The University of Massachusetts Amherst
 
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Lisa Minter

Associate Professor

My area of research focuses on the role NOTCH1 signaling plays in autoimmune responses. We are currently investigating how NOTCH signaling contributes to pathology and disease progression during immune-mediated bone marrow failure (BMF). We have established two new models of BMF, both of which are highly representative of the human immune-meditated BMF syndrome, Aplastic Anemia. In our first model, we transfer bulk splenocytes from a parental C57BL/6 strain into recipient mice that are the F1 hybrid progeny of a C57BL/6 x BALB/c cross. The result is a robust graft-versus-host response whereby the transferred splenocytes selectively target the bone marrow for destruction. The onset of disease is precipitous and symptoms include loss of repopulating stem cells from the bone marrow and immune cells from the periphery, infiltration of destructive CD4+ and CD8+ T cells into the recipient BM, as well as increased levels of the pro-inflammatory cytokines, interferonγ and TNF in the circulation. Our “humanized” model utilizes a recently developed transgenic mouse strain, Nod/SCID/IL2Rγcnull (NSG), in which BMF is induced following the transfer of human peripheral blood mononuclear cells.

Current Research
Using our two established models of BMF, we are continuing to probe the role of NOTCH1signaling in Aplastic Anemia. We are currently investigating how NOTCH1 cooperates with proteins essential for T cell activation to drive disease pathogenesis, as well as how novel target genes of NOTCH1 may contribute to Aplastic Anemia in the context of aberrant NOTCH1 signaling. We are also pursuing interdisciplinary collaborations we hope will allow us to specifically target NOTCH1signaling in the immune system using novel nanotechnology-based delivery platforms.

