The Doctor of Philosophy Seminar and Examination of Brie Trusiano

Biography

Brie grew up in Albuquerque, New Mexico and left as soon as she turned 18 to pursue her dream of becoming a veterinarian. She attended the University of Arizona where she received her bachelor’s degree in veterinary science in 2013. She then attended Colorado State University from 2013-2017, received her DVM, and fell in love with the clinical pathology specialty. After graduating veterinary school, she worked as a general practitioner with Banfield for two years gaining clinical experience. She was accepted into the clinical pathology/PhD program at VMCVM in 2019 where she began her training as a clinical pathologist and scientist. She completed her residency in 2022 and passed her boards that same year. Her clinical and research interests include hematopathology (especially the subtypes of myeloid leukemias and Hypereosinophilic syndrome) and flow cytometry. In her free time, she loves to travel, spend time with her pets, fiancé, friends. family, and celebrate the beauty of tattoo artistry. 

Funded by

• National Institutes of Health
• National Cancer Institute
• The Virginia-Maryland College of Veterinary Medicine
• VMCVM Office of Research and Graduate Studies
• The Via College of Osteopathic Medicine
• The Virginia Tech Carilion School of Medicine
• The Virginia Tech Institute for Critical Technology and Applied Science 

Awards and Academic Achievements

• 2023 Davis-Thompson Foundation pathology training and scholarship award for Virginia Tech
• September 2023: Diplomate of the American College of Veterinary Pathologists (clinical 
• 2019-2023: ICTAS Doctoral Scholar 

Lay Language Abstract 

White blood cells (WBC) are the cornerstone of the immune response. WBC mature in the bone marrow, thymus and spleen throughout the life of some species. WBC are subsequently released into the blood and then carried to the tissues so that the immune response can be properly engaged. A less well-known albeit important WBC is the eosinophil which is essential for combating parasitic infections but is also involved in the perpetuation of allergic responses. There is a syndrome known as Hypereosinophilic Syndrome (HES) which is an umbrella term encompassing a variety of diseases that affects both human and veterinary patients. It results in an overproduction of eosinophils not associated with a parasitic infection or an allergic response. Although several variants of the disease exist, diagnosing subsets of HES poses a diagnostic challenge for many medical doctors and veterinarians and can impact patient care and prognosis long term. 

There is a mouse model of HES which carries a genetic deletion (Map3k14) that encodes a kinase known as NF-kB inducing kinase (NIK); these mice are hereafter referred to as Nik^-/- mice. Nik^-/- mice develop a HES-like syndrome secondary to NIK loss in Th2 lymphocytes (another type of WBC) and tissues besides the bone marrow and spleen. NIK is an upstream regulator of the noncanonical NF-kB pathway. This pathway is involved in regulating WBC, lymph node, and spleen development. NIK also has other functions including regulation of molecules associated with the canonical NF-kB signaling pathway and can function independent of NF-kB signaling. Despite previous work studying HES-like syndrome in Nik^-/- mice, the specifics of the bone marrow and eosinophil development have not been fully characterized. 

In the present work, we initially reviewed current data exploring the role of the noncanonical NF-kB pathway and NIK specifically in the development of WBC cancers and how this might manifest in subvariants of HES. We then studied eosinophil development in the bone marrow and spleen in Nik^-/- and wild-type (WT) mice via assessment of the cells and tissues, cell surface marker expression, and response to Th2 signaling molecules. We then utilized various cell culture methods to explore how the microenvironment influences eosinophil development in Nik^-/- mice outside of the body to track cellular growth, death, metabolism, proliferation, and cytokine production. Overall, our findings suggest that NIK is essential for eosinophil growth, metabolism, and survival. We also noted differences in a molecule known as TNFR1in Nik^-/- cultures on day 13. This molecule is important in regulating cell survival and death and suggests an NF-kB independent function of NIK in regulating these differences. This information may prove useful in discovering potential treatment options underlying HES in both human and veterinary patients.  

