Presenting a Linear Neutralizing Domain of S. aureus Hla Elicits Protective Immunity. Toxins, vol. 12, Issue 7
Journal Article
Pokhrel, S, Triplett, K, D Daly, Seth, Joyner, J, A Sharma, G, Hathaway, H, J Prossnitz, E, R Hall, Pamela, R 2020 Complement Receptor 3 Contributes to the Sexual Dimorphism in Neutrophil Killing of Staphylococcus aureus. Journal of immunology (Baltimore, Md. : 1950), vol. 205, Issue 6, 1593-1600
Journal Article
Daly, S, M Joyner, J, A Triplett, K, D Elmore, B, O Pokhrel, S, Frietze, K, M Peabody, D, S Chackerian, B, Hall, Pamela, R 2017 VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation. Scientific reports, vol. 7, Issue 1, 637
Research and Scholarship
1. Pokhrel S, Triplett KD, Daly SM, Joyner JA, Sharma G, Hathaway HJ, Prossnitz ER and PR Hall*. Complement Receptor 3 contributes to the sexual dimorphism in neutrophil killing of Staphylococcus aureus (2020) J Immunol. Aug 7:ji2000545. doi: 10.4049/jimmunol.2000545. Online ahead of print. PMID: 32769122
2. Joyner JA, Daly SM, Peabody J, Triplett KD, Pokhrel S, Elmore BO, Adebanjo D, Peabody DS, Chackerian B and PR Hall*. Vaccination with VLPs Presenting a Linear Neutralizing Domain of S. aureus Hla Elicits Protective Immunity (2020) Toxins, 12(7), 450; https://doi.org/10.3390/toxins12070450.
3. Triplett KD, Pokhrel S, Castleman MJ, Daly SM, Elmore BO, Joyner JA, Sharma G, Herbert G, Campen MJ, Hathaway HJ, Prossnitz ER and PR Hall*. GPER activation protects against epithelial barrier disruption by Staphylococcus aureus ?-toxin (2019) Scientific Reports. Feb 4;9(1):1343. doi: 10.1038/s41598-018-37951-3.PMCID: 6362070.
4. Castleman MJ, Pokhrel S, Triplett KD, Kusewitt DF, Elmore BO, Joyner JA, Femling JK, Sharma G, Hathaway HJ, Prossnitz ER and PR Hall*. Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by ?-Hemolysin.(2017) J Immunol. Dec 8. pii: ji1700810. doi: 10.4049/jimmunol.1700810. Epub ahead of print.
5. Daly SM, Joyner JA, Triplett KD, Elmore BO, Pokhrel S., Frietze K, Peabody D, Chackerian B and PR Hall* (2017). VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation. Scientific Reports, 2017 Apr 4;7(1):637. doi: 10.1038/s41598-017-00753-0. PubMed Central PMCID: PMC5429642.