About

Lisa M. Minter is the Department Head and a Professor in the Department of Veterinary and Animal Sciences at the University of Massachusetts Amherst. She earned her Ph.D. from UMass Amherst in 2001 and completed postdoctoral training at the same institution. Her research focuses on the mechanisms of aberrant immune system responses, particularly the molecular and cellular pathways involved in autoimmunity and autoimmune diseases such as Aplastic Anemia. Her work aims to identify key regulatory molecules, including NOTCH1, a transmembrane receptor critical for T cell activation, proliferation, and differentiation, which has been shown to contribute to disease pathology in Aplastic Anemia. Minter's research involves dissecting the pathways mediating Notch signaling, exploring its interacting partners, and understanding their roles in autoimmune bone marrow failure and graft-vs-host disease using animal models. She collaborates with faculty in polymer sciences and chemistry to develop novel therapeutic strategies, including targeted delivery systems for immune modulation. Her efforts are directed toward developing new approaches for controlling autoimmune responses and advancing therapeutic interventions for immune-mediated diseases.

Research topics

• Biology
• Genetics
• Medicine
• Immunology
• Computational biology
• Biochemistry
• Cancer research
• Internal medicine
• Bioinformatics
• Microbiology

Selected publications

• PRMT5 regulates epigenetic changes in suppressive Th1-like iTregs in response to IL-12 treatment

  Frontiers in Immunology · 2024-01-08 · 7 citations

  articleOpen accessSenior authorCorresponding

  Background: Induced regulatory T cells (iTregs) are a heterogeneous population of immunosuppressive T cells with therapeutic potential. Treg cells show a range of plasticity and can acquire T effector-like capacities, as is the case for T helper 1 (Th1)-like iTregs. Thus, it is important to distinguish between functional plasticity and lineage instability. Aplastic anemia (AA) is an autoimmune disorder characterized by immune-mediated destruction of hematopoietic stem and progenitor cells in the bone marrow (BM). Th1-like 1 iTregs can be potent suppressors of aberrant Th1-mediated immune responses such as those that drive AA disease progression. Here we investigated the function of the epigenetic enzyme, protein arginine methyltransferase 5 (PRMT5), its regulation of the iTreg-destabilizing deacetylase, sirtuin 1 (Sirt1) in suppressive Th1-like iTregs, and the potential for administering Th1-like iTregs as a cell-based therapy for AA. Methods: We generated Th1-like iTregs by culturing iTregs with IL-12, then assessed their suppressive capacity, expression of iTreg suppression markers, and enzymatic activity of PRMT5 using histone symmetric arginine di-methylation (H3R2me2s) as a read out. We used ChIP sequencing on Th1 cells, iTregs, and Th1-like iTregs to identify H3R2me2s-bound genes unique to Th1-like iTregs, then validated targets using CHiP-qPCR. We knocked down PRMT5 to validate its contribution to Th1-like iTreg lineage commitment. Finally we tested the therapeutic potential of Th1-like iTregs using a Th1-mediated mouse model of AA. Results: promoter region in Th1-like iTregs to negatively regulate its expression. Furthermore, administering Th1-like iTregs to AA mice provided a survival benefit. Conclusions: Knocking down PRMT5 in Th1-like iTregs concomitantly reduced their suppressive capacity, supporting the notion that PRMT5 is important for the superior suppressive capacity and stability of Th1-like iTregs. Conclusively, therapeutic administration of Th1-like iTregs in a mouse model of AA significantly extended their survival and they may have therapeutic potential.

  PublisherOA PDFDOI

• Oxidized Polyunsaturated Fatty Acid Promotes Colitis and Colitis-Associated Tumorigenesis in Mice

