BIOL442/542: This is a molecular neurobiologycourse for undergraduate and graduate-students. Topics covered are all aspectsof neuronal function at the molecular level.  A discussion of severalneurodegenerative diseases including Parkinson's, Alzheimer’s, andSchizophrenia are a few of diseases covered.  

BIOL 431/531:  This is a general pharmacologycourse for undergraduate and graduate-students.  Topics include thepharmacokinetics and pharmacodynamics.  All major drug classes are coveredin this course.

The primary focus of my laboratory is involved in the research involving neurodegenerative diseases including to a large extent, Alzheimer's disease (AD). During the progression of Alzheimer’s disease, many neurons die particularly in the area of the hippocampus. Because the hippocampus is an area of the brain involved in memory, AD is primary a disease where afflicted individuals lose their capacity for memory. A primary question in this field is how are neurons dying during the progression of AD. Our lab, as well as many others, is convinced that the primary cause of neuronal cell death associated with AD is caused by neurons undergoing apoptosis. Apoptosis, or programmed cell death, is a genetically driven form of cell death that plays an important function for living organisms. Upon activation of apoptosis, a series of steps occur, ultimately leading to cell death. One of the most important early steps in apoptosis is the activation of a family of proteases termed, caspases. Thus, caspase cleavage of critical proteins is believed to be responsible for the morphological and functional changes observed when cells undergo apoptosis. Biochemical markers are being developed that are designed to follow specific cleavage products produced from caspases. In this way, we can use these markers as footprints to the contribution of apoptosis in certain neurodegenerative diseases including AD. More recently, we have begun to examine if caspases are in fact the link between NFTs and senile plaques due to their ability to cleave tau. We have developed a transgenic mouse model of AD that overexpresses the antiapoptic protein, Bcl-2.  As shown in the Figure to the right, overexpression of Bcl-2 (A) prevented the formation of plaques (C and E) versus 24 month-old littermates that were negative for the human Bcl-2 protein (B, D and F).  In addition, overexpression of Bcl-2 enhanced place recognition memory as compared to Bcl-2 negative littermates (G).

More recently, we are expanding these initial findings by generating an additional Tg mouse model that overexpress human Bcl-2.  These mice overexpress mutant APP and develop beta-amyloid pathology and memory deficits. A major drawback to utilizing the 3xTg-AD/Bcl-2 OE mouse model is the difficulty in producing large enough numbers of animals to perform statistically meaningful experiments.  This can be attributed to both the difficulty in obtaining the right genotype when dealing with a quadruple-transgenic mouse model and to the fact the 3xTg-AD mice have to age to approximately 18-24 months of age before seeing significant pathology and behavioral deficits.  Because TgCRND8 mice develop pathology and memory deficits at a much early age, more experiments can be performed in a shorter time frame then with 3xTg-AD mice.  In addition, larger numbers of animals can be generated over a shorter time frame, allowing for a greater statistical power of study then with 3xTg-AD mice.  Moreover, because TgCRND8 mice represent a different model exhibiting, for example, neuronal degeneration, we will be able to examine the mechanism by which Bcl-2 may afford protection in greater detail following overexpression of Bcl-2.  Finally, because TgCRND8 mice do not overexpress the P301L tau mutation, we will be able to examine the potential role of caspases on tau accumulation and modification on endogenous levels of tau expressed in these mice.  Taken together, TgCRND8 mice represent an excellent model to confirm and extend our previous findings in 3xTg-AD mice.