Mark D. Okusa

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Primary Appointment

John C. Buchanan Distinguished Professor of Medicine and Chief, Division of Nephrology, Medicine- Nephrology

Education

  • Fellowship, Yale School of Medicine
  • MD, Medical College of Virginia
  • Residency, Medical College of Virginia, VCU, Richmond, VA

Research Interests

Immune mechanisms of acute kidney injury and fibrosis. Pulsed ultrasound in acute kidney injury

Research Description

My laboratory is interested in innate and adaptive immunity in acute and chronic kidney injury. Dendritic cells play an early role in activation of lymphocytes through antigen presentation of peptides to T cells or glycolipids to natural killer T cells. Through an understanding of the mechanisms that participate in the early activation and modulation of tissue injury we have developed pharmacological and cell based approaches to block these pathways. We use a variety of molecular, cell biological and immunological methods and in vivo models in our studies.
(1) Kidney ischemia-reperfusion injury: In vivo studies are aimed at determining the contribution of immune cells to ischemia-reperfusion injury and therapeutic strategies to reduce injury following acute kidney injury with the ultimate goal of bringing novel compounds to clinical trials. Current studies target adenosine 2A receptors and sphingosine 1 phosphate receptors as potential therapeutic approaches to block inflammation and tissue injury. These studies have led to a better understanding of the mechanisms of T cell activation by ischemia-reperfusion and tolerance induction by adenosine 2A compounds.
(2) Diabetic nephropathy: Our approach is to understand the immune mechanisms of injury in diabetic nephropathy and use novel compounds to reduce functional and morphological consequences of diabetic nephropathy.

Personal Statement

My laboratory is interested in innate and adaptive immunity in acute and chronic kidney injury. Dendritic cells play an early role in activation of lymphocytes through antigen presentation of peptides to T cells or glycolipids to natural killer T cells. Through an understanding of the mechanisms that participate in the early activation and modulation of tissue injury we have developed pharmacological and cell based approaches to block these pathways. We use a variety of molecular, cell biological and immunological methods and in vivo models in our studies.  (1) Kidney ischemia-reperfusion injury:  In vivo studies are aimed at determining the contribution of immune cells to ischemia-reperfusion injury and therapeutic strategies to reduce injury following acute kidney injury with the ultimate goal of bringing novel compounds to clinical trials. Current studies target adenosine 2A receptors and sphingosine 1 phosphate receptors as potential therapeutic approaches to block inflammation and tissue injury. These studies have led to a better understanding of the mechanisms of T cell activation by ischemia-reperfusion and tolerance induction by adenosine 2A compounds. (2) Diabetic nephropathy:  Our approach is to understand the immune mechanisms of injury in diabetic nephropathy and use novel compounds to reduce functional and morphological consequences of diabetic nephropathy.

Training

  • Basic Cardiovascular Research Training Grant
  • Interdisciplinary Training Program in Immunology

Selected Publications

Sung SJ, Ge Y, Dai C, Wang H, Fu SM, Sharma R, Hahn YS, Yu J, Le TH, Okusa MD, Bolton WK, Lawler JR, Dependence of Glomerulonephritis Induction on Novel Intraglomerular Alternatively Activated Bone Marrow-Derived Macrophages and Mac-1 and PD-L1 in Lupus-Prone NZM2328 Mice., 2017; Journal of immunology (Baltimore, Md. : 1950). 198(7) 2589-2601. PMID: 28219886 | PMCID: PMC5360484

Abe C, Inoue T, Inglis MA, Viar KE, Huang L, Ye H, Rosin DL, Stornetta RL, Okusa MD, Guyenet PG, C1 neurons mediate a stress-induced anti-inflammatory reflex in mice., 2017; Nature neuroscience. 20(5) 700-707. PMID: 28288124 | PMCID: PMC5404944

Stremska ME, Jose S, Sabapathy V, Huang L, Bajwa A, Kinsey GR, Sharma PR, Mohammad S, Rosin DL, Okusa MD, Sharma R, IL233, A Novel IL-2 and IL-33 Hybrid Cytokine, Ameliorates Renal Injury., 2017; Journal of the American Society of Nephrology : JASN. 28(9) 2681-2693. PMID: 28539382 | PMCID: PMC5576940

Tanaka S, Inoue T, Hossack JA, Okusa MD, Nonpharmacological, Biomechanical Approaches to Control Inflammation in Acute Kidney Injury., 2017; Nephron. () . PMID: 28595190

Inoue T, Tanaka S, Okusa MD, Neuroimmune Interactions in Inflammation and Acute Kidney Injury., 2017; Frontiers in immunology. 8() 945. PMID: 28848551 | PMCID: PMC5552660

