Paytsar Topchyan, PhD

T cell exhaustion, cancer immunology/immunotherapy and the tumor microenvironment

Research Experiences

Medical College of Wisconsin, 2018-2022
Advisor: Weiguo Cui, PhD
Project: Reprogramming tumor reactive CD8 T cells by targeting the IL-21-BATF pathway to treat melanoma (F30CA246920)

University of California-Los Angeles, 2012-2016
Advisor: Anahid Jewett, PhD, MPH
Master's Thesis: Adjuvant therapy with probiotic bacteria increases in vivo survival and function of natural killer cells in humanized mice 

Publications

Kasmani, M. Y, Zander, R, Chung, H. K, Chen, Y, Khatun, A, Damo, M, Topchyan, P, Johnson, K. E, Levashova, D, Burns, R, Lorenz, U. M, Tarakanova, V. L, Joshi, N. S, Kaech, S. M, Cui, W., Clonal lineage tracing reveals mechanisms skewing CD8+ T cell fate decisions in chronic infection. J Exp Med 2023, 220 (1).

Zander, R, Kasmani, M. Y, Chen, Y, Topchyan, P, Shen, J, Zheng, S, Burns, R, Ingram, J, Cui, C, Joshi, N, Craft, J, Zajac, A, Cui, W., Tfh-cell-derived interleukin 21 sustains effector CD8(+) T cell responses during chronic viral infection. Immunity 2022, 55 (3), 475-493.e5.

Topchyan, P, Zander, R, Kasmani, M. Y, Nguyen, C, Brown, A, Lin, S, Burns, R, Cui, W., Spatial transcriptomics demonstrates the role of CD4 T cells in effector CD8 T cell differentiation during chronic viral infection. Cell Rep 2022, 41 (9), 111736.

Gupta, P, Kadamberi, I. P, Mittal, S, Tsaih, S. W, George, J, Kumar, S, Vijayan, D. K, Geethadevi, A, Parashar, D, Topchyan, P, McAlarnen, L, Volkman, B. F, Cui, W, Zhang, K. Y. J, Di Vizio, D, Chaluvally-Raghavan, P, Pradeep, S., Tumor Derived Extracellular Vesicles Drive T Cell Exhaustion in Tumor Microenvironment through Sphingosine Mediated Signaling and Impacting Immunotherapy Outcomes in Ovarian Cancer. Adv Sci (Weinh) 2022, e2104452.

Zhu, W, Zheng, Y, Yu, M, Wei, J, Zhang, Y, Topchyan, P, Nguyen, C, Janecke, R, Kreuziger, L. B, White, G. C, Hari, P, Aster, R, Cui, W, Jobe, S, Graham, M. B, Wang, D, Wen, R., SARS-CoV-2 receptor binding domain-specific antibodies activate platelets with features resembling the pathogenic antibodies in heparin-induced thrombocytopenia. Res Sq 2021.

Xin, G, Chen, Y, Topchyan, P, Kasmani, M. Y, Burns, R, Volberding, P. J, Wu, X, Cohn, A, Chen, Y, Lin, C. W, Ho, P. C, Silverstein, R, Dwinell, M. B, Cui, W., Targeting PIM1-Mediated Metabolism in Myeloid Suppressor Cells to Treat Cancer. Cancer Immunol Res 2021, 9 (4), 454-469.

Topchyan, P, Xin, G, Chen, Y, Zheng, S, Burns, R, Shen, J, Kasmani, M. Y, Kudek, M, Yang, N, Cui, W., Harnessing the IL-21-BATF Pathway in the CD8(+) T Cell Anti-Tumor Response. Cancers (Basel) 2021, 13 (6).

Cheng, G, Hardy, M, Topchyan, P, Zander, R, Volberding, P, Cui, W, Kalyanaraman, B., Mitochondria-targeted hydroxyurea inhibits OXPHOS and induces antiproliferative and immunomodulatory effects. iScience 2021, 24 (6), 102673.

Chen, Y, Shen, J, Kasmani, M. Y, Topchyan, P, Cui, W., Single-Cell Transcriptomics Reveals Core Regulatory Programs That Determine the Heterogeneity of Circulating and Tissue-Resident Memory CD8(+) T Cells. Cells 2021, 10 (8).

Xin, G, Khatun, A, Topchyan, P, Zander, R, Volberding, P. J, Chen, Y, Shen, J, Fu, C, Jiang, A, See, W. A, Cui, W., Pathogen-Boosted Adoptive Cell Transfer Therapy Induces Endogenous Antitumor Immunity through Antigen Spreading. Cancer Immunol Res 2020, 8 (1), 7-18.

Cheng, G, Hardy, M, Topchyan, P, Zander, R, Volberding, P, Cui, W, Kalyanaraman, B., Potent inhibition of tumour cell proliferation and immunoregulatory function by mitochondria-targeted atovaquone. Sci Rep 2020, 10 (1), 17872.

Kaur, K, Kozlowska, A. K, Topchyan, P, Ko, M. W, Ohanian, N, Chiang, J, Cook, J, Maung, P. O, Park, S. H, Cacalano, N, Fang, C, Jewett, A., Probiotic-Treated Super-Charged NK Cells Efficiently Clear Poorly Differentiated Pancreatic Tumors in Hu-BLT Mice. Cancers (Basel) 2019, 12 (1).

