Dr. Nichol E. Holodick did her undergraduate work at Northeastern University in Boston, Massachusetts. She received her PhD in Immunology from Boston University in 2009, working on signaling and development of B-1 cells. Dr. Holodick expanded her work on B-1 cells during a postdoctoral fellowship at the Feinstein Institute for Medical Research. During this time, she focused her research on the role of B-1 cells in infection during aging.
B-1 cells are essential for immediate protection and therefore survival against bacterial and vial infections. Murine B-1a cells are defined by unique surface marker expression (CD45loCD5+IgMhighIgDlowCD43+CD19highMAC1+) as well distinct functional characteristics. B-1a cells arise mainly during fetal development, and their persistence throughout adult life is maintained through self-renewal.
Our work is focused on how B-1 cells change with age in relation to their ability to protect against infection. We study these changes with age in relation to B-1 cell development and mechanism of antibody secretion. Streptococcus pneumoniae is the most common cause of pneumonia, which claims the lives of people over the age of 65 seven times more frequently than those aged 5-49. B-1a cells provide immediate and essential protection from S. pneumoniae through production of natural antibody. Our research is aimed at understanding the mechanism of natural Ig change with age but also during disease.
Sickle cell disease (SCD) is one of the most common blood disorders affecting millions of people worldwide. One of the major causes of death for those with SCD is infection, in particular Streptococcus pneumoniae infection. Despite current interventions such as prophylactic antibiotics and vaccination, pneumococcal infection still poses a great risk to sickle cell patients. Our current studies are aimed at understanding whether B-1a cells and the protective antibodies they produce are altered in sickle cell disease.
Title: Research Assistant
PhD in Immunology 2003 - 2009
Boston University, Boston, MA
Department of Pathology
B.S. in Biology 1998 - 2003
Northeastern University, Boston, MA
Postdoctoral Fellow, The Feinstein Institute for Medical Research, Manhasset, NY
Honors and Awards
AAI Public Policy Fellow 2014-2015
IEDB Workshop Travel Fellowship Award. October 2013.
Immune Epitope Database user workshop training.
Merinoff Symposium: Systemic Lupus: Bringing science to the patient. September, 2008
Poster presentation award, poster title: Origin of Constitutive pERK in Normal B-1 Cells.
Review Editor, Frontiers in B Cell Biology
Scientific organizer, Merinoff World Congress 2014: B-1 Cell Development and Function, Tarrytown, NY
Most Recent Publications
1. Holodick NE, Vizconde T, Hopkins TJ, Rothstein TL. Age-Related Decline in Natural IgM Function: Diversification and Selection of the B-1a Cell Pool with Age. J Immunol. 2016 May 15;196(10):4348-57.
2. Holodick NE, Zeumer L, Rothstein TL, Morel L. Expansion of B-1a Cells with Germline Heavy Chain Sequence in Lupus Mice. Front Immunol. 2016 Mar 24;7:108.
3. Holodick NE, Rothstein TL. B cells in the aging immune system: time to consider B-1 cells. Ann N Y Acad Sci. 2015 Dec;1362:176-87.
4. Holodick NE*, Vizconde TC, Rothstein TL. B-1a Cell Diversity: N-addition in B-1a immunoglobulin is determined by progenitor population and developmental location. J Immunol. 2014. Mar 1;192(5):2432-41.
5. Holodick NE*, Vizconde TC, Rothstein TL. Splenic B-1a cells expressing CD138 spontaneously secrete large amounts of immunoglobulin in naïve mice. Front Immunol. 2014. Mar
6. Holodick NE* and Rothstein TL. Atypical Response of B-1 Cells to BCR Ligation: A Speculative Model. Front Immunol. 2013 Dec 16;4:457.
7. Rothstein TL, Griffin DO, Holodick NE, Quach TD, Kaku H. Human B-1 cells take the stage. Ann NY Acad Sci. 2013. May; 1285:97-114.
8. Chen SS, Batliwalla F, Holodick NE, Yan XJ, Yancopoulos S, Croce CM, Rothstein TL, Chiorazzi N. Autoantigen can promote progression to a more aggressive TCL1 leukemia by selecting variants with enhanced B-cell receptor signaling. Proc Natl Acad Sci. 2013 Apr 16;110(16):E1500-7.
9. Griffin DO, Holodick NE, and Rothstein TL. Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype, CD20+CD27+CD43+CD70-. J Exp Med. 2011 Jan 17;208(1):67-80. Erratum in J Exp Med. 2011 Feb 14;208(2):409.
10. Tumang JR, Holodick NE, Vizconde TC, Kaku H, Frances R, Rothstein TL. A CD25 Positive Population of Activated B1 Cells Expresses LIFR and Responds to LIF. Front Immunol. 2011 Mar 21; 2:6.
11. Holodick NE, Tumang JR, and Rothstein TL. Immunoglobulin Secretion by B1 Cells: Differential Intensity and IRF4-Dependence of Spontaneous IgM Secretion by Peritoneal and Splenic B1 Cells. Eur J Immunol. 2010 Nov;40(11):3007-16.
12. Holodick NE, Repetny K, Zhong X, and Rothstein TL. Adult Bone Marrow Generates CD5+ B1 Cells Containing Abundant N-region Additions. Eur J Immunol. 2009 Sep;39(9):2383-94.
13. Holodick NE, Tumang JR, and Rothstein TL. Continual Signaling Is Responsible for Constitutive ERK Phosphorylation in B-1a Cells. Mol Immunol. 2009 Sep;46(15):3029-36.