Lisa M. Minter

Lisa M. Minter

Associate Professor

Lisa M. Minter, Ph.D.

Office phone: 413-545-6327

Lab phone: 413-545-1364

Fax: 413-545-1446

Email: lminter [at] vasci [dot] umass [dot] edu

Office location: 427K ISB

Mailing address:

661 North Pleasant Street
University of Massachusetts Amherst
Amherst, MA 01003

Ph.D.: University of Massachusetts, 2001
Postdoctoral Training: UMass, Amherst

Classes:
ANIML SCI 365
- Fundamentals of Veterinary & Biomedical Laboratory Techniques
  

Mechanisms of aberrant immune system responses

The human immune system is a highly complex, exquisitely orchestrated hierarchy of responses to pathogenic insults. The efficiency and plasticity of the immune system provides us with protection from infections caused by bacteria or viruses. Furthermore, our ability to manipulate these natural responses underlies the basis of protection from infectious diseases and, now, certain cancers, through preventative vaccination programs.

Aberrant immune responses, however, can result in conditions of autoimmunity, during which cells of the immune system mistakenly identify cells and tissues normally found in the body as “foreign” and mount destructive attacks against them. We are working to identify key regulatory molecules that contribute to autoimmunity, especially the autoimmune bone marrow failure syndrome, Aplastic Anemia. We aim to detail at the molecular and cellular level, the mechanisms of disease, to extrapolate these findings to understand their impact at the systems (whole animal) level and, further, to develop novel therapeutic approaches for treating disease.

One of our key proteins of interest is NOTCH1, a transmembrane receptor, shown to be a critical regulator of T cell activation, proliferation, and differentiation. We have identified it as an important contributor to disease pathology in Aplastic Anemia. We are now investigating NOTCH1-interacting partners to explore their cooperative role in autoimmune bone marrow failure.

To achieve this goal, my research is focused on the following primary objectives:

Defining novel pathways that mediate Notch signaling, both upstream and downstream of its expression

We are interested in determining those partners which interact with NOTCH1, both in the cytosol and the nucleus, to mediate its effects. These include proteins which associate directly with NOTCH1, as well a micro-RNAs which may be acting immediately up- and downstream of NOTCH1.

Dissecting the mechanisms of (auto)immune-mediated diseases using animal models of immune-mediated bone marrow failure and graft-vs-host disease

We have established a highly representative animal model of Aplastic Anemia. Using this model we can confirm in vitro observations made using mouse immune cells or peripheral blood mononuclear cells from patients with Aplastic Anemia who have not received prior treatment. We can also use this model to test the therapeutic potential of pharmacological inhibitors under clinically relevant conditions. Using a “humanized” model of graft-vs-host disease we are further able to study the molecular mechanisms that underlie the aberrant immune signaling responsible for this post-bone marrow transplant condition.

Exploring novel strategies for modulating immune system responses in the context of these disease models

Strong collaborations with faculty in the Dept. of Polymer Sciences and Engineering and the Dept. of Chemistry, we are exploring novel means of therapeutically modulating immune responses so as to create novel, specific and tunable means of controlling autoimmune responses. Our approaches include systemic and targeted delivery of nanoplatform carriers designed to release intracellular cargos of small interfering RNAs (siRNA), protein-specific antibodies, or small molecule inhibitors.

  

 

 

