Brahm Segal, MD
Brahm Segal, MD
Chair, Department of Internal Medicine
Chief, Infectious Diseases
Professor of Oncology
Director of Faculty Development
Member, Department of Immunology
Roswell Park Comprehensive Cancer Center
Professor of Medicine
Jacobs School of Medicine and Biomedical Sciences, University at Buffalo
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Areas of Expertise:
Infections in patients with cancer
Primary immune disorders
Aspergillosis
Special Interests:
NADPH oxidase as a critical regulator of host defense, inflammation, and injury Innate immune responses in the tumor microenvironment
Pathogenesis of invasive aspergillosis
Evaluate the role of NADPH oxidase in tumor immunology
Biography
Prior to joining Roswell Park, Dr. Segal completed a fellowship in Infectious Diseases at the National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD. He joined the staff of Roswell Park in 1999, as Consultant, Division of Infectious Disease, Department of Medicine, and was appointed Chief of the Division in 2000.
He is currently Professor of Medicine, Vice Chair of Faculty Development in the Department of Medicine at the University at Buffalo School of Medicine & Biomedical Sciences and Professor of Oncology and Member, Dept. of Immunology at Roswell Park. Dr. Segal has authored or co-authored more than 100 peer-reviewed publications as well as numerous book chapters.
Background
Education and Training:
MD - Albert Einstein College of Medicine, Yeshiva University, Bronx, NY
Residency:
New England Medical Center, Boston, MA
Fellowship:
National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD
Board Certification:
Diplomate, Internal Medicine, American Board of Internal Medicine
Infectious Disease, American Board of Internal Medicine
Dr. Segal and his lab studies innate immune responses to infection, injury, and the tumor microenvironment. One major interest of his lab is to study NADPH oxidase as a critical regulator of inflammation and host defense. NADPH oxidase is an emergency host defense pathway that is rapidly activated in response to certain microbial products, and converts molecular oxygen to superoxide anion and downstream reactive oxidant intermediates (ROIs).
In addition to its critical host defense role, NADPH oxidase also functions to restrain inflammation by modulating redox-sensitive innate immune pathways during infection and injury. Over the past few years, they have extended their research to understand how products of cellular necrosis and the innate immune responses they induce affect the tumor microenvironment, with a specific focus on ovarian cancer. They found that innate immune responses in the tumor microenvironment mimic those stimulated by infection and likely contribute to tumor progression.
Current Program
- Innate immune responses during infection and injury
- Innate immune responses as prognostic biomarkers and therapeutic targets in ovarian cancer
- Tam JM, Mansour MK, Khan NS, Seward M, Puranam S, Tanne A, Sokolovska A, Becker CE, Acharya M, Baird MA, Choi AM, Davidson MW, Segal BH, Lacy-Hulbert A, Stuart LM, Xavier RJ, Vyas JM. Dectin-1 dependent LC3 recruitment to phagosomes enhances fungicidal activity in macrophages. J Infect Dis. 2014 May 19. pii: jiu290. [Epub ahead of print] PMID: 24842831
- Pomakova D, Segal BH. Prevention of infection in cancer patients. Cancer Treat Res. 2014;161:485-511. doi: 10.1007/978-3-319-04220-6_16. PMID: 24706235
