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Makio Iwashima PhD

Microbiology/ Immunology

Bio

  • Professor

Ongoing Research

In 2015, the WHO documented 4.5 million infant deaths worldwide. The infant immune system is highly tolerogenic.          While infants need this immunosuppressive state to prevent inflammation and disease when they first encounter environmental microorganisms after birth, this condition also impairs the infant’s immune responses to vaccines and pathogens. Surprisingly, we still do not know how the immunosuppressive state is maintained in infants, nor the mechanisms by which children outgrow this suppression and become immune- competent adults. Moreover, many phenomena that we observe in fetus also occur in the tumor environment. To develop better care for infants, there is a critical need to understand why the infant immune system is different from the adult immune system.

We currently have three major areas of interest: 1) How does neonatal immune system adjust to the new environment after birth? 2) What is the shared property of the fetal and tumor microenvironment and how do they inhibit immune responses? 3) What does environment change the fetal and neonatal immune system?

  • How does neonatal immune system adjust to the new environment after birth?
  • Immune modulation by normal and malignant developmental processes

In our recent work, we have demonstrated that human umbilical cord blood-derived cells differ in their surface antigen expression. Differing expression of these surface antigens suggests a lineage switch in these cells in cord blood versus adult blood. To understand this difference, we analyzed the expression of genes expressed by immune cells derived from cord and adult blood. Our data show expression of multiple genes differ between cord blood and adult blood cells. In this project, we will determine how such differences contribute to the characteristics of fetal/ neonatal immune system.

Transforming Growth Factor-β (TGF-β) signaling plays pivotal roles during the fetal development. Moreover, TGF-β signaling induces tumor metastasis and immune suppression. Paradoxically, TGF-β also induces inflammatory immune responses under certain conditions. Despite these significant and pleiotropic roles of TGF-β signaling in immune regulation, the molecular mechanism by which TGF-β signaling controls immune cell differentiation and suppression remain poorly understood. Our goal for this project is to elucidate how and when TGF-β is generated and find the direct targets of TGF-β signaling in activated immune cells. These studies could inform the design of therapeutics that modulate T cell responses and enhance immunity of infant and cancer patients. The outcome also will help to develop treatment of autoimmune disorders.

  • What do environmental factors such as nutrients do to the fetal and neonatal immune system? Vitamin D is an essential nutrient for healthy bone Recently, it was also recognized that vitamin D plays a significant role in inhibiting excessive inflammation. Generally, doctors recommend to take vitamin D supplement for many adults. But how does vitamin D work to control the immune system? We discovered that Vitamin D can change the type of immune responses against infections and cancers. We also found that these changes are reversed by some microbial metabolites. In this project, we will further study how vitamin D reduces inflammation. This study will help developing natural ways to reduce severe inflammatory conditions associated with pathogens such as COVID19.

