Maria Dall’Era | Chief of the Division of Rheumatology, University of California, San Francisco (UCSF), USA
Citation: AMJ Rheumatol. 2026; https://doi.org/10.33590/rheumatolamj/AK225Q6X
Your journey in immunology began during your undergraduate years at the University of California, Berkeley, USA, in the laboratory of Nobel laureate James Allison, MD Anderson Cancer Center, Houston, Texas, USA. How did that early immersion shape your scientific curiosity as you transitioned to the University of California, San Francisco (UCSF), USA, and what specific clinical encounter during your training convinced you to dedicate your career to systemic lupus erythematosus (SLE)?
I became enthralled by the human immune system during my undergraduate years and had the pleasure of working in several immunology labs on campus. These experiences taught me how to think in a mechanistic way and form and test hypotheses with scientific rigor. During my last year, I was excited to work in the lab of James Allison with brilliant people who were asking fundamental questions about the pathways of T cell activation and how to harness those pathways in ways that could be beneficial in treating disease. The lab was studying the function of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in restraining T cell activation. These early experiments set the stage for the groundbreaking development of anti-CTLA-4 and the revolutionary therapy of ipilimumab. Fast forward several years, when I entered fellowship at UCSF, I had the privilege of working with my mentor, , Professor of Medicine and Microbiology/Immunology at UCSF, USA, who performed the pioneering studies of CTLA4-Ig to treat murine lupus by suppressing T cell activation. David and I then worked together to study CTLA4-Ig in human lupus nephritis. It is interesting how my research of the immune system has come full circle, manipulating CTLA-4 to either activate or suppress T cell activation. My love for the intricacies and complexities of the immune system, my time with David as my mentor, and my enjoyment of caring for patients with multisystem disease across their lifespan led me to specialize in SLE.
Having witnessed the clinical transition away from highly toxic, broad-spectrum immunosuppressive regimens for severe lupus, what do you see as the next major therapeutic breakthrough needed to achieve a truly steroid-free state of remission? Furthermore, what role do you see for emerging platforms like CAR-T cell therapy in reaching this goal?
This is an exciting and innovative time in lupus drug development. For many decades, we were confined to treating our patients with non-specific cytotoxic or anti-metabolic agents that were ‘borrowed’ from other diseases. These medications have wide-sweeping effects on multiple cell types and lead to many potential toxicities and intolerabilities. However, the tide turned in 2011 with approval of the first biologic agent for the treatment of SLE, belimumab. Next came the approval of anifrolumab and then obinutuzumab. The creation of novel, targeted therapies has been made possible by our improved understanding of the immunologic pathways critical to lupus pathogenesis and major advances in genetic and biochemical engineering. I view the next therapeutic breakthrough as entailing the development of biomarkers to help us understand how to choose the ‘right’ therapy for the ‘right’ patient at the ‘right’ time, including how to safely and effectively combine targeted therapies. Novel approaches such as cellular therapies are groundbreaking in that they offer the hope of ‘immune reset’ or sustained remission off therapy. It is wonderful to have many different therapeutic approaches and clinical trials to offer our patients living with SLE.
Your collaborative study with the Accelerating Medicines Partnership (AMP) detailed serum soluble mediator signatures in lupus nephritis. How close are we to translating these blood-based molecular biomarkers into non-invasive clinical tools that can replace or supplement traditional kidney biopsies for guiding treatment decisions?
The AMP is a remarkable public–private partnership that exemplifies the power of various groups of people working together in a pre-competitive space to answer fundamental questions about mechanisms of disease. The AMP demonstrates the concept of team science at its best. Research emanating from the AMP have led to the creation of the first comprehensive single-cell atlas of lupus nephritis that has given us a window into the complex biology of this disease. Large-scale proteomic studies spurred the discovery of novel urinary biomarkers and serum soluble mediator signatures to predict the histologic class of lupus nephritis, degree of histologic activity and chronicity, and response to therapy. I am optimistic that studies such as this will transform the way we classify, evaluate, and manage patients with lupus nephritis, enabling a more rationale choice of targeted therapies to improve the long-term outcomes of our patients with lupus nephritis. For now, kidney biopsy remains the gold standard for lupus nephritis diagnosis. However, we are looking forward to the day when we are able to offer our patients less invasive, immunologically meaningful biomarker-guided options in their management.
