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 2012-2022

A. PERSONAL STATEMENT

1. I direct animal studies at the University of Maryland’s Marlene and Steward Greenebaum Comprehensive Cancer Center’s (UMGCCC) core facility for Translational Laboratory Shared Resource (TLSR) since the retirement of the Director of In Vivo Services, Dr. Passaniti. My role is to advise requesting PIs on experimental design for oncology animal experiments, aid in the preparation of animal use protocols (AUP) and amendments, and answer IACUC Reviewer queries. Upon IACUC approval, I supervise three TLSR technicians in executing the experiments in compliance with the approved protocols, including all record-keeping responsibilities, answer questions of post-approval monitoring inspectors from the Office of Laboratory Animal Welfare Assurance and/or the Association for Assessment and Accreditation of Laboratory Animal Care, and work with animal facility supervisors and the veterinarian team to assure animals receive appropriate care from their requisition to euthanasia.  I also maintain a core AUP that functions as a repository of previously approved procedures and exogenous substances, and allows for expansion of patient-derived xenografts for primary clinical samples, for biobank maintenance (run by TLSR’s In Vitro Branch, Director: Dr. Lapidus), and to generate tumor tissue for Requesters.  As of October 2024, experiments are reviewed for each Requester on their individual AUPs of which they are the PI.  I have worked with Dr. Hancai Dan since my transition to core facility management (Sept 2022) to investigate the treatment efficacy of kinase inhibitors alone or in combination against human Head-and-Neck cancers using patient-derived xenograft mouse models.

My background is in immunology research (Toll-like receptor 4 responses, vaccine development), with much hands-on experience working with mice. An academic promotion to Assistant Professor in the Department of Microbiology and Immunology (Chair: Dr. Kaper) is pending.  In summary, I have the training, expertise, leadership, and motivation to successfully carry out the proposed research project.

Publications that highlight my experience include:

1. Bollino D, Ma X, Tighe KM, Casildo A, Richard K, Passaniti A, Carter-Cooper B, Strovel ET, Emadi A. Long-acting coli-derived Asparaginase Potentiates the Anti-Leukemic Effect of BCL-2 Inhibition, but not MCL-1 Inhibition, in Preclinical Models of Acute Myeloid Leukemia. Int J Mol Sci. 2024 Dec 5; 25(23): 13091.
2. Ruditsky A, Fisher K, Tighe K, B’lanton J, Ma X, Jiang K, Byrne K, Carter-Cooper B, Casildo A, Passaniti A, Carrier F, Lapidus R, Richard K, Kallen ME, Ng VY. A Novel Approach to Potentially Improving Soft-Tissue Sarcoma Survival: Prophylactic Lung Radiotherapy Inhibits Growth of Lung Metastases and Prolongs Survival in a Murine Soft-Tissue Sarcoma Model. Cureus. 2024 Dec 24; 16(12): e76334.
3. Richard K, Piepenbrink KH, Shirey KA, Gopalakrishnan A, Nallar S, Prantner DJ, Perkins DJ, Lai W, Vlk A, Toshchakov VY, Feng C, Fanaroff R, Medvedev AE, Blanco JCG, Vogel SN. A mouse model of human TLR4 D299G/T399I SNPs reveals mechanisms of altered LPS and pathogen responses. J Exp Med. 2021 Feb 1;218(2):e20200675.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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. 
9. 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. Oncology studies performed through the Translational Laboratory Shared Resource In Vivo Service: My scientific input to work performed through the core facility has merited authorship in two publications to date. Emadi has developed asparaginase treatments for leukemia from basic benchwork to clinical studies and was interested in combining the novel treatment, which deprives cancer cells of essential amino acid asparaginase, with inhibitors targeting the overexpressed anti-apoptotic proteins BCL-2 and MCL-1.  Our core facility was able to help Dr. Emadi by performing combination-dose efficacy trials in two mouse models: MV411 and AML45, tracked via intravital imaging.  Results revealed that the metabolic drug CalPegA potentiates treatment efficacy of a novel BCL-2 inhibitor. // Dr. Ng recognized that surgical resection of soft-tissue sarcoma primary tumors increases the risk of metastasis to the lungs in human patients, which is difficult to treat and is a major cause of death in sarcoma patients. Prophylactic irradiation of the lungs may help eliminate circulating tumor cells and micro-metastases and thereby prevent clinical stages of metastatic cancer.  We used the HT1080 cell line tumor model in mice to grow primary tumors as subcutaneous flank models, as well as simulating metastasis by injecting luciferase-labeled HT1080 cells intravenously. Treatment regimens consisted of hemithoracic irradiation (right lung irradiated, left lung as control) alone or with resection of the primary tumor.  A single radiation treatment alone was able to delay lung metastasis by approximately two weeks, with significantly lower tumor burden in the right (irradiated) lung.  My contributions to these publications ranged from advising PIs on experimental design of animal experiments, drafting IACUC documents and ushering them through the review process, and supervising animal work, to analyzing data, generating figures for the publication, and providing methodological details for the manuscripts.
   1. Bollino D, Ma X, Tighe KM, Casildo A, Richard K, Passaniti A, Carter-Cooper B, Strovel ET, Emadi A. Long-acting coli-derived Asparaginase Potentiates the Anti-Leukemic Effect of BCL-2 Inhibition, but not MCL-1 Inhibition, in Preclinical Models of Acute Myeloid Leukemia. Int J Mol Sci. 2024 Dec 5; 25(23): 13091. PMID: 39684800
   2. Ruditsky A, Fisher K, Tighe K, B’lanton J, Ma X, Jiang K, Byrne K, Carter-Cooper B, Casildo A, Passaniti A, Carrier F, Lapidus R, Richard K, Kallen ME, Ng VY. A Novel Approach to Potentially Improving Soft-Tissue Sarcoma Survival: Prophylactic Lung Radiotherapy Inhibits Growth of Lung Metastases and Prolongs Survival in a Murine Soft-Tissue Sarcoma Model. Cureus. 2024 Dec 24; 16(12): e76334.
2. 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, Perkins DJ, Harberts EM, Song Y, Gopalakrishnan A, Shirey KA, Lai W, Vlk A, Mahurkar A, Nallar S, Hawkins LD, Ernst RK, Vogel SN. Dissociation of TRIF bias and adjuvanticity. Vaccine. 2020 Jun 2;38(27):4298-4308. PMID: 32389496
   2. 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).
   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.
3. 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. 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).
4. 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. 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.
5. 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. 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.
6. 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. 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