Education

  • PhD, Stanford University

Research Interests

  • Immunological tolerance and memory; their mechanisms and clinical applications

Publications/Research Listings

  • Gottlieb, J; Torres, F; Haddad, T; Dhillon, G; Dilling, DF; Knoop, C; Rampolla, R; Walia, R; Ahya, V; Kessler, R; Budev, M; Neurohr, C; Glanville, AR; Jordan, R; Porter, D; McKevitt, M; German, P; Guo, Y; Chien, JW; Watkins, TR; Zamora, MR A randomized controlled trial of presatovir for respiratory syncytial virus after lung transplant. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation;
  • Warrior, K; Dilling, DF Lung transplantation for lymphangioleiomyomatosis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation;
  • Mallea, JM; Hartwig, MG; Keller, CA; Kon, Z; Iii, RNP; Erasmus, DB; Roberts, M; Patzlaff, NE; Johnson, D; Sanchez, PG; D'Cunha, J; Brown, AW; Dilling, DF; McCurry, K Remote ex vivo lung perfusion at a centralized evaluation facility. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation;
  • Newton, CA; Oldham, JM; Applegate, C; Carmichael, N; Powell, K; Dilling, D; Schmidt, SL; Scholand, MB; Armanios, M; Garcia, CK; Kropski, J; Talbert, J The Role of Genetic Testing in Pulmonary Fibrosis: A Perspective from the Pulmonary Fibrosis Foundation Genetic Testing Work Group. Chest;
  • Warrior, K; Leard, LE; Nair, AR; Gries, CJ; Fisher, AJ; Johnson, SR; McCormack, FX; Dilling, DF A survey of use of mTOR inhibitors in patients with lymphangioleiomyomatosis listed for lung transplant. Respiratory medicine ; 195;
  • Swaminathan, A; Hellkamp, AS; Neely, ML; Bender, S; Paoletti, L; White, ES; Palmer, SM; Whelan, TP; Dilling, DF Disparities in Lung Transplant among Patients with Idiopathic Pulmonary Fibrosis: An Analysis of the IPF-PRO Registry. Annals of the American Thoracic Society;
  • Baldi, BG; Radzikowska, E; Cottin, V; Dilling, DF; Ataya, A; Ribeiro Carvalho, CR; Harari, S; Koslow, M; Grutters, JC; Inoue, Y; Gupta, N; Johnson, SR COVID-19 in lymphangioleiomyomatosis: an international study of outcomes and impact of mTOR inhibition. Chest;
  • Kuczewski, M; Wasson, K; Hutchison, PJ; Dilling, DF Putting ethics and clinical decision making before politics: requiring COVID-19 immunization for Solid Organ Transplantation (SOT) Candidates and their Support Team. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation;
  • Thomas, A; Sumughan, S; Dellacecca, ER; Shivde, RS; Lancki, N; Mukhatayev, Z; Vaca, CC; Han, F; Barse, L; Henning, SW; Zamora-Pineda, J; Akhtar, S; Gupta, N; Zahid, JO; Zack, SR; Ramesh, P; Jaishankar, D; Lo, AS; Moss, J; Picken, MM; Darling, TN; Scholtens, DM; Dilling, DF; Junghans, RP; Le Poole, IC Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice. JCI insight ; 6 22;
  • Crespo, MM; Lease, ED; Sole, A; Sandorfi, N; Snyder, LD; Berry, GJ; Pavec, JL; Venado, AE; Cifrian, JM; Goldberg, H; Dilling, DF; Gries, C; Nair, A; Willie, K; Meyer, KC; Shah, RJ; Tokman, S; Holm, A; Patterson, CM; McWilliams, T; Shtraichman, O; Bemiss, B; Salgado, J; Farver, C; Strah, H; Wassilew, K; Kaza, V; Howsare, M; Murray, M; Bhorade, S; Budev, M ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part I: Epidemiology, assessment of extrapulmonary conditions, candidate evaluation, selection criteria, and pathology statements. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation;
  • Martinez, FJ; Yow, E; Flaherty, KR; Snyder, LD; Durheim, MT; Wisniewski, SR; Sciurba, FC; Raghu, G; Brooks, MM; Kim, DY; Dilling, DF; Criner, GJ; Kim, H; Belloli, EA; Nambiar, AM; Scholand, MB; Anstrom, KJ; Noth, I Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis: The CleanUP-IPF Randomized Clinical Trial. JAMA ; 325 18;
  • Nolley, E; Fleck, J; Kavalieratos, D; Dew, MA; Dilling, D; Colman, R; Crespo, MM; Goldberg, H; Hays, S; Hachem, R; Lease, E; Lee, J; Reynolds, J; Morrell, M; Schenker, Y Lung Transplant Pulmonologists' Views of Specialty Palliative Care for Lung Transplant Recipients. Journal of palliative medicine ; 23 5;
