MICHIGAN MEDICINE DIVISION OF RHEUMATOLOGY SPRING 2021

Dear Faculty, Staff, Trainees, Alumni, and Friends,   The Division of Rheumatology is fully committed to the continued development and fostering of diversity, equity, inclusion, and well-being efforts within our Division. Providing an environment where our faculty, staff, and trainees feel valued, safe, and able to thrive is of the upmost importance to myself and our leadership team. We are in strong alignment with the Department of Internal Medicine Office of Equity, Diversity, and Well-Being (ODEW), and have two representatives serving on the ODEW IMPOWER Council - you will find more information about this farther down in this email. Our Division has lots of exciting news to share. We continue to make significant research advances in lupus, scleroderma, APS, gout, fibrosis, COVID-19, chronic pain, immune checkpoints, and other areas. Our faculty garner increasing national recognition, publish high-impact papers, and secure extensive research funding from NIH and other federal and industry sponsors to enable discoveries and clinical innovation. During the past few months, our faculty have participated in numerous conferences and webinars to educate healthcare providers and patients on a range of rheumatic conditions and their complications. Selected recent contributions from our faculty and staff are highlighted below.   I am pleased to announce our upcoming 3rd Annual Update in Rheumatic Diseases Conference, chaired by Dr. Dinesh Khanna. This live webinar, held on Saturday and Sunday, May 22-23, 2021, will feature experts from Michigan Medicine, and three guest speakers with support from the Bruce C. Richardson Lecture. This lectureship honors Dr. Richardson's pioneering contributions to understanding the role of epigenetics in rheumatic diseases. Learn more and register. I hope you will join us!   I want to express my gratitude to our talented and dedicated faculty, staff, and trainees. This past year has been unlike no other, with unprecedented challenges. Our team has been resilient, and I am inspired with its unwavering commitment to excellence in patient care, education, and research. I am thankful and proud to lead this amazing team.   To stay current on our work in patient care, research, and education, please regularly visit the Division of Rheumatology website. As always, we welcome your comments and suggestions - please send an email to umrheumatologydivision@umich.edu. Sincerely,   John Varga, MD Chief, Division of Rheumatology Frederick G. L. Huetwell Research Professor of Rheumatology Professor of Internal Medicine Professor of Dermatology

In the News

Tocilizumab Approved for the Management of Scleroderma-Related Lung Fibrosis On March 4, 2021, the Food and Drug Administration (FDA) approved tocilizumab for the management of scleroderma-related lung fibrosis. Dinesh Khanna, MD, MSc led the drug development with Genentech/Roche Group over the past decade and was the lead investigator for the phase 2 and phase 3 trials: Phase 2 Trial: Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate): A Phase 2, Randomised, Controlled Trial Phase 3 Trial: Tocilizumab in Systemic Sclerosis: A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial Read the press release. Dr. Dinesh Khanna and his team’s work on the phase 3 trial was highlighted in Protein Linked to Progressive Lung Scarring in Scleroderma Patients and Repurposing Tocilizumab in Scleroderma Patients May Prevent Early Lung Disease.

Prothrombotic Autoantibodies in Serum from Patients Hospitalized with COVID-19 The study, Prothrombotic Autoantibodies in Serum from Patients Hospitalized with COVID-19, conducted by Yu (Ray) Zuo, MD; Jason Knight, MD, PhD; and team, finds that a significant percentage of patients hospitalized with COVID-19 had autoimmune antiphospholipid antibodies, likely contributors to the increased risk of blood clotting inherent to severe COVID-19. The publication has been featured in over 95 news outlets and 9 blogs, including the NIH Director’s Blog, Time, Jama Network, and Michigan Medicine Health Lab. Dr. Ray Zuo presented this study and their findings on JRNLclub. Watch the video. This paper was also selected as one of 64 entries across the country to compete in this year's STAT Madness, an annual online bracket-based competition that recognizes the best innovations in biomedicine. Their paper advanced to round #2 in the competition.

National Research Effort Discovers Relationship Between Inflammation, Metabolism, and Scleroderma Scarring John Varga, MD and team find NAD+ break down leads to multi-organ scarring, providing now a previously undiscovered pathogenic role of the enzyme CD38 in disease scarring. Read more.

