Rheumatic and Autoimmune Diseases- Our Faculty

Bio

Administrator Info
Name: Susan Prause
Phone: 6512103876
Email: sprause@umn.edu

Summary
Dr. Elfishawi graduated from Kasr-Alainy School of Medicine - Cairo University where he also completed rheumatology training and Masters' degree in rheumatology in 2016. He completed internal medicine residency at Icahn School of Medicine at Mount Sinai - Queens Hospital Center program, New York City, NY where he also served as chief resident and as a member in the Mount Sinai Graduate Medical Education committee. He completed rheumatology fellowship as well as VCRC-Vasculitis Foundation fellowship at the Mayo Clinic - Rochester, MN. He served as a member at the American College of Rheumatology (ACR) Fellows-in-Training (FIT) subcommittee responsible for planning educational sessions by the ACR for rheumatology fellows. 

His Clinical and research interest include Vasculitis, Aortitis, IgG4-related disease as well as Gout and Musculoskeletal ultrasound-guided procedures.

Research Summary

• Large vessel vasculitis
• Aortitis
• ANCA-associated vasculitis
• Gout

Teaching Summary

• Vasculitis lectures for fellows and residents
• Musculoskeletal ultrasound guided procedures

Clinical Summary

• Vasculitis
• Non-infectious Aortitis
• Gout
• Ultrasound guided musculoskeletal injections
• IgG4 related disease

Bio

Administrator Info
Name: Rheumatology
Email: rheumadm@umn.edu
Mail: 420 Delaware Street SE
MMC 108
Minneapolis, MN 55455

Summary
Dr. Parastoo Fazeli is an Assistant Professor of Medicine in the Division of Rheumatology and is the Director of the Lupus Clinic. In 2008, she completed Internal Medicine Internship and Residency at St. Agnes Hospital; one of The Johns Hopkins affiliated hospitals. She was honored with the award of the best intern of the year. She was a chief resident during her third year of residency. In 2009, she completed Lupus Fellowship at the Johns Hopkins University. In 2011, she finished fellowship training in Rheumatology at the University of Virginia and served as a chief fellow during her second year of fellowship. She joined the division in August, 2011 and was elected as the director of lupus clinic. Dr. Fazeli has clinical and research interest in systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), lupus in pregnancy and APS in pregnancy.

Clinical Summary

• Lupus
• Lupus in pregnancy
• Anti-phospholipid syndrome (APS)
• APS in pregnancy
• Sjogren's syndrome

Bio

Administrator Info
Name: Drew Keup
Lab Phone: 612-624-6149
Email: keupx013
Mail: Director, Center for Autoimmune Disease Research
2101 6th ST SE, 3-146 WMBB
Minneapolis, MN 55455

Summary
Dr. Brian Fife is a Professor of Medicine within the Division of Rheumatic and Autoimmune Diseases at the University of Minnesota Medical School. He joined the division in February 2008. He is also a member of the interdisciplinary Center for Immunology and Director of the Center for Autoimmune Disease Research (CADRe). Within the Center for Immunology, Dr. Fife also serves as the Imaging Core Director using advanced imaging techniques in his own research program. In December 2001, Dr. Fife graduated from Northwestern University Medical School. It is there that he initiated his research interests in autoimmune mediated diseases. Following graduation, Dr. Fife joined the Diabetes Center in the Department of Medicine at the University of California at San Francisco for postdoctoral research with Dr. Jeffrey Bluestone. The major focus of his research program is the restoration of immunological self tolerance for treatment of autoimmunity. Dr. Fife is interested in understanding immuological tolerance during Type 1 diabetes and focuses his efforts on understanding checkpoint blockade and the role for inhibitory pathways such as CTLA-4 and PD-1. This work has extending into tumor immunology and understanding the mechanisms involved in checkpoint blockade. Most recently his work has focused on chimeric antigen receptor T cells (CAR T cells) for novel treatment approaches for autoimmunity.