  Journal of Crohn s and Colitis · 2024-09-14 · 12 citations

  articleOpen access

  BACKGROUND AND AIMS: Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk of inflammatory bowel disease (IBD). PUFA is highly prone to oxidation. To date, it is unclear whether unoxidized or oxidized PUFA is involved in the development of IBD. Here, we aim to compare the effects of unoxidized PUFA vs oxidized PUFA on the development of IBD and associated colorectal cancer. METHODS: We evaluated the effects of unoxidized and oxidized PUFA on dextran sodium sulfate (DSS)-induced and IL-10 knockout-induced colitis, and azoxymethane/DSS-induced colon tumorigenesis in mice. Additionally, we studied the roles of gut microbiota and Toll-like receptor 4 (TLR4) signaling involved. RESULTS: Administration of a diet containing oxidized PUFA, at human consumption-relevant levels, increases the severity of colitis and exacerbates the development of colitis-associated colon tumorigenesis in mice. Conversely, a diet rich in unoxidized PUFA does not promote colitis. Furthermore, oxidized PUFA worsens colitis-associated intestinal barrier dysfunction and leads to increased bacterial translocation, and it fails to promote colitis in TLR4 knockout mice. Finally, oxidized PUFA alters the diversity and composition of gut microbiota, and it fails to promote colitis in mice lacking the microbiota. CONCLUSIONS: These results support that oxidized PUFA promotes the development of colitis and associated tumorigenesis in mouse models via TLR4- and gut microbiota-dependent mechanisms. Our findings highlight the potential need to update regulation policies and industrial standards for oxidized PUFA levels in food.

  PublisherOA PDFDOI

• Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract

  UNC Libraries · 2024-08-14

  articleOpen access
  PublisherDOI

• The Testing of Copper Intrauterine Devices to Mitigate Uterine Infections in Mares: A Preliminary Study

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-01

  preprintOpen accessSenior author

  Abstract This preliminary study evaluated the effectiveness of a novel hormone- and drug-free copper intrauterine device POD (CuiUPOD) with one to three copper-coated magnetic units in controlling Streptococcus equi subsp. zooepidemicus in seven intrauterine-inoculated mares. Initially, one unit was inserted into each mare and animals were followed weekly with trans-rectal ultrasonography, blood progesterone assay, uterine swabs for cytology and microbial culture, uterine specimens for biopsy, and trans-abdominal detection of the CuiUPOD using a handheld magnetic detector or a cell phone compass. Infection persisted after a CuiUPOD with one magnetic unit was inserted, but subsided shortly after two additional magnetic units were added. By day 60, at device removal, and after a 30-day exposure to copper, none of the mares presented with clinical signs of infection. On a scale of I-III (I, IIA, IIB, III), with I representing a healthy uterus, endometrial biopsies at the time of CuiUPOD removal, showed improved biopsy scores in two of seven mares (29%; p < 0.05). The in vivo experiments, complemented by an in vitro experiment, demonstrated a time- (24-96 hours) and dose-dependent response to Cu: three CuiUPODs - OD readings = 0.538; two CuiUPODs - OD = 0.513; and one CuiUPOD - OD = 0.452. As the concentration of copper increased, so did the antimicrobial effect. These findings suggest a promising use for the one-time application of a CuiUPOD with two or three magnetic units to mitigate uterine infections in mares. Simple Summary Only a limited number of antimicrobials are effective against most resistant bacteria. Several studies have demonstrated the biocidal effect of copper on bacteria, fungi, and viruses. Copper-containing intrauterine devices provide a non-pharmacological solution to prevent and treat uterine infections in equids. This preliminary study provides evidence of the antimicrobial properties of copper both in vivo and in vitro and explores its possible application in mare reproductive practice. A 30-day intrauterine exposure to copper showed no clinical signs of infection with a common bacterium in horses - Streptococcus equi subsp. zooepidemicus - in intrauterine-inoculated mares. As the concentration of copper increased, so did the antimicrobial effect. Copper intrauterine devices show promise in mitigating uterine infections in mares.

  PublisherOA PDFDOI

• Combating bone marrow failure with polymer materials

  Frontiers in Immunology · 2024-04-17 · 2 citations

  articleOpen accessSenior authorCorresponding

  Bone marrow failure (BMF) has become one of the most studied autoimmune disorders, particularly due to its prevalence both as an inherited disease, but also as a result of chemotherapies. BMF is associated with severe symptoms such as bleeding episodes and susceptibility to infections, and often has underlying characteristics, such as anemia, thrombocytopenia, and neutropenia. The current treatment landscape for BMF requires stem cell transplantation or chemotherapies to induce immune suppression. However, there is limited donor cell availability or dose related toxicity associated with these treatments. Optimizing these treatments has become a necessity. Polymer-based materials have become increasingly popular, as current research efforts are focused on synthesizing novel cell matrices for stem cell expansion to solve limited donor cell availability, as well as applying polymer delivery vehicles to intracellularly deliver cargo that can aid in immunosuppression. Here, we discuss the importance and impact of polymer materials to enhance therapeutics in the context of BMF.

