Lisa M. Minter

Lisa M. Minter

Professor

Department Head

she, her, hers

Office: 

427A ISB

Mailing address: 

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

Office phone: 

413-545-6327

Lab phone: 

413-545-1364

Fax: 

413-545-1446

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

Classes: 


 

Research Interests

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.

  

 

 

Lab Personnel

Name Email Phone Office
Jadon, Nidhi
Graduate Student - ABBS
njadon [at] umass.edu 413-545-1364 ISB 455
Shanthalingam, Sudarvili
Senior Research Fellow
sudarvili [at] umass.edu 413-545-1364 470 ISB

Publications

Zhang, J., Walker, M. E., Sanidad, K. Z., Zhang, H., Liang, Y., Zhao, E., et al.. (2022). Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract. Nat Commun, 13(1), 136. presented at the 2022 01 10. doi:10.1038/s41467-021-27762-y
Majumder, S., Crabtree, J. S., Golde, T. E., Minter, L. M., Osborne, B. A., & Miele, L.. (2021). Targeting Notch in oncology: the path forward. Nat Rev Drug Discov, 20(2), 125-144. presented at the 2021 02. doi:10.1038/s41573-020-00091-3
Majumder, S., Crabtree, J. S., Golde, T. E., Minter, L. M., Osborne, B. A., & Miele, L.. (2021). Targeting Notch in oncology: the path forward. Nat Rev Drug Discov, 20(2), 125-144. presented at the 2021 02. doi:10.1038/s41573-020-00091-3
Hango, C. R., Backlund, C. M., Davis, H. C., Posey, N. D., Minter, L. M., & Tew, G. N.. (2021). Non-Covalent Carrier Hydrophobicity as a Universal Predictor of Intracellular Protein Activity. Biomacromolecules, 22(7), 2850-2863. presented at the 2021 07 12. doi:10.1021/acs.biomac.1c00242
Trivedi, P., Patel, S. Kumar, Bellavia, D., Messina, E., Palermo, R., Ceccarelli, S., et al.. (2021). When Viruses Cross Developmental Pathways. Front Cell Dev Biol, 9, 691644. presented at the 2021. doi:10.3389/fcell.2021.691644
Anastasiadou, E., Minter, L. M., & Felli, M. Pia. (2021). Editorial: Targeting Developmental Pathways in Inflammation and Disease. Front Cell Dev Biol, 9, 791115. presented at the 2021. doi:10.3389/fcell.2021.791115
Minter, L. M., & Osborne, B. A.. (2012). Canonical and Non-Canonical Notch Signaling in CD4(+) T Cells. Current topics in microbiology and immunology. presented at the 2012 Jun 15.
Minter, L. M., & Osborne, B. A.. (2012). Notch and the survival of regulatory T cells: location is everything!. Science signaling, 5(234), pe31. presented at the 2012.
Cho, O. Hyun, Shin, H. Mu, Miele, L., Golde, T. E., Fauq, A., Minter, L. M., & Osborne, B. A.. (2009). Notch regulates cytolytic effector function in CD8+ T cells. Journal of immunology (Baltimore, Md. : 1950), 182(6), 3380-9. presented at the 2009 Mar 15.
Osborne, B. A., & Minter, L. M.. (2007). Notch signalling during peripheral T-cell activation and differentiation. Nature reviews. Immunology, 7(1), 64-75. presented at the 2007 Jan.
Minter, L. M., & Osborne, B. A.. (2003). Cell death in the thymus--it' s all a matter of contacts. Seminars in immunology, 15(3), 135-44. presented at the 2003 Jun.
D Jerry, J., Minter, L. M., Becker, K. A., & Blackburn, A. C.. (2002). Hormonal control of p53 and chemoprevention. Breast Cancer Res, 4(3), 91-4. presented at the 2002.
D Jerry, J., Minter, L. M., Becker, K. A., & Blackburn, A. C.. (2002). Hormonal control of p53 and chemoprevention. Breast cancer research : BCR, 4(3), 91-4. presented at the 2002.