Research Focus

Ms. Miller studies Merkel Cell Carcinoma (MCC), a rare but lethal skin cancer associated with UV exposure, advanced age, immune suppression and a recently discovered Merkel cell polyomavirus (MCPyV). MCPyV is present in 80% of Merkel cell carcinoma (MCC) tumors, and MCPyV oncoproteins induce virus- specific CD8 T cell responses. Infiltration of CD8 T cells into tumors is associated with 100% survival, but is present in only a small fraction of patients. The importance of the immune response to MCC has been recognized and translated into T cell-stimulating therapies, many of which are currently in clinical trials for metastatic MCC.

Ms. Miller is elucidating the repertoire of MCPyV-specific CD8 T cell receptors (TCRs) recognizing one prevalent epitope of the virus. During this work, she will learn about the diversity of the immune response to MCPyV among different patients, and whether T cells with more avid TCRs are able to better infiltrate MCCs. In addition, avid TCRs found from this work could be used to create transgenic TCR T cells for therapy in patients who lack their own endogenous effector population.

In addition, Ms. Miller is studying how new therapeutics are altering the function and abundance of MCPyV-specific T cells in patients enrolled in clinical trials. These studies will contribute to our understanding of the agents’ mechanism of action, as well as elucidate alternative therapies that could be used for patients who do not respond to these therapies.

Awards

F30 NRSA Predoctoral Fellowship
Environmental Pathology and Toxicology Training Grant
ARCS Fellowship (Achievement Rewards for College Scientists)
Adaptive Biotechnologies Young Investigator Award
Joshua Green Foundation Scholarship

Publications

Iyer JG, Parvathaneni P, Gooley T, Miller NJ, et al.: Single fraction radiation therapy in patients with metastatic Merkel cell carcinoma. Cancer Med. 2015 Aug;4(8):1161-70.

Afanasiev O, Yelistratova L, Miller N, Kotaro N, Paulson K, Iyer J, Ibrani D, Koelle D, Nghiem P. Merkel cell carcinoma-specific T cells fluctuate with tumor burden and express therapeutically targetable PD-1 and Tim-3 exhaustion markers. Clin Cancer Res. 2013 Oct 1;19(19):5351-60.

Mital J, Miller NJ, Dorward DW, Dooley CA, Hackstadt T. Role for chlamydial inclusion membrane proteins in inclusion membrane structure and biogenesis. PLoS One. 2013 May 17; 8(5). PMID: 23696825. PMCID: PMC3656976

Miller NJ, Bhatia S, Parvatheneni U, Iyer JG, Nghiem P. Emerging and Mechanism-Based Therapies for Recurrent or Metastatic Merkel Cell Carcinoma. Curr Treat Options Oncol. 2013 Feb 23. 14(2):249-63.

Mital J, Miller NJ, Fischer ER, Hackstadt T. Specific chlamydial inclusion membrane proteins associate with active Src family kinases in microdomains that interact with the host microtubule network. Cell Microbiol. 2010 Sept 1;12(9):1235-49. PMID: 20331642. PMCID: PMC2923664

Jewett TJ, Miller NJ, Dooley CA, Hackstadt T. The conserved Tarp actin binding domain is important for chlamydial invasion. PLoS Pathog. 2010 Jul 15;6(7). PMID: 20657821. PMCID: PMC2904776

Grieshaber SS, Grieshaber NA, Miller N, Hackstadt T. Chlamydia trachomatis causes centrosomal defects resulting in chromosomal segregation abnormalities. Traffic. 2006 Aug; 7(8):940-9. PMID:16882039