Mary Jo LaDu

    Email Address: mladu@uic.edu
    College: Medicine Department: Anatomy and Cell Biology
    Secondary Department: Bioengineering
    Title: Professor
    Office: COMRB 7091 Phone: 312-355-4795
    Webpage: ladu.lab.uic.edu
    Participating in the Chancellor’s Undergraduate Research Awards program: Yes

    Research Interest:
    Neurobiology, Neurodegeneration, Alzheimer's disease.

    Alzheimer's disease (AD) is a rapidly growing epidemic, particularly in the United States as the "baby boomers" reach the age of onset for AD. Advancing our understanding of disease onset and progression, as well as the best pathways to intervene for its prevention and treatment, is critical to overcoming this growing health care burden. Currently, there is no cure and therapy for AD is limited to symptomatic treatment because relatively little is known about the biological underpinnings of the disease.

    Genetic mutations that result in the over-production of amyloid-beta peptide (AB) cause the familial form of AD. Sticky masses of AB develop into large plaques in the brain during the progression of AD, and are a defining pathological hallmark of the disease. Increasing evidence suggests that the accumulation of AB in neurons may be a critical, initial step in a cascade that results in neuronal death. In 1993, it was found that individuals possessing a certain naturally occurring form of apolipoprotein E (apoE) called apoE4 have a greater risk for developing AD than individuals possessing the apoE2 or apoE3 form of the protein. Indeed, APOE4 is the primary genetic risk factor for the disease. Although the roles of apoE in normal brain function and in the development of AD remain unclear, apoE effects on AD are often attributed to modulation of the function of AB. Recent re-interpretation of decades of human studies suggests that the risk imparted by APOE4 is actually specific only to females, introducing an important new component to the mechanistic hypothesis. Currently, the primary focus of the lab is understanding the significant increased risk for AD in females carrying the APOE4 gene. Our hypothesis is that apoE4 and female sex play a synergistic role in the progression AD to compromise women.

    To study these effects, we have developed a novel AD transgenic mouse that mimics the genetics and pathology of human disease by having both human familial AD mutations that increase specifically the peptide Aβ42 and the human genotypes of APOE. This allows for the study of therapeutic strategies for AD, currently focusing on understanding and targeting the interaction between AB, APOE, and estrogen. This novel AD transgenic mouse model is now the preferred preclinical AD model.

    In summary, we are working to elucidate the biochemistry of Alzheimer’s disease. With these developed tests and a new, fully-humanized transgenic mouse model, we have established biomarkers and an animal model that track progression of the disease and could revolutionize the development of candidate drugs to prevent or treat the disease in its earliest phases. Currently, our lab has projects focusing on everything from protein biochemistry, immunohistochemistry, preclinical therapeutic testing in transgenic mice to human trials with the "mechanistic biomarkers" developed in our lab.

    Minimum time commitment in hours per week: 12-15

    Qualifications of a Student:
    We are currently looking for students to begin being trained ASAP. In reference to above, a minimum 12-15 hrs/wk with 3-5 hour chunks of time required. Students that are motivated and have experience in our lab are eligible and encouraged to work full or half time during the summers and school year as hourly paid employees. All students applying must be in or eligible for the UIC Honors College.

    Successful candidates will enhance their experience by immersing themselves in the scientific background/literature relevant to the lab’s research (described above). Our preference is for freshmen and sophomore (explanation below) and work-study students. No experience is necessary; only a commitment to scientific research and a strong willingness to learn.

    Brief Summary of what is expected from the student:
    Our general goal is a productive, professional, and harmonious work environment.
    The following expectations apply to employees in our lab, as appropriate to one's position (manager, research scientists, post-docs, graduate students, and work-study undergraduates):

    1. Share your skills, talents and creativity with the lab. Conversely, take advantage of educational and growth opportunities available.
    a. A commitment to learning both correct lab technique and the biology and pathology of Alzheimer disease (AD) is expected, as appropriate to one's position in the lab.
    b. Attendance at weekly journal club with Dr. LaDu and postdocs is required to learn, discuss and critically evaluate recent findings in AD research.
    c. Learning can be facilitated by scientific interactions with other lab members, active participation in lab meetings, attendance at research conferences, and guided reading of AD literature.

    2. At least once per semester, meet with Dr. LaDu for a performance review/evaluation.

    4. For undergrads in particular, we look for:
    a. Students who demonstrate an eagerness to learn the scientific basis of the lab’s past, current and future research direction(s).
    b. Freshman or sophomore students who are willing to work during subsequent school years, culminating in an Honor’s capstone project. Full-time summer employment, that will continue into part time school year employment, is also possible. Junior and senior students need specific research experience.

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