P30 CA134274

Ambulos, Nicholas. (PI): Shared Resources Management

Role: Assistant Director of In Vivo Service, Translational Laboratory Shared Resource

Oncology, Pre-clinical, In Vivo Models, Innate Immunity, Macrophages, TLR4, Metabolism, Catanionic Surfactant Nanoparticles, Vaccines, Francisella tularensis

Service to Research at UMB:

1. Bollino D, Ma X, Tighe KM, Casildo A, Richard K, Passaniti A, Carter-Cooper B, Strovel ET, Emadi A. Long-acting coli-derived Asparaginase Potentiates the Anti-Leukemic Effect of BCL-2 Inhibition, but not MCL-1 Inhibition, in Preclinical Models of Acute Myeloid Leukemia. Int J Mol Sci. 2024 Dec 5; 25(23): 13091. PMID: 39684800
2. Ruditsky A, Fisher K, Tighe K, B’lanton J, Ma X, Jiang K, Byrne K, Carter-Cooper B, Casildo A, Passaniti A, Carrier F, Lapidus R, Richard K, Kallen ME, Ng VY. A Novel Approach to Potentially Improving Soft-Tissue Sarcoma Survival: Prophylactic Lung Radiotherapy Inhibits Growth of Lung Metastases and Prolongs Survival in a Murine Soft-Tissue Sarcoma Model. Cureus. 2024 Dec 24; 16(12): e76334.

Highlighted own Research:

1. Richard K, Piepenbrink KH, Shirey KA, Gopalakrishnan A, Nallar S, Prantner DJ, Perkins DJ, Lai W, Vlk A, Toshchakov VY, Feng C, Fanaroff R, Medvedev AE, Blanco JCG, Vogel SN. A mouse model of human TLR4 D299G/T399I SNPs reveals mechanisms of altered LPS and pathogen responses. J Exp Med. 2021 Feb 1;218(2):e20200675.
2. 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 tularensis Schu S4 challenge by augmenting both humoral and cellular immunity. Clin. Vacc. Immunol. 2017 Mar; 24(3) e00574-16.
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 mice against Francisella tularensis LVS and confer significant partial protection against F. tularensis Schu S4. Clin Vaccine Immunol. 2014. Feb; 21(2):212-26.
4. 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.