Peter O’Connell

Education

B.A. Biology (1974) Brandeis University
Ph.D. Biology (1983) Brandeis University (mentor: Michael Rosbash)
Postdoctoral Fellowship in Human Genetics (1982 to 1984) University of Utah Medical Center (mentor: Ray White)

Professional experience

• 1984: Research associate, Howard Hughes Medical Institute, Department of Human & Molecular Genetics, University of Utah Medical School, Salt Lake City, Utah
• 1986: Research assistant professor, Department of Human & Molecular Genetics, University of Utah Medical School, Salt Lake City, Utah
  
• 1988: Senior research associate, Howard Hughes Medical Institute, Department of Human & Molecular Genetics, University of Utah Medical School, Salt Lake City, Utah
  
• 1991: Associate professor, Departments of Pathology and Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas
  
• 1992: Associate professor, Departments of Pathology and Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas
  
• 1996: Professor, Departments of Pathology and Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas
  
• 1999: Professor, Departments of Cell Biology, Molecular and Human Genetics, and Pathology, Baylor College of Medicine, Houston, Texas
  
• 2002 to present: Professor and chairman, Department of Human & Molecular Genetics, VCU

Honors

• 1979: Recipient, NIH Graduate Training Award
• 1982: Recipient, Howard Hughes Medical Institute Fellowship
• 1987: Co-inventor, Genetic Identification with Variable Number of Tandem Repeat Markers. U.S.
• Patent No. 5,411,859 (with co-inventors M Leppert, Y Nakamura, R White)
• 1990: Co-inventor, Neurofibromatosis Type 1 Gene, U.S. Patent Application 5,227,292 (with coinventors RM Cawthon, D H Viskochil, R White)
• 2002: Co-inventor, Differential patterns of gene expression that predict for Docetaxel chemosensitivity and chemoresistance U.S. Provisional Application No. 60/381,141 (with co-inventor JC Chang)

Research support (active)

• P50 CA58183 (Osborne, CK) (08/01/01 – 07/31/06) NIH/NC1 SPORE in Breast Cancer, Project 2 "Molecular Classification and Prognostic Profiling of Ductal Carcinoma In Situ"; project co-principal investigators: D. Craig Allred, M.D., Peter O’Connell, Ph.D.

• P50 CA58183 (Osborne CK) (08/01/01 – 07/31/06) NIH/NC1 SPORE in Breast Cancer, Project 5 "Genetic Expression Profile of Taxotere versus AC Sensitivity"; project principal investigators: Jenny C. Chang, M.D., Michael Lewis, Ph.D., and Peter O’Connell, Ph.D.

• V Foundation/AACRTranslational Research Award (11/01/04-10/31/07) “Tumor Genetic Profiling: New predictive assays for breast cancer therapy”; project principal investigators: Peter O’Connell, Ph.D., Harry D. Bear, M.D., Ph.D.

Research interests

Breast cancer can arise from inherited mutations (eg, BRCA1, BRCA2), but more than 90% arise due to acquired stem cell somatic mutations and epigenetic alterations. These genetic lesion continue to accumulate over the course of tumor evolution, and ultimately define breast tumor malignancy and cancer outcomes. To study how tumor genetic differences define breast cancer risk, we correlate tumor-to-tumor DNA copy number and/or gene expression differences with patient-to-patient differences in recurrence risk and treatment responses. Ongoing studies focus on prognostic factors that infer risk of metastasis, predictive markers that estimate sensitivity to specific chemotherapy agents, and how co-morbidity between breast cancer and common gene/environment disorders (eg, obesity) enhance risk. For example, node-negative breast tumors that over-express a chromatin remodeling protein called MTA1 are 2.7-fold more likely to recur, but patients who develop MTA1-associated recurrences show enhanced treatment response and improved survival, while, in contrast, obesity blunts chemotherapy responses. The objectives of these studies are to develop genetic assays that define when breast cancer patients require chemotherapy, which chemotherapy drug to use, and strategies to augment obese patients’ chemotherapy responses (eg, adding dietary interventions to standard treatme

Selected publications

Past three years and selected earlier reports (chronological order, from a total of 24 reviews/chapters, 134 papers, 135 brief communications)

