About

Elena Pobezinskaya is a Research Assistant Professor in the Department of Veterinary and Animal Sciences at the University of Massachusetts Amherst. She holds a Ph.D. from the Cancer Research Center in Moscow, Russia, obtained in 2002, and completed postdoctoral training in Cell and Cancer Biology at NIH/NCI. Her research focuses on intercellular communication in healthy organisms and under conditions of infections and cancer. She investigates how cells of the immune system communicate with each other and with other cells through receptor-ligand interactions, transfer of molecules, and transfer of organelles, exploring the functional significance of these processes in vivo. Her work employs various transgenic and knockout mouse models, as well as in vivo tumor models, to understand what information is shared during intercellular communication and how this influences cellular functions.

Research topics

• Biology
• Immunology
• Cell biology
• Genetics
• Cancer research
• Computational biology
• Biochemistry

Selected publications

• A Dapl1+ subpopulation of naive CD8 T cells contains committed precursors of memory lineage.

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-08 · 2 citations

  preprint

  Memory CD8 T cells play a vital role in providing lasting immune protection, yet their origins remain incompletely understood. Contrary to classical models, emerging evidence suggests that heterogeneity within the naive T cell pool may influence fate decisions prior to antigen encounter. However, the markers of naive T cell heterogeneity have not yet been clearly defined. Here, we describe intraclonal heterogeneity within the naive T cell population marked by the protein Dapl1. Using novel monoclonal antibodies and a reporter-knockout mouse model, we found that Dapl1-positive naive CD8 T cells exhibit distinct phenotypes compared to their Dapl1-negative counterparts. Furthermore, this population includes a subset of pre-programmed precursors biased toward memory lineage fate. The differentiation of these precursors is independent of Dapl1 but relies on the transcription factor Bcl11b, resulting in the generation of Dapl1-positive central memory-like CD8 T cells in response to infection, and stem-like memory cells in response to cancer. Notably, naive Dapl1-positive T cells originate in the thymus among mature thymocytes and gradually appear in the periphery within several days after birth. Our findings suggest that committed memory precursors in the Dapl1-positive population may represent an alternative pathway for memory CD8 T cell generation, offering new avenues for therapeutic application.

  PublisherDOI

• Heterogeneity of CD8αα intraepithelial lymphocytes is transcriptionally conserved between TCRαβ and TCRγδ cell lineages

  Frontiers in Immunology · 2025-08-05 · 3 citations

  articleOpen accessCorresponding

  Intestinal intraepithelial lymphocytes (IELs) are a versatile population of immune cells with both effector and regulatory roles in gut immunity. Although this functional diversity is thought to arise from distinct IEL subpopulations, the heterogeneity of TCRαβ + and TCRγδ + IELs have not been well characterized. Using scRNAseq, we identified CD8αα + T cell subsets with memory-like ( Tcf7 + ) and effector-like ( Prdm1 + ) profiles in both TCRαβ + and TCRγδ + IELs. Using CD160 and CD122 as markers of memory-like and effector-like cells, respectively, we found that while effector-like cells dominated the small intestine, memory-like IELs were more prevalent in the large intestine, suggesting a functional specialization of immune responses along the gut. Further transcriptional analysis revealed shared profiles between TCRαβ + and TCRγδ + small intestinal IEL subsets, suggesting conserved functional roles across these populations. Finally, our analysis indicated that TCRαβ + memory-like IELs arise from Tcf7 + double-negative (DN) precursors, and that effector-like IELs subsequently differentiate from the memory-like population. In contrast, TCRγδ + IELs appear to originate from two distinct precursor populations, one expressing Tcf7 and the other Zeb2 , indicating the presence of parallel developmental pathways within this lineage. Overall, our findings reveal that both TCRαβ + and TCRγδ + cells contain memory-like and effector-like subsets, which may contribute to the functional heterogeneity of IELs.

  PublisherOA PDFDOI

• A Dapl1 ⁺ subpopulation of naïve CD8 T cells is enriched for memory-lineage precursors

  Science Advances · 2025-08-22 · 1 citations

  articleOpen accessCorresponding

  Memory CD8 T cells provide long-lasting immunity, but their developmental origins remain incompletely defined. Growing evidence suggests that functional heterogeneity exists within the naïve T cell pool, shaping lineage potential before antigen stimulation. Here, we identify a subpopulation of naïve CD8 T cells expressing death-associated protein-like 1 (Dapl1) that contains preprogrammed precursors biased toward memory differentiation. The differentiation of these precursors is independent of Dapl1 but relies on the transcription factor B-cell lymphoma/leukaemia 11b (Bcl11b), resulting in the generation of Dapl1 + central memory–like CD8 T cells after infection and stem-like memory cells in cancer. Dapl1 + naïve T cells originate among mature thymocytes and gradually appear in the periphery postnatally. Peripheral Dapl1 + and Dapl1 − populations show limited plasticity, supporting a thymic-imprinting model. These findings reveal a developmentally imprinted subset of naïve CD8 T cells committed to memory fate, uncovering an alternative pathway for memory T cell generation offering new avenues for therapeutic application.

