Mary Tomayko, MD, PhD
Associate Professor of Dermatology and of Pathology; Director Yale Immunobullous Clinic, Dermatology; Director Dermatology Medical Student Education, Dermatology
Research & Publications
Biography
News
Research Summary
The ability to develop “immunological memory” to infectious diseases is critical for health and survival. Our laboratory studies how this long-term immunity is established and maintained in order to better understand natural immunity, improve vaccine design and develop more effective therapies for autoimmune disease.
Specialized Terms: Immunologic memory; B cell response; Autoimmunity; Bullous pemphigoid; Pemphigus vulgaris
Extensive Research Description
Memory B cells that differentiate into antigen presenting and antibody-producing cells are important in natural and vaccine-mediated protection and are targets of B cell-directed therapies for malignancy and autoimmune disease. Thus, there is great interest in elucidating their unique biological properties in order to understand how they form, function and modulate recall responses. However, progress in elucidating these properties has been limited, particularly in mice, by the lack of adequate markers to distinguish memory cells. Our group has had a long-standing interest in this area and has made a number of contributions.
Using mouse systems developed in our laboratory that overcome significant barriers to the study of B cell memory, we compared gene expression between memory B cells and their naïve precursors using Affymetrix microarrays. We confirmed the differential expression of several conceptually important families at the mRNA and protein level. These initial findings were the foundation of several research projects. Some key findings and areas of ongoing research include:
1. Memory B cells are wired to signal differently than their naïve precursors.
2. There are subsets of murine memory B cells that form a spectrum from more naïve-like to more-memory-like.
3. Specific pathways regulate self-renewal and differentiation to antibody forming cells.
4. Specific pathways regulate the quality of the T-dependent B cell immune response.
Coauthors
Research Interests
Dermatology; Immunologic Memory; Pemphigoid, Bullous; Pemphigus; Autoimmunity
Selected Publications
- Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine ProtectionKim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection. Small Methods 2023, 7: e2300594. PMID: 37312418, PMCID: PMC10592458, DOI: 10.1002/smtd.202300594.
- Immune checkpoint inhibitor-induced bullous pemphigoid is characterized by interleukin (IL)-4 and IL-13 expression and responds to dupilumab treatmentShipman W, Singh K, Cohen J, Leventhal J, Damsky W, Tomayko M. Immune checkpoint inhibitor-induced bullous pemphigoid is characterized by interleukin (IL)-4 and IL-13 expression and responds to dupilumab treatment. British Journal Of Dermatology 2023, 189: 339-341. PMID: 37140007, PMCID: PMC10947518, DOI: 10.1093/bjd/ljad149.
- High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seqLiu Y, DiStasio M, Su G, Asashima H, Enninful A, Qin X, Deng Y, Nam J, Gao F, Bordignon P, Cassano M, Tomayko M, Xu M, Halene S, Craft J, Hafler D, Fan R. High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq. Nature Biotechnology 2023, 41: 1405-1409. PMID: 36823353, PMCID: PMC10567548, DOI: 10.1038/s41587-023-01676-0.
- 030 Immune checkpoint inhibitor-induced bullous pemphigoid skin has elevated interleukin-4 and interleukin-13 expression and responds to IL-4R inhibitionShipman W, Singh K, Cohen J, Leventhal J, Damsky W, Tomayko M. 030 Immune checkpoint inhibitor-induced bullous pemphigoid skin has elevated interleukin-4 and interleukin-13 expression and responds to IL-4R inhibition. Journal Of Investigative Dermatology 2022, 142: s5. DOI: 10.1016/j.jid.2022.05.084.
- COVID‐19 outcomes in patients with autoimmune blistering diseaseHwang E, Tomayko M. COVID‐19 outcomes in patients with autoimmune blistering disease. British Journal Of Dermatology 2021, 185: 1048-1050. PMID: 34107059, PMCID: PMC8239772, DOI: 10.1111/bjd.20571.