Kaur, K, Topchyan, P, Kozlowska, A. K, Ohanian, N, Chiang, J, Maung, P. O, Park, S. H, Ko, M. W, Fang, C, Nishimura, I, Jewett, A., Super-charged NK cells inhibit growth and progression of stem-like/poorly differentiated oral tumors in vivo in humanized BLT mice; effect on tumor differentiation and response to chemotherapeutic drugs. Oncoimmunology 2018, 7 (5), e1426518.

Kaur, K, Chang, H. H, Topchyan, P, Cook, J. M, Barkhordarian, A, Eibl, G, Jewett, A., Deficiencies in Natural Killer Cell Numbers, Expansion, and Function at the Pre-Neoplastic Stage of Pancreatic Cancer by KRAS Mutation in the Pancreas of Obese Mice. Front Immunol 2018, 9, 1229.

Kozlowska, A K*; Topchyan, P*; Kaur, K, Tseng, H C, Teruel, A, Hiraga, T, Jewett, A, Differentiation by NK cells is a prerequisite for effective targeting of cancer stem cells/poorly differentiated tumors by chemopreventive and chemotherapeutic drugs. J Cancer 2017, 8 (4), 537-554.

Kozlowska, A K, Kaur, K, Topchyan, P, Jewett, A, Novel strategies to target cancer stem cells by NK cells; studies in humanized mice. Front Biosci (Landmark Ed) 2017, 22 (2), 370-384.

Kaur, K, Cook, J, Park, S H, Topchyan, P, Kozlowska, A, Ohanian, N, Fang, C, Nishimura, I, Jewett, A, Novel Strategy to Expand Super-Charged NK Cells with Significant Potential to Lyse and Differentiate Cancer Stem Cells: Differences in NK Expansion and Function between Healthy and Cancer Patients. Front Immunol 2017, 8, 297.

Kozlowska, A. K, Tseng, H. C, Kaur, K, Topchyan, P, Inagaki, A, Bui, V. T, Kasahara, N, Cacalano, N, Jewett, A., Resistance to cytotoxicity and sustained release of interleukin-6 and interleukin-8 in the presence of decreased interferon-γ after differentiation of glioblastoma by human natural killer cells. Cancer Immunol Immunother 2016, 65 (9), 1085-97.

Kozlowska, A. K, Kaur, K, Topchyan, P, Jewett, A., Adoptive transfer of osteoclast-expanded natural killer cells for immunotherapy targeting cancer stem-like cells in humanized mice. Cancer Immunol Immunother 2016, 65 (7), 835-45.

Tseng, H. C, Arasteh, A, Kaur, K, Kozlowska, A, Topchyan, P, Jewett, A., Differential Cytotoxicity but Augmented IFN-γ Secretion by NK Cells after Interaction with Monocytes from Humans, and Those from Wild Type and Myeloid-Specific COX-2 Knockout Mice. Front Immunol 2015, 6, 259.

Bui, V. T, Tseng, H. C, Kozlowska, A, Maung, P. O, Kaur, K, Topchyan, P, Jewett, A., Augmented IFN-γ and TNF-α Induced by Probiotic Bacteria in NK Cells Mediate Differentiation of Stem-Like Tumors Leading to Inhibition of Tumor Growth and Reduction in Inflammatory Cytokine Release; Regulation by IL-10. Front Immunol 2015, 6, 57.

Meeting Abstracts

Topchyan P, Zander R, Kasmani MY, Nguyen C, Brown AK, Lin S, Burns R, Cui W. ""Spatial transcriptomics reveals the role of CD4 T cells in effector CD8 T cell differentiation during chronic viral infection"", Annual Autumn Immunology Conference, 2022. Oral Presentation and Poster. *AAI Young Investigator Award recipient.

Topchyan P, Xin G, Chen Y, Kasmani MY, Zheng S, Burns R, Shen J, Cui W. ""BATF metabolically reprograms CD8 T cells for ACT therapy in melanoma"", Annual Autumn Immunology Conference, 2021. Oral Presentation and Poster. *AAI Young Investigator Award recipient.

Topchyan P, Xin G, Chen Y, Kasmani MY, Zheng S, Burns R, Shen J, Cui W. ""BATF metabolically reprograms CD8 T cells for ACT therapy in melanoma"", Cold Spring Harbor Laboratory Conference, Single Cell Analyses, 2021. Poster.

Topchyan P, Xin G, Chen Y, Kasmani MY, Zheng S, Burns R, Shen J, Cui W. ""Harnessing the IL-21-BATF pathway in the CD8 T cell anti-tumor response"", 36th Annual National MD-PhD Student Conference, 2021. Oral Presentation.

Topchyan P, Kaur K, Kozlowska A, Tseng-Dick H, Jewett A. ""Super NKs prevent tumor CSC growth in BLT humanized mice"", AADR/CADR Annual Meeting & Exhibition, 2016. Oral Presentation.

P. Topchyan, K. Kaur, A. Kozlowska, H. Tseng-Dick, A. Jewett. ""Super NKs prevent tumor CSC growth in BLT humanized mice"", 2016 AADR/CADR Annual Meeting & Exhibition. Los Angeles, CA.

General Interests

Indoor gardening, cooking, and Armenian dancing