Lobo PI, Schlegel KH, Bajwa A, Huang L, Okusa MD, Natural IgM and TLR Agonists Switch Murine Splenic Pan-B to "Regulatory" Cells That Suppress Ischemia-Induced Innate Inflammation via Regulating NKT-1 Cells., 2017; Frontiers in immunology. 8() 974. PMID: 28878768 | PMCID: PMC5572342

Okusa MD, Rosin DL, Tracey KJ, Targeting neural reflex circuits in immunity to treat kidney disease., 2017; Nature reviews. Nephrology. 13(11) 669-680. PMID: 28970585

Perry HM, Huang L, Wilson RJ, Bajwa A, Sesaki H, Yan Z, Rosin DL, Kashatus DF, Okusa MD, Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI., 2017; Journal of the American Society of Nephrology : JASN. () . PMID: 29084809 | PMCID: PMC5748924

Perry HM, Okusa MD, Endothelial Dysfunction in Renal Interstitial Fibrosis., 2016; Nephron. 134(3) 167-171. PMID: 27576317 | PMCID: PMC5089917

Inoue T, Rosin DL, Okusa MD, CAPing inflammation and acute kidney injury., 2016; Kidney international. 90(3) 462-5. PMID: 27521104

Perry HM, Huang L, Ye H, Liu C, Sung SJ, Lynch KR, Rosin DL, Bajwa A, Okusa MD, Endothelial Sphingosine 1âPhosphate Receptorâ1 Mediates Protection and Recovery from Acute Kidney Injury., 2016; Journal of the American Society of Nephrology : JASN. 27(11) 3383-3393. PMID: 26961351 | PMCID: PMC5084889

Askenazi DJ, Heung M, Connor MJ, Basu RK, Cerdá J, Doi K, Koyner JL, Bihorac A, Golestaneh L, Vijayan A, Okusa MD, Faubel S, Optimal Role of the Nephrologist in the Intensive Care Unit., 2016; Blood purification. 43(1) 68-77. PMID: 27923227 | PMCID: PMC5340591

Bajwa A, Huang L, Kurmaeva E, Ye H, Dondeti KR, Chroscicki P, Foley LS, Balogun ZA, Alexander KJ, Park H, Lynch KR, Rosin DL, Okusa MD, Sphingosine Kinase 2 Deficiency Attenuates Kidney Fibrosis via IFN-γ., 2016; Journal of the American Society of Nephrology : JASN. 28(4) 1145-1161. PMID: 27799486 | PMCID: PMC5373443

Inoue T, Abe C, Sung SS, Moscalu S, Jankowski J, Huang L, Ye H, Rosin DL, Guyenet PG, Okusa MD, Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes., 2016; The Journal of clinical investigation. 126(5) 1939-52. PMID: 27088805 | PMCID: PMC4855936

Caprara C, Kinsey GR, Corradi V, Xin W, Ma JZ, Scalzotto E, Martino FK, Okusa MD, Nalesso F, Ferrari F, Rosner M, Ronco C, The Influence of Hemodialysis on T Regulatory Cells: A Meta-Analysis and Systematic Review., 2016; Blood purification. 42(4) 307-313. PMID: 27694753

Sung SJ, Li L, Huang L, Lawler J, Ye H, Rosin DL, Vincent IS, Le TH, Yu J, Görldt N, Schrader J, Okusa MD, Proximal Tubule CD73 Is Critical in Renal Ischemia-Reperfusion Injury Protection., 2016; Journal of the American Society of Nephrology : JASN. 28(3) 888-902. PMID: 27628903 | PMCID: PMC5328157

Maursetter LJ, Stern LD, Sozio SM, Patel AB, Rao R, Shah HH, Leight K, Okusa MD, Zeidel ML, Parker MG, Enhancing Nephrology Career Interest through the ASN Kidney TREKS Program., 2016; Journal of the American Society of Nephrology : JASN. 27(6) 1604-7. PMID: 27026364 | PMCID: PMC4884123

Hu SL, Chang A, Perazella MA, Okusa MD, Jaimes EA, Weiss RH, The Nephrologist's Tumor: Basic Biology and Management of Renal Cell Carcinoma., 2016; Journal of the American Society of Nephrology : JASN. 27(8) 2227-37. PMID: 26961346 | PMCID: PMC4978061

Chopra TA, Brooks CH, Okusa MD, Acute Kidney Injury Prevention., 2016; Contributions to nephrology. 187() 9-23. PMID: 26881939

Heung M, Faubel S, Watnick S, Cruz DN, Koyner JL, Mour G, Liu KD, Cerda J, Okusa MD, Lukaszewski M, Vijayan A, Outpatient Dialysis for Patients with AKI: A Policy Approach to Improving Care., 2015; Clinical journal of the American Society of Nephrology : CJASN. 10(10) 1868-74. PMID: 26220818 | PMCID: PMC4594066

