Katharina Richard, PhD

St. Mary's College of Maryland, BA, 2004 

NIAMS, NIH, Postbac 2004-2005

NIAID, NIH, Graduate Partnership Student 2006-2011

University of Maryland, College Park, PhD, 2011

University of Maryland, School of Medicine, Research Fellow 2011-2012

University of Maryland, School of Medicine, Postdoctoral Study 2012-2018

University of Maryland, School of Medicine, BSL-3 training 2012-present

A. PERSONAL STATEMENT

I received my Ph.D. in cell biology for work on immune memory cells and have continued to work in the fields of microbiology and immunology as a postdoctoral fellow for the past 7 years. My research focuses on vaccine development against the pathogen Francisella tularensis (Ft) through the host’s innate and adaptive immune responses. The most promising vaccine candidates I am working on are Ft subunit vaccines on a nanoparticle platform known as functionalized catanionic surfactant vesicles (FCSV). My long-term goal is to become an independent investigator in vaccine development.

My recent work studying macrophage responses to Ft infection and in comparing different vaccine adjuvants in vitro have lead to the investigation of cell energetic changes during the course of infection/immunization. 

These references are most relevant to the proposed project:

1. Richard K, Mann BJ, Qin A, Barry EM, Ernst RK, Vogel SN. Monophosphoryl Lipid A enhances efficacy of a Francisella tularensis LVS-catanionic nanoparticle subunit vaccine against F. tularensis Schu S4 challenge by augmenting both humoral and cellular immunity. Clin Vaccine Immunol. 2017 Mar 6;24(3). Pii: e00574-16. PubMed PMID: 28077440; PubMed Central PMCID: PMC5339645.
2. Richard K, Vogel SN, Perkins DJ. Type I interferon licenses enhanced innate recognition and transcriptional responses to Francisella tularensis live vaccine strain. Innate Immun. 2016 Jul;22(5):363-72. PubMed PMID: 27231145; PubMed Central PMCID: PMC4955828.
3. Richard K, Mann BJ, Stocker L, Barry EM, Qin A, Cole LE, Hurley MT, Ernst RK, Michalek SM, Stein DC, Deshong P, Vogel SN. Novel catanionic surfactant vesicle vaccines protect against Francisella tularensis LVS and confer significant partial protection against F. tularensis Schu S4 strain. Clin Vaccine Immunol. 2014 Feb;21(2):212-26. PubMed PMID: 24351755; PubMed Central PMCID: PMC3910930.
4. DeShong PR, Stocker L, Stein DC, Vogel SN, Richard K. , inventors. Compositions and Vaccines Comprising Vesicles and Method of Using the Same. United States of America US-2014-0356415. 2014 December 04.
5. Cole LE, Mann BJ, Shirey KA, Richard K, Yang Y, Gearhart PJ, Chesko KL, Viscardi RM, Vogel SN. Role of TLR signaling in Francisella tularensis-LPS-induced, antibody-mediated protection against Francisella tularensis challenge. J Leukoc Biol. 2011 Oct;90(4):787-97. PubMed PMID: 21750122; PubMed Central PMCID: PMC3177696. 
6. Richard K, Pierce SK, Song W. The agonists of TLR4 and 9 are sufficient to activate memory B cells to differentiate into plasma cells in vitro but not in vivo. J Immunol. 2008 Aug 1;181(3):1746-52. PubMed PMID: 18641311; PubMed Central PMCID: PMC2679533.

