Molecular Biology

Eric Moss PhD

Faculty and Research Interests

Renée M. Demarest, PhD

Assistant Professor
856 566-6402
Science Center 276
demarest@rowan.edu

Education

Temple University School of Medicine
 Ph.D. (Molecular Biology & Genetics), 2005

Research Interests

Acute lymphoblastic leukemia (ALL) is a neoplastic disorder of lymphoblasts that are committed to the B-cell lineage (B-ALL) or the T-cell lineage (T-ALL).  Five-year survival rates (FSR) for children and adolescents with this disease are 75–85%, whereas, adult T-ALL patients have a 35–40% FSR.  T-ALL patients have essentially the same FSR of patients with B-ALL.  However, certain aspects about T-ALL make it a more aggressive disease with a poorer clinical outcome than B-ALL.  T-ALL patients have a higher percentage of induction failure and rate of relapse and invasion into the central nervous system than B-ALL.  The challenge to acquiring 100% remission in T-ALL treatment is the subset of patients (20–25%) whose disease is refractory to initial treatments or relapses after a short remission period due to drug resistance.  Therefore, it is imperative to delineate the molecular blueprint that collectively accounts for the variety of subtypes in T-ALL. The intracellular portion of Notch (Nic) is rendered constitutively active in more than half of all human T-ALL cases examined, by alternative mutations in the Notch1 gene.  Furthermore, the expression of Ikaros (Ik) isoforms that are capable of inhibiting Notch-mediated gene transcription are lost in 100% of childhood and adolescent T-ALL cases examined. 

The goal of my lab is to delineate the molecular pathways required for T-ALL formation, maintenance, and relapse. Particularly, we are currently identifying genes coordinately and independently regulated by Notch and Ik in T-ALL using mouse models in which we can independently modulate Notch and Ik activity during and after tumor development.

Recent Publications

  1. Demarest, RM; Dahmane N; Capobiano, AJ. Notch is oncogenic dominant in T-ALL tumors. (2011) Blood, Mar 10;117(10):2901-9.
  2. Arthur LM; Demarest RM; Clark L; Gourevitch D; Bedelbaeva K; Anderson R; Snyder A; Capobianco AJ; Lieberman P; Feigenbaum L; Heber-Katz E. (2010) Epimorphic regeneration in mice is p53-independent. Cell Cycle Sep;9(18):3667-73
  3. Hanlon, L; Avila, JL; Demarest, RM; Troutman, S; Allen, M; Ratti F; Rustigi, AK; Stanger, BZ; Radtke, F; Adsay, V; Long, F; Capobianco, AJ; Kissil, JL. (2010) Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Research—Priority Report. Jun 1;70(11): 4280-6.
  4. Joshi I; Minter LM; Telfer J; Demarest RM; Capobianco AJ; Aster JC; Sicinski P; Fauq A; Golde TE; Osborne BA. (2009) Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Blood 113(8):1689-1698.
  5. Marie-Clotilde Alves-Guerra*, Renée M. Demarest* and Anthony J. Capobianco, Notch/Jagged Signaling, Encyclopedia of Cancer, 2009, Part 14, 2110-2116; *authors contributed equally
  6. Demarest, RM; Ratti, F; Capobianco, AJ. (2008). Invited Review: It’s T-ALL about Notch. Oncogene 38): 5082-5091.
  7. Salerno, D; Hasham, MG; Marshall, RM; Garriga, J.; Tsygankov, AY; and Grana, X. (2007). Direct inhibition of CDK9 blocks HIV-1 replication without preventing T-cell activation in primary human peripheral blood lymphocytes. Gene 405 (1-2): 65-78.
  8. Marshall, RM and Graña, X. (2006) Invited Review: Mechanisms controlling CDK9 activity. Frontiers in Bioscience (11): 2598-2613.
  9. Marshall RM; Salerno, D; Garriga, J.; Graña, X. (2005) Multiple signaling pathways regulate cyclin T1 expression by two distinct mechanisms during activation of human peripheral blood lymphocytes. Journal of Immunology (175): 6402-6411.
  10. Garriga, J; Bhattacharya, S; Calbo, J; Marshall, RM; Truongcao, M; Haines, DS; Graña, X. (2003) CDK9 is constitutively expressed throughout the cell cycle and its steady-state expression is independent of SKP2. Molecular and Cellular Biology (15): 5165-5173.
  11. Strauss, KI; Barbe, MF; Marshall, RM; Raghupathi, R; Mehta, S; Narayan, RJ. (2000) Prolonged cyclooxygenase-2 induction in neurons and glia following traumatic brain injury in the rat. Journal of Neurotrauma 17, 8, 695-711.

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