Gigliotti JC, Huang L, Bajwa A, Ye H, Mace EH, Hossack JA, Kalantari K, Inoue T, Rosin DL, Okusa MD, Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI., 2015; Journal of the American Society of Nephrology : JASN. 26(10) 2470-81. PMID: 25644106 | PMCID: PMC4587697

Scindia Y, Dey P, Thirunagari A, Liping H, Rosin DL, Floris M, Okusa MD, Swaminathan S, Hepcidin Mitigates Renal Ischemia-Reperfusion Injury by Modulating Systemic Iron Homeostasis., 2015; Journal of the American Society of Nephrology : JASN. () . PMID: 25788528 | PMCID: PMC4625680

Swaminathan S, Rosner MH, Okusa MD, Emerging therapeutic targets of sepsis-associated acute kidney injury., 2015; Seminars in nephrology. 35(1) 38-54. PMID: 25795498 | PMCID: PMC4369320

Vincent IS, Okusa MD, Adenosine 2A receptors in acute kidney injury., 2015; Acta physiologica (Oxford, England). 214(3) 303-10. PMID: 25877257 | PMCID: PMC4470817

Cerdá J, Liu KD, Cruz DN, Jaber BL, Koyner JL, Heung M, Okusa MD, Faubel S, Promoting Kidney Function Recovery in Patients with AKI Requiring RRT., 2015; Clinical journal of the American Society of Nephrology : CJASN. 10(10) 1859-67. PMID: 26138260 | PMCID: PMC4594060

Bajwa A, Huang L, Kurmaeva E, Gigliotti JC, Ye H, Miller J, Rosin DL, Lobo PI, Okusa MD, Sphingosine 1-Phosphate Receptor 3-Deficient Dendritic Cells Modulate Splenic Responses to Ischemia-Reperfusion Injury., 2015; Journal of the American Society of Nephrology : JASN. 27(4) 1076-90. PMID: 26286732 | PMCID: PMC4814185

Inoue T, Okusa MD, Neuroimmune Control of Acute Kidney Injury and Inflammation., 2015; Nephron. 131(2) 97-101. PMID: 26376049 | PMCID: PMC4618761

Bonomo JA, Palmer ND, He JC, Fan Y, Hicks PJ, Lea JP, Okusa MD, Bowden DW, Freedman BI, Association Analysis of the Reticulon 1 Gene in End-Stage Kidney Disease., 2015; American journal of nephrology. 42(4) 259-64. PMID: 26496126 | PMCID: PMC4651726

Matejovic M, Ince C, Chawla LS, Blantz R, Molitoris BA, Rosner MH, Okusa MD, Kellum JA, Ronco C, Renal Hemodynamics in AKI: In Search of New Treatment Targets., 2015; Journal of the American Society of Nephrology : JASN. 27(1) 49-58. PMID: 26510884 | PMCID: PMC4696587

Okusa MD, Rosner MH, Kellum JA, Ronco C, Therapeutic Targets of Human AKI: Harmonizing Human and Animal AKI., 2015; Journal of the American Society of Nephrology : JASN. 27(1) 44-8. PMID: 26519086 | PMCID: PMC4696586

Lobo PI, Schlegel KH, Bajwa A, Huang L, Kurmaeva E, Wang B, Ye H, Tedder TF, Kinsey GR, Okusa MD, Natural IgM Switches the Function of Lipopolysaccharide-Activated Murine Bone Marrow-Derived Dendritic Cells to a Regulatory Dendritic Cell That Suppresses Innate Inflammation., 2015; Journal of immunology (Baltimore, Md. : 1950). 195(11) 5215-26. PMID: 26519533 | PMCID: PMC4655187

de Caestecker M, Humphreys BD, Liu KD, Fissell WH, Cerda J, Nolin TD, Askenazi D, Mour G, Harrell FE, Pullen N, Okusa MD, Faubel S, Bridging Translation by Improving Preclinical Study Design in AKI., 2015; Journal of the American Society of Nephrology : JASN. 26(12) 2905-16. PMID: 26538634 | PMCID: PMC4657852

Abdel-Rahman EM, Okusa MD, Recovery from acute kidney injury: predicting outcomes., 2015; American journal of kidney diseases : the official journal of the National Kidney Foundation. 65(4) 528-9. PMID: 25791960

Perry HM, Okusa MD, Driving change: kidney proximal tubule CSF-1 polarizes macrophages., 2015; Kidney international. 88(6) 1219-1221. PMID: 26649657 | PMCID: PMC4976441

Gigliotti JC, Okusa MD, The spleen: the forgotten organ in acute kidney injury of critical illness., 2014; Nephron. Clinical practice. 127(1) 153-7. PMID: 25343841 | PMCID: PMC5048741

