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NINDSNIMHNICHDNIDCDNEINIDCRNIANIAAANIDANHGRI NCCIHNIEHS

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Investigator

Bibiana Bielekova, M.D.

Neuroimmunological Diseases Unit


Building 10 Room 5C103
10 Center Drive MSC1400
Bethesda MD 20892-
Office: (301) 402-4488

Fax: (301) 402-0373
Bibi.Bielekova@nih.gov

Dr. Bielekova received an M.D. degree in 1993 from Comenius University in Bratislava, Slovakia. After a medical internship at SUNY Downstate, Medical Center in Brooklyn and a neurology residency at Boston University, she did a 3 year postdoctoral research fellowship at the NIH/NINDS/Neuroimmunology Branch (NIB). She remained at NIB for additional 5 years as a staff physician, focusing on development of novel therapies for multiple sclerosis (MS). In 2005, she became associate professor of neurology with tenure and director of the Waddell Center for MS at University of Cincinnati. In 2008, she moved back to NINDS as an investigator. Her laboratory is studying mechanisms of immunoregulation and immune-mediated central nervous system (CNS) tissue injury in MS and other neuroimmunological diseases with a long-term goal of developing effective therapies. In addition, Dr. Bielekova is a principal investigator on several innovative protocols including adaptively-designed Phase I/II clinical trials.



Our long-term goal is to understand the mechanisms that participate in central nervous system (CNS) injury and those that have neuroprotective functions to develop effective therapies for neuroimmunological diseases, especially multiple sclerosis (MS). Because observational studies cannot determine causal relationships, we use proof-of-principle interventional trials supported by biomarker/mechanistic studies and mathematical modeling to investigate major hypotheses about the pathophysiology of MS.  

Our studies revealed that relapsing-remitting MS (RRMS) and progressive MS are categorical descriptions of early, versus evolved stages of the identical continuous disease process characterized by aberrant activation of adaptive immunity that targets CNS tissue, which evolves by progressive intrathecal compartmentalization and terminal differentiation of T and B cells to a treatment-resistant stage. The multiplicity of potential pathogenic processes in evolved MS makes it unlikely that a single therapeutic agent will have major clinical efficacy. Analogous to cardiovascular diseases, effective therapy will require combinations of therapeutics that target patient-specific drivers of disability. We believe that the development of such combination treatments requires the ability to reliably measure the diverse CNS pathophysiological processes in living people and thereby define process-specific biomarkers to use as outcomes in Phase II trials. Indeed, using cerebrospinal fluid (CSF) biomarkers and systems biology methodology we have defined (and validated in an independent cohort) molecular signature(s) that differentiate MS from other CNS diseases and those that can reliably measure the levels of intrathecally-compartmentalized inflammation and CNS tissue destruction. Our goal is to formulate (and validate) a framework where a combinatorial CSF biomarker(s) can provide reliable diagnostic, prognostic and therapeutically-predictive information that will empower neurologists to practice precision medicine.


Staff Image
  • Shania Dowd, DNP, CRNP, Lt, USPHS
    Patient Care Coordinator
    301-496-8911

