Remembering Mary Jo LaDu
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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
References
News Citations
Paper Citations
- LaDu MJ, Falduto MT, Manelli AM, Reardon CA, Getz GS, Frail DE. Isoform-specific binding of apolipoprotein E to beta-amyloid. J Biol Chem. 1994 Sep 23;269(38):23403-6. PubMed.
- Jordán J, Galindo MF, Miller RJ, Reardon CA, Getz GS, LaDu MJ. Isoform-specific effect of apolipoprotein E on cell survival and beta-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures. J Neurosci. 1998 Jan 1;18(1):195-204. PubMed.
- Tai LM, Bilousova T, Jungbauer L, Roeske SK, Youmans KL, Yu C, Poon WW, Cornwell LB, Miller CA, Vinters HV, Van Eldik LJ, Fardo DW, Estus S, Bu G, Gylys KH, LaDu MJ. Levels of soluble apolipoprotein E/amyloid-β (Aβ) complex are reduced and oligomeric Aβ increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples. J Biol Chem. 2013 Feb 22;288(8):5914-26. PubMed.
- Tai LM, Koster KP, Luo J, Lee SH, Wang YT, Collins NC, Ben Aissa M, Thatcher GR, LaDu MJ. Amyloid-β pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo. J Biol Chem. 2014 Oct 31;289(44):30538-55. Epub 2014 Sep 12 PubMed.
- Youmans KL, Tai LM, Nwabuisi-Heath E, Jungbauer L, Kanekiyo T, Gan M, Kim J, Eimer WA, Estus S, Rebeck GW, Weeber EJ, Bu G, Yu C, LaDu MJ. APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease. J Biol Chem. 2012 Dec 7;287(50):41774-86. PubMed.
External Citations
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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.
Georgetown University
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.
Hong Kong University of Science & Technology
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.
I was very lucky to know MJ as my friend and collaborator. Her passion and enthusiasm for science was electric. I treasured her as a colleague who was genuinely driven to take on our collaborative projects and pursue them wholeheartedly. Of course those of you who knew her well understand that she could also be exasperating. We would argue over everything from broader methodological approaches to the phrasing of sentences in grants and even the choice of symbols for figures. Such were my experiences with MJ, both exhausting and enthralling. But there was something truly unique in this blend—in the honesty of her craft, dedication to science, and loyalty to her lab members and colleagues—that insisted you embrace all that was MJ. I will miss her dearly.
Stealth Biotech
I’m just now learning of MJ’s passing and I’m numb. It was over 30 years ago that MJ and I first met when she was doing her postdoc in lipid metabolism at U Chicago and I was leading an Alzheimer’s lab at Abbott Laboratories. The linkage of ApoE4 to AD had just been reported, and a person in my lab made the connection to MJ. An initial lunch led to a collaboration, where she worked in my lab exploring the different mechanisms by which apoE isoforms may impact Alzheimer’s.
Back then there were still some walls between industry and academia but, in ways that are now forgotten, we overcame the logistical challenges to make several discoveries, including those in the 1994 JBC paper.
Through her spirit, drive and questions, MJ was a force to be reckoned with. In reflection, I too was young in my career, and MJ taught be some valuable lessons regarding managing innovative personalities that have served me well ever since. Her gumption could have been misread; alas, she didn’t wish to break systems but to improve them. To that end, it’s gratifying to read that she was very deeply involved in the governance of UIC and the College of Medicine.
MJ and I connected periodically over time to catch up, perhaps most memorably for one of my “decade” birthdays in Amsterdam after a conference there. It’s wonderful to hear the reflection of others regarding her career, her mentorship, her impact, and her zest. She will be missed. Gives us all pause to think about the important things.
University of Minnesota, Twin Cities
I was so saddened to hear the shocking news of Mary Jo’s passing. I could not believe that MJ, who had always been full of life, is no longer with us. I first met MJ in person at a conference in 2009, although I had been well aware of her impressive work on APOE and AD through the literature. Our mutual interests in lipoprotein metabolism overall and AD in particular bonded us immediately.
What a unique individual MJ was! She was so straightforward and never hid her opinions about anything. Her fearlessness might seem rough, but deep inside she had a gentle soul. She was indeed very kind and helpful. When she heard our needs in preparing some synthetic Aβ peptide for an ongoing study, she enthusiastically offered help with her expertise in this area right away. Soon after our encounter at the conference, we collaborated and published an important paper in JBC in 2010 on the role of ApoA-I/HDL in AD, which had led to additional lines of research and findings in the field.
Over the years, MJ has been generous with her expertise in Aβ preparation and sharing her research materials. Her research team established and published detailed protocols for preparing different forms of Aβ, along with thorough characterization of those preparations. These valuable technical resources will continue to benefit the AD research community.
In addition to those scientific symposia she organized, MJ was a lot of fun outside of science. In 2015 when SfN was held in Chicago, she invited many friends and colleagues to her home for a wonderful party, with a beautiful night view of Chicago from the balcony. She particularly had all her students and trainees participate, interacting with the guest scientists. It was obvious to see how supportive MJ had been with her lab members and how much they loved her. Although MJ had left us prematurely, her legacy remains. She will be missed forever.
