Dr. James Wachira
Assistant Professor
Director, Molecular & Cell Biology Core Laboratory
Department of Biology
School of Computer, Mathematical and Natural Sciences
Morgan State University
1700 E. Coldspring Lane
Baltimore, Maryland 21251

Dixon 109
(tel) 443-885-3632
jwachir@morgan.edu

Research Interest

High blood pressure is a major risk factor for serious diseases such as heart-failure, kidney-failure and stroke and the incidence of hypertension and end-stage organ damage is reportedly 10-17 fold higher in minorities. Essential hypertension is the most common form of human hypertension, however, its etiology has not been fully understood. This lack of insight possibly reflects the complex interaction between multiple tissues and genes in blood pressure regulatory mechanisms. Autonomic control of cardiovascular function is critical for the maintenance of blood pressure within a narrow range and increased sympathetic nervous system activity acutely elevates blood pressure through stimulation of the heart, kidney and peripheral vasculature. Sympathetic output to peripheral tissues such as the heart and the kidney is determined by intrinsic rhythms generated in the central nervous system and the cyclic baroreceptor input. Thus, changes in the baroreceptor reflex are likely to be modified during sustained hypertension. Indeed, some experimental forms of hypertension are associated with increased activation of neurons in cardiovascular control regions of the brain-stem. The regulation of re-absorption of sodium in kidney tubules is critically important in blood pressure control and hence genes that play a role in this function have been associated with some forms of hypertension. The multiplicity of mechanisms leading to pathological elevation of blood pressure suggest that the identification of a few key downstream signaling components that are associated with hypertension and end organ damage offer the best strategy towards the biochemical modeling of hypertension related pathologies and the development of more effective therapies. Our current projects are aimed at identifying the points of convergence in signal transduction pathways in the brain and kidney upon perturbation of cardiovascular homeostasis through sleep deprivation stress or high dietary salt intake.

Project 1

Melanocortin receptors have been implicated in autonomic functions including cardiovascular homeostasis and energy balance but the biochemical mechanisms have not been elucidated. This project aims to elucidate such mechanisms by analyzing the expression of the receptor proteins in the brains of rats that have been exposed to prolonged stress to modify cardiovascular parameters and to identify other signaling components in the melanocortin pathway in autonomic centers with cardiovascular relevance.

Project 2

This project is testing the hypothesis that the molecular events leading to severe hypertension and subsequent organ damage are mediated by a few specific effector kinases. The aims are to identify the relevant kinases by revealing protein phosphorylation responses in kidneys and regions of the brain with cardiovascular relevance in an animal model of severe hypertension. The studies will be carried out in tissue slices.

These projects involve the use of a combination of the following techniques: Protein and nucleic acid analyses through blotting and amplification techniques; analysis of protein expression in tissues using immunohistochemistry and immunofluorescence techniques; protein kinase assays; ELISA based assays; 2-D protein gels; immunoprecipitation/autoradiography and pulldown assays; nucleic acid sequencing; bioinformatics; protein expression and purification.

Research opportunities in Dr James Wachira laboratory for PHD candidates in bioenvironmental sciences will involve training in biomarker discovery. Although the role of environmental factors such as pollutants and stress is well recognized, their role in the other major health concern, cardiovascular diseases, is not well understood. Nonetheless, there is clearly an overlap between the risk factors for cancer and cardiovascular diseases such as diet, air pollution including smoking and inhalation of particulate matter.

Professional Society Membership

1. American Association for the Advancement of Science (AAAS)
2. American Society for Biochemistry and Molecular Biology (ASBMB)
3. American Chemical Society (ACS)
4. Association of Biomolecular Resource Facilities (ABRF)

Peer-reviewed publications

1. Wilson S. A., WACHIRA S. J., Drew R. E., Jones D. and Pearl L. H. 1993. Antitermination of amidase expression in Pseudomonas aeruginosa is controlled by a novel cytoplasmic amide binding protein. EMBO J. 12. 3637-3642
2. Wilson S. A., WACHIRA S. J. M., Norman R. A., Pearl L. H., Drew R. E. 1996. Transcription antitermination regulation of the Pseudomonas aeruginosa amidase operon. EMBO J. 15 (21). 5907-5916
3. Wachira S. J. M., Mampuru L. J., Shai L. J., Tyobeka E. M. and Abotsi E. K. 1998. Analysis of the molecular mechanism of lithium on mammalian cells in culture. In: The Biological and Clinical Actions of Lithium: New Perspectives (Becker R. W., Lucas K. C. and Gallicchio V. S. Eds) Weidner Publishing, Chesire, Connecticut, USA. pp 67-82
4. Mampuru L. J., Abotsi E. K. and WACHIRA S. J. M. 1999. Calyculin-A potentiates growth and apoptotic effects of lithium in HL-60 cells. J. Trace and Microprobe Tech. 17(3), 367-378.
5. Roy, S.K., WACHIRA S.J., Weihua X., Junbo Hu, and Kalvakolanu D.V. 2000. CCAAT/Enhancer-binding Protein-beta Regulates Interferon-induced Transcription through a Novel Element. J. Biol. Chem. 275: 12626-12632.
6. Kgokong JL, WACHIRA JM. 2001. Cytotoxicity of novel trifluoromethylquinoline derivatives on human leukemia cells. Eur J Pharm Sci. 12(4): 369-376.
7. Cleo A. Hughes-Darden, S. JAMES WACHIRA, *Frank J. Denaro, Christopher V. Taylor, Kiana J. Brunson, and T.J. Robinson 2001. Expression and Distribution of protein kinase C isozymes in brain tissue of Spontaneous Hypertensive rats (SHR). Cellular and Mol. Biol. 47 (6): 1077-1088
8. Cleo A. Hughes-Darden, S. JAMES WACHIRA, Esther Batta, and T. Joan Robinson. 2001. Effects of gamma-2-melanocyte-stimulating hormone on Protein Kinase C activity and expression in spontaneous hypertensive rats (SHR). Cellular and Mol. Biol. 47 (6): 1069-1075
9. S. JAMES WACHIRA, Cleo A. Hughes-Darden, Christopher V.Taylor, Richard Ochillo and T. Joan Robinson. 2003. Evidence for the Interaction of Protein Kinase C and Melanocortin 3-receptor Signaling Pathways. Neuropeptides. 37 (4): 201-210
10. Shai LJ, Abotsi EK, Tyobekai EM, WACHIRA JM. Partial involvement of c-jun protooncogene in growth enhancing and cytotoxic effects of lithium in vitro. Cell Mol Biol . 2003 Nov;49(7):1137-43.
11. S. JAMES WACHIRA, Cleo A. Hughes-Darden, Christopher V.Taylor and T. Joan Robinson. 2003. Neural melanocortin receptors are differentially expressed and regulated by stress in rat hypothalamic-pituitary-adrenal axis. Cell Mol Biol. 2004 Sep; 50(6):703-13.