- 30 RituximabGehlhausen J, Heffernan M, Tomayko M. 30 Rituximab. 2021, 330-338.e3. DOI: 10.1016/b978-0-323-61211-1.00030-9.
- RituximabGelhausen, J.R., Heffernan, M. P. and Tomayko, M.M. Chapter 30: Rituximab. In Comprehensive Dermatologic Drug Therapy, 4th Edition. Ed. S. E. Wolverton and J.J. Wu. 2020.
- A Niche for Plasma Cells: The SkinKaraaslan S, Tomayko MM. A Niche for Plasma Cells: The Skin. Journal Of Investigative Dermatology 2019, 139: 2411-2414. PMID: 31753124, DOI: 10.1016/j.jid.2019.06.133.
- B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitorsDamsky W, Jilaveanu L, Turner N, Perry C, Zito C, Tomayko M, Leventhal J, Herold K, Meffre E, Bosenberg M, Kluger HM. B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors. Journal For ImmunoTherapy Of Cancer 2019, 7: 153. PMID: 31200747, PMCID: PMC6567557, DOI: 10.1186/s40425-019-0613-1.
- What B cell memories are made ofTomayko MM, Allman D. What B cell memories are made of. Current Opinion In Immunology 2019, 57: 58-64. PMID: 30861463, DOI: 10.1016/j.coi.2019.01.003.
- Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for managementColeman E, Ko C, Dai F, Tomayko MM, Kluger H, Leventhal JS. Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management. Journal Of The American Academy Of Dermatology 2018, 80: 990-997. PMID: 30399387, PMCID: PMC6420863, DOI: 10.1016/j.jaad.2018.10.062.
- Bullous disorders associated with anti–PD-1 and anti–PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapySiegel J, Totonchy M, Damsky W, Berk-Krauss J, Castiglione F, Sznol M, Petrylak DP, Fischbach N, Goldberg SB, Decker RH, Stamatouli AM, Hafez N, Glusac EJ, Tomayko MM, Leventhal JS. Bullous disorders associated with anti–PD-1 and anti–PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy. Journal Of The American Academy Of Dermatology 2018, 79: 1081-1088. PMID: 30025829, DOI: 10.1016/j.jaad.2018.07.008.
- B Cell BiologySadanand S, Tomayko M. B Cell Biology. 2017, 97-119. DOI: 10.1007/978-3-319-29785-9_7.
- Development of bullous pemphigoid during nivolumab therapyDamsky W, Kole L, Tomayko MM. Development of bullous pemphigoid during nivolumab therapy. JAAD Case Reports 2016, 2: 442-444. PMID: 27981213, PMCID: PMC5144742, DOI: 10.1016/j.jdcr.2016.05.009.
- Nodular plaque in a cardiac transplant patientWaldman A, Ezaldein H, Tomayko M, Galan A. Nodular plaque in a cardiac transplant patient. Journal Of The American Academy Of Dermatology 2015, 72: e111-e112. DOI: 10.1016/j.jaad.2014.12.037.
- Pemphigus vulgaris presenting as gingival hypertrophy in a childHaberland C, Johnson M, Tomayko M. Pemphigus vulgaris presenting as gingival hypertrophy in a child. Oral Surgery Oral Medicine Oral Pathology And Oral Radiology 2014, 118: e191. DOI: 10.1016/j.oooo.2014.05.088.
- CD80 and PD-L2 define functionally distinct memory B cell subsets that are independent of antibody isotypeZuccarino-Catania GV, Sadanand S, Weisel FJ, Tomayko MM, Meng H, Kleinstein SH, Good-Jacobson KL, Shlomchik MJ. CD80 and PD-L2 define functionally distinct memory B cell subsets that are independent of antibody isotype. Nature Immunology 2014, 15: 631-637. PMID: 24880458, PMCID: PMC4105703, DOI: 10.1038/ni.2914.