Mitra A, Shanthalingam S, Sherman HL, Singh K, Canakci M, Torres JA, Lawlor R, Ran Y, Golde TE, Miele L et al..  2020.  CD28 Signaling Drives Notch Ligand Expression on CD4 T Cells. Frontiers in Immunology. 11
Ozay IE, Shanthalingam S, Torres JA, Osborne BA, Tew GN, Minter LM.  2020.  Protein Kinase C Theta Modulates PCMT1 through hnRNPL to Regulate FOXP3 Stability in Regulatory T Cells. Molecular Therapy. 28:2220–2236.
Ozay IE, Shanthalingam S, Sherman HL, Torres JA, Osborne BA, Tew GN, Minter LM.  2020.  Cell-Penetrating Anti-Protein Kinase C Theta Antibodies Act Intracellularly to Generate Stable, Highly Suppressive Regulatory T Cells. Molecular Therapy. 28:1987–2006.
Xie M, Yang J, Zhang J, Sherman HL, Zhang Z, Minter LM, Hammock BD, Park Y, Zhang G.  2020.  Effects of Linoleic Acid-Rich Diet on Plasma Profiles of Eicosanoids and Development of Colitis in Il-10–/– Mice. Journal of Agricultural and Food Chemistry. 68:7641–7647.
Lessard CB, Rodriguez E, Ladd TB, Minter LM, Osborne BA, Miele L, Golde TE, Ran Y.  2020.  y-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse y-secretase modulators do not. Alzheimer{\textquotesingle}s Research {&} Therapy. 12
Angelou CC, Wells AC, Vijayaraghavan J, Dougan CE, Lawlor R, Iverson E, Lazarevic V, Kimura MY, Peyton SR, Minter LM et al..  2020.  Differentiation of Pathogenic Th17 Cells Is Negatively Regulated by Let-7 MicroRNAs in a Mouse Model of Multiple Sclerosis. Frontiers in Immunology. 10
Xie M, Zhang H, Wang W, Sherman HL, Minter LM, Cai Z, Zhang G.  2019.  Triclocarban Exposure Exaggerates Spontaneous Colonic Inflammation in Il-10-/- Mice. Toxicological Sciences. 174:92–99.
Geiger S, Ozay EI, Geumann U, Hereth MK, Magnusson T, Shanthalingam S, Hirsch D, Kälin S, Günther C, Osborne BA et al..  2019.  Alpha-1 Antitrypsin-Expressing Mesenchymal Stromal Cells Confer a Long-Term Survival Benefit in a Mouse Model of Lethal GvHD. Molecular Therapy. 27:1436–1451.
Lessard CB, Rodriguez E, Ladd TB, Minter LM, Osborne BA, Miele L, Golde TE, Ran Y.  2019.  Individual and combined presenilin 1 and 2 knockouts reveal that both have highly overlapping functions in HEK293T cells. Journal of Biological Chemistry. 294:11276–11285.
Backlund CM, Parhamifar L, Minter L, Tew GN, Andresen TL.  2019.  Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes. Molecular Pharmaceutics. 16:2462–2469.
Sorrentino C, Hossain F, Rodriguez PC, Sierra RA, Pannuti A, Hatfield S, Osborne BA, Minter LM, Miele L, Morello S.  2019.  Corrigendum: Adenosine A2A Receptor Stimulation Inhibits TCR-Induced Notch1 Activation in CD8+T-Cells. Frontiers in Immunology. 10
Wang W, Yang J, Edin ML, Wang Y, Luo Y, Wan D, Yang H, Song C-Q, Xue W, Sanidad KZ et al..  2019.  Targeted Metabolomics Identifies the Cytochrome P450 Monooxygenase Eicosanoid Pathway as a Novel Therapeutic Target of Colon Tumorigenesis. Cancer Research. 79:1822–1830.
Sorrentino C, Hossain F, Rodriguez PC, Sierra RA, Pannuti A, Hatfield S, Osborne BA, Minter LM, Miele L, Morello S.  2019.  Adenosine A2A Receptor Stimulation Inhibits TCR-Induced Notch1 Activation in CD8+T-Cells. Frontiers in Immunology. 10
Sorrentino C, Hossain F, Rodriguez PC, Sierra RA, Pannuti A, Hatfield S, Osborne BA, Minter LM, Miele L, Morello S.  2019.  Corrigendum: Adenosine A2A Receptor Stimulation Inhibits TCR-Induced Notch1 Activation in CD8+T-Cells. Frontiers in Immunology. 10
Hossain F, Sorrentino C, Ucar DA, Peng Y, Matossian M, Wyczechowska D, Crabtree J, Zabaleta J, Morello S, Valle LD et al..  2018.  Notch Signaling Regulates Mitochondrial Metabolism and NF-kB Activity in Triple-Negative Breast Cancer Cells via IKKa-Dependent Non-canonical Pathways. Frontiers in Oncology. 8
