Reproductive toxicants are ubiquitous in our modern day environment. The major focus of our research is directed at understanding the molecular signaling pathways responsible for germ cell survival in the male and female reproductive system. Ionizing radiation, phthalates, and thyroid toxicants are areas of current research interest in our laboratory.

Institutions

UNC at Chapel Hill

Research Description

Understanding the effects of toxicants on reproductive health both from an environmental and physiological perspective requires understanding, at the molecular level, the mechanisms that control cell growth and development during normal in utero and postnatal development. The importance of this type of scientific inquiry is due to the emerging paradigm known as the fetal basis of adult disease. This paradigm asserts that diseases such as cancer, diabetes, obesity, and cardiovascular disease have their origins early in development and are due in part to environmental exposures and diet. Based on this premise, the overall broad objective of my research laboratory has been to understand how exposure to environmental reproductive toxicants affects reproductive human health and disease. In order to do this, my lab has utilized in vivo transgenic mouse models applying toxicogenomic approaches to anchor both phenotypic and toxicological endpoints with changes in gene-expression profiles. My current research focuses on three major areas of study which include: 1) signal transduction pathways activated by toxicant exposure in both the male and female reproductive system; 2) gene products regulated by these pathways in the male and female reproductive system; and 3) their consequences on germ cell survival in both the male and female reproductive system.

Awards

Brown/NSF ADVANCE Career Development Award
Manning Assistant Professor of Pathology and Laboratory Medicine
2004 Dean's Teaching Excellence Award

Affiliations

Society of Toxicology

Northeastern Society of Toxicology

American Society of Andrology

Funded Research

Funding:
Current:
NIH 1R01 ES015704-01 "Gene Networks in Peri-pubertal Sertoli Cell Injury. "Project Period: 7/17/07- 5/31/11

The grant seeks to establish critical signaling networks utilized by Sertoli cell toxicants during postnatal testis development. Approaches taken include mouse models to determine phenotypic anchoring via gene array and bioinformatic technologies.

NIH ES013660 NIEHS: SUPERFUND BASIC RESEARCH PROGRAM
Title: Reuse in Rhode Island: A State-based Approach to Complex Exposures
Role: Core Leader; Project Period: 4/1/2009 – 3/31/2014

The grant seeks to understand both the biological mechanisms following exposures to mixtures and the engineering/technology needed to allow for remediation of Superfund contaminants. A third aspect is involved in outreach to the community through the university and the departments of environmental management and public health in Rhode Island.

Advance: Career Development Award
Title: Ovarian Cancer Research Symposium at Brown University
CoPIs: R. Freiman and M. Hixon.
Project Period: 3/1/2009 – 2/29/2010

The grant seeks to establish a mentoring relationship in the area of ovarian cancer research and to organize a small symposium on the topic of ovarian cancer at Brown.

Strategic Alliance Research Collaboration, Pfizer Inc.
Title: Pharmacodynamics of the IGF-IR Inhibitor Figitumumab (CP-751,871) in Cancer Patients
Research Scientist: Mary L. Hixon, Ph.D.
Pfizer's Collaborator Scientist: Antonio Gualberto, M.D. Ph.D.
Project period: 4/14/2009-4/13/2010.

The grant seeks to determine the correlation between free IGF3 and IGF1 levels and bound lGF1 levels in the serum of cancer patients and the clinical benefit to the inhibitor Figitumumab (CP-751,871) in combination with various chemotherapy regimens in lung cancer.


Completed:
P20 RR 16457 NIH/NCRR Idea Network of Biomedical Research Excellence Grant. "Growth Control in the Testis and Molecular Mechanisms of Testicular Homeostasis in Toxicant-Induced Testicular Injury."
Project Leader: M. Hixon; Project period: 7/1/2004-4/30/2007

P20RR018728 "Examination of Stress Response Genes following MEHP-induced testicular injury. Role: Pilot Project Leader; Project Period: 7/1/2006 – 6/30/2007

Rhode Island Science and Technology " In vivo and In vitro Targeting of Akt and p53 Signaling Networks in Testicular Cancer." Project Period: 1/1/2007 – 12/31/2007

Brown University National Center of Excellence in Women's Health "Mouse Models of Female Reproductive Anomalies" Role: Co-PIs: M.Hixon and R. Freiman; Project Period: 11/1/2006 – 10/31/2007;

Courses Taught

• Environmental Health and Diseas (BI0182)
• Independent study (BI0196)
• Science Writing (BI0095)

