BOSTON—The Evelyn V. Hess Award is presented annually by the Lupus Foundation of America (LFA) to a researcher who has made outstanding contributions to the understanding of lupus, its diagnosis and treatment. The presentation was made on Nov. 17, 2014, during a reception at the ACR/ARHP Annual Meeting in Boston. Gary S. Gilkeson, MD, a professor of medicine/microbiology and immunology at Medical University of South Carolina in Charleston, introduced the winners:
“If you have been in attendance at the Hess Awards these past years, you have heard us talk about Dr. Hess’ many professional achievements.
“We are all indebted to Dr. Hess’ contributions that have helped shape our understanding of lupus, which includes the connection between the environment and lupus. Dr. Hess has led by example, and by doing so has shown that one person can make a difference. We are grateful for Dr. Hess’ years of research and her commitment to patient care.
“Dr. Hess was not able to make it to ACR this year. Her imprint on the field and lifetime achievements, along with the countless people whose lives have been impacted by her work and her mentoring, prompted the LFA to establish this award in her honor 10 years ago.
“This year, for the first time ever, we have two Hess awardees. They are Dr. Jane Salmon and Dr. George Tsokos.”
About Dr. Salmon
“Dr. Jane Salmon graduated Magna Cum Laude from New York University and earned her medical degree from the College of Physicians and Surgeons at Columbia University, where she was the first woman enrolled in their medical scientist training program.
“She continued her training in internal medicine at the New York Hospital and in rheumatology at the Hospital for Special Surgery (HSS), where she has been a faculty member since 1983. She is currently the Collette Kean Research Professor at HSS and a professor of medicine and professor of obstetrics and gynecology at Weill Cornell Medical College.
“During her training, Jane worked under the mentorship of Dr. Robert Kimberly, characterizing the function of FC receptors for immunoglobulins on lupus immune cells. Jane made the major discovery that a genetic variation of the FC-gamma receptor was an inheritable risk factor for lupus nephritis in African Americans. This was the first time a genetic variation of an immune cell receptor was associated with lupus.
“This finding was truly a game changer. As her colleague, Dr. Jill Buyon, noted, ‘Current and future insights into the reasons for disparities in nephritis may be provided in part by Jane’s discovery of these genetic variations. Jane was truly ahead of the curve in thinking about the structure and function of genes in lupus.’
“Jane then went on to redefine the standard of care for pregnant women with lupus with her paradigm-shifting translational research in pregnancy and antiphospholipid antibodies. Jane’s findings from her novel mouse model went against the long-held thought that thrombosis was the main culprit of complications and fetal loss in women with lupus and antiphospholipid antibodies. Instead, Jane’s seminal work demonstrated that complement activation, not thrombosis, was the major cause of placental dysfunction and fetal loss in these women.
“Jane took her initial groundbreaking results and initiated a novel, multicenter prospective clinical trial we all know as PROMISSE, or the predictors of pregnancy outcome: biomarkers in antiphospholipid antibody syndrome and systemic lupus erythematosus study.
“Jane and her team have prospectively collected data from more than 700 women across 10 centers in the U.S., Canada and the UK, making it the largest ever study on pregnancy loss and lupus.
“Jane’s hard work has made a major impact on the field, providing insights for clinicians, for women with lupus who are or may become pregnant one day, and for their babies.
“We would be remiss tonight if we didn’t talk about Jane’s commitment to training the next generation of investigators. Jane shares Dr. Hess’ philosophy about the need to mentor and advance physician scientists in their research work and in academic medicine.
“She is a role model for both young women and men embarking on careers in medicine and science. Her legacy of training young lupologists is deep. Many of her mentees have gone on to rheumatology faculty positions, focusing on lupus research.
“Jane has served on the Board of Directors of the American College of Rheumatology and on the NIH advisory boards for the North American Rheumatoid Arthritis Consortium and the Lupus Multiplex Registry. She was co-editor of Arthritis & Rheumatism and is currently an associate editor of the Annals of Rheumatic Diseases, as well as Lupus Science and Medicine.