As an educator who received the Clinician Scholar Educator Award, you developed Practice Improvement Using Virtual Online Training (PIVOT) to gamify clinical reasoning for medical What has this digital platform taught you about how the next generation of physicians learn, and how can we best preserve the art of direct patient engagement in a virtual training environment?
One of the most satisfying and joyful aspects of my career is the opportunity to educate the next generation of physicians, including rheumatologists. I am grateful to the Rheumatology Research Foundation for providing me the opportunity to devote time to work closely with a team to develop PIVOT, a mobile learning platform designed to teach clinical reasoning in a fun and exciting way, using gamification. We received a lot of positive feedback from the students that they enjoyed the way in which our application simulated a real patient with SLE, with elements of the patient case unfolding over a series of days. Our students watched videos of real patient interviews and were even able to order laboratory studies and radiology studies through the platform. Plus, we incorporated real-time feedback to the students. This experience taught me that students learn clinical information best when they are actively engaged with the content, solving problems, and repeatedly revisiting the content in different contexts. They appreciate learning through real patient cases such that they see the direct application of the knowledge they are building.
As the Principal Investigator of the CDC-funded California Lupus Epidemiology Study (CLUES) cohort, how has tracking this highly diverse, real-world population challenged the clinical assumptions typically made in controlled industry trials?
I have been honored to work with a diverse group of collaborators within UCSF and at the National Institutes of Health (NIH) over the past 2 decades to run the CLUES cohort. The federal investment of funding for this cohort has been instrumental in our ability to conduct transformative studies to improve our understanding of the genetics and genomics of SLE, along with the drivers of good and poor quality of life and health outcomes in our patients living with SLE. Clinical trials are essential to the study and approval of novel therapies, but longitudinal registries with matched biospecimens (such as CLUES) are critical to studying diverse real-world populations. Over the years, CLUES has given us the opportunity to study questions that are of great importance to patients, such as the role of environmental exposures and stress in the development and worsening of SLE, causes of morbidity and mortality, and the triggers and biology of SLE flares. Unlike the highly selected populations enrolled in clinical trials, observational studies such as this allow us to observe and capture the true experience of the patient journey of SLE.
Through your advocacy work with the Lupus Accelerating Breakthroughs Consortium (ABC), you have championed elevating the patient’s How does actively integrating patients’ lived experiences and self-reported outcomes redefine what we consider a ‘successful’ clinical trial outcome, especially for subjective symptoms like chronic pain and fatigue?
I am privileged to be a part of the Lupus Research Alliance’s Lupus ABC, a public–private partnership involving academic investigators, industry partners, patients living with SLE, regulators, and advocacy organizations. As you mentioned, the patient voice is front and center in this consortium. Over the years, I have learned that patients living with SLE are essential to include in every research program because they inform us about the top priorities and needs facing our patients. At the end of the day, we are all working hard to improve the lives of patients living with SLE. Historically, important issues such as fatigue, pain, and cognitive dysfunction were not the centerpiece of many of our SLE research trials and studies. However, because of the advocacy of brave patients and their families, these manifestations are being given the attention they deserve. It is exciting that one of the projects of the Lupus ABC is to understand how best to capture the patient experience through patient-reported outcomes and how these measurements can be incorporated into clinical trial endpoints.
As the UCSF Division Chief of Rheumatology, you manage a major academic department while continuing to care for hundreds of patients with complex lupus. What is your most critical advice for early-career clinicians trying to balance rigorous academic leadership with compassionate, highly individualized bedside medicine?
This is a thrilling time to be an academic rheumatologist with a multitude of opportunities in our sight, including rapid advancements in our understanding of the mechanisms of disease, the use of AI, and the development of a variety of novel therapeutics targeting virtually every aspect of the immune system. At the same time, clinical needs and pressures are expanding as we seek to provide access to the highest quality care for all the patients who need us. First and foremost, it is critical for early career physicians to listen to their inner voice and follow the questions that intrigue them. Establish a mentoring team who can guide you in each of the missions of the academic environment and utilize all of the resources at your disposal. Always remain humble and continue to be curious. Stay strong and persevere even when things don’t initially work out. Every ‘failure’ is an opportunity to learn, and you will eventually succeed. Build strong relationships with your colleagues and lift others up. Lastly, listen to your patients, as they will tell you the questions you need to study and will always bring you the greatest satisfaction in the work that you do.