  • Laura Kannaiana, R.N.
    Research Nurse
    301-402-9373

  • Peter Kosa, Ph.D.
    Contract Scientist
    301-594-5104

  • Ruturaj Masvekar, Ph.D.
    Visiting Fellow

  • Jordan Mizrahi, DNP, CRNP, Lt, USPHS
    Special Volunteer

  • John Park, B.S.
    Post baccalaureate IRTA Fellow

  • Elena Romm, M.S.
    Research Assistant
    (301) 594-2697

  • Jason Stein, B.A.
    Post baccalaureate IRTA Fellow

  • Marco Tapia Maltos, DNP, CRNP, Lt, USPHS
    Visiting Medical Student

  • Ann Marie Weideman, M.S.
    Post baccalaureate IRTA Fellow

  • Alison Wichman, M.D.
    Clinician
    301-451-9298

  • 1) Lin YC,Winokur P,Blake A,Wu T,Manischewitz J,King LR,Romm E,Golding H,Bielekova B (2016)
  • Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccination.
  • Neurol Neuroimmunol Neuroinflamm , 3, e196
  • 2) Kosa P,Komori M,Waters R,Wu T,Cortese I,Ohayon J,Fenton K,Cherup J,Gedeon T,Bielekova B (2016)
  • Novel composite MRI scale correlates highly with disability in multiple sclerosis patients.
  • Mult Scler Relat Disord, 4, 526-35
  • 3) Natrajan MS,Komori M,Kosa P,Johnson KR,Wu T,Franklin RJ,Bielekova B (2016)
  • Pioglitazone regulates myelin phagocytosis and multiple sclerosis monocytes.
  • Ann Clin Transl Neurol, 2, 1071-84
  • 4) Lin YC,Winokur P,Blake A,Wu T,Manischewitz J,King LR,Romm E,Golding H,Bielekova B (2016)
  • Insufficient disease inhibition by intrathecal rituximab in progressive multiple sclerosis.
  • Ann Clin Transl Neurol, 3, 166-79
  • 5) Kosa P,Ghazali D,Tanigawa M,Barbour C,Cortese I,Kelley W,Snyder B,Ohayon J,Fenton K,Lehky T,Wu T,Greenwood M,Nair G,Bielekova B (2016)
  • Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment.
  • Front Neurol, 7, 131
  • 6) Elkins J, Sheridan J, Amaravadi L, Riester K, Selmaj K, Bielekova B, Parr E, Giovannoni G (2015)
  • CD56(bright) natural killer cells and response to daclizumab HYP in relapsing-remitting MS.
  • Neurol Neuroimmunol Neuroinflamm, 2(2), e65
  • 7) Komori M, Blake A, Greenwood M, Lin YC, Kosa P, Ghazali D, Winokur P, Natrajan M, Wuest SC, Romm E, Panackal AA, Williamson PR, Wu T, Bielekova B (2015)
  • Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis.
  • Ann Neurol, 78(1), 3-20
  • 8) Bielekova B, McDermott MP (2015)
  • Will CSF biomarkers guide future therapeutic decisions in multiple sclerosis?
  • Neurology, 84(16), 1620-1
  • 9) Lin YC, Winokur P, Blake A, Wu T, Romm E, Bielekova B (2015)
  • Daclizumab reverses intrathecal immune cell abnormalities in multiple sclerosis.
  • Ann Clin Transl Neurol, 2(5), 445-55
  • 10) Panackal AA, Wuest SC, Lin YC, Wu T, Zhang N, Kosa P, Komori M, Blake A, Browne SK, Rosen LB, Hagen F, Meis J, Levitz SM, Quezado M, Hammoud D, Bennett JE, Bielekova B, Williamson PR (2015)
  • Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis.
  • PLOS Pathog, 11(5), e1004884
  • 11) Wuest SC, Mexhitaj I, Chai NR, Romm E, Scheffel J, Xu B, Lane K, Wu T, Bielekova B (2014)
  • A complex role of herpes viruses in the disease process of multiple sclerosis.
  • PLoS One, 9(8), e105434
  • 12) Zhang Y, McClellan M, Efros L, Shi D, Bielekova B, Tang MT, Vexler V, Sheridan JP. (2014)
  • Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis.
  • Mult Scler, 20(2), 156-64
  • 13) Bielekova B, Vodovotz Y, An G, Hallenbeck J. (2014)