Bajwa A, Rosin DL, Chroscicki P, Lee S, Dondeti K, Ye H, Kinsey GR, Stevens BK, Jobin K, Kenwood BM, Hoehn KL, Lynch KR, Okusa MD, Sphingosine 1-Phosphate Receptor-1 Enhances Mitochondrial Function and Reduces Cisplatin-Induced Tubule Injury., 2014; Journal of the American Society of Nephrology : JASN. () . PMID: 25145931

Kinsey GR, Okusa MD, Expanding role of T cells in acute kidney injury., 2013; Current opinion in nephrology and hypertension. 23(1) 9-16. PMID: 24231312 | PMCID: PMC3909711

Okusa MD, Li L, Dendritic cells in acute kidney injury: cues from the microenvironment., 2013; Transactions of the American Clinical and Climatological Association. 123() 54-62; discussion 62-3. PMID: 23303968 | PMCID: PMC3540592

Bajwa A, Huang L, Ye H, Dondeti K, Song S, Rosin DL, Lynch KR, Lobo PI, Li L, Okusa MD, Dendritic cell sphingosine 1-phosphate receptor-3 regulates Th1-Th2 polarity in kidney ischemia-reperfusion injury., 2012; Journal of immunology (Baltimore, Md. : 1950). 189(5) 2584-96. PMID: 22855711 | PMCID: PMC3433235

Kinsey GR, Okusa MD, Role of leukocytes in the pathogenesis of acute kidney injury., 2012; Critical care (London, England). 16(2) 214. PMID: 22429752 | PMCID: PMC3681359

Sharma AK, LaPar DJ, Zhao Y, Li L, Lau CL, Kron IL, Iwakura Y, Okusa MD, Laubach VE, Natural killer T cell-derived IL-17 mediates lung ischemia-reperfusion injury., 2011; Am J Respir Crit Care Med. 183(11) 1539-49. PMID: | PMCID: PMC3137143

Bajwa A, Jo SK, Ye H, Huang L, Dondeti KR, Rosin DL, Haase VH, Macdonald TL, Lynch KR, Okusa MD, Activation of sphingosine-1-phosphate 1 receptor in the proximal tubule protects against ischemia-reperfusion injury., 2010; J Am Soc Nephrol. 21(6) 955-65. PMID: | PMCID: PMC2900956

Li L, Huang L, Vergis AL, Ye H, Bajwa A, Narayan V, Strieter RM, Rosin DL, Okusa MD, IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury., 2010; J Clin Invest. 120(1) 331-42. PMID: | PMCID: PMC2798679

Jo SK, Bajwa A, Ye H, Vergis AL, Awad AS, Kharel Y, Lynch KR, Okusa MD, Divergent roles of sphingosine kinases in kidney ischemia-reperfusion injury., 2009; Kidney Int. 75(2) 167-75. PMID: | PMCID: PMC2646633

Li L, Huang L, Sung SS, Vergis AL, Rosin DL, Rose Jr, Lobo PI, Okusa MD, The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia-reperfusion injury., 2008; Kidney Int. 74(12) 1526-37. PMID: | PMCID: PMC2652647

Jo SK, Bajwa A, Awad AS, Lynch KR, Okusa MD, Sphingosine-1-phosphate receptors: biology and therapeutic potential in kidney disease., 2008; Kidney Int. 73(11) 1220-30. PMID: | PMCID: PMC2614447

Awad AS, Rouse M, Liu L, Vergis AL, Rosin DL, Linden J, Sedor JR, Okusa MD, Activation of adenosine 2A receptors preserves structure and function of podocytes., 2008; J Am Soc Nephrol. 19(1) 59-68. PMID: | PMCID: PMC2391028

Foss Jr, Snyder AH, Davis MD, Rouse M, Okusa MD, Lynch KR, Macdonald TL, Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists., 2007; Bioorg Med Chem. 15(2) 663-77. PMID: | PMCID: PMC1963459

Kinsey GR, Okusa MD, Pathogenesis of acute kidney injury: foundation for clinical practice., ; Am J Kidney Dis. 58(2) 291-301. PMID: | PMCID: PMC3144267

Awad AS, Rouse MD, Khutsishvili K, Huang L, Bolton WK, Lynch KR, Okusa MD, Chronic sphingosine 1-phosphate 1 receptor activation attenuates early-stage diabetic nephropathy independent of lymphocytes., ; Kidney Int. 79(10) 1090-8. PMID: | PMCID: PMC3155206

Okusa MD, Lynch KR, Targeting sphingosine 1 phosphate receptor type 1 receptors in acute kidney injury., ; Drug Discov Today Dis Mech. 4(1) 55-59. PMID: | PMCID: PMC2682423