  PublisherDOI

• Heterogeneity of CD8αα intraepithelial lymphocytes is transcriptionally conserved between TCRαβ and TCRγδ cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-25

  preprintOpen access

  Abstract Intestinal intraepithelial lymphocytes (IELs) are a versatile population of immune cells with both effector and regulatory roles in gut immunity. Although this functional diversity is thought to arise from distinct IEL subpopulations, the heterogeneity of TCRαβ + and TCRγδ + IELs have not been well-characterized. Using scRNAseq, we identified CD8αα + T cell subsets with memory-like ( Tcf7 ⁺) and effector-like ( Prdm1 ⁺) profiles in both TCRαβ + and TCRγδ + IELs. Using CD160 and CD122 as markers of memory-like and effector-like cells, respectively, we found that while effector-like cells dominated the small intestine, memory-like IELs were more prevalent in the large intestine, suggesting a functional specialization of immune responses along the gut. Further transcriptional analysis revealed shared profiles between TCRαβ + and TCRγδ + small intestinal IEL subsets, suggesting conserved functional roles across these populations. Finally, our analysis indicated that TCRαβ + memory-like IELs arise from Tcf7⁺ double-negative (DN) precursors, and that effector-like IELs subsequently differentiate from the memory-like population. In contrast, TCRγδ + IELs appear to originate from two distinct precursor populations, one expressing Tcf7 and the other Zeb2 , indicating the presence of parallel developmental pathways within this lineage. Overall, our findings reveal that both TCRαβ + and TCRγδ + cells contain memory-like and effector-like subsets, which may contribute to the functional heterogeneity of IELs.

  PublisherOA PDFDOI

• The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer

  Frontiers in Immunology · 2023-12-20 · 2 citations

  articleOpen accessSenior authorCorresponding

  The phenomenon of intercellular transfer of cellular material, including membranes, cytoplasm, and even organelles, has been observed for decades. The functional impact and molecular mechanisms of such transfer in the immune system remain largely elusive due to the absence of a robust in vivo model. Here, we introduce a new tumor mouse model, where tumor cells express the soluble ultra-bright fluorescent protein ZsGreen, which allows detection and measurement of intercellular transfer of cytoplasm from tumor cells to infiltrating immune cells. We found that in addition to various types of myeloid lineage cells, a large fraction of T regulatory cells and effector CD8 T cells acquire tumor material. Based on the distribution of tumor-derived ZsGreen, the majority of T cells integrate captured cytoplasm into their own, while most myeloid cells store tumor material in granules. Furthermore, scRNA-seq analysis revealed significant alterations in transcriptomes of T cells that acquired tumor cell cytoplasm, suggesting potential impact on T cell function. We identified that the participation of T cells in intercellular transfer requires cell-cell contact and is strictly dependent on the activation status of T lymphocytes. Finally, we propose to name the described phenomenon of intercellular transfer for tumor infiltrating T cells the “mosquito effect”.

  PublisherOA PDFDOI

• LKB1 isoform expression modulates T cell plasticity downstream of PKCθ and IL-6

  Molecular Immunology · 2023-04-03 · 4 citations

  articleOpen access

  Following activation, CD4 T cells undergo metabolic and transcriptional changes as they respond to external cues and differentiate into T helper (Th) cells. T cells exhibit plasticity between Th phenotypes in highly inflammatory environments, such as colitis, in which high levels of IL-6 promote plasticity between regulatory T (Treg) cells and Th17 cells. Protein Kinase C theta (PKCθ) is a T cell-specific serine/threonine kinase that promotes Th17 differentiation while negatively regulating Treg differentiation. Liver kinase B1 (LKB1), also a serine/threonine kinase and encoded by Stk11, is necessary for Treg survival and function. Stk11 can be alternatively spliced to produce a short variant (Stk11S) by transcribing a cryptic exon. However, the contribution of Stk11 splice variants to Th cell differentiation has not been previously explored. Here we show that in Th17 cells, the heterogeneous ribonucleoprotein, hnRNPLL, mediates Stk11 splicing into its short splice variant, and that Stk11S expression is diminished when Hnrnpll is depleted using siRNA knock-down approaches. We further show that PKCθ regulates hnRNPLL and, thus, Stk11S expression in Th17 cells. We provide additional evidence that exposing induced (i)Tregs to IL-6 culminates in Stk11 splicing downstream of PKCθAltogether our data reveal a yet undescribed outside-in signaling pathway initiated by IL-6, that acts through PKCθ and hnRNPLL to regulate Stk11 splice variants and facilitate Th17 cell differentiation. Furthermore, we show for the first time, that this pathway can also be initiated in developing iTregs exposed to IL-6, providing mechanistic insight into iTreg phenotypic stability and iTreg to Th17 cell plasticity.