  • How implementation of systems biology into clinical trials accelerates understanding of diseases.
  • Front Neurol, 5, 102
  • 14) Han S, Lin YC, Wu T, Salgado AD, Mexhitaj I, Wuest SC, Romm E, Ohayon J, Goldbach-Mansky R, Vanderver A, Marques A, Toro C, Williamson P, Cortese I, Bielekova B. (2014)
  • Comprehensive immunophenotyping of cerebrospinal fluid cells in patients with neuroimmunological diseases.
  • J Immunol, 192(6), 2551-63
  • 15) Oh J, Saidha S, Cortese I, Ohayon J, Bielekova B, Calabresi PA, Newsome SD (2014)
  • Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis.
  • Neurology, 82(11), 984-8
  • 16) Bielekova B. (2013)
  • Daclizumab therapy for multiple sclerosis
  • Neurotherapeutics, 10(1), 55-67
  • 17) Ohayon J, Oh U, Richert N, Martin J, Vortmeyer A, McFarland H, Bielekova B. (2013)
  • CNS vasculitis in a patient with MS on daclizumab monotherapy.
  • Neurology, 80(5), 453-7
  • 18) Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, Phan GQ, Hughes MS, Kammula US, Miller AD, Hessman CJ, Stewart AA, Restifo NP, Quezado MM, Alimchandani M, Rosenberg AZ, Nath A, Wang T, Bielekova B, Wuest SC, Akula N, McMahon FJ, Wilde S, Mosetter B, Schendel DJ, Laurencot CM, Rosenberg SA. (2013)
  • Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy.
  • J Immunother, 36(2), 133-51
  • 19) Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, Shiee N, McFarland H, Bielekova B, Reich DS. (2013)
  • The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis.
  • Mult Scler Relat Disord, 2(2), 133-140
  • 20) Ikonomidou VN, Richert ND, Vortmeyer A, Tovar-Moll F, Bielekova B, Cook NE, Duyn JH, Bagnato F (2013)
  • Evolution of tumefactive lesions in multiple sclerosis: a 12-year study with serial imaging in a single patient.
  • Mult Scler, 19(11), 1539-43
  • 21) Bielekova B, McFarland H. (2012)
  • Comment on "Interleukin-2/interleukin-2 antibody therapy induces target organ natural killer cells that inhibit central nervous system inflammation".
  • Ann Neurol, 71(1), 148-9
  • 22) Jia Y, Wu T, Jelinek CA, Bielekova B, Chang L, Newsome S, Gnanapavan S, Giovannoni G, Chen D, Calabresi PA, Nath A, Cotter RJ. (2012)
  • Development of protein biomarkers in cerebrospinal fluid for secondary progressive multiple sclerosis using selected reaction monitoring mass spectrometry (SRM-MS).
  • Clin Proteomics, 9(1), 9
  • 23) Perry JS, Han S, Xu Q, Herman ML, Kennedy LB, Csako G, Bielekova B. (2012)
  • Inhibition of LTi cell development by CD25 blockade is associated with decreased intrathecal inflammation in multiple sclerosis
  • Sci Transl Med, 4(145), 145ra106
  • 24) Bielekova B, Komori M, Xu Q, Reich DS, Wu T. (2012)
  • Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation
  • PLoS One, 7(11), e48370
  • 25) Jiang W, Chai NR, Maric D, Bielekova B. (2011)
  • Unexpected role for granzyme K in CD56bright NK cell-mediated immunoregulation of multiple sclerosis
  • J Immunol, 187(2), 871-90
  • 26) Wuest SC, Edwan JH, Martin JF, Han S, Perry JS, Cartagena CM, Matsuura E, Maric D, Waldmann TA, Bielekova B. (2011)
  • A vital role for IL-2 trans-presentation in DC-mediated T cell activation as revealed by daclizumab therapy
  • Nat Med, 17(5), 604-609