“Jane has received a number of awards for her outstanding contributions to the field. Among them are the Virginia Kneeland Frantz Award for Distinguished Women in Medicine, and The Carol Nachman Prize in Rheumatology. Now, Jane can add the Hess Award to the list.”
Dr. Salmon Talks about her Research on Lupus & Pregnancy
Dr. Salmon then took the stage to accept the award:
“I am humbled to have been selected to receive the Evelyn V. Hess Award—and immensely grateful for the recognition of my contributions to lupus research by my peers. I also want to acknowledge the LFA. All of us here are grateful for their commitment to the lupus community.
“I first met lupus patients as a rheumatology fellow at HSS. They were my age and faced a mysterious and terrifying disease and a very uncertain future. I felt a kinship with these women. At that time, not so long ago, little was known about lupus, few therapies were available, and lupus research was in its infancy. Indeed, diseases that predominantly affected women were largely overlooked.
“Nonetheless, patients with lupus came to HSS because they knew we were interested in understanding their illness. They are our indispensable partners in research. The thousands of blood samples they donated are a storehouse of data waiting to be deciphered, of mysteries waiting to be solved. This collection enabled us to perform one of the earliest studies of a candidate gene in SLE. We identified variants of FcRII, the first non-MHC genes that could predict severity of disease. We also described the marked increase in prevalence of preclinical atherosclerosis in young women with lupus, an area of intense study by many of you.
‘Patients with lupus came to HSS because they knew we were interested in understanding their illness. They are our indispensible partners in research.’
“But there was more to know. When I tell a woman that she has lupus, one of her first questions is, ‘Doctor, will I be able to have children?’ For many years, we thought that pregnancy caused lupus to flare and should be avoided. This recommendation, however, was not based on strong data, and we knew that some women with lupus had uncomplicated pregnancies, while others had miscarriages or preeclampsia.
“To understand the mechanism of pregnancy failure in lupus, we developed a model of the disease in mice. It was a new area for me, and, perhaps because I approached it without a bias, I could test and prove a hypothesis that challenged long-held dogma. We showed that inflammation, particularly complement activation (and not thrombosis), was a key mediator of poor pregnancy outcome in APL-treated mice. We also found that drugs that block complement could prevent fetal death, growth restriction and preeclampsia in mice.
“But, of course, the ultimate goal of the mice experiments was to help patients. The first step in applying our findings to lupus patients was to identify those destined for poor pregnancy outcome. Lupus is not a common disease. Pregnant lupus patients are less common, and those willing to participate in studies, even harder to come by. Moreover, we had to convince the NIH that a large, multicenter study, expensive study was likely to yield markers that predicted outcome. Here, I was fortunate that foundations (Alliance for Lupus Research) and individual donors—most generously Kit and Arnie Snider who funded the MKCLC at HSS—supported preliminary studies that made possible a compelling proposal, one that was awarded federal funding. I must thank Susana Serrate-Sztein of NIAMS, a dedicated and visionary steward of the public trust, for believing in us and helping us gain permission to submit what some could have been construed as an audacious proposal to NIAMS.
“The PROMISSE study has exceeded my expectations for success in enrolling patients and generating important new information. Over 11 years of funding, $14 million all told, we studied 755 pregnant patients monthly. They were recruited at eight centers in the U.S. and Canada, and from them, we collected nearly a quarter-million samples. Ours is the largest prospective study of lupus pregnancies.
“PROMISSE taught us that pregnancy in lupus patients with quiescent disease is safe. This reassuring finding will enable physicians to counsel patients about how to time pregnancy. PROMISSE also allowed us to identify biomarkers that, early in pregnancy, predict life-threatening complications for mother and fetus.
“Now, 12 years later, I am poised to take the next step, a trial to prevent poor pregnancies in patients we know to be at very high risk. We propose to administer drugs that inhibit the inflammatory pathways we characterized in mice. It is still a dream that I will work to fund and to implement.