Publications

** denotes shared first authorship 

• Trusiano, B., Smith, R., Poole, C. Morrison, H.A., Yeasmen, D., Steinmann, M., Allen, I.C.  “Loss of NF-kB inducing Kinase (NIK) affects eosinophilopoiesis in a murine model of Hypereosinophilic Syndrome.” Blood- submitted 
• Trusiano, B., Zimmerman, K. L., Morrison, H.A., Allen, I.C. “Not just for lymphoid cells: The role of the noncanonical NF-kB signaling pathway in early and late myelopoiesis with a focus on hypereosinophilic disorders” Journal of Leukocyte Biology.- Accepted, in review. 
• Mott, M., Trusiano, B., Allen, I.C. “Buena VISTA: A Promising Outlook on targeting Immune Checkpoint Regulators to Combat Sepsis.” Journal of Leukocyte Biology. – Accepted. 
• Morrison, H. A**. Eden, K.**, Trusiano, B.**, Rothschild, D.E.,Qin, Y., Wade, P.A., Rowe, A.J., Mounzer, C., Stephens, M.C., Hanson, K.M., Brown, S.L., Holl, E.K., Allen, I.C. “NF-κB Inducing Kinase Attenuates Colorectal Cancer by Regulating Noncanonical NF-κB Mediated Colonic Epithelial Cell Regeneration” – Accepted, in review. 
• Morrison, H. A., Trusiano, B., Rowe, A J., Allen, I.C. “Negative regulatory NLRs mitigate inflammation via NF-ΚB pathway signaling in inflammatory bowel disease.” Biomedical Journal, vol. 46, no. 5, Oct. 2023, p. 100616, https://doi.org/10.1016/j.bj.2023.100616.
• Trusiano, B., Tupik, J.D., Allen, I.C. “Cold Sensor, Hot Topic: TRPM8 Plays a Role in Monocyte Function and Differentiation.” Journal of Leukocyte Biology, vol. 112, no. 3, 2022, pp. 361–363., https://doi.org/10.1002/jlb.3ce0222-099r.
• Gidcumb, E. M., Bolton, T.A., Trusiano, B., Zimmerman, K.L., Oakes, V.J. “Probable Paraneoplastic Leukocytosis in a Dog with a Gastrointestinal Stromal Tumor.” Veterinary Clinical Pathology, 2022, https://doi.org/10.1111/vcp.13143.
• Trusiano, B., Todd, S.M., Barrett, S., Ciepluch, M., Fox, A., McClendon, D.,...LeCuyer, T.E. “Necrotizing hepatitis caused by Clostridium novyi type B. in a dog with no predisposing liver lesions: a case report.” BMC Veterinary Research, 2022.
• Davis, A.M., Lahmers, K., Trusiano, B., Zimmerman, K., Romeiser, J., Tuohy, J. “Cholesterol Granuloma of the Cranial Mediastinum in a Dog.” Journal of the American Animal Hospital Association, vol. 58, no. 3, 2022, pp. 129–136., https://doi.org/10.5326/jaaha-ms-7186.
• Gal, A, Trusiano, B., French, A.F., Lopez-Villalobos, N., MacNeill, A.L. “Serum Fructosamine Concentration in Uncontrolled Hyperthyroid Diabetic Cats Is within the Population Reference Interval.” Veterinary Sciences, vol. 4, no. 4, 2017, p. 17., https://doi.org/10.3390/vetsci4010017.

Presentations

• Trusiano, B., Smith, R., Morrison, H.A., Imran, K.M., Allen, I.C. The noncanonical NF-B signaling pathway influences eosinophilopoiesis in the marrow and spleen of the Nik^-/- murine model. ASVCP Annual Meeting, oral presentation and poster presentation, Chicago, IL, October 2023
• Trusiano, B., Smith, R., Morrison, H.A., Imran, K.M., Allen, I.C. The noncanonical NF-B signaling pathway influences eosinophilopoiesis in the marrow and spleen of the Nik^-/- murine model. Southeastern Immunology Symposium, poster presentation, Nashville, TN, June 2023. 
• Trusiano, B., Smith, R., Morrison, H.A., Imran, K.M., Allen, I.C. The noncanonical NF-B signaling pathway influences eosinophilopoiesis in the marrow and spleen of the Nik^-/- murine model. American Association of Immunologists annual meeting, poster presentation, Washington, DC, May 2023. 
• Trusiano, B., Smith, R., Morrison, H.A., Imran, K.M., Allen, I.C. The noncanonical NF-B signaling pathway influences eosinophilopoiesis in the marrow and spleen of the Nik^-/- murine model. BMVS Annual Research Symposium, poster presentation, Blacksburg, VA, March 2023. 
• Trusiano, B., Smith, R., Morrison, H.A., Imran, K.M., Allen, I.C. Proliferation, Plasticity, and Migration: Getting to the root of the problem for Hypereosinophilic Syndrome. Graduate and Professional Student Senate Research Symposium, oral presentation, Blacksburg VA, March 2023.
• Trusiano, B., Smith, R., Morrison, H.A., Imran, K.M., Allen, I.C. Proliferation, Plasticity, and Migration: Getting to the root of the problem for Hypereosinophilic Syndrome. ICTAS Doctoral Scholars Annual Research Symposium, poster presentation, Blacksburg VA, March 2023.
• Trusiano, B., Serpa, P. Mystery Case #15 – A Case of Anemia caused by erythrocyte oxidative Injury.  ASVCP Annual Meeting, oral presentation, Boston, MA, November 2023
• Trusiano, B., Morrison, H.A., Imran, K.M., Allen, I.C. Proliferation or Migration? The role of NIK in the development of Hypereosinophilic Syndrome. ICTAS Doctoral Scholars Annual Research Symposium, poster presentation, Blacksburg VA, March 2022.
• Trusiano, B., Todd M.S., Barret, S., Ciepluch, M., Fox, A., McClendon, D., Lahmers, K.K., Oakes, V.J., Carvallo, F., Corrigan, V., LeCuyer, T.E. Necrotizing Infectious Hepatitis Caused by Clostridium novyi Type B in a Dog with No Predisposing Liver Lesions: A Case Report . ASVCP Annual meeting, oral presentation, virtual, November 2021. 
• Trusiano, B., Allen, I.C. The potential role of NIK and the noncanonical NFkB signaling pathway during steady state granulopoiesis and inflammation associated with hemolytic anemia. . ICTAS Doctoral Scholars Annual Research Symposium, oral presentation, virtual, March 2021.

Examination Graduate Committee

Major Advisor/Chair:

James Weger-Lucarelli, PhD
Assistant Professor
Department of Biomedical Sciences and Pathobiology VA-MD College of Veterinary Medicine 

Graduate Advising Committee Members:

Sally L. Paulson, PhD
Associate Professor
Veterinary and Medical Entomology

Nisha K. Duggal, PhD
Associate Professor
Department of Biomedical Sciences and Pathobiology VA-MD College of Veterinary Medicine

Tanya LeRoith, DVM, PhD, DACVP
Clinical Professor
Department of Biomedical Sciences and Pathobiology VA-MD College of Veterinary Medicine