- CD73 Expression Is Dynamically Regulated in the Germinal Center and Bone Marrow Plasma Cells Are Diminished in Its AbsenceConter LJ, Song E, Shlomchik MJ, Tomayko MM. CD73 Expression Is Dynamically Regulated in the Germinal Center and Bone Marrow Plasma Cells Are Diminished in Its Absence. PLOS ONE 2014, 9: e92009. PMID: 24664100, PMCID: PMC3963874, DOI: 10.1371/journal.pone.0092009.
- Cutting Edge: Hierarchy of Maturity of Murine Memory B Cell SubsetsTomayko MM, Steinel NC, Anderson SM, Shlomchik MJ. Cutting Edge: Hierarchy of Maturity of Murine Memory B Cell Subsets. The Journal Of Immunology 2010, 185: 7146-7150. PMID: 21078902, PMCID: PMC3133669, DOI: 10.4049/jimmunol.1002163.
- PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cellsGood-Jacobson KL, Szumilas CG, Chen L, Sharpe AH, Tomayko MM, Shlomchik MJ. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nature Immunology 2010, 11: 535-542. PMID: 20453843, PMCID: PMC2874069, DOI: 10.1038/ni.1877.
- BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intactScholz JL, Crowley JE, Tomayko MM, Steinel N, O'Neill PJ, Quinn WJ, Goenka R, Miller JP, Cho YH, Long V, Ward C, Migone TS, Shlomchik MJ, Cancro MP. BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 15517-15522. PMID: 18832171, PMCID: PMC2563088, DOI: 10.1073/pnas.0807841105.
- BLyS Neutralization Ablates Primary But Not Memory B Cell PoolsCrowley J, Scholz J, Tomayko M, Steinel N, O'Neill P, Miller J, Cho Y, Long V, Ward C, Migone T, Shlomchik M, Cancro M. BLyS Neutralization Ablates Primary But Not Memory B Cell Pools. The FASEB Journal 2008, 22: 366-366. DOI: 10.1096/fasebj.22.2_supplement.366.
- B cell maturation and selection at the marrow-periphery interfaceCancro M, Allman D, Hayes C, Lentz V, Fields R, Sah A, Tomayko M. B cell maturation and selection at the marrow-periphery interface. Immunologic Research 1998, 17: 3-11. PMID: 9479562, DOI: 10.1007/bf02786425.
- Human neuroblastoma cell lines regain catecholamine fluorescence when xenografted into athymic (nude) miceTomayko M, Triche T, Reynolds C. Human neuroblastoma cell lines regain catecholamine fluorescence when xenografted into athymic (nude) mice. International Journal Of Developmental Neuroscience 1996, 14: 771-777. PMID: 8960984, DOI: 10.1016/s0736-5748(96)00050-0.
- Human neuroblastoma cell lines that express N‐myc without gene amplificationWada R, Seeger R, Brodeur G, Einhorn P, Rayner S, Tomayko M, Reynolds C. Human neuroblastoma cell lines that express N‐myc without gene amplification. Cancer 1993, 72: 3346-3354. PMID: 8242562, DOI: 10.1002/1097-0142(19931201)72:11<3346::aid-cncr2820721134>3.0.co;2-e.
- Determination of subcutaneous tumor size in athymic (nude) miceTomayko M, Reynolds C. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemotherapy And Pharmacology 1989, 24: 148-154. PMID: 2544306, DOI: 10.1007/bf00300234.
- Cell Biology, in Clinical and Basic ImmunodermatologySadanand, SS and Tomayko, MM. B Cell Biology, in Clinical and Basic Immunodermatology, Eds. Kaplan DH, Gaspari, AA, Stingl, G. In press.
Clinical Trials
| Conditions | Study Title |
|---|---|
| Diseases of the Nervous System | Evaluating the Immune Response to COVID-19 Vaccination in B-cell Depleted Patients |