- Zucker SN, Fink EE, Bagati A, Mannava S, Bianchi-Smiraglia A, Bogner PN, Wawrzyniak JA, Foley C, Leonova KI, Grimm MJ, Moparthy K, Ionov Y, Wang J, Liu S, Sexton S, Kandel ES, Bakin AV, Zhang Y, Kaminski N, Segal BH, Nikiforov MA. Nrf2 amplifies oxidative stress via induction of Klf9. Mol Cell. 2014 Mar 20;53(6):916-28. doi: 10.1016/j.molcel.2014.01.033. Epub 2014 Mar 6. PMID: 24613345
- Röhm M, Grimm MJ, D'Auria AC, Almyroudis NG, Segal BH, Urban CF. NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis. Infect Immun. 2014 May;82(5):1766-77. doi: 10.1128/IAI.00096-14. Epub 2014 Feb 18. PMID: 24549323
- Li H, Han W, Polosukhin V, Yull FE, Segal BH, Xie CM, Blackwell TS. NF-κB inhibition after cecal ligation and puncture reduces sepsis-associated lung injury without altering bacterial host defense. Mediators Inflamm. 2013;2013:503213. doi: 10.1155/2013/503213. Epub 2013 Nov 18. PMID: 24347827
- Godoy HE, Khan AN, Vethanayagam RR, Grimm MJ, Singel KL, Kolomeyevskaya N, Sexton KJ, Parameswaran A, Abrams SI, Odunsi K, Segal BH. Myeloid-derived suppressor cells modulate immune responses independently of NADPH oxidase in the ovarian tumor microenvironment in mice. PLoS One. 2013 Jul 26;8(7):e69631. doi: 10.1371/journal.pone.0069631. Print 2013. PMID: 23922763
- Han W, Li H, Cai J, Gleaves LA, Polosukhin VV, Segal BH, Yull FE, Blackwell TS. NADPH oxidase limits lipopolysaccharide-induced lung inflammation and injury in mice through reduction-oxidation regulation of NF-κB activity. J Immunol. 2013 May 1;190(9):4786-94. doi: 10.4049/jimmunol.1201809. Epub 2013 Mar 25. PMID: 23530143
- Grimm MJ, Vethanayagam RR, Almyroudis NG, Dennis CG, Khan AN, D'Auria AC, Singel KL, Davidson BA, Knight PR, Blackwell TS, Hohl TM, Mansour MK, Vyas JM, Röhm M, Urban CF, Kelkka T, Holmdahl R, Segal BH. Monocyte- and macrophage-targeted NADPH oxidase mediates antifungal host defense and regulation of acute inflammation in mice. J Immunol. 2013 Apr 15;190(8):4175-84. doi: 10.4049/jimmunol.1202800. Epub 2013 Mar 15. PMID: 23509361
- Zaynagetdinov R, Sherrill TP, Kendall PL, Segal BH, Weller KP, Tighe RM, Blackwell TS. Identification of myeloid cell subsets in murine lungs using flow cytometry. Am J Respir Cell Mol Biol. 2013 Aug;49(2):180-9. doi: 10.1165/rcmb.2012-0366MA. PMID: 23492192
- Almyroudis NG, Grimm MJ, Davidson BA, Röhm M, Urban CF, Segal BH. NETosis and NADPH oxidase: at the intersection of host defense, inflammation, and injury. Front Immunol. 2013 Mar 1;4:45. doi: 10.3389/fimmu.2013.00045. eCollection 2013. PMID: 23459634
- Davidson BA, Vethanayagam RR, Grimm MJ, Mullan BA, Raghavendran K, Blackwell TS, Freeman ML, Ayyasamy V, Singh KK, Sporn MB, Itagaki K, Hauser CJ, Knight PR, Segal BH. NADPH oxidase and Nrf2 regulate gastric aspiration-induced inflammation and acute lung injury. J Immunol. 2013 Feb 15;190(4):1714-24. doi: 10.4049/jimmunol.1202410. Epub 2013 Jan 7. PMID: 23296708
- Jhingran A, Mar KB, Kumasaka DK, Knoblaugh SE, Ngo LY, Segal BH, Iwakura Y, Lowell CA, Hamerman JA, Lin X, Hohl TM. Tracing conidial fate and measuring host cell antifungal activity using a reporter of microbial viability in the lung. Cell Rep. 2012 Dec 27;2(6):1762-73. doi: 10.1016/j.celrep.2012.10.026. Epub 2012 Nov 29. PMID: 23200858
- Han W, Li H, Segal BH, Blackwell TS. Bioluminescence imaging of NADPH oxidase activity in different animal models. J Vis Exp. 2012 Oct 22;(68). pii: 3925. doi: 10.3791/3925. PMID: 23117583