B. POSITIONS AND HONORS

Positions and Employment

Other Experience and Professional Memberships

Honors

C. Contribution to Science

1. Novel vaccine development against the pathogen Francisella tularensis, utilizing functionalized catanionic surfactant vesicles as vaccine carriers: The paradigm in Francisella tularensis (Ft) vaccine development is the generation of live attenuated mutants, since subunit vaccines, though much safer, have not shown significant efficacy. The most important contribution I have made to science thus far is the development of a model for using functionalized catanionic surfactant vesicles (FCSV), a highly stable and versatile type of nanoparticle, as a novel vaccine carrier that allows Ft subunit vaccines to achieve levels of immunization that are akin to those achieved by some live attenuated vaccine candidates. My personal role in this study has been experimental design and analysis, the production and purification of the nanoparticle vaccines, mouse work related to immunization, challenge, and tissue harvest, analysis of sera by ELISA and Western blot, and the synthesis of ideas as the lead author on the first manuscript describing the use of FCSVs in Ft vaccine. Two follow-up papers, one identifying some of the major immunogenic antigens targeted by sera from fully protected mice and the other detailing enhanced vaccine response with LVS-V formulations including synthetic monophosphoryl lipid A, will be submitted for peer review in the next few weeks.
   1. Richard K, Mann BJ, Qin A, Barry EM, Ernst RK, Vogel SN. Monophosphoryl Lipid A enhances efficacy of a Francisella tularensis LVS-catanionic nanoparticle subunit vaccine against F. tularensis Schu S4 challenge by augmenting both humoral and cellular immunity. Clin Vaccine Immunol. 2017 Mar 6;24(3). Pii: e00574-16. PubMed PMID: 28077440; PubMed Central PMCID: PMC5339645 (available 2017-09-06).
   2. Richard K, Mann BJ, Stocker L, Barry EM, Qin A, Cole LE, Hurley MT, Ernst RK, Michalek SM, Stein DC, Deshong P, Vogel SN. Novel catanionic surfactant vesicle vaccines protect against Francisella tularensis LVS and confer significant partial protection against F. tularensis Schu S4 strain. Clin Vaccine Immunol. 2014 Feb;21(2):212-26. PubMed PMID: 24351755; PubMed Central PMCID: PMC3910930.
   3. DeShong PR, Stocker L, Stein DC, Vogel SN, Richard K., inventors. Compositions and Vaccines Comprising Vesicles and Method of Using the Same. United States of America US-2014-0356415. 2014 December 04.
   4. Interplay of innate immunity and humoral immune responses in controlling Francisella tularensis infection: I have also had a chance to contribute to the understanding of how Ft infection can be controlled in TLR2^-/- mice. This work was led by Dr. Leah Cole, who originally established the role of TLR2 in the cytokine response to Ft by macrophages. B-1a cell derived natural antibodies that recognize Ft LPS contribute to the protection in WT mice, but not TLR2^-/- mice. In this study, we established that an alternate TLR ligand, monophosphoryl lipid A, can compensate for the defective recognition of Ft in TLR2^-/- mice, and initiate protective responses. I contributed with the execution and analysis of in vitro infection of primary mouse macrophages, and in vivo challenge experiments in which mice innate immune cells were primed with monophosphoryl lipid A (TLR4 agonist) or flagellin (TLR5 agonist) and the non-toxic lipopolysaccharides derived from the Ft LVS strain.
      1. Cole LE, Mann BJ, Shirey KA, Richard K, Yang Y, Gearhart PJ, Chesko KL, Viscardi RM, Vogel SN. Role of TLR signaling in Francisella tularensis-LPS-induced, antibody-mediated protection against Francisella tularensis challenge. J Leukoc Biol. 2011 Oct;90(4):787-97. PubMed PMID: 21750122; PubMed Central PMCID: PMC3177696.
      2. Richard K, Vogel SN, Perkins DJ. Type I Interferon enhances early innate recognition and signaling of Francisella tularensis in a TLR2-dependent fashion. Innate Immun. Innate Immun. 2016 Jul;22(5):363-72. PubMed PMID: 27231145; PubMed Central PMCID: PMC4955828 (available 2017-07-01).
   5. Cell biological study of the activation of memory B cells: I developed a functional assay for the quantification of antigen-specific memory B cells, by capitalizing on their ability to differentiate into antibody-secreting cells in vitro under specific activation conditions. Using this assay and multi-color flow cytometric approaches, I was able to determine that memory B cells, in contrast to naïve B cells, can be reactivated with CpG-motif containing DNA, a TLR9 agonist. Both naïve and memory B cells were able to respond to LPS, a TLR4 agonist. This work was published at the time that B cells were just starting to be recognized as antigen-presenting cells, adding special interest to their innate-like activation. I also plan to use this functional assay in the proposed research of this K22.
      1. Richard K, Pierce SK, Song W. The agonists of TLR4 and 9 are sufficient to activate memory B cells to differentiate into plasma cells in vitro but not in vivo. J Immunol. 2008 Aug 1;181(3):1746-52. PubMed PMID: 18641311; PubMed Central PMCID: PMC2679533.
      2. Liu C, Richard K, Wiggins M, Zhu X, Conrad D, Song W. CD23 can negatively regulate B-cell receptor signaling. Sci Rep. 2016 May 16;6:25629. PubMed PMID: 27181049; PubMed Central PMCID: PMC4867583.
   6. Cell biological studies of innate immune signaling pathways and inflammasome activation: I was able to contribute to the work led by Drs. Jae Jin Chae and Daniel L. Kastner, elucidating the relationship between their newly discovered protein, Pyrin, and Caspase-1. This work contributed to the recognition of inflammasomes as molecular complexes that serve as mediators of inflammation. My personal contribution focused on the execution of experiments planned by and analyzed in concert with Dr. Chae, including cell culture of primary mouse and human cells and Western blot analysis. I have also been able to contribute to more recent inflammasome activation studies highlighting the differences between the activation of AIM2 and NLRC4 inflammasomes.
      1. Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ, Kastner DL. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9982-7. PubMed PMID: 16785446; PubMed Central PMCID: PMC1479864.
      2. Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT, Masters SL, Gumucio DL, Shoham NG, Kastner DL. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment. Blood. 2008 Sep 1;112(5):1794-803. PubMed PMID: 18577712; PubMed Central PMCID: PMC2518886.
      3. Wang X, Shaw D, Sakhon O, Snyder G, Sundberg E, Santambrogio L, Sutterwala F, Dumler JS, Shirey KA, Perkins D, Richard K, Chagas A, Calvo E, Kopecky J, Kotsyfakis M, Pedra J. The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated Inflammasome Activation. Infect. Immun. In Press. Epub 4/4/2016. PMID: 27045038.
   7. Identification of genes: I assisted in the localization of two genes using PCR-based approach, one responsible for the human disease Familial Pityriasis Rubra Pilaris, and the other for the embryonic development 'No turning' mutation.
      1. Chatterjee B, Richard K, Bucan M, Lo C. Nt mutation causing laterality defects associated with deletion of rotatin. Mamm Genome. 2007 May;18(5):310-5. PubMed PMID: 17551791.
      2. Fuchs-Telem D, Sarig O, van Steensel MA, Isakov O, Israeli S, Nousbeck J, Richard K, Winnepenninckx V, Vernooij M, Shomron N, Uitto J, Fleckman P, Richard G, Sprecher E. Familial pityriasis rubra pilaris is caused by mutations in CARD14. Am J Hum Genet. 2012 Jul 13;91(1):163-70. PubMed PMID: 22703878; PubMed Central PMCID: PMC3397268.