Cancer Immunotherapy May Also Treat Certain Autoimmune Diseases David Fox, MD and team find that disrupting the interaction between cancer cells and certain immune cells is more effective at killing cancer cells than current immunotherapy treatments. Read more.

Identifying Disease Pathways Offers Hope for More Personalized Medicine in Pediatric Rheumatology Jessica Turnier, MD and J. Michelle Kahlenberg, MD, PhD find that although juvenile myositis and lupus share an inflammatory pathway, its their pathophysiological differences that may serve as diagnostic biomarkers in future studies. Read more.

Subset of COVID-19 Patients Have Increased Bleeding Risk Yu (Ray) Zuo, MD; Jason Knight, MD, PhD; and team identify a potential clinical biomarker for high bleeding risk and poorer outcomes in COVID-19. Read more.

Ginger Counters Certain Autoimmune Diseases in Mice Ramadan Ali, PhD and Jason Knight, MD, PhD discover that the main bioactive compound of ginger root helps halt disease progression in mice with antiphospholipid syndrome and lupus. Read more.

Reducing the Immunogenicity of Pegloticase in Patients with Refractory Gout Puja Khanna, MD, MPH reviews the presentation she gave at the American College of Rheumatology Convergence 2020 on reducing the immunogenicity of pegloticase and improving its efficacy. Read more.

Research Group Identifies Potential Therapeutic Target for Lupus Gautam Sule, PhD, Jason Knight, MD, PhD, and team find that inhibiting IRE1α, a molecule activated by the endoplasmic reticulum in neutrophils, counters disease progression in lupus mice. Read more.

Faculty Features in Hometown Papers

From Mowing Lawns to the Research Lab: Southwood Grad Leads Study in Autoimmune Disease Jason Knight, MD, PhD discusses his current research, and the education and teachers he had while growing up that had an impact on him. Read more.

Local Epidemiologist Is a Rock Star in Science's Intense Battle to Contain COVID-19 Emily Somers, PhD, ScM discusses her COVID-19 research work and her role in helping the medical community and schools grow safer. Read more.

Faculty Spotlight - Dr. Zeinab Saleh

Zeinab Saleh, MD is a Clinical Assistant Professor in the Division of Rheumatology. Dr. Saleh received her medical degree from Lebanese University in Fanar, Lebanon, and completed her residency and fellowship at Tufts Medical Center in Boston, Massachusetts. Dr. Saleh joined Michigan Medicine in 2016 and cares for patients at the Northville Health Center Rheumatology Clinic. Learn more about Dr. Saleh.

Awards, Honors & Recognition

Congratulations to Jason Knight, MD, PhD, the recipient of this year's Lupus Foundation of America Mary Betty Stevens Young Investigator Prize.

Congratulations to Beth Wallace, MD, MSc who was promoted to Assistant Professor of Internal Medicine.

Skin Biology and Diseases Resource-Based Center (UM-SBDRC) Virtual Annual Symposium The below Division of Rheumatology faculty and staff received Poster Presentation Awards at the 2021 University of Michigan Skin Biology and Diseases Resource-Based Center (UM-SBDRC) Virtual Annual Symposium. Second Place "A20 and Its Repressor DREAM Expression Govern Susceptibility to Fibrosis in Systemic Sclerosis (SSc)" - Swarna Bale, Swati Bhattacharyya, John Varga "Novel Targeting of Intracellular Fibro-inflammatory Kinases TAK1 and IRAK4 for the Treatment of Systemic Sclerosis" - Swarna Bale, Swati Bhattacharya, John Varga Third Place "Interferon Alpha Promotes Extrinsic Apoptosis of Keratinocytes Following Exposure to Ultraviolet B Radiation" - Shannon Estadt, J. Michelle Kahlenberg "Interferon Kappa Enhanced Psoriasis Disease Severity" - Mehrnaz Gharaee-Kermani, Shannon Estadt, J. Michelle Kahlenberg

Deeba Minhas, MD and Gail Quaderer were selected as division representatives for the Department of Internal Medicine Office of Diversity, Equity, and Well-Being IMPOWER Council. The IMPOWER (Inspiring Medicine to Promote Opportunities for Well-being, Equity and Diversity) Council is comprised of faculty and staff representatives from every division and was created to facilitate multidirectional communication and support initiatives to drive culture change.