IIBB/CSIC/CIBERNED
I consider MJ a great scientist whom I admired even more after I met her. We first met in Steamboat, at the Winter Conference on Brain Research. I was impressed by the clarity and depth of her thinking, as well as her vitality and resilience. I shared her critical spirit and her passion for science. She helped me with advice and both critical and positive reviews of our work. I am deeply sorry to hear of her loss and send my condolences to her friends and family. I know that her mentorship of generations of scientists and her contributions will endure.
University of Wisconsin-Milwaukee
My collaboration with MJ arose from random chance—a grad student met MJ at a meeting and thought we should connect. That led to many perplexing and sometime exasperating phone calls as we wrote our first Alzheimer's Association grant and I started to learn how MJ worked. To my surprise, we got the grant and were soon in the thick of our first studies, with me wondering what I'd gotten myself into. But we quickly settled into a groove, and I started to appreciate that her assertiveness, high standards, and the 24/7 work ethic that reflected passion, brilliance, and an all-consuming desire to do the best science possible. When we applied for a subsequent Alzheimer's Association grant last year and she decided we should completely rewrite it in the final days before the deadline, it didn't faze me at all—that was just MJ doing what she thought was best, and she was right.
When we started writing our first paper together, MJ didn't hesitate to tell us what was wrong with it and had us extensively rewrite and graphically illustrate the results (using her symbols and color scheme of course!) in a way that, in retrospect, was more clear and simple. When the paper was accepted, we wrote two more in exactly the same style so we didn't have to incur her writing wrath yet again. :)
Despite being separated by just 90 miles, MJ and I didn't meet in person for two years after we started collaborating. That meeting occurred at an ASN conference in California, where I was immediately engulfed by all the good that was MJ—her humor, wit, warmth, generosity, and willingness to indulge in treats like the cupcakes at the bakery next to the hotel.
Underneath her tough outer shell, MJ was a softie at heart. She was tough on her lab "kids" and her collaborators, but once you were in her "family" she would go to the mat for you. She was a generous and kind host, insisting I stay with her during AAIC in Chicago, throwing a party for our labs during SfN in Chicago, and inviting me down for a talk at UIC, among other things. At all times, she and her beloved cats were consummate hosts.
As others have said, MJ was unique. I've never met anyone like her and truly value our scientific and personal friendship. I am devastated that there will be no more crazy unexpected phone calls, texts, or evenings gazing at the Chicago skyline from her balcony. I have yet to fully comprehend that she's gone and take some solace from continued collaboration with Leon and her lab on our Alzheimer's project. I will miss her terribly and am fortunate to have been pulled into her orbit.
Indiana University School of Medicine
Like many friends and colleagues, I was surprised and saddened to hear about the unexpected passing of Mary Jo LaDu, so untimely! Mary’s seminal contribution to the apolipoprotein (ApoE) field is well-known.
I first met Mary at a Society for Neuroscience meeting and was deeply impressed with her ApoE studies. I learned immeasurably from her about the role of ApoE isoforms on LTP, and, later, its role in glial activation (Trommer et al., 2004; Rodriguez et al., 2014), topics she made quite fascinating.
Mary and I had warm and wonderful interactions, specifically when my lab was working on APOE gene regulation comparing the APOE gene promoter, where we reported significant differences between humans and rodents I sought her advice and to my delight, she was intrigued and supportive of our work (Maloney et al., 2007). In those days, pre- and post-transcriptional (e.g., microRNA) gene regulation were not hot topics and, consequently, obtaining NIH funding was difficult. Mary's creative mind did see their potential and later on, in collaboration with John Hardy’s group, we elucidated the functions of three SNPs in the human APOE promoter that were not present in mouse Apoe sequences (Maloney et al., 2010).
Our best times were at Study Section meetings. Section members were seated alphabetically, so we were seated next to each other and I had a great opportunity to see her creativity firsthand. Unlike my shyness, her comments on the proposal were thoughtful, provocative and sometimes "blunt”—all helpful to move the field forward.
In our personal interaction, I found Mary to be kind and witty. We will sorely miss her, and her legacy will remain.
References:
Trommer BL, Shah C, Yun SH, Gamkrelidze G, Pasternak ES, Ye GL, Sotak M, Sullivan PM, Pasternak JF, LaDu MJ. ApoE isoform affects LTP in human targeted replacement mice. Neuroreport. 2004 Dec 3;15(17):2655-8. PubMed.
Rodriguez GA, Tai LM, LaDu MJ, Rebeck GW. Human APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Aβ deposition. J Neuroinflammation. 2014 Jun 19;11:111. PubMed.
Maloney B, Ge YW, Alley GM, Lahiri DK. Important differences between human and mouse APOE gene promoters: limitation of mouse APOE model in studying Alzheimer's disease. J Neurochem. 2007 Nov;103(3):1237-57. PubMed.
Maloney B, Ge YW, Petersen RC, Hardy J, Rogers JT, Pérez-Tur J, Lahiri DK. Functional characterization of three single-nucleotide polymorphisms present in the human APOE promoter sequence: Differential effects in neuronal cells and on DNA-protein interactions. Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):185-201. PubMed.
Zhu Y, Nwabuisi-Heath E, Dumanis SB, Tai LM, Yu C, Rebeck GW, LaDu MJ. APOE genotype alters glial activation and loss of synaptic markers in mice. Glia. 2012 Apr;60(4):559-69. PubMed.
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