Researcher Spotlight: Dr. Paul Nghiem
Paul Nghiem, MD, PhD
Associate Professor of Dermatology/Medicine, University of Washington, Michael Piepkorn Endowed Chair in Dermatology Research
Outside the lab:
I play the violin, bike ride and play tennis with my two boys. Though, not necessarily all at the same time.
Game Change about the 2008 presidential election.
What’s your focus?
Our lab focuses on studying an uncommon but fascinating skin cancer called Merkel Cell Carcinoma (MCC). MCC is associated with immunosuppression, UV exposure, age over 50 and a newly discovered polyomavirus that is common on the normal-appearing skin of most people. The cause of MCC has not yet been firmly established, and therapeutic interventions at late stage disease are frustratingly ineffective, with the likelihood of mortality being three times greater for MCC than for malignant melanoma. We are investigating immune evasion strategies employed by MCC, and how to overcome them using immunotherapy approaches.
How are you using immunoSEQ?
We have recently characterized several viral epitopes that are recognized by CD8 T cells. Using immunoSEQ and the tools we have developed to sort out virus-specific T cells, we are able to track the diversity and persistence of individual clones in MCC patients’ blood and tumors. Furthermore, we can monitor changes in the T cell repertoire in response to therapy.
So what did you think?
We have been very excited about the results from immunoSEQ. The turnaround from sample submission to
data analyses is fast and efficient. (We would have otherwise probably not even approached the daunting task of TCR sequencing.) The software analysis program is intuitive enough to very quickly pull out our relevant clones and trends. Meanwhile, the sophistication of the program also allows for deep data mining.
It’s been amazing to be able to follow specific T cell clones over time in multiple patients. Interestingly, we have observed that immunotherapy often favors persistence of clones that may have not been the most prevalent ones to start with. These observations raise interesting biological questions: What are the favorable characteristics for T cell persistence? Importantly, these questions are then testable.
When do you anticipate to submit your findings?
We are working hard on completing the results from our study and submitting our findings within the next year.
Most recent publications:
Dr. Nghiem has quite an impressive publishing record. The following represents the most recent from 57 peer-reviewed publications. Dr. Nghiem’s publications have been cited 1944 times as of May 2012.
Iyer JG, Afanasiev OK, McClurkan C, Paulson KG, Nagase K, Jing L, Marshak JO, Dong L, Carter JJ, Lai I, Farrar EA, Byrd D, Galloway DA, Yee C, Koelle DM, Nghiem P.
Merkel cell polyomavirus-specific CD8+ and CD4+ T-cell responses identified in Merkel cell carcinomas and blood. Clin Cancer Res. 2011 Sep 9. PMCID: 3207011
Kawasumi M, Lemos B, Bradner JE, Thibodeau R, Kim YS, Schmidt M, Higgins E, Koo SW, Angle-Zahn A, Chen A, Levine D, Nguyen L, Heffernan TP, Longo I, Mandinova A, Lu YP, Conney AH, Nghiem P.
Protection from UV-induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase. Proc Natl Acad Sci USA. 108:13716-21, 2011. PMCID: 3158235
Huryn DM, Brodsky JL, Brummond KM, Chambers PG, Eyer B, Ireland AW, Kawasumi M, Laporte MG, Lloyd K, Manteau B, Nghiem P, Quade B, Seguin SP, Wipf P.
Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators. Proc Natl Acad Sci USA. 108:6757-62, 2011. PMCID: 3084104 (Authors listed in alphabetical order except for first author)