The overall research goal of Dr. Heaphy's laboratory is to further understand the contribution of telomere biology in cancer development and progression.
For a variety of human cancers (e.g., prostate, breast, ovarian, brain, pancreas), new molecular biomarkers are urgently needed for improving risk assessment and for accurate prognostication of the disease to improve upon current prevention and treatment strategies. One molecular marker that may address these clinical problems is tissue-based telomere length measurements.
Telomeres are nucleoprotein complexes that function to protect and stabilize the chromosomal ends by preventing chromosome fusions, masking inappropriate double-strand DNA break damage signals, and inhibiting exonucleolytic degradation. In addition to assessing the translational potential of telomere length measurements, his laboratory is working to elucidate the underlying mechanisms of tumor initiation and progression (e.g., through telomere length alterations), as well as understanding how the interactions between the tumor and its tissue microenvironment may facilitate this process.
Lab Website: Meeker-Heaphy Lab
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Rodriguez FJ, Brosnan-Cashman JA, Allen SJ, Vizcaino MA, Giannini C, Camelo-Piragua S, Webb M, Matsushita M, Wadhwani N, Tabbarah A, Hamideh D, Jiang L, Chen L, Arvantis L, Alnajar HH, Barber JR, Rodriguez-Velasco A, Orr B, Heaphy CM. Alternative Lengthening of Telomeres, ATRX loss and H3 p.K27M mutations in histologically defined anaplastic pilocytic astrocytoma. Brain Pathology. 2019; 29:126-140.
Kim JY, Brosnan-Cashman JA, An S, Kim SJ, Song KB, Kim MS, Kim MJ, Hwang DW, Meeker AK, Yu E, Kim SC, Hruban RH, Heaphy CM, Hong SM. Alternative lengthening of telomeres in primary pancreatic neuroendocrine neoplasms is associated with aggressive clinical behavior and poor survival. Clinical Cancer Research. 2017; 23:1598-1606.
Heaphy CM, Yoon GS, Peskoe SB, Joshu CE, Lee TK, Giovannucci E, Mucci LA, Kenfield SA, Stampfer MJ, Hicks JL, De Marzo AM, Platz EA, Meeker AK. Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death. Cancer Discovery. 2013; 3:1130-41.
Heaphy CM, Subhawong AP, Hong SM, Goggins MG, Montgomery EA, Gabrielson E, Netto GJ, Epstein JI, Lotan TL, Westra WH, Shih IM, Iacobuzio-Donahue CA, Maitra A, Li QK, Eberhart CG, Taube JM, Rakheja D, Kurman RJ, Wu T, Roden RB, Argani P, De Marzo AM, Terracciano L, Torbenson M, Meeker AK. Prevalence of the Alternative Lengthening of Telomeres (ALT) telomere maintenance mechanism in human cancer subtypes. The American Journal of Pathology. 2011; 179:1608-1615.
Heaphy CM, de Wilde RF*, Jiao Y*, Klein AP, Edil BH, Shi C, Bettegowda C, Rodriguez FJ, Eberhart CG, Hebbar S, Offerhaus GJ, McLendon R, Rasheed BA, He Y, Yan H, Bigner DD, Oba-Shinjo SM, Nagahashi Marie SK, Riggins GJ, Kinzler KW, Vogelstein B, Hruban RH, Maitra A, Papadopoulos N, Meeker AK. Altered telomeres in tumors with ATRX and DAXX mutations. Science. 2011; 333:425.a