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Mohammad Afzal Khan, MSc, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Surgery

Phone (Primary):

4437225022

Education and Training

Position

Institution

Term

Discipline

Scientist

King Faisal Specialist Hospital & RC, KSA.

14-22

Immunology

Assistant Professor

University of Sharjah, UAE.

13-14

Immunology

Research Associate

Stanford University, USA.

08-13

Immunology

Post-Doctoral

McMaster University, Canada.

05-08

Immunology

Research Fellow

Central Drug Research Institute, India.

03-04

Immunology

Ph.D.

Aligarh Muslim University, India.

99-03

Biotechnology

M.Sc.

Aligarh Muslim University, India.

97-99

Biotechnology

Biosketch

After earning my PhD in biotechnology in 2004 at Aligarh Muslim University, India, I was recruited to McMaster University in Canada for a postdoctoral position on "studies of cellular and biological effects of COPDs". As a part of my further research in pulmonary medicine, I moved to Stanford University USA in 2008, where I spent almost five years optimizing a mouse model of airway transplantation and investigating inflammation's role in rejection. A year after I moved to Saudi Arabia, and established a transplant immunotherapy laboratory at the King Faisal Specialist Hospital and Research Centre, Riyadh. 

As part of my current research at University of Maryland, Baltimore, I am looking into immunoregulation and immune tolerance in mice that have been orthotopically transplanted with MHC mismatched donor airways. A lung transplant is the only effective treatment for many end-stage lung diseases. As of now, lung transplantation has one of the lowest survival rates of any major organ transplant. This is because the body's immune system attacks the transplanted lung, causing irreversible damage that leads to chronic rejection, currently, there are no effective therapies to prevent chronic rejection following lung transplantation. To promote immune tolerance, we have optimized a variety of immunotherapies, including regulatory T cells, cytokines, and stem cell-based approaches. We use a wide array of microsurgical, translational, immunological, confocal imaging, cell, and molecular biology techniques to dissect the potential benefits of single and combined immunotherapies.

Research/Clinical Keywords

Transplantation, Immune tolerance, Regulatory T cells, Complement cascade.

