Remembering Mary Jo LaDu
Mary Jo LaDu, or MJ, as she was affectionately known among her many close friends and colleagues, passed away on March 28 after a prolonged illness. On May 8, scientists and friends gathered in person and online for a memorial service, many recounting her dedication to science and to her students.
LaDu, who worked at the University of Illinois, Chicago, when she passed, will be best remembered in the Alzheimer’s field for her studies on the roles of ApoE and sex in AD pathology. Her early work focused on the relationship between ApoE and amyloid, teasing out the effects of the different apolipoprotein isoforms (LaDu et al., 1994; Jordan et al., 1998; Tai et al. 2013).
LaDu uncovered how these two proteins modulate other pathways, both physiological and pathological, helping identify and understand potential drug targets, including retinoid receptors, and modulators of ApoE lipidation (Tai et al., 2014; Sep 2014 news). Her EFAD transgenic mice, which express human ApoE isoforms in a 5xFAD mouse background, are widely used today (Youmans et al. 2012).
Over a 30-year career, LaDu nurtured numerous fruitful collaborations. If you would like to celebrate her life with a memory, anecdote, photo, or story that captures the MJ you knew, please use the comment box below.—Tom Fagan
David Geffen School of Medicine at UCLA
I first met Mary Jo at Harvard Medical School, where she gave a seminar about her work on ApoE. At that time, ca. 1993, the linkage between ApoE4 and Alzheimer's disease had just been reported, so I was excited to hear about Mary Jo's work in this new area. After the seminar I introduced myself to this vivacious and knowledgeable scientist, two qualities that were to serve her and the AD community well for the next three decades.
As a protein chemist, I was particularly interested in understanding the differential interactions among the three isoforms of ApoE protein and the Aβ protein. Mary Jo provided a much-needed link between the in vitro world in which I lived and the in vivo world in which the actual disease occurred, and I did the opposite for her. Her work was vital for keeping my own "biologically relevant." My work informed her own work on cell biological and genetic aspects of AD. This was a scientific synergy "made in heaven," which led to a lifelong professional, and especially personal, relationship.
Anyone who knew Mary Jo as a person can appreciate her energy. She radiated a contagious enthusiasm that made interacting with her a joy. I know so because of our numerous, and humorous, interactions sitting next to each other at study sections. (So humorous, in fact, that like bad children, section chairs had us sit next to them so we would be quiet.)
Mary Jo was dedicated to truth. She refused to publish results until they were mature, which, to her, meant doing many more experiments than the average scientist would find sufficient. MPUs (minimal publishable units) were an anathema to Mary Jo, which meant sometimes she would get scooped, a sacrifice she gladly made in the interest of doing science for science's sake and not for aggrandizement or fame. When Mary Jo published a paper, one knew that the data supported the conclusions.
One of the many admirable traits of Mary Jo was her commitment to her students, be they undergraduates, graduate students, or postdoctoral fellows. Mary Jo was the lab "mom" in every sense of that word, nurturing her students, protecting them from the sometimes-onerous bureaucracy, helping them with problems both personal and professional, ensuring their time in the laboratory would be productive, and shepherding their transition from the cloistered halls of knowledge in the university into the real world.
What some will not know is Mary Jo accomplished all this while dealing with often painful and incapacitating illness. I often wondered how this was possible. Repeated exhortations to take it easier and take better care of herself were always trumped by her sense of responsibility to her scientific "children." As time passed, I hoped she would be more responsible to herself and retire, knowing her children would be fine regardless, but her selflessness stifled that hope.
Mary Jo had planned a relaxing trip to Paris later this year, and retirement—in some years to come. But this was not to be.
Words clearly are insufficient to express the depth of our collective grief. The world has become a much sadder place since we lost our colleague, and friend.
We miss you, MJ.
Mary Jo was a constant in the field of APOE and Alzheimer's disease from the very beginning. She brought an expertise in lipid biology to the questions of neurodegeneration related to APOE. Over her nearly 30 years in the field, she organized many of the rare meetings and symposia that existed dedicated to APOE and Alzheimer's disease, some via an APOE program project grant that she directed from 2009 through 2013. Along the way, she made many research contributions that she shared freely with the community, including the EFAD mouse model of amyloid deposition. She had a lasting impact on the field of lipid biology in AD pathogenesis, which continues to grow.