New Appointments

Welcome to the below faculty members who recently received appointments in the Division of Rheumatology. We look forward to sharing our faculty recruitment updates in the next issue. Girish Gandikota, MBBS - Professor of Radiology (primary) and Internal Medicine (secondary) Johann Gudjonsson, MD, PhD - Associate Professor of Dermatology (primary) and Internal Medicine (secondary) Danielle Robinett, MD - Adjunct Clinical Instructor in Internal Medicine, Metro Health Jessica Turnier, MD - Assistant Professor of Pediatrics (primary) and Internal Medicine (secondary)

Patient Care

Can Systemic Scleroderma Affect the Kidneys? Vivek Nagaraja, MBBS was invited to speak at an educational webinar series for people with scleroderma, organized by the Scleroderma Foundation – Michigan Chapter, on February 12, 2021. Dr. Nagaraja discussed kidney involvement in scleroderma and emphasized the risk factors and early indications of scleroderma renal crisis. He also encouraged patients to be advocates of their medical condition and to be aware of all potential organ involvement. The talk will be available for online viewing in Fall 2021.

Scleroderma Program: COVID-19 Vaccine Updates David Roofeh, MD discussed the COVID-19 vaccines and addressed frequently asked questions as part of a patient educational social event hosted by the Scleroderma Peer Mentor Program and Scleroderma Backers. Watch the video.

Provider Education & Training

Connective Tissue Disease-Related Interstitial Lung Disease: Newer Insights Vivek Nagaraja, MBBS spoke at the Division of Pulmonary and Critical Care Medicine Grand Rounds at Banner University of Arizona Medical Center on February 2, 2021. Dr. Nagaraja's talk was aimed to provide a broad overview of the exciting, recent advances in management and therapeutics in patients with rheumatic disease related-interstitial lung diseases (ILD). Dr. Nagaraja also highlighted the new approaches in identifying certain high risk patients who could develop ILD in the context of certain rheumatic diseases.

Lung Fibrosis Congress The 1st International Symposium on Interstitial Lung Disease in Rheumatic Diseases was held virtually on February 19 and 20, 2021. The symposium was chaired by Dinesh Khanna, MD, MSc and Marco Matucci Cerinic, MD, PhD (University of Florence). The meeting attracted over 1,500 attendees from over 55 countries. Learn more.

Upcoming CME Event

Update in Rheumatic Diseases CME Webinar The Update in Rheumatic Diseases CME live webinar, directed by Dinesh Khanna, MD, MSc, will be taking place on Saturday and Sunday, May 22-23, 2021. The objective of the program is to educate healthcare providers on the most up-to-date management and treatment options for different rheumatic diseases with the goal of improving patient outcomes. Learn more and register.

Research & Proposals

Fibrosis Interest Group   The Fibrosis Interest Group was initiated by Eliza Tsou, PhD; John Varga, MD; and Steven Huang, MD (Division of Pulmonary & Critical Care Medicine) in September 2020. Since its establishment, the group has attracted faculty members from many specialties including Internal Medicine, Dermatology, Pathology, Biomedical Engineering, and the Dental School, from the University of Michigan and other institutions. The meetings allow members to brainstorm novel research ideas and promote collaboration and facilitate research among groups. The goal is to build a platform from which researchers in various fields can come together to facilitate research and collaboration in fibrosis.

Vascular Ultrasound for Diagnosis of Giant Cell Arteritis Ora Gewurz-Singer, MD; Julia Ford, MD; and team submitted their project “Vascular Ultrasound for Diagnosis of Giant Cell Arteritis” for this year’s Frankel Cardiovascular Center Innovation Challenge, which was implemented to empower their community of trainees, faculty, staff, patients, and families to propose, test, and implement new innovations. The top teams will pitch their ideas for up to $100,000 in funding on May 20, 2021. Watch their proposal video.