Selected Publications

• Brown C, Larocca J, Pietruska J, Ota M, Anderson L, Duncan Smith S, Weston P, Rasoulpour T, Hixon ML. Subfertility Caused by Altered Follicular Development and Oocyte Growth in Female Mice Lacking PKBalpha/Akt1. Biol Reprod. 2009 Sep 30. [Epub ahead of print] PMID: 19794155(2009)
• Karp DD, Pollak MN, Cohen RB, Eisenberg PD, Haluska P, Yin D, Lipton A, Demers L, Leitzel K, Hixon ML, Terstappen LW, Garland L, Paz-Ares LG, Cardenal F, Langer CJ, Gualberto A. Safety, Pharmacokinetics, and Pharmacodynamics of the Insulin-Like Growth Factor Type 1 Receptor Inhibitor Figitumumab (CP-751,871) in Combination with Paclitaxel and Carboplatin. J Thorac Oncol. 2009 Sep 10. [Epub ahead of print] PMID: 19745765(2009)
• Moyer, B. and Hixon, M. 2009. Trimethyl H3K27 and SCP3 Staining of the Mouse Postnatal Seminiferous Epithelium. Molecular Reproduction and Development. 76(6): 601.(2009)
• Rogers, R, Ouellet, G, Brown C., Moyer B., Rasoulpour T., and Hixon, M. 2008. Crosstalk between the Akt and NFkB signaling pathways inhibits MEHP-induced germ cell apoptosis. Toxicol Sci. 106(2):497-508.(2008)
• Rasoulpour, T, DiPalma, K., Kolvek, B. and Hixon ML. 2006. Akt1 suppresses radiation-induced germ cell injury in vivo. Endocrinology 147(9): 4213-4221.(2006)
• M. L. Hixon and K. Boekelheide. Expression and Localization of Akt1 in the Rat Seminferous Epithelium (2003). J. of Androl.24(6); 891-898.(2003)
• M. W. Burney, X. Yang, K. Jardine, M. L. Hixon, K. Boekelheide, J. Webb, P. M. Lansdorp, M. Lemieux (2003). The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol. 23:38-54.(2003)
• D. M. Gascoyne, M. L. Hixon , A. Gualberto, M.dM Vivanco (2003). Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development. Cell Cycle 2:238-245.(2003)
• M. L. Hixon and A. Gualberto. Vascular smooth muscle polyploidization: from mitotic checkpoints to hypertension. (2003). Cell Cycle 2:105-111.(2003)
• M. L. Hixon, C. Obejero-Paz, C. Muro-Cacho, M. W. Wagner, E. Millie, J. Nagy, T. J. Hassold, A. Gualberto (2000). Cks1 mediates vascular smooth muscle cell polyploidization. J Biol. Chem. 275:40434-40442.(2000)
• Y. Eto, K. Yonekura, M. Sonoda, N. Arai, M. Sata, S. Sugiura, K. Takenaka, A. Gualberto, M. L. Hixon, M. W. Wagner, T. Aoyagi (2000). Calcineurin is activated in rat hearts with physiological left ventricular hypertrophy induced by voluntary exercise training. Circulation 101:2134-2137.(2000)
• M. L. Hixon, C. Muro-Cacho, C. Obejero-Paz, A. Gualberto (2000.) Altered Mitotic Checkpoint in rats Predisposed to hypertension. In "Vascular Protection: Molecular mechanisms, Novel therapeutic Principles and Clinical Application" Ed. G.M. Rubanyi, V.J. Dzau, and J.P. Cooke. Harwood, London U.K.(2000)
• M. L. Hixon, A. Flores, M. Wagner, A. Gualberto (2000). Gain of function properties of mutant p53 proteins at the mitotic spindle cell cycle checkpoint. Histol Histopathol. 15:551-556.(2000)
• M. L. Hixon and A. Gualberto (2000). The control of mitosis. Front Biosci. 5:D50-57.(2000)
• M. L. Hixon, C. Muro-Cacho, M. W. Wagner, C. Obejero-Paz, E. Millie, Y. Fujio, Y. Kureishi, T. Hassold, K. Walsh, A. Gualberto (2000). Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization. J Clin Invest. 106:1011-1020.(2000)
• P. Ruiz-Lozano, M. L. Hixon, M. W. Wagner, A. I. Flores, S. Ikawa, A. S. Baldwin, K. R. Chien, A. Gualberto (1999). p53 is a transcriptional activator of the muscle-specific phosphoglycerate mutase gene and contributes in vivo to the control of its cardiac expression. Cell Growth Differ. 10:295-306.(1999)
• M. L. Hixon, A. I. Flores, M. W. Wagner, A. Gualberto (1998). Ectopic expression of cdc2/cdc28 kinase subunit Homo sapiens 1 uncouples cyclin B metabolism from the mitotic spindle cell cycle checkpoint. Mol Cell Biol. 18:6224-6237.(1998)
• M. L. Hixon, E. Millie, L. A. Judis, S. Sherman, K. Allran, L. Taft, T. Hassold (1998). FISH studies of the sperm of fathers of paternally derived cases of trisomy 21: no evidence for an increase in aneuploidy. Hum. Genet. 103:654-657.(1998)
• Y. Xiong, D. Kuppuswamy, Y Li, E. M. Livanos, M. L. Hixon, A. White, D. Beach, T. D. Tlsty (1996). Alteration of cell cycle kinase complexes in human papillomavirus E6- and E7-expressing fibroblasts precedes neoplastic transformation. J Virol. 70:999-1008.(1996)
• T. D. Tlsty, A. Briot, A. Gualberto, I. Hall, S. Hess, M. L. Hixon, D. Kuppuswamy, S. Romanov, M. Sage, A. White (1995). Genomic instability and cancer. Mutat Res. 337:1-7.(1995)
• A. Gualberto, M. L. Hixon, T. S. Finco, N. D. Perkins, G. J. Nabel, A. S. Baldwin (1995). A proliferative p53-responsive element mediates tumor necrosis factor alpha induction of the human immunodeficiency virus type 1 long terminal repeat. Mol Cell Biol. 15:3450-3459.(1995)