Behdad (Ben) Afzali, M.D., Ph.D.
Immunoregulation Section, Kidney Diseases Branch
The immunoregulation section studies the basic mechanisms of tissue inflammation and its resolution. Our research focusses on the micro-environmental signals that drive inflammation in tissues and how these are integrated by networks of transcription factors in immune cells, such as T cells. By understanding the basic mechanisms of disease we endeavor to prevent tissue inflammation, accelerate its resolution and minimize loss of inflamed tissues from scarring.
Chronic inflammatory diseases, excluding infectious disease, account for more than 50% of deaths world-wide. The molecular mechanisms of tissue inflammation remain poorly understood. Moreover, there are no specific therapies to prevent tissue inflammation beyond broad-spectrum immunosuppressive drugs, which are non-specific and toxic, predisposing patients to infections and cancer development. When inflammation does resolve, there is often irreversible loss of function as a result of scarring processes initiated during the disease. The kidneys are exemplars of organs uniquely susceptible to autoimmune or inflammatory insults that result in progressive scarring and loss of function over time.
T cells are widely-recognized mediators of tissue inflammation. They are induced to differentiate from naïve precursors to either inflammatory or regulatory T cell lineages. The choice of differentiation pathway (“fate decisions”) are directed by environmental signals and interplay between a number of transcription factors. Once differentiated, T cells migrate to target tissues where they effect inflammation, regulation and tissue healing or healing through the expression of physical and soluble factors. Regulatory T cells (Tregs) are arguably the most important naturally-occurring anti-inflammatory cells in the body. They have highly potently immunosuppressive function and carry out a non-redundant role in preventing autoimmunity and in resolving inflammation. Mammals with loss of, or functional impairment in, these cells succumb to life-threatening multi-organ autoimmune diseases as a result of failure to regulate the immune system.
Research in the immunoregulation section is divided into two main themes:
- Understanding the origins and functions of microenvironmental signals that drive tissue inflammation; and
- Understanding how these are integrated by networks of transcription factors in T cells to determine inflammatory versus regulatory T cell differentiation and effector function.
In both themes our focus is to determine how transcription factors function within networks to initiate and drive gene regulation in both immune and non-immune cells within tissues such as the kidneys.
Applying Our Research
Our aim is to identify key nodes in the differentiation or function of T cells or kidney cells that can be therapeutically targeted by the development of novel treatments, in order to tip the balance between regulatory and inflammatory behavior and between tissue healing and scarring. We believe that successfully targeting these pathways could decrease inflammation or accelerate its resolution and thereby reduce the volume of kidney tissue lost due to scarring as inflammation is resolved.
Need for Further Study
These measures would reduce kidney injury, prolong the lifespan of injured kidneys, reduce the number of patients progressing to dialysis and increase the longevity of transplanted kidneys. By doing so the quality of life of patients that have had kidney injury will also be improved. All of these are areas in which new therapies with greater efficacy and reduced toxicity are currently required.
- Fellow of the Royal College of Physicians, United Kingdom, 2022
- American Society for Clinical Investigation Young Physician-Scientist Award, 2022
- Earl Stadtman Investigator and Consultant Nephrologist, NIDDK, 2018
- Wellcome Trust Intermediate Clinical Research Fellow, King’s College London and O’Shea lab (NIAMS), 2012-2017
- Honorary Consultant Nephrologist, Guy’s Hospital, UK, 2013
- Nephrology Fellowship and Clinical Lectureship, Nephrology South Thames Training Program, UK, 2004-2012
- Residency Oxford Medical Rotation, UK, 2001-2003
- Fellow of the Higher Education Academy (FHEA), UK, 2013
- Postgraduate Diploma in Medical Education (PGDip), Institute of Education, London, 2013
- Member by recognition of the Academy of Medical Educators (MAcadMEd), 2010
- Ph.D. Immunology, King’s College London, University of London, 2009
- Membership of the Royal College of Physicians London (UK), 2003
- MB. BS. (M.D.), Gold Medal, King’s College London, University of London, 2000
- B.Sc. Immunology, Guy’s and St Thomas’ Hospitals, University of London, 1997
- Chauss D, Freiwald T, McGregor R, Yan B, Wang L, Nova-Lamperti E, Kumar D, Zhang Z, Teague H, West EE, Vannella KM, Ramos-Benitez MJ, Bibby J, Kelly A, Malik A, Freeman AF, Schwartz DM, Portilla D, Chertow DS, John S, Lavender P, Kemper C, Lombardi G, Mehta NN, Cooper N, Lionakis MS, Laurence A, Kazemian M, Afzali B. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells. Nat Immunol. 2021.
- Yan B, Freiwald T, Chauss D, Wang L, West E, Mirabelli C, Zhang CJ, Nichols EM, Malik N, Gregory R, Bantscheff M, Ghidelli-Disse S, Kolev M, Frum T, Spence JR, Sexton JZ, Alysandratos KD, Kotton DN, Pittaluga S, Bibby J, Niyonzima N, Olson MR, Kordasti S, Portilla D, Wobus CE, Laurence A, Lionakis MS, Kemper C, Afzali B, Kazemian M. SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation. Sci Immunol. 2021;6(58).
- Kolev M, West EE, Kunz N, Chauss D, Moseman EA, Rahman J, Freiwald T, Balmer ML, Lötscher J, Dimeloe S, Rosser EC, Wedderburn LR, Mayer-Barber KD, Bohrer A, Lavender P, Cope A, Wang L, Kaplan MJ, Moutsopoulos NM, McGavern D, Holland SM, Hess C, Kazemian M, Afzali B, Kemper C. Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells. Immunity. 2020;52(3):513-527.e8.
- Povoleri GAM, Nova-Lamperti E, Scottà C, Fanelli G, Chen YC, Becker PD, Boardman D, Costantini B, Romano M, Pavlidis P, McGregor R, Pantazi E, Chauss D, Sun HW, Shih HY, Cousins DJ, Cooper N, Powell N, Kemper C, Pirooznia M, Laurence A, Kordasti S, Kazemian M, Lombardi G, Afzali B. Human retinoic acid-regulated CD161+ regulatory T cells support wound repair in intestinal mucosa. Nat Immunol. 2018;19(12):1403-1414.
- Afzali B, Grönholm J, Vandrovcova J, O'Brien C, Sun HW, Vanderleyden I, Davis FP, Khoder A, Zhang Y, Hegazy AN, Villarino AV, Palmer IW, Kaufman J, Watts NR, Kazemian M, Kamenyeva O, Keith J, Sayed A, Kasperaviciute D, Mueller M, Hughes JD, Fuss IJ, Sadiyah MF, Montgomery-Recht K, McElwee J, Restifo NP, Strober W, Linterman MA, Wingfield PT, Uhlig HH, Roychoudhuri R, Aitman TJ, Kelleher P, Lenardo MJ, O'Shea JJ, Cooper N, Laurence ADJ. BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency. Nat Immunol. 2017;18(7):813-823.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on Monday, December 5, 2022