Research Interest: Genetic Heterogeneity in Breast Cancer
Advisor: Edward Gunther, MD
Graduate Program: Cell & Molecular Biology
Description: Though a breast cancer originates from clonal expansion of a single aberrant mammary epithelial cell, overt malignancies display marked cellular and genetic heterogeneity. While some of this heterogeneity derives from the recruitment of normal host cells to the malignant micro-environment, recent findings highlight additional heterogeneity within the tumor cell compartment itself. Notably, tumor cell sub-clones - each harboring distinct genetic lesions - typically coexist within individual breast cancers. How cooperation between these distinct sub-clones influences tumor initiation and progression remains unknown. Complex interactions between tumor cell sub-clones may contribute to the variable clinical course of breast cancers, which are heterogeneous with respect to disease progression and drug resistance.
Using a transgenic mouse model of mammary tumorigenesis, we aim to understand the role intra-tumor heterogeneity plays in tumor initiation and progression. By flow cytometry, we are able to isolate genetically distinct subclonal populations of tumor cells from mouse mammary tumors. We then assess the tumorigenic contribution of these separate subpopulations in isolation and in combination.
Penn State College of Medicine Graduate Research Forum, Hershey, PA
Konhilas JP, Widegren U, Allen DL, Paul AC, Cleary A, Leinwand LA (2005) Loaded wheel running and muscle adaptation in the mouse Am J Physiol Heart Circ Physiol 289(1):H455-65 PMID: 15734890
Allen DL, Cleary AS, Speaker KJ, Lindsay SF, Uyenishi J, Reed JM, Madden MC, Mehan RS. (2008) Myostatin, Activin Receptor IIb, and Follistatin-Like-3 Gene Expression is Altered in Adipose Tissue and Skeletal Muscle of Obese Mice Am J Physiol Endocrin Metab 294(5):E918-27 PMID: 18334608
Allen DL, Uyenishi JJ, Cleary AS, Mehan RS, Lindsay SF, Reed JM (2010) Calcineurin activates interleukin-6 transcription in mouse skeletal muscle in vivo and in C2C12 myotubes in vitro Am J Physiol Regul Integr Comp Physiol 298(1):198-210 PMID: 19907005 PMCID: PMC2806210
Allen DL, Cleary AS, Lindsay SF, Loh A, Reed JM (2010) Myostatin Expression is Increased by Food Deprivation in a Muscle-Specific Manner and Contributes to Muscle Atrophy during Prolonged Food Deprivation in Mice J Appl Physiol PMID: 20595541
Allen DL, Greyback BJ, Hanson AM, Cleary AS, Lindsay SF (2010) Skeletal muscle expression of bone morphogenetic protein-1 and tolloid-like-1 extracellular proteases in different fiber types and in response to unloading, food deprivation and differentiation J Physiol Sci PMID: 20658214
Allen DL, Cleary AS, Hanson AM, Lindsay SF, Reed JM, (2010) CCAAT/enhancer binding protein-delta expression is increased in fast skeletal muscle by food deprivation and regulates myostatin transcription in vitro Am J Physiol Regul Integr Comp Physiol 299(6):R1592-601 PMID: 20844262 PMCID: PMC3007187
Cleary AS, Leonard TL, Gestl SA, Gunther EJ (2014) Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers Nature 508(7494):113-7 PMID: 24695311