  PublisherOA PDFDOI

• Testing copper intrauterine devices to mitigate uterine infections in mares: a pilot study

  Research Square · 2024-06-26

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• Intracellular Salmonella delivery of an exogenous immunization antigen refocuses CD8 T cells against cancer cells, eliminates pancreatic tumors and forms antitumor immunity

  Frontiers in Immunology · 2023-10-05 · 19 citations

  articleOpen access

  Introduction: Immunotherapies have shown great promise, but are not effective for all tumors types and are effective in less than 3% of patients with pancreatic ductal adenocarcinomas (PDAC). To make an immune treatment that is effective for more cancer patients and those with PDAC specifically, we genetically engineered Salmonella to deliver exogenous antigens directly into the cytoplasm of tumor cells. We hypothesized that intracellular delivery of an exogenous immunization antigen would activate antigen-specific CD8 T cells and reduce tumors in immunized mice. Methods: To test this hypothesis, we administered intracellular delivering (ID) Salmonella that deliver ovalbumin as a model antigen into tumor-bearing, ovalbumin-vaccinated mice. ID Salmonella delivers antigens by autonomously lysing in cells after the induction of cell invasion. Results: We showed that the delivered ovalbumin disperses throughout the cytoplasm of cells in culture and in tumors. This delivery into the cytoplasm is essential for antigen cross-presentation. We showed that co-culture of ovalbumin-recipient cancer cells with ovalbumin-specific CD8 T cells triggered a cytotoxic T cell response. After the adoptive transfer of OT-I CD8 T cells, intracellular delivery of ovalbumin reduced tumor growth and eliminated tumors. This effect was dependent on the presence of the ovalbumin-specific T cells. Following vaccination with the exogenous antigen in mice, intracellular delivery of the antigen cleared 43% of established KPC pancreatic tumors, increased survival, and prevented tumor re-implantation. Discussion: This response in the immunosuppressive KPC model demonstrates the potential to treat tumors that do not respond to checkpoint inhibitors, and the response to re-challenge indicates that new immunity was established against intrinsic tumor antigens. In the clinic, ID Salmonella could be used to deliver a protein antigen from a childhood immunization to refocus pre-existing T cell immunity against tumors. As an off-the-shelf immunotherapy, this bacterial system has the potential to be effective in a broad range of cancer patients.

  PublisherOA PDFDOI

• Exopolysaccharide-Treated Dendritic Cells Effectively Ameliorate Acute Graft-versus-Host Disease

  Transplantation and Cellular Therapy · 2023-11-02 · 4 citations

  articleOpen access
  PublisherOA PDFDOI

• Supplementary Figure S1-S7 from Targeted Metabolomics Identifies the Cytochrome P450 Monooxygenase Eicosanoid Pathway as a Novel Therapeutic Target of Colon Tumorigenesis

  2023-03-31

  preprintOpen access

  <p>SF1: CYP monooxygenase expression in human colon cancer cells; SF2: gene expression of Cyp2e1 in the liver of Cyp2c+/+, Cyp2c+/-, and Cyp2c-/- mice; SF3: liver inflammation in Cyp2c+/+, Cyp2c+/-, and Cyp2c-/- mice; SF4: survival curve of the AOM/DSS-stimulated Cyp2c+/+, Cyp2c+/-, and Cyp2c-/- mice; SF5: pharmacological inhibition of CYP monooxygenases suppresses AOM/DSS-induced colon tumorigenesis in mice; SF6: effects of 12,13-EpOME on MC38 tumor growth in C57BL/6 mice; SF7: mRNA expression levels of CYP monooxygenases in control subjects and colon cancer patients</p>

  PublisherDOI

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

  Molecular Immunology · 2023-04-03 · 4 citations

  articleOpen accessSenior authorCorresponding

  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

Frequent coauthors

• Todd E. Golde

  Emory University

  57 shared

• Lucio Miele

  51 shared

• Barbara A. Osborne

  University of Massachusetts Amherst

  50 shared

• Yong Ran

  Emory University

  35 shared

• Keli Xu

  University of Mississippi Medical Center

  33 shared

• Yaguang Xi

  University of Georgia

  31 shared

• Gregory N. Tew

  University of Massachusetts Amherst

  29 shared

• DA Ucar

  Tulane University

  25 shared

Labs

• Department of Veterinary and Animal Sciences, UMass AmherstPI