- Banik D, Khan AN, Walseng E, Segal BH, Abrams SI. Interferon regulatory factor-8 is important for histone deacetylase inhibitor-mediated antitumor activity. PLoS One. 2012;7(9):e45422. doi: 10.1371/journal.pone.0045422. Epub 2012 Sep 19. PMID: 23028998
- Capitano ML, Nemeth MJ, Mace TA, Salisbury-Ruf C, Segal BH, McCarthy PL, Repasky EA. Elevating body temperature enhances hematopoiesis and neutrophil recovery after total body irradiation in an IL-1-, IL-17-, and G-CSF-dependent manner. Blood. 2012 Sep 27;120(13):2600-9. Epub 2012 Jul 17. PMID: 22806894
- Almyroudis NG, Segal BH. Transmission of resistant bacteria in intensive care. N Engl J Med. 2011 Aug 25;365(8):762-3; author reply 764-5. doi: 10.1056/NEJMc1107077#SA4. No abstract available. PMID: 21864175
- Jarkowski A 3rd, Forrest A, Sweeney RP, Tan W, Segal BH, Almyroudis N, Wang ES, Wetzler M.Characterization of vancomycin pharmacokinetics in the adult acute myeloid leukemia population.Journal of oncology pharmacy practice 2012; 181:91-96
- Banik D, Khan AN, Walseng E, Segal BH, Abrams SI. Interferon regulatory factor-8 is important for histone deacetylase inhibitor-mediated antitumor activity. PloS one 2012; 79:e45422
- Pizzolla A, Hultqvist M, Nilson B, Grimm MJ, Eneljung T, Jonsson I-M, Verdrengh M, Kelkka T, Gjertsson I,Segal BH, Holmdahl R. Reactive oxygen species produced by the NADPH oxidase 2 complex in monocytes protect mice from bacterial infections. Journal of immunology (Baltimore, Md. : 1950) 2012;18810:5003-5011
- Segal BH, Grimm MJ, Khan ANH, Han W, Blackwell TS. Regulation of innate immunity by NADPH oxidase.Free radical biology and medicine 2012; 531:72-80
- Segal BH, Veys P, Malech H, Cowan MJ. Chronic granulomatous disease: lessons from a rare disorder.Biology of blood and marrow transplantation 2011; 171 Suppl.:S123-S131
- Almyroudis NG, Wetzler M, McCarthy PL Jr, Wang ES, Wongkittiroch K, Hazamy PA, Samonis G, Hahn T, Lesse AJ, Segal BH. Molecular epidemiology and risk factors for colonization by vancomycin-resistant Enterococcus in patients with hematologic malignancies. Infection control and hospital epidemiology2011; 325:490-496
- Lugade AA, Vethanayagam RR, Nasirikenari M, Bogner PN, Segal BH, Thanavala Y. Nrf2 regulates chronic lung inflammation and B-cell responses to nontypeable Haemophilus influenzae. American journal of respiratory cell and molecular biology 2011; 453:557-565
- Segal BH, Cornely O, Bromley M. Proceedings from the 4th Advances Against Aspergillosis conference.Medical mycology 2011; 49Suppl. 1:S5-S6
- Grimm MJ, Robert Vethanayagam R, Almyroudis NG, Lewandowski D, Rall N, Blackwell TS, Segal BH.Role of NADPH oxidase in host defense against aspergillosis. Medical mycology 2011; 49Suppl. 1:S144-S149
- Vethanayagam RR, Almyroudis NG, Grimm MJ, Lewandowski DC, Pham CT, Blackwell TS, Petraitiene R, Petraitis V, Walsh TJ, Urban CF, Segal BH. Role of NADPH oxidase versus neutrophil proteases in antimicrobial host defense. PloS one 2011; 612:e28149
- Rahman M, Segal BH. Thematic issue: immunity, inflammation and fungal infections. Immunological investigations 2011; 407-8:670-675
- Nasirikenari M, Chandrasekaran EV, Matta KL, Segal BH, Bogner PN, Lugade AA, Thanavala Y, Lee JJ, Lau JTY. Altered eosinophil profile in mice with ST6Gal-1 deficiency: an additional role for ST6Gal-1 generated by the P1 promoter in regulating allergic inflammation. Journal of leukocyte biology 2010;873:457-466