• Nakamura Y, Leppert M, O’Connell P, Wolff R, Culver M, Martin C, Fujimoto E, Hoff M, Kumlin E, White R (1987) VNTR markers for human gene mapping. Science 235:1616-1622
• Viskochil D, Buchberg AM, Xu G, Cawthon RM, Stevens J, Wolff R., Culver M, Carey JC, Copeland NG, Jenkins NA, White R, O'Connell P (1990). Deletions and translocations interrupt a cloned gene at the neurofibromatosis type 1 locus.  Cell 62:187-192.
• Cawthon, RM, Weiss R, Xu G, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O'Connell P, White R (1990). A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations.  Cell 62:193-201.
• Lemons RS, Eilender D, Waldman R, Rebentisch M, Frej A-K, Ledbetter DH, Willman C, McConnell T, O’Connell P (1990) Cloning and characterization of the t(15;17) translocation breakpoint region in acute promyelocytic leukemia. Genes Chrom Cancer, 2:79-87
• O’Connell P, Pekkel V, Fuqua SAW, Osborne CK, Allred DC (1998) Loss of heterozygosity in breast cancer precursors: Analysis of 399 lesions at 15 genetic loci, J Natl Cancer Inst 90:697-703
• Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Elledge R, Mohsin S, Osborne CK, Chamness G, Allred DC, O’Connell P (2003). Gene expression profiling predicts therapeutic response to docetaxel (Taxotere™) in breast cancer patients. Lancet 362:364-369
• Castro-Chavez F, Yechoor VK, Saha PK, Martinez-Botas J, Wooten EC, Sharma S, O'Connell P, Taegtmeyer H, Chan L (2003) Coordinated upregulation of oxidative pathways & downregulation of lipid biosynthesis underlie obesity resistance in perilipin knockout mice: a microarray gene expression profile. Diabetes 52:2666-74
• Lehman DM, Arya R, Blangero J, Almasy L, Puppala S, Dyer TD, Leach RJ, O'Connell P, Stern MP, Duggirala R (2005) Bivariate linkage analysis of the insulin resistance syndrome phenotypes on chromosome 7q. Hum Biol 77:231-46
• Arya R, Duggirala R, Jenkinson CP, Almasy L, Blangero J, O'Connell P, Stern MP (2004) Evidence of a novel quantitative-trait locus for obesity on chromosome 4p in Mexican Americans. Am J Hum Genet 74:272-82
• Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Mohsin S, Osborne CK, Chamness G, Allred DC, Lewis MT, O’Connell P (2005). Patterns of resistance and incomplete response to docetaxel, J Clin Oncol 23:1169-1177
• Moshin SK, O’Connell P, Allred DC, Libby AL (2005) Biomarker Profile and genetic abnormalities in lobaular cancinoma in situ Breast Cancer Res and Treat 90: 249-256
• Martin MD, Hilsenbeck SG, Mohsin SK, Hopp TA, Clark GM, Osborne CK, Allred DC, O'Connell P (2006) Breast tumors that overexpress nuclear metastasis-associated 1 (MTA1) protein have high recurrence risks but enhanced responses to systemic therapies. Breast Cancer Res Treat 95:7-12
• Nguyen DM, Sam K, Tsimelzon A, Li X, Wong H, Mohsin S, Clark GM, Hilsenbeck SG, Elledge RM, Allred DC, O'Connell P, Chang JC (2006) Molecular heterogeneity of inflammatory breast cancer: a hyperproliferative phenotype. Clin Cancer Res12:5047-54.
• Cleator S, Tsimelzon A, Ashworth A, Dowsett M, Dexter T, Powles T, Hilsenbeck S, Wong H, Osborne CK, O'Connell P, Chang JC (2006) Gene expression patterns for doxorubicin (Adriamycin) and cyclophosphamide (cytoxan) (AC) response and resistance, Breast Cancer Res Treat 95:229-33.
• Townson SM, O'Connell P (2006) Identification of estrogen receptor alpha variants in breast tumors: implications for predicting response to hormonal therapies. J Surg Oncol 94:271-3. (Comment on: J Surg Oncol. 2006 Sep 15;94(4):332-7)
• Medina D, Tsimelzon A, O’Connell, P, Allred DC (2007). Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution (manuscript submitted to Clinical Cancer Research)