Highlighted Publications

  • Khan MA, Talal S, Abdulah A. Assiri AM, and Broering DC (2022): CTLA4-Ig mediated immunosuppression favors immunotolerance and restores graft in mouse airway transplants. Pharmacological Research, 26 (178).
  • Kazmi S, Khan MA, Talal S, Abdulah A. Assiri AM, and Broering DC (2022): Targeting Interleukin-10 restores graft microvascular supply and airway epithelium in rejecting allografts. International Immunopharmacology, 106 (22)
  • Kazmi S, Khan MA, Talal S, Abdulah A. Ahmad H, Assiri AM, and Broering DC (2022): Targeting Interleukin-10 restores graft microvascular supply and airway epithelium in rejecting allografts. International Journal of Molecular Sciences, 23 (3).
  • Khan MA, Ghazi A, Alanazi F, Talal S, Abdulah A. Ahmad H, Kazmi S, Assiri AM, and Broering DC (2021): IL-10 mediated immunomodulation limits subepithelial fibrosis and
    repairs airway epithelium in rejecting airway allografts. Cells, 10 (5).
  • Khan MA (2020): Regulatory T cells mediated immunomodulation during asthma: a therapeutic standpoint. Journal of Translational Medicine, 18;456.
  • Evaristus CM, Chinwike TA, Yuanlong Z, Olivia KL, Kimberly HT, Shannon K, Khan MA, Justin O, Irina S, Michael S, Luke P, Nicolls MR, Theodore J, Alex L, Paul B, Franco F, Hsieh M, (2020): IPSE, an Abundant Egg-Secreted Protein of the Carcinogenic Helminth Schistosoma haematobium, Promotes Proliferation of Bladder Cancer Cells and Angiogenesis. Infectious agents and cancer, 15;63.
  • Khan MA, Talal S, Shadab, K, Abdulah, A. Ahmad H, Assiri, AM and Broering DC (2020): Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants. Journal of Translational Medicine, 18; 147.
  • Khan MA, Fatimah A, Ahmad H, Kilian K, Assiri, AM and Broering DC (2019): iPSC-derived MSC therapy induces immune-tolerance and supports long-term graft survival in mouse orthotopic tracheal transplants. Stem Cell Research and Therapy, 10; 290.
  • Heim, Khan MA, B. Motsch, A. Gocht, M. Ramsperger-Gleixner, T. Stamminger, M.R. Nicolls, M. Weyand, S. Ensminger (2019): Preservation of microvascular integrity in murine orthotopic tracheal allografts by Clopidogrel. Transplantation, 103 (5): 899.
  • Khan MA, Shamma T (2019): Complement factor and T cell interaction during transplantation. Journal of Leukocyte Biology, 105(4):681.
  • Khan MA, Talal S., Ahmad H, Assiri, AM and Broering DC (2018): CD55/Crry and complement C3d expression during microvascular rejection in mouse airway allografts. Immunome Research 14.
  • Khan MA, Vater A, Fatimah A, Ahmad H, Assiri, AM and Broering DC (2018): C5a blockade protects against inflammation-driven microvascular loss through T regulatory cell induction in mouse airway allografts. Frontier in Immunology, 24 (9) 1010.
  • Heim, B. Motsch, A. Gocht, M. Ramsperger-Gleixner, T. Stamminger, M.A. Khan, M.R. Nicolls, M. Weyand, S. Ensminger (2017): Microvascular Loss in Experimental Murine Tracheal Transplantation can be Prevented by Anti-Platelet Therapy and in Combination with mTOR Inhibitor. Thorac cardiovasc Surg, 65(S 01): S1-S110.
  • Heim, Khan M.A, B. Motsch, A. Gocht, M. Ramsperger-Gleixner, T. Stamminger, M.R. Nicolls, M. Weyand, S. Ensminger (2017): Microvascular integrity can be preserved by anti-platelet therapy and in combination with mTOR inhibitor. Journal of Heart and Lung Transplantation, 36, 4.
  • Ansari AW, Khan MA, Schmidt RE, and Broering DC (2017): Harnessing the Immunotherapeutic Potential of T-lymphocyte Co-signaling Molecules in Transplantation.
    Immunology letters. 183: 8.
  • Khan MA, Fatimah A, Ahmad H, Falah, HA, Assiri, AM and Broering DC (2017): FOXP3+ regulatory T cell ameliorates microvasculature in the rejection of mouse orthotopic tracheal transplants. Clinical Immunology, 174: 84.
  • Khan M A (2016): T regulatory cell-mediated immunotherapy for solid organ transplantation: A clinical perspective. Molecular Medicine, 22:892.
  • Khan MA, Fatimah A, Ahmad H, Falah, HA, Assiri, AM and Broering DC (2016): The therapeutic potential of Treg cells in preserving microvascular health in a mouse model of orthotopic tracheal transplantation. Journal of Clinical & Cellular Immunology, 7(3) 89.
  • Khan MA (2016): Dynamics of airway response in lung microsections: a tool of studying airway-extracellular matrix interactions. Biomedical Science 23(1):43.
  • Khan MA, Joe Sue, Assiri, AM and Broering DC (2016): Targeted complement inhibition and microvasculature in transplants: A therapeutic perspective. Clinical and Experimental Immunology, 183: 175.
  • Khan MA, Assiri, AM and Broering DC (2015): Complement cascade mediators: key regulators of airway tissue remodeling in asthma. Journal of Translational Medicine, 13, 272.
  • Khan MA, Assiri, AM and Broering DC (2015): Complement and macrophage crosstalk during process of angiogenesis in tumor progression. Biomedical Science, 22:58.
  • Khan MA, and Nicolls MR (2014): Complement components as potential therapeutic targets for asthma treatment. Respiratory Medicine 108(4).
  • Heim, Khan M A, B. Motsch, S. Müller, M. Ramsperger-Gleixner, T. Stamminger, M.R. Nicolls, M. Weyand, S. Ensminger. (2014): Clopidogrel Preserves Microvascular Integrity in Orthotopic Tracheal Transplants affected by Obliterative Bronchiolitis. JHLT
  • Hsu JL, Khan MA, Sobel R, Clemons KV, Nguyen T, Stevens DA, Martinez M, Nicolls MR (2013): Aspergillus fumigatus invasion increases with progressive airway ischemia. Plos One, Oct 14; 8(10).
  • Khan MA, Maasch C, Vater A, Klussmann S, Morser J, Leung LL, Atkinson C, Tomlinson S, Heeger PS, Nicolls MR (2013): Targeting C5a promotes vascular integrity and limits airway remodeling. Proc Natl Acad Sci U S A, Apr 9; 110(15).
  • Thai K, Khan M A, Nicolls MR, Ray D, Nelson T, Fu C, Patel S, Gong D, Odegaard J, Knudsen D, Hsieh M. (2013) Chronic Inflammation-induced hematuria involves molecular modulation of the urothelial barrier and bladder vasculature. The Journal of Urology. 189 (4).
  • Khan MA, Khan, S, Akhtar, S (2013): T-regulatory cell-mediated immune tolerance as a potential immunotherapeutic strategy to facilitate graft survival. Blood transfusion, May 7. 
  • Khan MA (2013): Inflammation signals airway smooth muscle cell proliferation in asthma pathogenesis. Multi Discp. Respiratory Med. Feb 6; 8(1):11.
  • Khan MA, Nicolls MR (2013): Complement-mediated microvascular injury leads to chronic rejection. Exp. Med. Biol. 734.
  • Khan MA (2013): Potential new therapeutic targets to rescue solid organ transplants. Journal of Innovative Medicine and Biology, No 8.
  • Khan MA, Gundeep D, Xinguo J, Nicolls, MR (2012): New Methods for Monitoring Dynamic Airway Tissue Oxygenation and Perfusion in Experimental and Clinical Transplantation. J.Physiol-Lung Cell Mol.Physiol. Vol. 303, no. 10.
  • Khan M A and Moeez S (2012): Biomedical applications of engineered nanoparticles in diagnosis and therapeutics. Journal of Immunological Studies, Vol. 1, No.4.
  • Khan MA, Xinguo J, Gundeep D, Beilke J, Atkinson C, M.Holers, Tomlinson S, Nicolls MR (2011): CD4+ T cells and complement independently mediate graft ischemia in the rejection of mouse orthotopic tracheal transplants. Circulation Research, Vol. 109.
  • Xinguo J, Khan M A, Tian W, Beilke J, Natrajan R, Yoder M, Semenza GL, Nicolls MR (2011): Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection. Journal of Clinical Investigation, 121(6).

