Jeffrey Holt, MD

 
Jeffrey Holt, MD
Professor of Pathology
570.504.7000
jholt@tcmedc.org 
 

Research Specialty:
Cancer Genetics; breast and ovarian cancer

Research Description:
We have used genetic and biochemical analysis of human BRCA1 and BRCA2 genes to study the role of these genes in breast, ovary, and prostate cancer. Our access to families with hereditary breast cancer and identification of human cancer cell lines which are hemizygous for the Ashkenazi BRCA1 and BRCA2 mutations have allowed us to demonstrate that BRCA1 functions as a growth inhibitor and tumor suppressor, and that both BRCA1 and BRCA2 function in DNA repair. We have extended these studies to demonstrate that BRCA2 is rapidly induced by estrogen and that a specific phosphorylation site in BRCA2 has a key role in BRCA2 function in DNA repair. We have also developed a novel diagnostic test which identifies BRCA1 and BRCA2 mutations in cancer samples using an antibody-based method and are presently developing simple ways to identify patients without cumbersome and expensive DNA sequencing methods.

Publications:

• Brown ET and JT Holt. Rad51 overexpression rescues radiation resistance in BRCA2-defective cells. Mol Carcinogen 48:105-109, 2009. PMID: 18618591
• Brown ET, Robinson-Benion C, and JT Holt. Radiation Enhances caspase-3 cleavage of Rad51 in BRCA2-defective Cells.  Rad Res 169: 595-601, 2008.  PMID: 18439040
• Holt JT, Toole WP, Patel VR, Hwang HY, and Brown ET. Restoration of Capan1 cells with functional BRCA2 provides insight into the DNA repair activity of individuals who are heterozygous for BRCA2 mutations. Cancer Genet Cytogenet 186:85-94, 2008. PMID: 18940471
• Thompson ME, Robinson-Benion CL, Holt JT. An Amino-terminal Motif Functions as a Second Nuclear Export Sequence in BRCA1. J Biol Chem.280:21854-7, 2005. PMID: 15811849
• Malone JL, Nelson AC, Lieberman R, Gibson KA, Anderson SM. and JT Holt. Estrogen mediated phosphorylation and stabilization of BRCA2 protein in breast. J Pathology 217:380-388. PMID: 19016568
• Patrice Watson, Rita Lieberman, Carrie Snyder, Vanessa Clark, Henry T Lynch, and Jeffrey T. Holt. Detecting BRCA2 Protein Truncation in Tissue Biopsies to Identify Hereditary Cancer. In Press. J Clin Oncology

Jeffrey Holt, MD Biosketch