Posey ND, Hango CR, Minter LM, Tew GN.  2018.  The Role of Cargo Binding Strength in Polymer-Mediated Intracellular Protein Delivery. Bioconjugate Chemistry. 29:2679–2690.
Chandiran K, Lawlor R, Pannuti A, Perez GG, Srinivasan J, Golde TE, Miele L, Osborne BA, Minter LM.  2018.  Notch1 primes CD4 T cells for T helper type I differentiation through its early effects on miR-29. Molecular Immunology. 99:191–198.
Hossain F, Majumder S, Ucar DA, Rodriguez PC, Golde TE, Minter LM, Osborne BA, Miele L.  2018.  Notch Signaling in Myeloid Cells as a Regulator of Tumor Immune Responses. Frontiers in Immunology. 9
Sanidad KZ, Yang H, Wang W, Ozay IE, Yang J, Gu M, Karner E, Zhang J, Kim D, Minter LM et al..  2018.  Effects of Consumer Antimicrobials Benzalkonium Chloride, Benzethonium Chloride, and Chloroxylenol on Colonic Inflammation and Colitis-Associated Colon Tumorigenesis in Mice. Toxicological Sciences. 163:490–499.
Yang H, Wang W, Romano KA, Gu M, Sanidad KZ, Kim D, Yang J, Schmidt B, Panigrahy D, Pei R et al..  2018.  A common antimicrobial additive increases colonic inflammation and colitis-associated colon tumorigenesis in mice. Science Translational Medicine. 10:eaan4116.
Hossain F, Sorrentino C, Ucar DA, Peng Y, Matossian M, Wyczechowska D, Crabtree J, Zabaleta J, Morello S, Valle LD et al..  2018.  Notch Signaling Regulates Mitochondrial Metabolism and NF-kB Activity in Triple-Negative Breast Cancer Cells via IKKa-Dependent Non-canonical Pathways. Frontiers in Oncology. 8
Ran Y, Hossain F, Pannuti A, Lessard CB, Ladd GZ, Jung JI, Minter LM, Osborne BA, Miele L, Golde TE.  2017.  γ-Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct.. {EMBO} Molecular Medicine. 9:950–966.
Sgolastra F, Backlund CM, Ozay EI, deRonde BM, Minter LM, Tew GN.  2017.  Sequence segregation improves non-covalent protein delivery. Journal of Control Release. 254:131–136.
Sarapas JM, Backlund CM, deRonde BM, Minter LM, Tew GN.  2017.  ROMP- and RAFT-Based Guanidinium-Containing Polymers as Scaffolds for Protein Mimic Synthesis. Chemistry - A European Journal. 23:6858–6863.
deRonde BM, Posey ND, Otter R, Caffrey LM, Minter LM, Tew GN.  2016.  Optimal Hydrophobicity in Ring-Opening Metathesis Polymerization-Based Protein Mimics Required for siRNA Internalization. Biomacromolecules. 17:1969–1977.
Ozay EI, Gonzalez-Perez G, Torres JA, Vijayaraghavan J, Lawlor R, Sherman HL, Garrigan DT, Burnside AS, Osborne BA, Tew GN et al..  2016.  Intracellular Delivery of Anti-pPKC0 (Thr538) via Protein Transduction Domain Mimics for Immunomodulation. Molecular Therapy. 24:2118–2130.
Backlund CM, Sgolastra F, Otter R, Minter LM, Takeuchi T, Futaki S, Tew GN.  2016.  Increased hydrophobic block length of PTDMs promotes protein internalization. Polymer Chemistry. 7:7514–7521.
Caffrey LM, deRonde BM, Minter LM, Tew GN.  2016.  Mapping Optimal Charge Density and Length of ROMP-Based PTDMs for siRNA Internalization. Biomacromolecules. 17:3205–3212.
deRonde BM, Posey ND, Otter R, Caffrey LM, Minter LM, Tew GN.  2016.  Optimal Hydrophobicity in Ring-Opening Metathesis Polymerization-Based Protein Mimics Required for siRNA Internalization. Biomacromolecules. 17:1969–1977.
deRonde BM, Torres JA, Minter LM, Tew GN.  2015.  Development of Guanidinium-Rich Protein Mimics for Efficient siRNA Delivery into Human T Cells. Biomacromolecules. 16:3172–3179.
Dongre A, Surampudi L, Lawlor RG, Fauq AH, Miele L, Golde TE, Minter LM, Osborne BA.  2014.  Non-Canonical Notch Signaling Drives Activation and Differentiation of Peripheral CD4(+) T Cells.. Front Immunol. 5:54.
