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James Alvarez

Assistant Professor
Pharmacology and Cancer Biology
(919) 681-5479
Research Interest: 
Cell cycle
Genetics
Signal transduction
Research Summary: 
Intratumor heterogeneity and its contribution to tumor progression using mouse models.
Research Description: 

The major goal of our laboratory is to use mouse models to understand the origins and consequences of intratumor heterogeneity. In particular, we are interested in exploring the stresses that tumors encounter during their development, and understanding how these stresses act as selective pressures that shape the clonal architecture of tumors. Further, we aim to explore how this heterogeneity contributes to critical aspects of tumor progression, including metastasis, dormancy, resistance to therapy, and recurrence.

As one window into these questions, we are studying the tumor suppressor par-4. Par-4 is heterogeneously down-regulated in primary tumors, and tumor cells with par-4 down-regulation have an increased propensity to metastasize, persist as dormant cells, and recur following targeted therapy. We are exploring the molecular mechanisms of par-4 down-regulation and how this promotes tumor progression.

Publications: 
Oncogene pathway activation in mammary tumors dictates FDG-PET uptake.
Alvarez JV, Belka GK, Pan TC, Chen CC, Blankemeyer E, Alavi A, Karp JS, Chodosh LA.
Cancer Res. 2014. 74:7583-98.

SPSB1 promotes breast cancer recurrence by potentiating c-MET signaling.
Feng Y, Pan TC, Pant DK, Chakrabarti KR, Alvarez JV, Ruth JR, Chodosh LA.
Cancer Discov. 2014. 4:790-803.

Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy.
Alvarez JV, Pan TC, Ruth J, Feng Y, Zhou A, Pant D, Grimley JS, Wandless TJ, Demichele A, I-SPY 1 TRIAL Investigators, Chodosh LA.
Cancer Cell. 2013. 24:30-44.

Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor.
Alvarez JV, Greulich H, Sellers WR, Meyerson M, Frank DA.
Cancer Res. 2006. 66:3162-8.

Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors.
Alvarez JV, Febbo PG, Ramaswamy S, Loda M, Richardson A, Frank DA.
Cancer Res. 2005. 65:5054-62.