  • Case, AH; Hellkamp, AS; Neely, ML; Bender, S; Dilling, DF; Gulati, M; Hotchkin, DL; Huie, TJ; Lancaster, L; Snyder, LD; Conoscenti, CS; Palmer, SM Associations between Patient-reported Outcomes and Death or Lung Transplant in Idiopathic Pulmonary Fibrosis. Data from the Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry. Annals of the American Thoracic Society ; 17 6;
  • Han, F; Dellacecca, ER; Barse, LW; Cosgrove, C; Henning, SW; Ankney, CM; Jaishankar, D; Yemelyanov, A; Krymskaya, VP; Dilling, DF; Le Poole, IC Adoptive T-Cell Transfer to Treat Lymphangioleiomyomatosis. American journal of respiratory cell and molecular biology ; 62 6;
  • Chung, PA; Dilling, DF Immunosuppressive strategies in lung transplantation. Annals of translational medicine ; 8 6;
  • Dilling, D Hiding in Plain Sight: A Tool to Reveal Undiagnosed ILD in Our PFT Labs. Chest ; 158 2;
  • Dilling, D The National Heart, Lung, and Blood Institute Lymphangioleiomyomatosis Registry: Making LAMonade out of LAMons. Chest ; 155 2;
  • Patel, NM; Kulkarni, T; Dilling, D; Scholand, MB Preoperative Evaluation of Patients With Interstitial Lung Disease. Chest ; 156 5;
  • Khawar, MU; Yazdani, D; Zhu, Z; Jandarov, R; Dilling, DF; Gupta, N Clinical outcomes and survival following lung transplantation in patients with lymphangioleiomyomatosis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation ; 38 9;
  • Formanek, PE; Dilling, DF Advances in the Diagnosis and Management of Invasive Fungal Disease. Chest ; 156 5;
  • Wajda, N; Zhu, Z; Jandarov, R; Dilling, DF; Gupta, N Clinical outcomes and survival following lung transplantation in patients with pulmonary Langerhans cell histiocytosis. Respirology (Carlton, Vic.) ; 25 6;
  • Crow, LD; Jambusaria-Pahlajani, A; Chung, CL; Baran, DA; Lowenstein, SE; Abdelmalek, M; Ahmed, RL; Anadkat, MJ; Arcasoy, SM; Berg, D; Bibee, KP; Billingsley, E; Black, WH; Blalock, TW; Bleicher, M; Brennan, DC; Brodland, DG; Brown, MR; Carroll, BT; Carucci, JA; Chang, TW; Chaux, G; Cusack, CA; Dilling, DF; Doyle, A; Emtiazjoo, AM; Ferguson, NH; Fosko, SW; Fox, MC; Goral, S; Gray, AL; Griffin, JR; Hachem, RR; Hall, SA; Hanlon, AM; Hayes, D; Hickey, GW; Holtz, J; Hopkins, RS; Hu, J; Huang, CC; Brian Jiang, SI; Kapnadak, SG; Kraus, ES; Lease, ED; Leca, N; Lee, JC; Leitenberger, JJ; Lim, MA; Longo, MI; Malik, SM; Mallea, JM; Menter, A; Myers, SA; Neuburg, M; Nijhawan, RI; Norman, DJ; Otley, CC; Paek, SY; Parulekar, AD; Patel, MJ; Patel, VA; Patton, TJ; Pugliano-Mauro, M; Ranganna, K; Ravichandran, AK; Redenius, R; Roll, GR; Samie, FH; Shin, T; Singer, JP; Singh, P; Soon, SL; Soriano, T; Squires, R; Stasko, T; Stein, JA; Taler, SJ; Terrault, NA; Thomas, CP; Tokman, S; Tomic, R; Twigg, AR; Wigger, MA; Zeitouni, NC; Arron, ST Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines. Transplant international : official journal of the European Society for Organ Transplantation ; 32 12;
  • Van Raemdonck, D; Keshavjee, S; Levvey, B; Cherikh, WS; Snell, G; Erasmus, M; Simon, A; Glanville, AR; Clark, S; D'Ovidio, F; Catarino, P; McCurry, K; Hertz, MI; Venkateswaran, R; Hopkins, P; Inci, I; Walia, R; Kreisel, D; Mascaro, J; Dilling, DF; Camp, P; Mason, D; Musk, M; Burch, M; Fisher, A; Yusen, RD; Stehlik, J; Cypel, M Donation after circulatory death in lung transplantation-five-year follow-up from ISHLT Registry. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation ; 38 12;
  • Swigris, JJ; Brown, KK; Abdulqawi, R; Buch, K; Dilling, DF; Koschel, D; Thavarajah, K; Tomic, R; Inoue, Y Patients' perceptions and patient-reported outcomes in progressive-fibrosing interstitial lung diseases. European respiratory review : an official journal of the European Respiratory Society ; 27 150;
  • Rynar, LZ; Merchant, MS; Dilling, DF Suicidal ideation in lung transplant recipients: A case series. Clinical transplantation ; 32 6;
  • Young, KA; Dilling, DF Ahead of the Curve: The Future of Lung Transplantation. Chest ;