Research Summary

• Autoimmunity
• Type 1 diabetes
• Regulatory T cells
• CAR T cells
• CAR Tregs
• Checkpoint immunotherapy
• PD-1
• PD-L1
• T cell tolerance and transplantation tolerance

Research being conducted by the Fife Laboratory:

Research in our lab is focused on understanding the fundamental mechanisms that regulate T lymphocytes during autoimmune disease such as Type 1 diabetes mellitus (T1DM). T1DM is an autoimmune disorder resulting from the T cell mediated destruction of the insulin producing cells within the pancreas. At the root of autoimmunity lies the most important aspect of immune regulation, the ability to discriminate between self and non-self. This highly selective response is characterized by a complicated set of mechanisms which regulate T lymphocyte activity. Autoimmunity results when these mechanisms fail. We have generated a powerful treatment protocol to selectively target autoreactive cells. Using this type of approach allows us to re-educate the immune system to selectively silence destructive immune responses. Thus in effect, restore a state of self-tolerance and prevent further tissue destruction. We have identified two key regulatory pathways that control diabetes and promote tolerance, Cytotoxic T lymphocyte antigen-4 (CTLA-4) and Programmed Death-1 (PD-1). We have shown that these pathways control both anergy induction and long term maintenance of tolerance. Using our tolerance protocol will allow us to determine the precise roles of these negative regulatory pathways at different stages during disease pathogenesis to control immunity and enhance tolerance. More recent studies are focused on T1DM therapies including the use of regulatory T cells or Tregs. In addition to this approach we several projects focused on the generate of chimeric antigen receptor T cells or CAR T cells. These projects will determine if antigen-specific approaches will be a viable therapy for autoimmunity.

Research Video

Bio

Administrator Info
Name: Drew Keup
Email: keupx013@umn.edu

Summary
Dr. Ghattaura earned her MBBS from the Government Medical College in Amritsar, India in 2006. She did an Externship in Internal Medicine at Providence Hospital in Washington, DC in 2011 and the completed her Internal Medicine Residency at George Washington University in 2014. She came to the University of Minnesota in as a fellow in the Rheumatology Fellowship Program in 2014, which she graduated from in 2016. After five years as a University of Minnesota Physicians rheumatologist at Maple Grove, we are pleased to welcome Dr. Ghattaura to the Division of Rheumatic and Autoimmune Diseases as an academic physician and Assistant Professor. Dr. Ghattaura is also trained in Musculoskeletal Ultrasound, which has become a focal training area for our Rheumatology Fellowship Program.

Teaching Summary

Education of Rheumatology fellows, Internal Medicine residents and medical students in rheumatic and autoimmune diseases

Clinical Summary

Inflammatory arthritis; inflammatory eye diseases; Systemic lupus; Sjogren's, Systemic Sclerosis; Gout; vasculitis

Bio

Administrator Info
Name: Rheumatology
Email: rheumdiv@umn.edu

Summary
Dr. Jacob Ijdo received his clinical training at Yale University School of Medicine, where he completed both his Internal Medicine Residency and Rheumatology Fellowship. Post-fellowship, Dr. Ijdo was member of the faculty at the University of Iowa Hospitals and Clinics for 15 years. For the latter part he served as Director of the Rheumatology Fellowship program. In December 2014 Dr. Ijdo moved to Australia, where he became Director of the Rheumatology Department at the Gold Coast University Hospital in Queensland. He was also the Supervisor of Advanced Trainees at Gold Coast University Hospital.

Research Summary

Dr. Ijdo has research interests in the areas of vasculitis and the pathogenesis of tick-borne illness and was awarded an R01 on "Subverted host cell signaling by AnkA in Anaplasma phagocytophilum infection" in 2009. The study investigated the effect of the virulence factor AnkA on host signaling pathways, resulting in inhibition of the respiratory burst and delay of neutrophil apoptosis.