Sgolastra F, Minter LM, Osborne BA, Tew GN.  2014.  Importance of sequence specific hydrophobicity in synthetic protein transduction domain mimics.. Biomacromolecules. 15(3):812-20.
Shin HM, Tilahun ME, Cho OH, Chandiran K, Kuksin CA, Keerthivasan S, Fauq AH, Golde TE, Miele L, Thome M et al..  2014.  NOTCH1 Can Initiate NF-κB Activation via Cytosolic Interactions with Components of the T Cell Signalosome.. Front Immunol. 5:249.
Tezgel ÖA, Gonzalez-Perez G, Telfer JC, Osborne BA, Minter LM, Tew GN.  2013.  Novel protein transduction domain mimics as nonviral delivery vectors for siRNA targeting NOTCH1 in primary human T cells.. Mol Ther. 21(1):201-9.
Roderick JE, Gonzalez-Perez G, Kuksin CA, Dongre A, Roberts ER, Srinivasan J, Andrzejewski C, Fauq AH, Golde TE, Miele L et al..  2013.  Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia.. J Exp Med. 210(7):1311-29.
Minter LM, Osborne BA.  2012.  Canonical and Non-Canonical Notch Signaling in CD4(+) T Cells.. Current topics in microbiology and immunology.
Minter LM, Osborne BA.  2012.  Notch and the survival of regulatory T cells: location is everything!. Science signaling. 5(234):pe31.
Das P, Verbeeck C, Minter L, Chakrabarty P, Felsenstein K, Kukar T, Maharvi G, Fauq A, Osborne BA, Golde TE.  2012.  Transient pharmacologic lowering of Aß production prior to deposition results in sustained reduction of amyloid plaque pathology.. Molecular neurodegeneration. 7(1):39.
Keerthivasan S, Suleiman R, Lawlor R, Roderick J, Bates T, Minter L, Anguita J, Juncadella I, Nickoloff BJ, Le Poole IC et al..  2011.  Notch signaling regulates mouse and human Th17 differentiation.. J Immunol. 187(2):692-701.
Joshi I, Minter LM, Telfer J, Demarest RM, Capobianco AJ, Aster JC, Sicinski P, Fauq A, Golde TE, Osborne BA.  2009.  Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases.. Blood. 113(8):1689-98.
Cho OH, Shin HM, Miele L, Golde TE, Fauq A, Minter LM, Osborne BA.  2009.  Notch regulates cytolytic effector function in CD8+ T cells.. Journal of immunology (Baltimore, Md. : 1950). 182(6):3380-9.
Samon JB, Champhekar A, Minter LM, Telfer JC, Miele L, Fauq A, Das P, Golde TE, Osborne BA.  2008.  Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells.. Blood. 112(5):1813-21.
Osborne BA, Minter LM.  2007.  Notch signalling during peripheral T-cell activation and differentiation.. Nature reviews. Immunology. 7(1):64-75.
Shin HM, Minter LM, Cho OH, Gottipati S, Fauq AH, Golde TE, Sonenshein GE, Osborne BA.  2006.  Notch1 augments NF-kappaB activity by facilitating its nuclear retention.. The EMBO journal. 25(1):129-38.
Minter LM, Turley DM, Das P, Shin HM, Joshi I, Lawlor RG, Cho OH, Palaga T, Gottipati S, Telfer JC et al..  2005.  Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21.. Nature immunology. 6(7):680-8.
Minter LM, Osborne BA.  2003.  Cell death in the thymus--it' s all a matter of contacts.. Seminars in immunology. 15(3):135-44.
Jerry JD, Minter LM, Becker KA, Blackburn AC.  2002.  Hormonal control of p53 and chemoprevention.. Breast cancer research : BCR. 4(3):91-4.
Minter LM, Dickinson ES, Naber SP, Jerry JD.  2002.  Epithelial cell cycling predicts p53 responsiveness to gamma-irradiation during post-natal mammary gland development.. Development (Cambridge, England). 129(12):2997-3008.
Jerry JD, Minter LM, Becker KA, Blackburn AC.  2002.  Hormonal control of p53 and chemoprevention.. Breast Cancer Res. 4(3):91-4.
Name Phone Office
Mohan , Deeksha Graduate Student, ABBS 413-545-2339 ISB 455
Shanthalingam , Sudarvili Postdoctoral Research Associate 413-545-1364 ISB 470