Behdad (Ben) Afzali, M.D., Ph.D.
Immunoregulation Section, Kidney Diseases Branch
Building 10, Room 8D12C
10 Center Dr
Bethesda, MD 20814
+1 301 443 2055
The Immunoregulation Section studies how transcriptional signals from the environment are integrated within immune cells to instruct fate decisions and direct effector function. Our aim is to better understand how immunoregulation is perturbed in diseases of autoimmunity that affect the kidneys and why resolution of inflammation can be followed either by tissue healing or irreversible scarring. Our goal is to develop novel strategies that manipulate the balance between inflammatory and regulatory immune responses and to minimize or prevent kidney scarring.
Kidney diseases are highly prevalent and often the result of autoimmune or inflammatory insults to the kidneys. Current therapies to treat such injuries are broad-spectrum immunosuppressive drugs, which are non-specific and invariably toxic, predisposing patients to infectious agents and cancer development. When inflammation does resolve, there is often irreversible loss of kidney tissue as a result of scarring processes initiated during the disease. These processes result in progressive loss of kidney function over time.
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. Tregs are induced to develop dichotomously from naïve precursors that also have the ability to differentiate to inflammatory 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.
Research in the immunoregulation section is divided into two main themes:
- Understanding how transcriptional signals from the environment are integrated in T cells to determine inflammatory versus regulatory T cell differentiation and effector function; and
- Understanding how mediators produced by T cells in tissues determine whether inflammation results in tissue healing or scarring.
In both themes our focus is to determine how transcription factors function within networks to initiate and drive gene regulation in both T cells and local cells within 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.
- Earl Stadtman Investigator, 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
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<sup>+</sup> 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.
Liszewski MK, Kolev M, Le Friec G, Leung M, Bertram PG, Fara AF, Subias M, Pickering MC, Drouet C, Meri S, Arstila TP, Pekkarinen PT, Ma M, Cope A, Reinheckel T, Rodriguez de Cordoba S, Afzali B, Atkinson JP, Kemper C. Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. Immunity. 2013;39(6):1143-57.
Kolev M, Dimeloe S, Le Friec G, Navarini A, Arbore G, Povoleri GA, Fischer M, Belle R, Loeliger J, Develioglu L, Bantug GR, Watson J, Couzi L, Afzali B, Lavender P, Hess C, Kemper C. Complement Regulates Nutrient Influx and Metabolic Reprogramming during Th1 Cell Responses. Immunity. 2015;42(6):1033-47.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on October 15th, 2020