The following link provides a full list of my published work:

http://www.ncbi.nlm.nih.gov/sites/myncbi/katharina.richard.1/bibliography/47919649/public/?sort=date&direction=ascending.

D. RESEARCH SUPPORT

Ongoing Research Support

R56 AI18797

Vogel, Stefanie N. (PI): Differentiative Signals for Macrophage Activation

Role: research associate

Innate Immunity, Macrophages, TLR4, Metabolism, Catanionic Surfactant Nanoparticles, Vaccines, Francisella tularensis

1. Richard K, Mann BJ, Stocker L, Barry EM, Qin A, Cole LE, Hurley MT, Ernst RK, Michalek SM, Stein DC, DeShong P, Vogel SN. Novel catanionic surfactant vesicle vaccines protect mice against Francisella tularensis LVS and confer significant partial protection against F. tularensis Schu S4. Clin Vaccine Immunol. 2014. Feb; 21(2):212-26.
2. Richard K, Vogel SN, Perkins DJ. Type I Interferon enhances early innate recognition and signaling of Francisella tularensis in a TLR2-dependent fashion. Innate Immun. 2016. Jul; 22(5):363-72.
3. Richard K, Mann BJ, Qin A, Barry E, Ernst RK, Vogel SN. Monophosphoryl Lipid A enhances efficacy of a Francisella tularensis LVS-Catanionic nanoparticle subunit vaccine against F. tularensis Schu S4 challenge by augmenting both humoral and cellular immunity. Clin. Vacc. Immunol. 2017 Mar 6;24(3).