 

 

 

Research Interests

Lung transplantation is a major surgical procedure, which temporarily restores normal lung functioning and provides years of life for patients suffering from major lung diseases. Lung transplant recipients are at high risk of primary graft dysfunction, acute graft rejection, and chronic lung allograft dysfunction (CLAD) in the form of progression of bronchiolitis obliterative syndrome (BOS) and restrictive allograft syndrome post-transplantation. The protective role of peripheral CD4+CD25highCD127 Regulatory T cell (pTreg) cells in solid-organ transplantation have been key to investigate the kinetics of disease progression. Tregs have been associated with peripheral graft deposition during acute rejection, less is known about the possibilities of Tregs to modulate the onset of chronic rejection, nor is it recognized whether these cells can be a prognostic biomarker for BOS. Our lab investigates the long-term kinetics of pTregs in a group of lung transplant recipients and correlates its association with clinical variables. We also investigate a cellular network between pTregs, antigen-presenting cells, and associated metabolites that have a direct or an indirect role in the progression of CLAD following transplantation. Our key approaches utilize Complement cascade, Costimulatory blockade, and cell-based therapies (Regulatory T cells/Stem Cells) to reestablish the phase of immunotolerance and thereby rescue graft failure in a well-established mouse model of large airway transplantation, and clinical samples (BAL and Blood).

In the News

https://files.cynata.com/506/19.09.04.Cynata-transplant-rejection-study-accepted-for-publication.pdf

Lab Techniques and Equipment

Analysis of regulatory biomarker in clinical samples, murine Orthotopic Trachea Transplantation, Cell therapy (Isolation and purification of specific Regulatory Cells, Real-time monitoring of Oxygen, and Blood flow in the graft. Microvasculature assay. Immunofluorescence, Histopathology (Fibrotic remodeling), Flow cytometry, PCR, and LUMINEX-ELISA.