Portal de Periódicos da CAPES

In memoriam: Judith A. Berliner, Ph.D.

2022; Elsevier BV; Volume: 63; Issue: 4 Linguagem: Inglês

10.1016/j.jlr.2022.100180

1539-7262

Mete Civelek, Alan M. Fogelman, Catherine C. Hedrick, Aldons J. Lusis, Casey E. Romanoski, Joseph L. Witztum,

Genetics, Bioinformatics, and Biomedical Research

Judy was born in Cincinnati, Ohio in September of 1939. Her fascination with science began when she attended middle school in Cincinnati, and this desire and love of science propelled her toward a lifelong pursuit of discovery. She studied at the University of Michigan in Ann Arbor, where she obtained her Bachelor of Science degree in zoology (with Honors) in 1961 and her Master’s degree in Zoology in 1964. She married her husband of 60 years, Michael Berliner in 1961, and their daughter, Dana, was born in 1967. She continued her education at Brown University, where she obtained a Ph.D. in Cell Biology in 1969. Her thesis was on “The effect of the epidermis on the basement lamella of anuran larval skin”. Judy began her professional career in science as a postdoctoral fellow in 1969, working with Dr Joel Rosenbaum at Yale University, in the Department of Biology studying the isolation and electrophoretic analysis of microtubules, matrix, membranes, and mastigonemes in Chlamydomonas flagella. She then moved to the West Coast, landing at UCLA for a postdoctoral fellowship in 1970, and joined Dr Larry Simpson’s laboratory where she worked on the characterization of kinetoplast DNA networks isolated from Leishmania tarentolae. She loved the collegiality of UCLA so much so that she never left. When she finished her postdoctoral fellowship with Larry Simpson, she worked with Mayer Davidson as an Assistant Research Endocrinologist studying the effects of insulin on carbohydrate metabolism and the effects of glucocorticoids on cultured cells. In 1973, she joined the UCLA Department of Pathology as an Assistant Professor, with a joint appointment as a Research Electron Microscopist in the Laboratory of Nuclear Medicine and Radiation Biology. Judy rose through the ranks to become Professor of Pathology, and she remained as an active faculty member until retirement. Judy was among the female pioneers of the atherosclerosis field (Fig. 1). She often described those early days attending national conferences, where she was often the sole female attendee, to her female mentees, including C.H. She found it sometimes lonely, sometimes amusing, sometimes intimidating, but she never allowed such feelings to dampen her enthusiasm or pursuit of scientific knowledge. She quietly spoke of the confidence that it gave her to strive for success in those early years as a woman scientist, and she wisely used the stories of these adventures to mentor C.H. and many other female mentees on self-confidence, career–family challenges, and the lifelong pursuit of scientific excellence. Many of these female trainees respected her strength, knowledge, and incredible integrity. As evidence for the tremendous wisdom that she imparted to her female trainees, in 2007, Judy was awarded the Outstanding Mentorship of Women Award from the Arteriosclerosis Thrombosis and Vascular Biology Council of the American Heart Association. Judy also was awarded the UCLA Woman of Science Award in 1993 and the American Heart Association Distinguished Scientist Award in 1997. Among Judy’s many scientific contributions, the identification of oxidized phospholipids (oxPLs) as key mediators of the biological effects of oxidized LDLs stands out. It set the stage for all to come in that area—there are now greater than 22,000 citations that appear in PubMed under term “oxidized phospholipids.” Judy was a founding member of a long running Program Project Grant headed by Alan Fogelman. Alan was a supportive mentor and collaborator, and together, they authored 43 publications. Together with other members of the grant, Judy examined mechanisms by which oxPLs induced monocytes to bind to endothelial cells and then enter the intimal layer of the vessel wall. In the late 1980s, she played an essential role in the identification of some of the earliest molecular events in the initiation of atherosclerosis, including the induction of colony stimulating factors and monocyte chemotactic protein (Fig. 2). In the mid 1990s, she and her graduate student Andrew Watson carried out key mass spectrometry analyses that identified individual oxPLs with biologic activity. In the late 1990s, Judy worked in collaboration with the group led by Dr Joe Witztum to identify the structural characteristics of biologically active oxPLs. Despite initially puzzling data, they together discovered that a naturally occurring antibody E06 recognizes the oxidized phosphocholine moiety of oxPLs, yet fails to recognize unoxidized phosphocholine. Interestingly, apoptotic cells present this epitope, raising interesting speculation about the evolutionary origins of oxPLs in eliciting immune responses. They also provided evidence that oxPLs, or oxPL-apolipoprotein B adducts, were involved in the uptake of oxidized LDL by scavenger receptors on macrophages. In the 2000s, Judy focused on understanding the interactions of oxPL with vascular cells. Among these important findings were the recognition of pathways such as the unfolded protein response in the activation of endothelial cells. Despite the proinflammatory effects of oxPLs on vascular cells, direct proof for the oxidation hypothesis of atherosclerosis has been difficult to obtain, and the fact that some “antioxidant” drugs have failed to reduce atherosclerosis has caused some to conclude that alternative mechanisms, such as aggregated