- Almyroudis NG , Segal BH. Antifungal prophylaxis and therapy in patients with hematological malignancies and hematopoietic stem cell transplant recipients. Expert review of anti-infective therapy2010; 812:1451-1466
- Segal BH, Christman JW, Sporn MB, Chan J, Vinh DC, Holland SM, Romani LR, Gaffen SL, Freeman ML, Minderman H, Wallace PK, Capitano M, Han W, Bushey JJ, Joo M, Bhatti Z, Feminella J, Dennis CG, Vethanayagam RR, Yull FE, Blackwell TS. NADPH oxidase limits innate immune responses in the lungs in mice. PloS one 2010; 53:e9631
- Hinckley KM , Liddell GM , Segal BH. Protect yourself from infection. Coping with cancer 2010; 244:16
- Sherif R, Segal BH. Pulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications. Current opinion in pulmonary medicine 2010; 163:242-250
- Segal BH. Aspergillosis. New England journal of medicine 2009; 36018:1870-1884
- Segal BH, Romani L, Puccetti P. Chronic granulomatous disease. Cellular and molecular life sciences : CMLS 2009; 664:553-558
- Marr KA, Bow E, Chiller T, Maschmeyer G, Ribaud P, Segal B, Steinbach W, Wingard JR, Nucci M. Fungal infection prevention after hematopoietic cell transplantation. Bone marrow transplantation 2009;448:483-487
- Partridge-Hinckley K, Liddell GM, Almyroudis NG, Segal BH. Infection control measures to prevent invasive mould diseases in hematopoietic stem cell transplant recipients. Mycopathologia 2009;1686:329-337
- Segal BH, Romani LR. Invasive aspergillosis in chronic granulomatous disease. Medical mycology 2009;47 Suppl. 1:S282-S290
- Almyroudis NG, Fabian J, Hahn T, Segal BH, Wetzler M, McCarthy Jr PL. Late infectious complications after cord blood stem cell transplantation. European journal of clinical microbiology and infectious diseases 2009; 2811:1405-1408
- Almyroudis NG, Segal BH. Prevention and treatment of invasive fungal diseases in neutropenic patients. Current opinion in infectious diseases 2009; 224:385-393
- Parameswaran GI, Segal BH, Almyroudis NG. Antifungal agents in hematopoietic stem cell transplantation. Current pharmaceutical design 2008; 1420:2011-2021
- Gonzalez AV, Ullmann AJ, Almyroudis NG, Segal BH. Broad-spectrum antifungal prophylaxis in patients with cancer at high risk for invasive mold infections: point. Journal of the National Comprehensive Cancer Network : JNCCN 2008; 62:175-182
- Romani L, Segal BH, Grohmann U, Fioretti MC, Bistoni F, Vacca C, Zelante T, D'Angelo C, Montagnoli C, De Luca A, Fallarino F, Puccetti P. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature 2008; 4517175:211-215
- Segal BH, Pappas PG, Bennett JE, Kontoyiannis DP, Cordonnier C, Viviani MA, Bille J, Almyroudis NG, Wheat LJ, Graninger W, Bow EJ, Holland SM, Kullberg BJ, Dismukes WE, Baden LR, Graybill JR, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, Walsh TJ, Maertens J, Patterson TF, Perfect JR, Dupont B, Wingard JR, Calandra T, Kauffman CA, De Pauw BE. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clinical infectious diseases2008; 475:674-683
- Segal BH, Rolston K, Engemann AM, Montoya JG, Marcucci G, Mackler E, King E, Kaul DR, Karp JE, Ito JI, Ison MG, Greene JN, Gelfand M, Dubberke E, Casper C, Brown AE, Baden LR, Freifeld AG, The AS.Prevention and treatment of cancer-related infections. Journal of the National Comprehensive Cancer Network : JNCCN 2008; 62:122-174
- De Pauw B, Kullberg BJ, Marr KA, Munoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, Kibbler CC, Hope WW, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clinical infectious diseases2008; 4612:1813-1821