I was, like many colleagues and friends, sad to hear that Mary Jo LaDu passed away unexpectedly. Mary Jo and I met in the mid-’90s right after the APOE gene was discovered as a strong genetic risk factor for Alzheimer’s disease.
By applying her experience and training in studying lipoproteins, Mary Jo’s earlier work included characterizing brain APOE lipoprotein particles. She was among the first to define the biochemical and biophysical properties of APOE particles isolated from CSF and those secreted by astrocytes, the main cell type in the brain that produce APOE. Her JBC paper in 1994 characterizing differential interactions between APOE isoforms and Aβ was well-regarded in the field and was a trigger for many more studies on this important subject area which relates to Aβ clearance and aggregation.
Mary Jo and I collaborated on defining interactions between APOE isoforms and Aβ and how the risk from APOE4 differs from APOE3 in lipidation and receptor binding. Our collaboration led to several publications and grant funding.
Those works also led to additional interactions with other APOE colleagues, including Bill Rebeck, Steve Estus, and Ed Weeber. The five of us formed a group to study APOE and Alzheimer’s disease, which led to the funding of a program project with Mary Jo as the lead PI. We also organized the annual APOE symposia rotating among the five institutions which were well-attended by colleagues from all over the world. Mary Jo’s collegiality and leadership were well-recognized and exemplified as she led that APOE PPG.
Mary Jo was a caring friend who also knew how to have fun and celebrate little joys in life. Her love for her cats was second to none. She also enjoyed travel with friends. Trainees from Mary Jo’s lab over the years would agree what a great mentor and friend Mary Jo was.
Mary Jo was too young to leave us, but her legacy, her laugh, her caring, and not least her contribution to science on APOE as it relates to Alzheimer’s disease will be with us forever!
University of Illinois at Chicago College of Medicine
Mary Jo was unique. I have never known another person quite like her and doubt that I ever will. MJ was a collaborator, a colleague, and a friend. She was smart, funny, and passionate about whatever she undertook: whether it was science, her students and postdocs, her friends and family, or her fellow scientists. She was impatient with dogmas in science, and questioned them routinely.
MJ was in many ways fearless and did not hesitate to speak up when she saw something that she thought was wrong. She may have bruised a few egos in the process, but her heart was big and she was always looking for the right answer. Many of us have a collection of MJ stories that we will cherish. Sadly, there will be no more. Her voice has been stilled, but her scientific legacy remains.
RUSH Medical College
I have been distraught about this terrible news. We had wonderful interactions as I was brought into Mary Jo’s orbit to assist her student with analyses of microbiome in the context of APOE genotype. At first, I found her intimidating, but then realized that she had an amazing temperament and dedication to science and her students. I think I saw what everyone else saw—just an amazing person and scientist. She will be sorely missed, but her legacy will remain for a very long time.
UCLA and VA
I am devastated by the loss of my dear friend. We met at a Society for Neuroscience meeting decades ago, before she made her E4 and E3 FAD mice, which we use today. In the first minute, at that time, MJ taught me about lipid particles and how important it was to lipidate ApoE to understand it. In the second minute we complained about the deficiency in knowledge on physiology and compensatory mechanism in the Alzheimer’s field; in the third minute, we commiserated about migraines and the importance of exercise in maintaining health (she was a swimmer at the time). Life is too short to beat around the bush to make a point and not to be blunt. We immediately connected; and from then on, we no longer had to speak to have a conversation.
We often met at conferences and sometimes she stayed at our house in Santa Monica when she was visiting and went hiking in the canyons. My son has many a story to relay about her colorful visits full of drama, fun, and love and brilliance. With her creativity, she was always looking for fun and drew out my shy son, and even though he was only 4 years old he still remembers her visits vividly. MJ was checking in on me every week or so to make sure I was okay and to tell me that she cared.
She was not so good at expressing how she was doing. Some of our favorite times were at Study Section. If you have ever been at a Study Section with MJ, you will know she would waste no time, making sure a proposal was being reviewed fairly. She listened carefully but was not afraid to tell a reviewer they were wrong and saved many a proposal.
Sometimes sitting next to her at lectures at SFN, she would critique the session during the session, which was as hilarious as it was inappropriate. We often got into fights because that comes with the territory of being blunt, and we knew it would be about a day before we laughed off the argument. She had this fearless integrity, and tenacity, guided by a strong moral compass, engaged to do something about the scourge of Alzheimer’s. I miss her deeply, but her inspiration and discoveries will live on in me, her students, and her colleagues.