“Just as PROMISSE has proved life changing for patients, it has been life changing for me. I had the privilege of assembling and working with an astounding multidisciplinary team, a cohesive, collaborative group. Jill Buyon has been my partner in this endeavor for all 11 years. She shared her knowledge from the SELENA trial and heart block registry. Her passion for lupus patients is unmatched. Mimi Kim, our statistician and methodologist, maintained the rigor of PROMISSE. Ware Branch was the voice of obstetrics in a sea of rheumatologists; he actually delivered PROMISSE babies. Mike Lockshin, Lisa Sammaritano, Michelle Petri, Joan Merrill, Eliza Chakravarty and Carl Laskin enrolled patients and made sure they were seen every month. And the heart of the study, Marta Guerra, is the project manager, without whom there would be no PROMISSE.
“My career has been deeply influenced by many people. The community of lupus clinicians and investigators embraced and nurtured me. Charles Christian, who somehow thought I had promise as a scientist, and Bob Kimberly, in whose lab I conducted my first experiments, were important early scientific mentors. From Mike Lockshin I learned about the complexity of lupus. He was my guidepost as I embarked upon studies in APS and pregnancy. From her perch in California, 3,000 miles away, Bevra Hahn inspired and encouraged me. Mike Holers taught me about complement. Ellen Ginzler, John Reveille and Chela Alarcon shared patient samples for our first genetic studies and taught me that large collaborative teams were necessary and possible. And with John Harley we confirmed the association of FcRs variants with SLE.
“I want to thank Peggy Crow, with whom I have worked since fellowship, for inspiring me with her generosity to our community, for her leadership, wisdom and dedication to the scientific mission. She is a role model we would do well to emulate.
“I am grateful to the ACR, where I was schooled in leadership and where I met physician-scientists and clinicians who continue to inspire and collaborate with me.
“And every day, I thank lupus patients and the stakeholder organizations (Lupus Foundation of America, Alliance for Lupus Research and Lupus Research Institute) for being our partners—participating in studies, fundraising for research and advocating for SLE to our government officials.
“I want to close by acknowledging the most important people in my life. My days are enriched by my husband, Jerry Gliklich, who values my work and shares my passion for medicine, and my children, who still think that having a physician-scientist for a mom is cool. When they were young, they would come home from school and ask, ‘Mom, what did you discover today?’
“Of course, discoveries are hard to come by, they don’t occur every day. Nevertheless, if we, the lupus community, commit to working together, if we share our successes and resources, and if we mentor and empower young physician-scientists, many important and life-altering discoveries lie in our future.”
About Dr. Tsokos
Dr. Gilkeson also introduced Dr. Tsokos:
“Dr. George C. Tsokos began his distinguished career at the University of Athens, where he received his medical degree. He went on to complete his medical residency at the University of Athens and Georgetown University in Washington, D.C., and his rheumatology and clinical immunology training at the National Institutes of Health.
“George spent much of his career as a member of the Uniformed Services and Walter Reed community, where he served in various positions, including vice chair for research in the Department of Medicine and Chief of the Department of Cell Injury.
“In 2007, George joined Beth Israel Deaconess Medical Center as chief of rheumatology and Harvard Medical School as professor of medicine. Upon his arrival, he set out working to build a comprehensive Lupus Center of Excellence.
“George is recognized as one of the leaders of modern lupus research. Although it is now widely acknowledged that abnormalities in T cell signaling play a role in the development of lupus, that was not the case when George began his career more than 30 years ago.
“George’s seminal studies in T cell signaling went against the popular belief that B cells were the only immune cells involved in lupus. His early research described the presence of activated T cells and the lack of antigen-specific suppressor cells in patients with lupus.
“George was the first to show that engagement of the T cell receptor–CD3 complex in T cells triggers abnormal signaling responses. Pursuing this observation, George discovered that inhibition of the signaling molecule SYK in mice contributed to lupus. These findings have led to the development of highly innovative therapeutic interventions targeting the SYK gene in patients with lupus, which are currently in clinical trials.
“Also in his early discoveries, George’s laboratory showed that lupus T cells have decreased production of interleukin 2 and an increased production of interleukin 17. He has pioneered studies to understand the science behind this phenotype.
“And in 2013, George received an NIH Merit Award to continue his work characterizing the biochemical and molecular events that lead to decreased interleukin 2 production in lupus patients. The prestigious NIH Merit Award is given to less than 5% of NIH-funded investigators and will last for an extended cycle of 10 years instead of the typical five years for an R01.
