Dr. Roger A. Acey
Developmental Biochemistry, Toxicology, and Environmental Chemistry
Teaching: Graduate & undergraduate biochemistry
Principle Courses Taught:
- Chem 441A/B General Biochemistry
- Chem 443 Biochemistry Laboratory
- Chem 542 Special Topics in Biochemistry: Molecular Immunology
- Chem 547 Biochemistry of Nucleic Acids
- Embryonic Development and Cell Differentiation
- Stem Cell Differentiation - The Role of Butyrylcholinesterase in Normal Neuron Development
- Nuclear Glycosylation - A mechanism for Regulating Gene Transcription
- Biochemical Toxicology/Pharmacology
- Effect of Environmental Contaminants on Neuron Development
- Heavy Metals
- Neurodegenerative diseases - The Role of Butyrylcholinesterase in Alzheimer's disease, Autism
- Pharmaceutical Drug Design for Neurodegenerative Diseases - Butyrylcholinesterase as the Target
- Bioorganic Chemistry (Dr. Nakayama)
- Enzyme Kinetics
- Structure Function Relationships
- Environmental Chemistry
- Use of Protein Based Technologies for Removing(Recovering) Toxic (Precious) Heavy Metals from the Environment
Biochemistry of Development
My laboratory is interested in the biochemical and genetic factors that control early embryonic development. We have been working with two unique biological systems, umbilical cord stem cells and the brine shrimp Artemia ( your garden variety "sea monkey"). We have been using the stem cells to study neuron development. In particular, we are focused on an enzyme known as butyrylcholinesterase. While the exact biochemical function of this enzyme is unknown, we have shown that the enzyme is expressed during the early stages of neural tissue formation. Our current experiments are designed to determine the cellular location of the protein and the factors that control its expression. A better understanding of the role of this enzyme in normal neuron development should provide insights into the biochemical mechanisms associated with neurological problems such as Alzheimer's disease and autism.
We have been using Artemia to study nuclear glycosylation and how this posttranslational modification may be involved in regulating gene transcription. Using LC MS/MS, we have shown that histone H1 exists in several different glycosylated isoforms. We are interested in identifying the actual structural differences between isoforms and the enzymes responsible for the modification. We ultimately are interested in how changes in glycosylation of histone H1influence gene transcription (epigenetics).
We have shown that di-n-butylphthalate (DBP), a common plasticizer and well documented environmental contaminant, is a substrate for butyrylcholinesterase. Bis-phenol A (BPA), another commonly used plasticizer, is a reversible inhibitor of this enzyme. As such, both of these compounds are toxic to developing neurons, i.e., they prevent the enzyme from performing its normal biological function. We are suggesting that a possible mechanism for the dramatic increase in autism may be due to exposure to these (or structurally similar) environmental contaminants during early neuron development. We are working to develop a better understanding of how these plasticizers interact with butyrylcholinesterase.
Heavy metals have also been implicated in a number of neurodegenerative diseases. As such, we are looking at the effects of heavy metals on neuron development. We are particularly interested in effects of thimerosal, a mercury based preservative used in flu vaccine.
Butyrylcholinesterase Inhibitors as a Therapeutic for Alzheimer's Disease.
Normal neural function is dependent on the neurotransmitter acetylcholine. In Alzheimer's patients, brain butyrylcholinesterase activity is elevated; this results in a lower than normal level of acetylcholine. The consequence is loss of cognitive function. Along with Dr. Nakayama, we are trying to develop a class of butyrylcholinesterase inhibitors that would increase brain levels of acetylcholine and return of cognitive function in Alzheimer's patients. The clinical implications of this research is enormous.
We have cloned the gene for a novel metal binding protein known as metallothionein from Artemia. This protein has the unique ability to selectively bind toxic and precious heavy metal, e.g., mercury, uranium, gold, and silver. We have patented a technology using this protein for water purification or environmental clean-up applications. We are now working to produce a prototype "heavy metal sponge". Students working on this project will gain experience in commercial, real life applications of basic research.
- Abstracts/Posters/Presentations (National/International meetings)
Acey, R. A., MacArthur, C. C., Cage, F Brown, M.W., Del Cid, J. , and Nakayama, K., Di-Alkyl Aryl Phosphates are Irreversible Inhibitors of Butyrylcholinesteraae; A Potential Therapeutic for the Treatment of Alzheimer.s Disease. ASBMB Meeting, April 24-28, Anaheim, CA, 2010. Abs. B168.