  PublisherDOI

• Let-7 enhances murine anti-tumor CD8 T cell responses by promoting memory and antagonizing terminal differentiation

  Nature Communications · 2023 · 34 citations

  • Cell biology
  • Biology
  • Cancer research

  The success of the CD8 T cell-mediated immune response against infections and tumors depends on the formation of a long-lived memory pool, and the protection of effector cells from exhaustion. The advent of checkpoint blockade therapy has significantly improved anti-tumor therapeutic outcomes by reversing CD8 T cell exhaustion, but fails to generate effector cells with memory potential. Here, using in vivo mouse models, we show that let-7 miRNAs determine CD8 T cell fate, where maintenance of let-7 expression during early cell activation results in memory CD8 T cell formation and tumor clearance. Conversely, let-7-deficiency promotes the generation of a terminal effector population that becomes vulnerable to exhaustion and cell death in immunosuppressive environments and fails to reject tumors. Mechanistically, let-7 restrains metabolic changes that occur during T cell activation through the inhibition of the PI3K/AKT/mTOR signaling pathway and production of reactive oxygen species, potent drivers of terminal differentiation and exhaustion. Thus, our results reveal a role for let-7 in the time-sensitive support of memory formation and the protection of effector cells from exhaustion. Overall, our data suggest a strategy in developing next-generation immunotherapies by preserving the multipotency of effector cells rather than enhancing the efficacy of differentiation.

  PublisherOA PDFDOI

• Pathogenic Th17 cell differentiation is negatively regulated by let-7 microRNAs in a mouse model of multiple sclerosis

  The Journal of Immunology · 2020-05-01

  article

  Abstract Autoimmune disorders such as multiple sclerosis (MS) are caused by proinflammatory events mediated by pathogenic Th17 cells. In MS, these cells arise in response to autoantigen recognition and exposure to the cytokines IL-1β and IL-23, migrate to the central nervous system (CNS) by following gradients of CCR2- and CCR5-cognate chemokines, and secrete GM-CSF. GM-CSF is essential for disease development, as it promotes the activation, differentiation, and recruitment of peripheral inflammatory myeloid cells to the CNS that directly demyelinate neurons and damage axons. Th17 cell pathogenicity in MS has been correlated with microRNA (miRNA) dysregulation, which leads to aberrant post-transcriptional regulation of gene expression and enhanced autoreactive phenotype. We found that the lethal-7 (let-7) miRNA family is abundantly expressed in naive CD4+ T cells, but gets dramatically downregulated over time following antigen encounter, indicating that let-7 may control the differentiation of pathogenic Th17 cells. To investigate a potential regulatory role for let-7 in Th17 cell autoreactivity, we used experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Specifically, we demonstrated that let-7 confers protection from EAE by negatively regulating the proliferation, IL-1β/IL-23-dependent differentiation, and CCR2/CCR5-dependent migration of pathogenic Th17 cells to the CNS. Conversely, absence of let-7 led to enhanced Th17 cell autoreactivity and aggravated disease. Therefore, our results identify a novel regulatory role for let-7 miRNAs in pathogenic Th17 differentiation during EAE development, suggesting a promising therapeutic application for the treatment of MS-related autoimmune diseases.

  PublisherDOI

• Non-coding RNAs in CD8 T cell biology

  Molecular Immunology · 2020 · 31 citations

  • Biology
  • Computational biology
  • Cell biology
  PublisherOA PDFDOI

• Differentiation of Pathogenic Th17 Cells Is Negatively Regulated by Let-7 MicroRNAs in a Mouse Model of Multiple Sclerosis

  Frontiers in Immunology · 2020 · 69 citations

  • Immunology
  • Biology
  • Genetics

  . Therefore, our results identify a novel regulatory role for let-7 miRNAs in pathogenic Th17 differentiation during EAE development, suggesting a promising therapeutic application for disease treatment.

  PublisherDOI

Frequent coauthors

• Zheng-gang Liu

  Chinese Academy of Sciences

  36 shared

• Swati Choksi

  National Cancer Institute

  32 shared

• Xiumei Cao

  22 shared

• Michael J. Morgan

  Northeastern State University

  22 shared

• Kun Chen

  Chinese Academy of Medical Sciences & Peking Union Medical College

  12 shared

• Yong Lin

  12 shared

• Leonid A. Pobezinsky

  11 shared

• Tao Li

  Tianjin Chest Hospital

  10 shared

Awards & honors

• Fellows Award for Research Excellence, 2009