Melissa Herbst-Kralovetz

Melissa Herbst-Kralovetz

Associate Professor, Basic Medical Sciences
Associate Professor, Clinical Translational Sciences
Associate Professor, Obstetrics and Gynecology
Associate Professor, BIO5 Institute
Contact
(602) 827-2247

Research Interest

Melissa Herbst-Kralovetz, PhD is an Associate Professor in the Departments of Basic Medical Sciences and Obstetrics and Gynecology and is Director of the Women's Health Microbiome Initiative at the UA College of Medicine-Phoenix. The Herbst-Kralovetz research lab is broadly interested in understanding innate mucosal immune responses to resident bacteria, pathogens (e.g HSV-2), and microbial products at mucosal sites, including the female reproductive tract. The mucosa provides a major immune barrier (physical, biological, and chemical) to microbial insult and her lab is interested in studying the mucosal barrier function of the lower female reproductive tract and its role in host defense against infection and inflammation as well as maintaining mucosal homeostasis. Dr. Herbst-Kralovetz has a long-standing interest and background in studying infections/conditions that impact women’s health.

Publications

Green, R., Herbst-Kralovetz, M. -., & Schountz, T. (2004). Genomic Organization of Deer Mouse (Peromyscus maniculatus) Tumor Necrosis Factor. Bios., 12-17.
Herbst-Kralovetz, M. M., Quayle, A. J., Ficarra, M., Greene, S., Rose, W. A., Chesson, R., Spagnuolo, R. A., & Pyles, R. B. (2008). Quantification and comparison of toll-like receptor expression and responsiveness in primary and immortalized human female lower genital tract epithelia. American journal of reproductive immunology (New York, N.Y. : 1989), 59(3).

To better understand innate immune responses to sexually-transmitted infection (STI) and the appropriateness of epithelial cell (EC) models of the vaginal and cervical mucosa, quantified toll-like receptor (TLR) expression from a population of women is needed.

Herbst-Kralovetz, M. M., Radtke, A. L., Lay, M. K., Hjelm, B. E., Bolick, A. N., Sarker, S. S., Atmar, R. L., Kingsley, D. H., Arntzen, C. J., Estes, M. K., & Nickerson, C. A. (2013). Lack of norovirus replication and histo-blood group antigen expression in 3-dimensional intestinal epithelial cells. Emerging Infectious Diseases, 19(3).

Noroviruses (NoVs) are a leading cause of gastroenteritis worldwide. An in vitro model for NoV replication remains elusive, making study of the virus difficult. A previous study, which used a 3-dimensional (3-D) intestinal model derived from INT-407 cells reported NoV replication and extensive cytopathic effects (CPE). Using the same 3-D model, but with highly purified Norwalk virus (NV), we attempted to replicate this study. Our results showed no evidence of NV replication by real-time PCR of viral RNA or by immunocytochemical detection of viral structural and nonstructural proteins. Immunocytochemical analysis of the 3-D cultures also showed no detectable presence of histo-blood group antigens that participate in NV binding and host tropism. To determine the potential cause of CPE observed in the previous study, we exposed 3-D cultures to lipopolysaccharide concentrations consistent with contaminated stool samples and observed morphologic features similar to CPE. We conclude that the 3-D INT-407 model does not support NV replication.

Herbst-Kralovetz, M. M., Pyles, R. B., Ratner, A. J., Sycuro, L. K., & Mitchell, C. (2016). New Systems for Studying Intercellular Interactions in Bacterial Vaginosis. The Journal of infectious diseases, 214 Suppl 1, S6-S13.

Bacterial vaginosis (BV) affects almost a quarter of US women, making it a condition of major public health relevance. Key questions remain regarding the etiology of BV, mechanisms for its association with poor reproductive health outcomes, and reasons for high rates of treatment failure. New model systems are required to answer these remaining questions, elucidate the complex host-microbe and microbe-microbe interactions, and develop new, effective interventions. In this review, we cover the strengths and limitations of in vitro and in vivo model systems to study these complex intercellular interactions. Furthermore, we discuss advancements needed to maximize the translational utility of the model systems. As no single model can recapitulate all of the complex physiological and environmental conditions of the human vaginal microenvironment, we conclude that combinatorial approaches using in vitro and in vivo model systems will be required to address the remaining fundamental questions surrounding the enigma that is BV.

Mathew, L. G., Herbst-Kralovetz, M. M., & Mason, H. S. (2014). Norovirus Narita 104 virus-like particles expressed in Nicotiana benthamiana induce serum and mucosal immune responses. BioMed research international, 2014, 807539.

Narita 104 virus is a human pathogen belonging to the norovirus (family Caliciviridae) genogroup II. Noroviruses cause epidemic gastroenteritis worldwide. To explore the potential of developing a plant-based vaccine, a plant optimized gene encoding Narita 104 virus capsid protein (NaVCP) was expressed transiently in Nicotiana benthamiana using a tobacco mosaic virus expression system. NaVCP accumulated up to approximately 0.3 mg/g fresh weight of leaf at 4 days postinfection. Initiation of hypersensitive response-like symptoms followed by tissue necrosis necessitated a brief infection time and was a significant factor limiting expression. Transmission electron microscopy of plant-derived NaVCP confirmed the presence of fully assembled virus-like particles (VLPs). In this study, an optimized method to express and partially purify NaVCP is described. Further, partially purified NaVCP was used to immunize mice by intranasal delivery and generated significant mucosal and serum antibody responses. Thus, plant-derived Narita 104 VLPs have potential for use as a candidate subunit vaccine or as a component of a multivalent subunit vaccine, along with other genotype-specific plant-derived VLPs.