DF/HCC Program Affiliation

Cutaneous Oncology and Melanoma

Research Abstract

My laboratory studies cell cycle control in normal and cancer cells with an ultimate goal of discovering new approaches to prevent and treat cancer. Our focus is a protein kinase called ATR that is required for the replication checkpoint -- the means by which a cell ensures it does not undergo mitosis before completely replicating its DNA. Our prior work has demonstrated that loss of tumor suppressors such as p53 markedly sensitizes cells to death by inhibition of ATR function.

We are using cell culture, transgenic mouse and chemical genetic approaches to study:
How does ATR function in normal cells? (What exactly goes wrong when it is inhibited?)
Does inhibiting ATR block generation of cancers?
Can we discover novel small molecule inhibitors of ATR? (Collaboration with Stuart Schreiber's lab and the Institute for Chemistry and Chemical Biology)


More details are available at:
http://cbrc-a12.mgh.harvard.edu/cbrc_nghiem.htm
http://www.pnlab.org/

Publications

• Roshal M, Kim B, Zhu Y, Nghiem P, Planelles V.Activation of the ATR-mediated DNA damage response by the HIV-1 viral protein R.J Biol Chem 2003 Jul 11;278(28):25879-86.
  12738771
• Casper AM, Nghiem P, Arlt MF, Glover TW.ATR regulates fragile site stability.Cell 2002 Dec 13;111(6):779-89.
  12526805
• Nghiem P, Park PK, Kim Ys YS, Desai BN, Schreiber SL.ATR is not required for p53 activation but synergizes with p53 in the replication checkpoint.J Biol Chem 2002 Feb 8;277(6):4428-34.
  11711532
• Nghiem P, Park PK, Kim Y, Vaziri C, Schreiber SL.ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation.Proc Natl Acad Sci U S A 2001 Jul 31;98(16):9092-7.
  11481475