LDL, are the triggers for inflammation. Recently, the monoclonal antibody E06 has proven invaluable for the realization that oxPL are a near-ubiquitous feature of inflammatory diseases including atherosclerosis, NASH, arthritis, osteoporosis, valvular calcification, lung fibrosis, and more. As Judy predicted, oxPLs appear to drive atherosclerotic progression, as shown by transgenic expression of E06 in athero-prone mice, which results in decreased atherosclerosis compared to nontransgenic controls. E06 transgenic mice also exhibit attenuated inflammatory disease burden including in the mouse models of NASH, myocardial ischemia-reperfusion, osteoporosis, and more. While the prevalence and importance of oxPLs are becoming increasingly evident, the cellular and molecular consequences of oxPLs elicit are just beginning to be elucidated, and much remains to be learned.. Future work in the field of oxPLs will be greatly facilitated by the foundation of knowledge and tools that Judy established over her career. In addition to being an exceptional scientist, Judy was a dedicated and supportive mentor to many trainees including three of the authors during their PhD (C.E.R.) and postdoctoral fellowships (C.H. and M.C.). Many of her former trainees have established their own independent scientific careers. When one trainee, Dr Rama Natarajan from the City of Hope, was a junior scientist in the late 90’s, Judy ensured that she served on the Path A study section to give her the experience and professional recognition that comes from working with colleagues from around the country. Another mentee, C.H., who worked with Judy in the mid 90’s, said: “Judy followed my career long after I left UCLA. She would ‘checkin’ with me on a regular basis to see how I was doing. Her mentoring of me continued until she became very ill. I remember asking her in 2008 about whether I should refocus my research toward immunology, and she assured me that I had both the drive and ability to do so successfully. She gave me that extra boost of confidence that I needed in order to make the switch. She was always there for us and genuinely eager to help”. Dr Farhad Parhami, who did his Ph.D. with Judy between 1990 and 1994, said: “Judy was the most incredible mentor that gave me the tools I have used in my career to succeed. She protected me from the beginning from everything that would come my way during the times that I was in her lab and then throughout my career at UCLA. I will value all that for the rest of my life.” Another mentee, Dr Norbert Leitinger, said the following about Judy, “The most impactful event in my work life happened when I met Judy Berliner at a conference in Montreal and she offered me to join her lab at UCLA. I had the privilege to work and learn from Judy during the years of 1995–1998. Judy was a wonderful person, a remarkable scientist, and a great mentor. Her work ethic was inspiring and her honest approach to mentoring is a leading example for me still today. Judy taught me how to become a researcher and she would continue to support my scientific career even later when I had my own lab. Investigations on the biological functions of oxidized phospholipids that were pioneered by Judy Berliner have inspired many researchers across the globe and are still a major focus of my own research.” These quotes nicely illustrate how Judy’s mentoring has had a positive influence on the career trajectories of her mentees. When Judy’s former trainees find themselves together at conferences, they love to speak warmly of ‘the good old days’ in Judy’s laboratory. What set her apart? It is difficult to describe. C.E.R. comments on one important attribute: “Judy wasted no time getting to the heart of the science or issue that was confusing or murky. She challenged trainees to distill and articulate their scientific message in a way that was simple and clear. In the 2000’s, as projects became more computationally intensive and omics in nature, Judy was not deterred; in fact, she was adamant that the messages hidden in the heatmaps and network graphs be articulated as clearly as possible. To this day, I strive for my work to pass ‘the Judy test’, which I am so grateful to have”. Judy was also a great role model and colleague. She was known to those in the Program Project Grant to be focused, down-to-business, and no-frills. Still, she did not come across as stern or harsh the way driven women are too often projected in our culture. It is unclear exactly how Judy was able to strike such a unique persona. Undoubtedly, her caring, genuine warmth, palpable curiosity, and strive for scientific excellence were recognized and honored by peers and trainees alike. In addition to her love of science, she shared her passions for her loving family and for classical music (especially the Viennese operettas of Emmerich Kálmán) with her trainees. She fondly spoke often of her husband Mike’s studies of philosophy and his work at the Ayn Rand Institute, where he was the founding executive director. She always was so proud of her daughter Dana’s many professional achievements as a distinguished constitutional lawyer, specializing in fighting eminent domain, and glowingly talked often of her. And of course, she loved being Grandma to Dana’s daughter, Lila (born in 2012). Her favorite singer was the German lyric tenor, Fritz Wunderlich, and she loved attending the Los Angeles Philharmonic’s rehearsals at the Hollywood Bowl. Judy (and Mike) avidly pursued many nonscience values, including overnight stays at Frank Lloyd Wright houses and, especially, numerous visits to their beloved Yorkshire Dales, home of James Herriot’s All Creatures Great and Small books.