Recent Publications

MARCH 2021 American Journal of Respiratory and Critical Care Medicine Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: A Multi-center, Double-blind, Randomized, Placebo-Controlled Trial   Arthritis & Rheumatology Acupuncture and Knee Osteoarthritis: Does Dose Matter? Arthritis & Rheumatology Dissecting the Cellular Mechanism of Prostacyclin Analog Iloprost in Reversing Vascular Dysfunction in Scleroderma BMJ Open Domains and Outcome Measures for the Assessment of Limited Cutaneous Systemic Sclerosis: A Scoping Review Protocol Current Opinion in Rheumatology Immunopathogenesis of Skin Injury in Systemic Lupus Erythematosus Current Opinion in Rheumatology Practical Management Strategies for Benign Hypermobility Syndromes Expert Review of Clinical Immunology Utilizing Type I Interferon Expression in the Identification of Antiphospholipid Syndrome Subsets JAMA Network Open Association of Anti-Tumor Necrosis Factor Therapy with Mortality Among Veterans with Inflammatory Bowel Disease Urology Including Medical Management in the Urologic Approach to Idiopathic Retroperitoneal Fibrosis FEBRUARY 2021 Arthritis & Rheumatology Genome-Wide Reduction in Chromatin Accessibility and Unique Transcription Factor Footprints in Endothelial Cells and Fibroblasts in Scleroderma Skin Arthritis & Rheumatology A Randomized, Phase 2 Study Evaluating the Efficacy and Safety of Anakinra in the Treatment of Gout Flares Arthritis Care & Research Barriers and Facilitators to Physical Activity for People with Scleroderma: A Scleroderma Patient-Centered Intervention Network (SPIN) Cohort Study Current Opinion in Rheumatology Glucocorticoid and Opioid Use in Rheumatoid Arthritis Management JCI Endoplasmic Reticulum Stress Sensor IRE1α Propels Neutrophil Hyperactivity in Lupus   Journal of Clinical Sleep Medicine  The Prevalence and Impact of Pre-Existing Sleep Disorder Diagnoses and Objective Sleep Parameters in Patients Hospitalized for COVID-19 Journal of Thrombosis and Thrombolysis Neutrophil Extracellular Traps and Thrombosis in COVID-19 Pathology - Research and Practice Pathological Pulmonary Vascular Remodeling is Induced by Type V Collagen in a Model of Scleroderma

JANUARY 2021 Arthritis & Rheumatology Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac-1 Arthritis & Rheumatology Prevalence of Systemic Lupus Erythematosus in the United States: Estimates from a Meta-Analysis of the Centers for Disease Control and Prevention National Lupus Registries   Arthritis Research & Therapy Lymphocyte Subset Abnormalities in Early Diffuse Cutaneous Systemic Sclerosis   Best Practice & Research: Clinical Rheumatology  The Interplay Between Neutrophils, Complement, and Microthrombi in COVID-19   Journal of Psychosomatic Research Factors Associated with Fears Due to COVID-19: A Scleroderma Patient-Centered Intervention Network (SPIN) COVID-19 Cohort Study Medical Education What Is the Association Between Student Well-Being and High-Stakes Examination Scores? Scientific Reports HLA-DRB1 Allelic Epitopes That Associate with Autoimmune Disease Risk or Protection Activate Reciprocal Macrophage Polarization   Transplantation COVID-19 Outcomes Among Solid Organ Transplant Recipients: A Case-Control Study DECEMBER 2020 Arthritis & Rheumatology Association of Dysregulated Central Pain Processing and Response to Disease-Modifying Antirheumatic Drug Therapy in Rheumatoid Arthritis   Arthritis & Rheumatology Greater Somatosensory Afference with Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular GABA: A Randomized Neuroimaging Trial   Current Rheumatology Reports Epigenetic Control of Scleroderma: Current Knowledge and Future Perspectives   Current Treatment Options in Rheumatology Rheumatoid Arthritis-Associated Interstitial Lung Disease: Current Update on Prevalence, Risk Factors, and Pharmacologic Treatment   JAMA Network Open Lung Cancer Survival in Patients with Autoimmune Disease Journal of Biomedical Optics Imaging of Enthesitis by an LED-Based Photoacoustic System Journal of Immunology  The Role of Cutaneous Type I IFNs in Autoimmune and Autoinflammatory Diseases Seminars in Arthritis and Rheumatism  Chemical Exposure-Induced Systemic Fibrosing Disorders: Novel Insights into Systemic Sclerosis Etiology and Pathogenesis

Visit the Michigan Medicine Division of Rheumatology Website