Acey, R. A., Del Cid, J. S. Cage, F.M., Poynter, S. T. MacArthur, C., and Nakayama, K., Di-Alkyl Aryl Phosphate Inhibitors of Butyrylcholinesterase as a Potential Therapeutic for the Treatment of Alzheimer.s Disease: Characteristics of Off- Target Effects. ASBMB Meeting, April 9-13, Washington, D.C., 2011. Abs. 763.1
Del Cid, J. S., Poynter, S. T., Nakayama, K., and Acey, R. A., Di-Alkyl Aryl Phosphate Inhibitors of Butyrylcholinesterase as a Potential Therapeutic for the Treatment of Alzheimer.s Disease: Characteristics of Off-Target Effects. Council of Undergraduate Research; Posters on the Hill, April 12-13, Washington, D.C., 2011. Abs. E1,
Moon, S., Meza, J. E., Ball, C., and Acey, R. A., Developmentally Regulated Posttranslational Modification of Histone H1. American Society of Mass Spectrometry, June 5-9, Denver, CO., 2011. Abs. 516.
Turner, A. D., Thou, Chanmeali, Nakayama, K., and Acey, R.A., Effects of Aryl Dialkyl Phosphates on Butyrylcholinesterase. Annual Biomedical Research Conference for Minority Students. November 10 -12, 2011, St. Louis, MO.
Tu, K.N., Suriano, A., Van Fossen, E. , Raya, R., Acey, R.A., and Nakayama, K., Tetra- Alkyl bis-Phosphates as Bivalent Inhibitors of Butyrylcholinesterase . Compounds with Potential for the Treatment of Alzheimer's Disease. American Chemical Society Western Regional Meeting, November 10-12, Pasadena, CA,
2011. Abs. RM_WRM 18. Acey, R. A., Madera, P., and Wilkerson, B. A Novel Metal Binding Protein from Artemia: Use as a Metal Sponge for Water Remediation. 22nd Annual International Conference on Soil, Water, Energy, and Air. March 19 to 22, 2012, San Diego.
Tu, K. N., Suriano, A., Tran, T., Van Fossen, E., Spurlock, N., Gallegos, O., Esquivel, R., Feng, J. J., Turner, A.D., Nakayama, K., and Acey, R. A., Tetra-Alkyl Bis-Phosphates as Bivalent Inhibitors of Butyrylcholinesterase: Compounds with Potential for Treatment of Alzheimer.s Disease. ACS Conference: Division of Medicinal Chemistry, March 25, 2012, San Diego, CA, Abs. 113.
Acey, R.A., Yoshida, B.Y., and Edep, M.E., Metalloproteins in Developing Artemia. In: Cell and Molecular Biology of Artemia Development. J.C.Bagshaw, T. MacRae, and A. Warner, eds., Plenum Publishing Corporation, New York, NY, 1989. pp. 203-220.
Miller, M.D., Acey, R.A., Lee, L.Y., Edwards, A.J., Digital Imaging Considerations for Gel Electrophoresis Analysis Systems, Electrophoresis 22(5), 791, 2001.
Acey, R.A., Bailey, S., Healy, P., Unger, T.F., and Hudson, R.A., A Pseudocholinesterase in the Early Development of the Brine Shrimp (Artemia salina) Larvae: A Target for Phthalate Ester Toxicity? BBRC 299(4), 659, 2002.
Law, K., Acey, R. A., Smith, C., Benton, D., and Nakayama, K., Dialkyl Phenyl Phosphates as Novel and Selective Inhibitors of Butyrylcholinesterase. BBRC, 355(2), 371, 2007.
Graziano, R.B. and Acey, R.A., Di-Alkyl 2-Halo Phenyl Phosphates: Effects on Butyrylcholinesterase Activity. McNair Scholars Research Journal 12, 41, 2008.
Acey, R.A. and Nakayama, K., The Effect of Di-Alkyl Aryl Phosphates on Butyrylcholinesterase (In preparation).
Acey, R.A., Harpham, B., Cloning and Expression of a Metallothionein-Like Protein from Artemia. (In preparation)
- US Patent 6,750,056, Issued 6/15/04.
- Australian Patent Number 2002316183, Issued 7/18/08.
- Japanese Patent Number 2003-526941, Allowed 3/10/10.
Acey, R.A. , Harpham, B. and Mustillo, M. Metal Binding proteins and Associated Methods. Patent Number 7,135,605, Issued 11/14/06.
- Chinese Patent Number 02822019.6 Issued 4/17/12
Acey, R.A. and Kanner, R. Thimerosal Removal Device. Serial Number 11/624,059, Patent Allowed 1/17/10.
Acey, R.A. and Nakayama, K., Butyrylcholinesterase Inhibitors. Application Number PCT/US2007/083262, Patent Pending.
- Student Theses
Purification and Characterization of RNA Polymersae II from Artemia. (2009)
Developmentally Regulated Glycosylation of Histone H1 in Artemia. (2012)
Cloning of the Gene for Metallothionein from Artemia. (2012)
Cellular Localization of CKLFSF3 in Rat Macrophages. (2012)