Clinical Summary

Vasculitis, pathogenesis of tick-borne illness

Bio

Administrator Info
Name: Drew Keup
Email: keupx013@umn.edu

Summary
Dr. Lotfi-Emran is a physician-scientist trained clinically in Rheumatology with a doctorate in Immunology. She received her MD and PhD from Virginia Commonwealth University and completed her Internal Medicine residency and Rheumatology Fellowship at University of Minnesota. Dr. Lotfi-Emran believes that understanding immunopathology mechanisms of autoimmune diseases will provide patients with answers as to and how and why they are sick. She is developing a basic science and translational research program examining the intersection of infection and autoimmunity through the lens of tissue resident immune networks. Currently, as a member of Dr. David Masopsust’s lab, she is focused on the interplay between viral infections, establishment of CD8+ T resident memory cells, and inflammatory arthritis.

Research Summary

• Mouse models of inflammatory arthritis
• Natural microbial exposure mouse models CD8+ T cells
• Tissue resident memory cells

Teaching Summary

Bench research on inflammatory arthritis

Clinical Summary

Rheumatologic, autoimmune and autoinflammatory disorders, including inflammatory arthritis

Bio

Administrator Info
Name: Rheum
Email: rheumdiv@umn.edu
Mail: 420 Delaware ST SE
MMC 108
Minneapolis, MN 55455

Summary
Dr. Jerry A. Molitor is an Associate Professor of Medicine in the Division of Rheumatic and Autoimmune Diseases at the University of Minnesota Medical School. Dr. Molitor earned his PhD in Microbiology and Immunology at Duke University, where he helped develop evidence of a family of NF-kappa B nuclear transcription factors in T lymphocytes. He completed his MD at the University Of Iowa College Of Medicine. Dr. Molitor completed his Internal Medicine Internship and Residency, as well as a Rheumatology Fellowship, at the University of Washington. Dr. Molitor conducted numerous clinical and translational research projects through the Benaroya Research Institute at Virginia Mason, where he was Director of the Arthritis Clinical Research Unit from 2001-2007, and Associate Director of Clinical Research from 2004-2007. He joined the University of Minnesota in 2007, where he heads the multidisciplinary Scleroderma clinic. He has participated in the Scleroderma GWAS, and in multiples studies of Systemic Sclerosis biomarkers and natural history, as well as in various aspects of drug development. Dr. Molitor has clinical research interests in Early Rheumatoid Arthritis and Systemic Sclerosis pathogenesis and disease prevention, and has been a consultant or investigator in multiple trials of candidate therapies for these conditions. His translational research focuses on understanding the interplay between impaired immune responses to infections and associated autoimmunity. He leads current studies examining this phenomenon in individuals with periodontal disease and the development of Rheumatoid Arthritis–associated autoantibodies.

Clinical Summary

Rheumatology; Early rheumatoid arthritis; Scleroderma; Systemic Sclerosis; Polymyocitis/Dermatomyositis

Bio

Administrator Info
Name: Susan Prause
Email: sprause@umn.edu

Summary
Dr. Luke Monteagudo obtained his medical degree through the Combined Program in Medicine, a dual degree BS/MD, at the University of Connecticut. He completed his Internal Medicine Residency with the VA at Tripler Army Medical Center in Honolulu, Hawaii before moving to Minnesota for his Rheumatology Fellowship training at the University of Minnesota. His clinical interests include rheumatoid arthritis, psoriatic arthritis, idiopathic inflammatory myopathies, vasculitis, gout and other autoimmune inflammatory diseases.

Research Summary

Autoimmune diseases

Clinical Summary

Clinical interests include inflammatory arthritis, idiopathic inflammatory myopathies, adult-onset Stills Disease, Macrophage Activation Syndrome, vasculitis and gout

Bio

Administrator Info
Name: Susan Prause
Email: sprause@umn.edu
Mail: 420 Delaware ST SE
MMC 108
Minneapolis, MN 55455

