![](https://i.irp.nih.gov/pi/0010013292.jpg)
Bibiana Bielekova, M.D.
Senior Investigator
Neuroimmunological Diseases Section
NIAID/DIR
Research Topics
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.
Biography
Dr. Bielekova is now a Senior Investigator with NIAID. Her office address remains the same, she can be reached by email at [email protected] or phone at 240-669-2724. 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. In 2018, Dr. Bielekova transferred as a Senior Investigator to NIAID. 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.
Selected Publications
- Barbour C, Kosa P, Komori M, Tanigawa M, Masvekar R, Wu T, Johnson K, Douvaras P, Fossati V, Herbst R, Wang Y, Tan K, Greenwood M, Bielekova B. Molecular-based diagnosis of multiple sclerosis and its progressive stage. Ann Neurol. 2017;82(5):795-812.
- 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. Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis. Ann Neurol. 2015;78(1):3-20.
- Kosa P, Barbour C, Varosanec M, Wichman A, Sandford M, Greenwood M, Bielekova B. Molecular models of multiple sclerosis severity identify heterogeneity of pathogenic mechanisms. Nat Commun. 2022;13(1):7670.
- Perry JS, Han S, Xu Q, Herman ML, Kennedy LB, Csako G, Bielekova B. Inhibition of LTi cell development by CD25 blockade is associated with decreased intrathecal inflammation in multiple sclerosis. Sci Transl Med. 2012;4(145):145ra106.
- Wuest SC, Edwan JH, Martin JF, Han S, Perry JS, Cartagena CM, Matsuura E, Maric D, Waldmann TA, Bielekova B. A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy. Nat Med. 2011;17(5):604-9.
Related Scientific Focus Areas
This page was last updated on Monday, March 25, 2024