  • 27) Bielekova B, Richert N, Herman ML, Ohayon J, Waldmann TA, McFarland H, Martin R, Blevins G. (2011)
  • Intrathecal effects of daclizumab treatment of multiple sclerosis
  • Neurology, 77(21), 1877-1886
  • 28) Gaitán MI, Shea CD, Evangelou IE, Stone RD, Fenton KM, Bielekova B, Massacesi L, Reich DS. (2011)
  • Evolution of the blood-brain barrier in newly forming multiple sclerosis lesions.
  • Ann Neurol, 70(1), 22-9
  • 29) Nussenblatt RB, Bielekova B, Childs R, Krensky A, Strober W, Trinchieri G. (2010)
  • National Institutes of Health Center for Human Immunology Conference, September 2009.
  • Ann N Y Acad Sci, 1200, E1-E23
  • 30) Bielekova B, Becker BL. (2010)
  • Monoclonal antibodies in MS: mechanisms of action
  • Neurology, 74 (Suppl 1), S31-S40
  • 31) Martin JF, Perry JS, Jakhete NR, Wang X, Bielekova B. (2010)
  • An IL-2 paradox: Blocking CD25 on T Cells Induces IL-2-driveb Activation of CD56bright NK cells
  • J Immunol, 185(2), 1311-1320
  • 32) Bielekova B, Richert N, Howard T, Packer AN, Blevins G, Ohayon J, McFarland HF, Stürzebecher CS, Martin R. (2009)
  • Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to inhibit blood--brain barrier disruption in multiple sclerosis.
  • Mult Scler, 15(10), 1206-14
  • 33) Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R. (2009)
  • The anti-CD25 Antibody Daclizumab Inhibits Inflammation and Stabilizes Disease Progression in MS
  • Arch Neurol, 66(4), 483-489
  • 34) Muraro PA, Bielekova B. (2007)
  • Emerging therapies for multiple sclerosis.
  • Neurotherapeutics , 4 (4), 676-692
  • 35) Martin R, Bielekova B, Hohlfeld R, Utz U. (2006)
  • Biomarkers in multiple sclerosis.
  • Dis Markers, 22(4), 183-5
  • 36) Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R. (2006)
  • Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Ra-targeted therapy (daclizumab) in multiple sclerosis
  • Proc Natl Acad Sci U S A, 103(15), 5941-5946
  • 37) Bielekova B, Kadom N, Fisher E, Jeffries N, Ohayon J, Richert N, Howard T, Bash CN, Frank JA, Stone L, Martin R, Cutter G, McFarland HF. (2005)
  • MRI as a marker for disease heterogeneity in multiple sclerosis.
  • Neurology , 65(7), 1071-1076
  • 38) Bielekova B, Sung MH, Kadom N, Simon R, McFarland H, Martin R. (2004)
  • Expansion and Functional Relevance of High-Avidity Myelin Specific T Cells in Multiple Sclerosis
  • J Immunol, 172(6), 3893-3904
  • 39) Bielekova B, Martin R. (2004)
  • Development of biomarkers in multiple sclerosis.
  • Brain, 127, 1463-78
  • 40) Bielekova B, Richert N, Howard T, Blevins G, Markovic-Plese S, McCartin J, Frank JA, Würfel J, Ohayon J, Waldmann TA, McFarland HF, Martin R. (2004)
  • Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta.
  • Proc Natl Acad Sci U S A, 101(23), 8705-8
  • 41) Muraro PA, Wandinger KP, Bielekova B, Gran B, Marques A, Utz U, McFarland HF, Jacobson S, Martin R. (2003)
  • Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders.
  • Brain, 126, 20-31
  • 42) Markovic-Plese S, Bielekova B, Kadom N, Leist TP, Martin R, Frank JA, McFarland HF. (2003)
  • Longitudinal MRI study: the effects of azathioprine in MS patients refractory to interferon beta-1b.
  • Neurology, 60(11), 1849-51
  • 43) Bomprezzi R, Ringnér M, Kim S, Bittner ML, Khan J, Chen Y, Elkahloun A, Yu A, Bielekova B, Meltzer PS, Martin R, McFarland HF, Trent JM. (2003)
  • Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease.
  • Hum Mol Genet, 12(17), 2191-9
  • 44) Wandinger KP, Stürzebecher CS, Bielekova B, Detore G, Rosenwald A, Staudt LM, McFarland HF, Martin R. (2001)
  • Complex immunomodulatory effects of interferon-beta in multiple sclerosis include the upregulation of T helper 1-associated marker genes.
  • Ann Neurol, 50(3), 349-57
  • 45) Martin R, Gran B, Zhao Y, Markovic-Plese S, Bielekova B, Marques A, Sung MH, Hemmer B, Simon R, McFarland HF, Pinilla C. (2001)
  • Molecular mimicry and antigen-specific T cell responses in multiple sclerosis and chronic CNS Lyme disease.
  • J Autoimmun, 16(3), 187-92
  • 46) Bielekova B, Martin R. (2001)
  • Antigen-specific immunomodulation via altered peptide ligands
  • J Mol Med (Berl), 79, 552-565
  • 47) Bielekova B, Goodwin B, Richert N, Cortese I, Kondo T, Afshar G, Gran B, Eaton J, Antel J, Frank JA, McFarland HF, Martin R. (2000)
  • Encephalitogenic Potential of Myelin Basic Protein Peptide (83-99) in Multiple Sclerosis - Results of a phase II clinical trial with an altered peptide ligand
  • Nat Med, 6(10), 1167-1175
  • 48) Bielekova B, Lincoln A, McFarland H, Martin R. (2000)
  • Therapeutic potential of phosphodiesterase-4 and -3 inhibitors in Th1-mediated autoimmune diseases.
  • J Immunol, 164(2), 1117-24
  • 49) Holz A, Bielekova B, Martin R, Oldstone MB (2000)
  • Myelin-associated oligodendrocytic basic protein: identification of an encephalitogenic epitope and association with multiple sclerosis.
  • J Immunol, 164(2), 1103-9
  • 50) Gran B, Tranquill LR, Chen M, Bielekova B, Zhou W, Dhib-Jalbut S, Martin R. (2000)
  • Mechanisms of immunomodulation by glatiramer acetate.
  • Neurology, 55(11), 1704-14
  • 51) Martin R, Bielekova B, Gran B, McFarland HF. (2000)
  • Lessons from studies of antigen-specific T cell responses in Multiple Sclerosis.
  • J Neural Transm, 60, 361-73
  • 52) Muraro PA, Pette M, Bielekova B, McFarland HF, Martin R. (2000)
  • Human autoreactive CD4+ T cells from naive CD45RA+ and memory CD45RO+ subsets differ with respect to epitope specificity and functional antigen avidity.
  • J Immunol, 164(10), 5474-81
  • 53) Muraro PA, Leist T, Bielekova B, McFarland HF. (2000)
  • VLA-4/CD49d downregulated on primed T lymphocytes during interferon-beta therapy in multiple sclerosis.
  • J Neuroimmunol, 111(1-2), 186-94
  • 54) Bielekova B, Muraro PA, Golestaneh L, Pascal J, McFarland HF, Martin R. (1999)
  • Preferential expansion of autoreactive T lymphocytes from the memory T-cell pool by IL-7.
  • J Neuroimmunol, 100(1-2), 115-23
  • 56) Hemmer B, Gran B, Zhao Y, Marques A, Pascal J, Tzou A, Kondo T, Cortese I, Bielekova B, Straus SE, McFarland HF, Houghten R, Simon R, Pinilla C, Martin R. (1999)
  • Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease.
  • Nat Med, 5(12), 1375-1382
  • 57) Jiang H, Bielekova B, Okazaki H, Clarence-Smith K, Johnson KP, Bergey G, Martin R, Dhib-Jalbut S. (1999)
  • The effect of vesnarinone on TNF alpha production in human peripheral blood mononuclear cells and microglia: a preclinical study for the treatment of multiple sclerosis.
  • J Neuroimmunol, 97(1-2), 134-45
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