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David Johnson

David Johnson

Distinguished Senior Lecturer

Professor

512-237-9511512-237-9511
[email protected]
MDA SRD1.136 (Unit 116)

The University of Texas MD Anderson Cancer Center
Department of Epigenetics & Molecular Carcinogenesis

My current research is focused on two transcription factors that respond to DNA damage and play important roles in regulating tumor development.  The first project focuses on E2F1, a regulator of genes important for cell cycle progression and apoptosis.  We have discovered that E2F1 localizes to sites of both DNA double-strand breaks and UV-induced DNA damage and that this involves the phosphorylation of E2F1 by the ATM or ATR kinases.  Moreover, our studies demonstrate that E2F1 recruits chromatin-modifying enzymes to sites of damage to facilitate access to the DNA repair machinery.  These findings indicate that E2F1 stimulates DNA repair through a non-transcriptional mechanism that functions in the context of chromatin.  The physiological relevance of E2F1 in the DNA damage response is now being explored using a novel knock-in mouse model we developed that blocks E2F1 phosphorylation by ATM/ATR.

The other project involves the study of a single nucleotide polymorphism (SNP) in the human p53 gene that results in either arginine (R) or proline (P) at position 72 of the p53 protein. This SNP affects the apoptotic activity of p53 but the mechanistic basis and physiologic relevance of this phenotypic difference remain unclear.  We have developed mouse models that mimic this human SNP and have demonstrated that the humanized p53 variants are functional and display the expected difference in apoptotic capacity in mouse tissues.  These models are being used to explore the roles of this human SNP in modulating cancer susceptibility and the response to DNA damaging agents, including chemotherapeutic drugs.

PubMed

MDACC Faculty

David Johnson Lab

Education & Training

PhD, The University of Texas-Southwestern Medical Center, 1991

Research Info

Epigenetics, DNA Repair and Cancer

Programs


Faculty Development