Postdoctoral Fellow, University of California Irvine, 1995
PhD, University of California Irvine, 1994
BS, University of Southern California, 1985
Regulation of Alzheimer’s disease pathogenesis
The role of sex steroid hormones in Alzheimer’s disease
Relationships between obesity, type 2 diabetes, and Alzheimer’s disease
Signaling pathways regulating neuronal apoptosis and neuroprotection
Research in my lab is broadly focused on Alzheimer’s disease (AD), with the general goals of elucidating factors that regulate AD pathogenesis and pursuing translational approaches that will be useful in the prevention and/or treatment of the disease. Our approach to investigating research questions involves the use of complementary cellular, biochemical and molecular techniques to analyze relationships in human tissues, wild-type and transgenic rodent models, and cultured cells.
A primary area of focus in my laboratory is the relationship between age-related loss of steroid hormones and the development of AD. For example, our research with postmortem human brain has helped to identify testosterone loss in aging men as a risk factor for AD. In rodent models, we observe that depletion of androgens accelerates development of AD-like neuropathology and increases neuronal vulnerability to toxic insult. Cell culture studies continue to identify the relevant underlying mechanisms for these androgen effects, including investigation of classic genomic actions (e.g., regulation of genes such as neprilysin) as well as activation of rapid cell signaling pathways (e.g., MAPK/ERK, CREB, PKC). In ongoing translational studies, we are building upon our basic science advances to develop specific therapeutic interventions that selectively activate protective androgen pathways (e.g., synthetic testosterone mimetics). Using this general research strategy, we are pursuing conceptually parallel basic science and translational projects to evaluate the interactions between estrogen and progesterone actions in the regulation of neurodegenerative cascades associated with AD.
A new area of research in the lab seeks to understand the relationships between obesity, type 2 diabetes, and AD. Recent epidemiological findings have identified obesity in middle age, and its downstream consequences metabolic syndrome and type 2 diabetes, as significant risk factors for the development of AD in old age. Our efforts are focused at understanding the mechanistic links between these conditions, including the interactive roles of adiposity, neuroinflammation, and age-related changes in testosterone and estrogen.
Gero 310 Physiology of Aging (4, Fa) Effects of normative aging processes on homeostatic mechanisms and how these changes relate to development of disorder and disease in later life. Lecture and discussion. Prerequisite: BISC 220L or BISC 221L.
Gero 416 Health Issues in Aging (4, Sp) Physiological, psychological, and social health problems of older people; organizational factors in health care delivery.
Rosario ER, Chang L, Head EH, Stanczyk FZ, Pike CJ (2011) Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease. Neurobiol Aging. 32 (4): 604-613. -PubMed
Carroll JC, Rosario ER, Villamagna A, Pike CJ (2010) Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3xTransgenic-Alzheimer’s disease mice.Endocrinology. 2010 Jun;151(6):2713-22. -PubMed
Pike CJ, Carroll JC, Rosario ER, Barron AM (2009) Protective actions of sex steroid hormones in Alzheimer’s disease. Front Neuroendocrinol. 30(2):239-258. -PubMed
Yao M, Nguyen TV, Rosario ER, Ramsden M, Pike CJ (2008)Androgens regulate neprilysin expression: role in reducing beta-amyloid levels. J Neurochem. 105(6): 2477-2488. -PubMed
Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, LaFerla FM, Pike CJ (2007) Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci. 27(48):13357-1336. -PubMed
Nguyen TV, Yao M, Pike CJ (2007) Flutamide and cyproterone acetate exert agonist effects:induction of androgen receptor-dependent neuroprotection. Endocrinology 148(6): 2936-2943. -PubMed
Yao M, Nguyen TV, Pike CJ (2007) Estrogen regulates Bcl-w and Bim expression: role in protection against beta-amyloid peptide-induced neuronal death. J Neurosci. 27(6):1422-1433. -PubMed
Rosario ER, Carroll JC, Oddo S, LaFerla FM, Pike CJ (2006) Androgens regulate development of neuropathology in a triple transgenic mouse model of Alzheimer disease. J Neurosci. 26(51):13384-13389. -PubMed
Yao M, Nguyen TV, Pike CJ (2005) Beta-amyloid-induced neuronal apoptosis involves c-Jun N-terminal kinase-dependent downregulation of Bcl-w. J Neurosci. 25(5):1149-1158. -PubMed