“George is the consummate translational researcher. To echo what lupus research Dr. William Stohl said of George in 2010, ‘George truly understood the concept of translational research long before it became a fashionable phrase, and he has lived by the bench-to-bedside and bedside-to-bench credos for the past 30 years.’
“In addition, George has a distinguished teaching career; his trainees have become leaders of rheumatology departments in the U.S. and worldwide.
“George is a tireless crusader for the organizations he supports. He has been a longtime active member of the LFA’s medical and scientific advisory council. Just last month, George attended the LFA’s Walk to End Lupus now here in Boston, where he not only formed his own team, but also spoke to patients, caregivers and other clinicians about the need to find new and safer treatments for this disease.
“George has served on editorial boards of dozens of scientific journals, including the Journal of Clinical Investigation, the Journal of Immunology and the Journal of Clinical Immunology. He has chaired numerous committees of the American College of Rheumatology and has been a member of the Board of Directors of LFA. Dr. Tsokos has been elected to the Association of American Physicians, and he is also a Fellow of the American Association for the Advancement of Sciences, as well as a Master of the American College of Physicians.
“Ultimately, George’s T cell studies have paved the way for lupologists today to better understand the underlying mechanisms of immune dysfunction in lupus.”
‘You can accomplish more through elegant pursuit than through aggressiveness & feistiness.’
Dr. Tsokos Calls for Action
Dr. Tsokos made a call for action during his acceptance:
“This is indeed a special honor for me, and I want to thank the Lupus Foundation of America for choosing me. I want to thank all my colleagues whose work is honored today. Sharing it with my friend Jane increases the honor.
“I started working with the LFA as a member of the Medical and Scientific Board in 1991, and from 1995 to 2004 Jenny Palter and I edited Lupus News, which became Lupus magazine.
“In 2001, I was elected to the Board of Directors. It was at that point that I worked closely with Evelyn Hess. From Evelyn, I learned that you can accomplish more through elegant pursuit than through aggressiveness and feistiness—I won’t tell you who was the aggressive one. In 2004, we appointed Sandra [Raymond] to lead LFA. The rest, as they say, is history.
“Max Perutz is my hero. Born in Austria to a rich family (they were in the chemical industry), he studied chemistry and was destined to pick up the family business. In 1936, he decided, to his parents’ chagrin, to pursue a PhD at the Cavendish Laboratory at Cambridge. He elected to reveal the structure of hemoglobin using crystallographic approaches. He stayed absolutely focused, and in 1963, he received the Nobel Prize.
“I want to stress the importance of staying focused, and this is true more for those of us in lupus research. I have tried to imitate Max Perutz and conduct research solely to understand the biochemistry of the lupus immune cells, keeping a deaf ear to the fashion sirens—such as GWAS, microbiome and so on. This award may indicate that I walked the line.
“In 1949, Max Perutz walked away from Bragg’s office (Bragg was the director of the Cavendish lab and a Nobel laureate at the age of 25) absolutely irritated and angry. A month later, he walked back into Bragg’s office with a picture proving 3.6 amino acids per turn in the alpha-helix generating 1.5—a parallel distance.
“Max would write later an autobiographical book, I Wish I Made You Angry Earlier.
“What is my point? I think that we, in lupus research, are docile, expecting a miracle to happen. And I think:
- Shouldn’t we be angry that we refer to lupus as a mystery disease?
- We should be angry that we do not understand its complexity, that we do not have tools for early diagnosis and that we do not have tools to follow disease activity.
- Shouldn’t we be angry that HMOs and insurances companies and hospitals tell us to deal with a myriad of problems each lupus patient has in 20 minutes?
- Shouldn’t we be upset that lupus philanthropy is scarce?
- Shouldn’t we be angry that federal funds for lupus are limited and dwindling?
“I think it is time do something similar to what a few Boston ladies did 250 or so years ago in this port, and they did what they did for a few tax dollars. We have something more serious in our hands—the lives of so many lupus patients.”