Summary
Dr. Daniel Mueller is a Professor of Medicine, and the Director of Rheumatic and Autoimmune Diseases at the University of Minnesota Medical School. He undertook his medical studies at the University of Wisconsin-Madison School of Medicine, and later obtained his Internal Medicine training at the Ohio State University Hospital. In 1986, he received training in basic molecular immunology in the Laboratory of Immunology at the National Institute for Allergy and Infectious Disease, NIH, under Drs. Ronald Schwartz and William Paul. It is there that he initiated his research into fundamental mechanisms involved in the development and maintenance of immune self-tolerance. In 1990, Dr. Mueller entered the Rheumatology Fellowship Training Program in the Rheumatic Diseases Division/Department of Internal Medicine at the University of Texas Southwestern Medical Center, under Dr. Peter Lipsky. Since the completion of his medical and research training, he has been on the University of Minnesota Medical School faculty. He currently holds the John F. Finn Arthritis Foundation Land Grant Chair. He is also a member of the Autoimmunity Program, within the University's Center for Immunology. The major focus of his academic program is the investigation of the biological and biochemical mechanisms that underlie the induction and maintenance of T- and B-cell tolerance within the peripheral immune system. His goal is the design of curative antigen-specific treatment strategies for autoimmune disease.

Research Summary

• Biological and biochemical nature of immune self-tolerance
• T cell immune tolerance
• T cell clonal expansion
• Breakdown of B cell tolerance during autoimmune disease development
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus

Current Research Efforts: 

Autoimmunity develops as the consequence of a loss of tolerance to self-antigens. Investigations carried out by Dr. Daniel Mueller are leading to a better understanding of the biological and biochemical nature of immune self-tolerance. Of particular interest are those factors that determine whether prolonged and continuous antigen stimulation of a T cell will lead to an increase in the clone size and the development of protective (or pathological) effector function, or alternatively lead to functional inactivation (anergy) and T regulatory cell (Treg) differentiation. To approach this problem, Mueller's research team is currently using an assortment of genomics and bioinformatics techniques (scRNA-Seq, ATAC-Seq) to characterize gene regulatory patterns in CD4 T cells that are associated with anergy induction and Foxp3+ Treg generation. Candidate gene regulators are being interrogated within neonatal mice--a time at which peripheral tolerance induction is essential for the avoidance of autoimmunity.

Loss of T cell tolerance also allows for the expansion and differentiation of autoreactive B cells, and the development of B-dependent autoimmune disease. Currently, these biological principles are being investigated in models of CD4 T cell-mediated immunopathology using both monoclonal TCR-transgenic T cells as well as self-antigen specific polyclonal responder cells. Additionally, translational experiments continue to detail the repertoire of human autoreactive B cells in normal subjects as well as in patients with Rheumatoid Arthritis. Currently, experiments are exploring the role of Ig gene somatic hypermutation in the generation of arthritogenic B cells by biochemically characterizing the antigen specificity of families of autoreactive B cell antigen receptors all derived from the same B cell progenitor.

Bio

Administrator Info
Name: Rheumatology
Lab Phone: 612-626-6100
Email: rheumdiv@umn.edu
Mail: 420 Delaware ST SE
MMC 108
Minneapolis, MN 55455

Summary
Dr. Erik Peterson joined the division of Rheumatic and Autoimmune Diseases in July, 2002. He is a member of the interdisciplinary Center for Immunology and its Autoimmunity Program, as well as a member of the Cancer Center. He is an immunologist with a scientific interest in those molecules that regulate the development and function of the immune system and prevent or promote the development of autoimmunity. He is also practices general rheumatology and participates in Resident and Fellow teaching.

Research Summary

Research in the Peterson laboratory

Dr. Erik Peterson has strong interests in the molecular underpinnings of autoimmune diseases, including rheumatoid arthritis, lupus, and myositis. His laboratory utilizes genetic, biochemical, and primary human sample-based approaches to investigating the mechanisms whereby recently identified “risk” genes predispose to development of autoimmune disease. Dr. Peterson's group recently identified a role for Ptpn22, a potent “risk” gene for many autoimmune diseases, in the promotion of toll-like receptor signaling and type 1 interferon production. He is currently investigating the role of Ptpn22 in myeloid cell functions in systemic lupus and in responses to immunization, and is characterizing the molecular mechanism of Ptpn22 promotion of type 1 interferon signals.

Leukocyte activation and development

Investigations carried out in Dr. Erik Peterson’s laboratory aim to increase understanding of the molecular mechanisms behind newly identified risk genes associated with autoimmune diseases. The laboratory uses human peripheral blood, genetically-altered mice, and transformed cell lines to approach questions concerning the biochemical, cellular, and immune response-modulating functions of susceptibility alleles.