Learn more at www.vasci.umass.edu/research-faculty/lisa-m-minter

Academic Background

  • PhD University of Massachusetts, 2001
  • Postdoctoral Training: UMass Amherst
Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation. Ozay EI, Gonzalez-Perez G, Torres JA, Vijayaraghavan J, Lawlor R, Sherman HL, Garrigan DT Jr, Burnside AS, Osborne BA, Tew GN, Minter LM. Mol Ther. 2016 Oct 18. doi: 10.1038/mt.2016.177. [Epub ahead of print]
Mapping Optimal Charge Density and Length of ROMP-Based PTDMs for siRNA Internalization. Caffrey LM, deRonde BM, Minter LM, Tew GN. Biomacromolecules. 2016 Oct 10;17(10):3205-3212. PMID: 27599388
Optimal Hydrophobicity in Ring-Opening Metathesis Polymerization-Based Protein Mimics Required for siRNA Internalization. deRonde BM, Posey ND, Otter R, Caffrey LM, Minter LM, Tew GN. Biomacromolecules. 2016 Jun 13;17(6):1969-77. doi: 10.1021/acs.biomac.6b00138. PMID: 27103189
Development of Guanidinium-Rich Protein Mimics for Efficient siRNA Delivery into Human T Cells. deRonde BM, Torres JA, Minter LM, Tew GN. Biomacromolecules. 2015 Oct 12;16(10):3172-9. doi: 10.1021/acs.biomac.5b00795. PMID: 26324222
The Link between Autoimmunity and Lymphoma: Does NOTCH Signaling Play a Contributing Role? Kuksin CA, Minter LM. Front Oncol. 2015 Feb 24;5:51. doi: 10.3389/fonc.2015.00051. Review. PMID: 25759795
CXCR4 expression on pathogenic T cells facilitates their bone marrow infiltration in a mouse model of aplastic anemia. Arieta Kuksin C, Gonzalez-Perez G, Minter LM. Blood. 2015 Mar 26;125(13):2087-94. doi: 10.1182/blood-2014-08-594796. PMID: 25647836
NOTCH1 Can Initiate NF-κB Activation via Cytosolic Interactions with Components of the T Cell Signalosome. Shin HM, Tilahun ME, Cho OH, Chandiran K, Kuksin CA, Keerthivasan S, Fauq AH, Golde TE, Miele L, Thome M, Osborne BA, Minter LM. Front Immunol. 2014 May 26;5:249. doi: 10.3389/fimmu.2014.00249. PMID: 24904593
Non-Canonical Notch Signaling Drives Activation and Differentiation of Peripheral CD4(+) T Cells. Dongre A, Surampudi L, Lawlor RG, Fauq AH, Miele L, Golde TE, Minter LM, Osborne BA. Front Immunol. 2014 Feb 12;5:54. doi: 10.3389/fimmu.2014.00054. PMID: 24611064
Importance of sequence specific hydrophobicity in synthetic protein transduction domain mimics. Sgolastra F, Minter LM, Osborne BA, Tew GN. Biomacromolecules. 2014 Mar 10;15(3):812-20. doi: 10.1021/bm401634r. PMID: 24506414
Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia. Roderick JE, Gonzalez-Perez G, Kuksin CA, Dongre A, Roberts ER, Srinivasan J, Andrzejewski C Jr, Fauq AH, Golde TE, Miele L, Minter LM. J Exp Med. 2013 Jul 1;210(7):1311-29. doi: 10.1084/jem.20112615. PMID: 23733784
NOTCH signaling in immune-mediated bone marrow failure of aplastic anemia. Minter LM. Rare Dis. 2013 Nov 6;1:e26764. doi: 10.4161/rdis.26764. PMID: 25003012
Novel protein transduction domain mimics as nonviral delivery vectors for siRNA targeting NOTCH1 in primary human T cells. Tezgel AÖ, Gonzalez-Perez G, Telfer JC, Osborne BA, Minter LM, Tew GN. Mol Ther. 2013 Jan;21(1):201-9. doi: 10.1038/mt.2012.209. PMID: 23070119
Notch and the survival of regulatory T cells: location is everything! Minter LM, Osborne BA. Sci Signal. 2012 Jul 24;5(234):pe31. doi: 10.1126/scisignal.2003358. PMID: 22827995
Canonical and non-canonical Notch signaling in CD4⁺ T cells. Minter LM, Osborne BA. Curr Top Microbiol Immunol. 2012;360:99-114. doi: 10.1007/82_2012_233. Review. PMID: 22695917
Notch regulates cytolytic effector function in CD8+ T cells. Cho OH, Shin HM, Miele L, Golde TE, Fauq A, Minter LM, Osborne BA. J Immunol. 2009 Mar 15;182(6):3380-9. doi: 10.4049/jimmunol.0802598. PMID: 19265115
Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Joshi I, Minter LM, Telfer J, Demarest RM, Capobianco AJ, Aster JC, Sicinski P, Fauq A, Golde TE, Osborne BA. Blood. 2009 Feb 19;113(8):1689-98. doi: 10.1182/blood-2008-03-147967. PMID: 19001083
Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells. Samon JB, Champhekar A, Minter LM, Telfer JC, Miele L, Fauq A, Das P, Golde TE, Osborne BA. Blood. 2008 Sep 1;112(5):1813-21. doi: 10.1182/blood-2008-03-144980. PMID: 18550850
Notch signalling during peripheral T-cell activation and differentiation. Osborne BA, Minter LM. Nat Rev Immunol. 2007 Jan;7(1):64-75. Review. PMID: 17170755
Notch1 augments NF-kappaB activity by facilitating its nuclear retention. Shin HM, Minter LM, Cho OH, Gottipati S, Fauq AH, Golde TE, Sonenshein GE, Osborne BA. EMBO J. 2006 Jan 11;25(1):129-38. PMID: 16319921
Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21. Minter LM, Turley DM, Das P, Shin HM, Joshi I, Lawlor RG, Cho OH, Palaga T, Gottipati S, Telfer JC, Kostura L, Fauq AH, Simpson K, Such KA, Miele L, Golde TE, Miller SD, Osborne BA. Nat Immunol. 2005 Jul;6(7):680-8. PMID: 15991363
Cell death in the thymus--it' s all a matter of contacts. Minter LM, Osborne BA. Semin Immunol. 2003 Jun;15(3):135-44. Review. PMID: 14563112
Hormonal control of p53 and chemoprevention. Jerry DJ, Minter LM, Becker KA, Blackburn AC. Breast Cancer Res. 2002;4(3):91-4. Review. PMID: 12052250
Epithelial cell cycling predicts p53 responsiveness to gamma-irradiation during post-natal mammary gland development. Minter LM, Dickinson ES, Naber SP, Jerry DJ. Development. 2002 Jun;129(12):2997-3008. PMID: 12050146
 
Contact Info

Department of Veterinary and Animal Sciences
427K Integrated Science Building
661 North Pleasant Street
Amherst, MA 01003

(413) 545-6327
lminter@vasci.umass.edu

www.vasci.umass.edu/research-faculty/lisa-m-minter