- Walsh TJ, Patterson TF, Wingard JR, van Burik JA, Stevens DA, Steinbach WJ, Segal BH, Morrison VA, Marr KA, Kontoyiannis DP, Herbrecht R, Denning DW, Anaissie EJ, Infectious Diseases Society of America.Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America.Clinical infectious diseases 2008; 463:327-360
- Segal BH, Davidson BA, Hutson AD, Russo TA, Holm BA, Mullan B, Habitzruther M, Holland SM, Knight PR 3rd. Acid aspiration-induced lung inflammation and injury are exacerbated in NADPH oxidase-deficient mice. American journal of physiology. Lung cellular and molecular physiology 2007;2923:L760-L768
- Segal BH, Freifeld AG. Antibacterial prophylaxis in patients with neutropenia. Journal of the National Comprehensive Cancer Network : JNCCN 2007; 52:235-242
- Segal BH, Steinbach WJ. Combination antifungals: an update. Expert review of anti-infective therapy2007; 55:883-892
- Battiwalla M, Hahn T, Padmanabhan S, Nakamura R, Wallace PK, Segal BH, Almyroudis NG, Radovic M, Bajwa RP, Wu Y, McCarthy PL Jr. Ganciclovir inhibits lymphocyte proliferation by impairing DNA synthesis. Biology of blood and marrow transplantation 2007; 137:765-770
- Stergiopoulou T, Segal B, Dad L, Harrington S, Roden M, Schaufele R, Kleiner DE, Roilides E, Meletiadis J, Walsh TJ. Host-dependent patterns of tissue injury in invasive pulmonary aspergillosis. American journal of clinical pathology 2007; 1273:349-355
- Parameswaran IG, Segal BH. Immunotherapy for fungal infections with special emphasis on central nervous system infections. Neurology India 2007; 553:260-266
- Battiwalla M, McCarthy PL, Becker J, Smith P, Elefante A, Abdelhalim A, McCarthy A, Almyroudis NG, Paplham P, Segal BH. Leflunomide failure to control recurrent cytomegalovirus infection in the setting of renal failure after allogeneic stem cell transplantation. Transplant infectious disease 2007; 91:28-32
- Brun YF, Dennis CG, Greco WR, Bernacki RJ, Pera PJ, Bushey JJ, Youn RC, White DB, Segal BH. Modeling the combination of amphotericin B, micafungin, and nikkomycin Z against Aspergillus fumigatus in vitro using a novel response surface paradigm. Antimicrobial agents and chemotherapy 2007;515:1804-1812
- Segal BH, Almyroudis NG, Battiwalla M, Herbrecht R, Perfect JR, Walsh TJ, Wingard JR. Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts.Clinical infectious diseases 2007; 443:402-409
- Segal BH. Role of macrophages in host defense against aspergillosis and strategies for immune augmentation. Oncologist 2007; 12 Suppl. 2:7-13
- Gupta S, Kwon-Chung J, Varma A, Paplham P, Ball D, Proefrock AD, McCarthy PL, Bambach BJ, Battiwalla M, Almyroudis NG, Segal BH. Successful treatment of disseminated fusariosis with posaconazole during neutropenia and subsequent allogeneic hematopoietic stem cell transplantation. Transplant infectious disease 2007; 92:156-160
- Walsh TJ, Segal BH, Stevens DA, van Burik JA, White CS, Corcoran G, Gogate J, Krishna G, Pedicone L, Hardalo C, Ribaud P, Louie A, Langston A, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, Greene RE, Hachem R, Hadley S, Herbrecht R, Perfect JR. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clinical infectious diseases 2007; 441:2-12
- Padmanabhan S, Battiwalla M, Hahn T, Ball D, Paplham P, Brown K, Segal BH, McCarthy P Jr, Almyroudis NG. Two cases of hepatic zygomycosis in allogeneic stem cell transplant recipients and review of literature. Transplant infectious disease 2007; 92:148-152