The PTPN22 gene is among the strongest genetic predisposition factors for major human autoimmune diseases, including type 1 diabetes (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). PTPN22 encodes lymphoid tyrosine phosphatase (Lyp); a Lyp variant bearing a R620W substitution (“LypW”) is causally associated with disease risk. Lyp is a well-known negative regulator of T cell receptor (TCR) signaling, and most functional genomic work to date has focused on the potential mechanisms of LypW variant action on adaptive immune processes. Despite intensive study, a comprehensive model for LypW mechanism(s) of action in autoimmune disease is lacking.

In collaboration with others at UMN and elsewhere, our group recently demonstrated that PTPN22 plays a critical positive role in regulating pattern recognition receptor (PRR) signaling leading to production of type 1 Interferons (IFN) by myeloid cells. We established that Lyp protein binds and promotes activation of TNF Receptor Associated Factor 3 (TRAF3) during myeloid cell PRR signaling. Lyp also promotes PRR-induced, type 1 IFN-driven anti-viral host defense and suppression of inflammation in the gut and in the joint lining synovium. Importantly, the LypW variant exhibits reduced-function behavior in PRR signaling and in type 1 IFN-governed suppression of inflammation.

Our observations that PTPN22 modulates myeloid cell signaling suggest new potential mechanisms whereby an autoimmunity-associated gene works in concert with suspected environmental stimuli (e.g. viral infections, inflammatory reactions) to result in tissue damage. Our working model holds that PTPN22 potentiates myeloid cell-directed type 1 IFN-dependent anti-microbial host defense andcounter-inflammatory mechanisms. The model also holds that the reduced function LypW variant enhances potential for autoimmunity by increasing host susceptibility to tissue damage by suboptimally-suppressed infections and/or inflammatory reactions. Major questions about the model remain:

1. Is myeloid cell-intrinsic Lyp function sufficient for major host defense and anti-inflammatory PTPN22 actions in vivo?
2. What is the molecular basis for Lyp promotion of TRAF3 signaling?
3. How does LypW function differently in myeloid cell signaling and type 1 IFN-driven processes in vivo?
4. How do Lyp functions in host-defense and inflammation suppression translate into autoimmune disease risk

By experimentally addressing questions such as these, we seek to identify novel therapeutic targets, high-quality biomarkers, and ultimately, the cure for systemic rheumatic diseases.

Clinical Summary

Rheumatoid arthritis; Psoriatic arthritis; Systemic lupus erythematosus

Bio

Administrator Info
Name: Rheumatology
Email: rheumdiv@umn.edu
Mail: 3-240 WMBB
2101 6th St SE
Minneapolis MN 55414

Summary
Dr. Spanier received his BS degree in Cell Biology ('03) and MS degree in Biology ('06) from the University of Minnesota Duluth. While in Duluth Dr. Spanier's research was focused on nutrient transporters in endothelial cells within the blood-brain barrier. Dr. Spanier then moved to the University of Wisconsin Madison where he received a PhD in Biochemistry in 2012. It was in Madison that Dr. Spanier developed his skills in immunology and a passion for understanding autoimmune disease, where his research focused on how vitamin D influences the immune system in context of Multiple Sclerosis. In 2013 Dr. Spanier joined the laboratory of Dr. Brian Fife at the University of Minnesota Center for Immunology. It was here that he began building molecular tools, called peptide: MHCII tetramers, to understand antigen-specific responses in both people and mice with autoimmune diabetes. Dr. Spanier's current research program is focused on understanding autoimmune CD4 T cell responses in type 1 diabetes, and the engineering of monoclonal antibodies and chimeric antigen receptors for the restoration of immune tolerance.

Research Summary

• Clinical Immunology
• Autoimmune Diabetes
• peptide:MHCII tetramers
• vitamin D
• monoclonal antibodies
• Chimeric Antigen Receptors

Teaching Summary

Biochemical Methods Seminar; Topics in Medical Biochemistry ; Advanced Molecular Biology Laboratory; Developmental Biology Laboratory; General Biology Laboratory