Mary Jo LaDu

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

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

    Since moving our lab here in 2005, 30 students have completed their honor's projects in our lab and graduated, and since 2013, our lab has received 19 Honor’s College research grants and 12 Chancellor’s Undergraduate Research Awards. Currently, we have 13 undergrads at various stages of their degree working in the lab. Simply stated, we could not function without them.

    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. A great deal of research has examined the formation and structure of these AB deposits. However, pathologists have long noted that the presence, size, and time of onset of these plaques do not correlate with degree of dementia as assessed clinically in AD patients. Increasing evidence suggests that the accumulation of AB in neurons may be a critical, initial step in a cascade that results in neuron 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. For over 15 years, our lab has focused on understanding the structural and functional interactions between apoE and AB, particularly the effects on the health of neurons. While it is well established that apoE associates with AB plaques, the effect of apoE on the small, soluble oligomeric form of the peptide (oAB) has not been investigated. Our hypothesis is that apoE4 is less efficient in binding and clearing specifically the toxic oAB, resulting in neuroinflammation and neurotoxicity.

    In addition, we have recently developed an innovative new genetically altered mouse model where human AB is over-produced by neurons, the source of AB in AD brains. In addition, these mice also produce the human forms of apoE2, apoE3, or apoE4. We will characterize the structural interactions between the three forms of apoE and AB in the context of a living neuron and in the brains of these transgenic mice. We believe modulating apoE/AB structural interactions within a neuron will alter toxic functions of both apoE4 and AB. Thus, these complexes may be an attractive therapeutic target for AD.

    In summary, we are working to elucidate the biochemistry of Alzheimer disease. Very recently, we developed an antibody and series of tests that allow the identification of the toxic oAB, believed to be one of the keys to the changes in the brain seen PRIOR to the cognitive loss that is characteristic of Alzheimer’s patients. 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 is has projects focusing on everything from protein biochemistry, neuronal cell culture, 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:
    In reference to above, a minimum 12-15 hrs/wk with 3-5 hour chunks of time is required. We are here Saturdays, very early mornings doing mouse behavior studies and evenings as some protocols require long days or 2 shifts of investigators. 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.

    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 freshman and sophomore (explanation below) and work-study students. No experience is necessary; only a commitment to scientific research and a strong willingness to learn. A successful candidate will follow directions precisely, pay close attention to details, and be adaptable to changing lab needs.

    Brief Summary of what is expected from the student:
    Expectations of All Lab Members

    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, undergraduate summer fellows, graduate rotation 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. Make practical use of classroom knowledge by integrating it into research in the laboratory.
    b. 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.
    c. Attendance at bi-monthly journal club with Dr. LaDu and postdocs is required to learn, discuss and critically evaluate recent findings in AD research.
    d. 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.
    e. Work together in problem solving. Use a pro-active approach to your work, the work of others and the overall focus of the lab. A pro-active approach includes both anticipating and avoiding potential problems in experimental design through careful planning, as well as timely corrective action when an experiment fails.

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

    3. While classroom work is the priority:
    a. Schedule time-off around exams or vacations as far in advance as possible
    b. Be at work promptly when scheduled or send an email that you will be late or unable to come.
    c. Please send an email if you are sick.
    d. Devote work time to work tasks and personal time to personal matters.

    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, if happy, are willing to work during subsequent school years, culminating in an Honor’s project. Full-time summer employment is also possible. Junior and senior students need specific research experience.
    c. Students who understand that research lab work skills must be developed over time. Initially, you will learn basic lab techniques and assist with routine maintenance of the lab. You will then choose senior lab member and work on their project to develop specific techniques. Finally you will identify a project that is appropriate for your time commitment and skill-set.

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