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Nichol E. Holodick, PhD

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Institute Scientist, Laboratory for Brain Tumor Biology and Therapy, The Feinstein Institute for Medical Research

Phone: (516) 562-3439
Email: nholodick@nshs.edu

About the Investigator

Dr. Holodick did her undergraduate work at Northeastern University in Boston, MA, where she received her PhD in Immunology 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.  

Dr. Holodick is the author or co-author of 16 peer-reviewed publications.  She has presented her work consistently at international meetings with 4 oral presentations and 10 poster presentations.

Research Focus

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.   

Dr. Holodick’s focus is on how B-1 cells change with age in relation to their ability to protect against infection.  She studies 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 immunoglobulin, which is germline-like due to minimal insertion of N-region additions. The germline-like Ig B-1a cells produce has been attributed to their unique development occurring mainly during fetal life while their persistence throughout adult life is maintained through self-renewal.  Yet, B-1a derived IgM moves away from the germline with age.  Dr. Holodick’s research is aimed at understanding the mechanism of natural Ig change with age.  

Natural antibodies produced by B-1a cells have also been shown to help reduce the onset of atherosclerosis, which is the number one cause of death globally and also affects the aging population more so than the young.  Therefore, the knowledge gained from the study of natural Ig produced by B-1 cells will not only aid in the understanding of this protective B cell subset for preventative strategies and/or treatments of S. pneumoniae infection, but will also further our knowledge of other age-related diseases.

Education

Boston University, Boston, MA
Degree: PhD
2009
Filed of Study: Immunology

Northeastern University, Boston, MA
Degree: BS
2003
Field of Study:  Biology

Awards and Honors

2013 IEDB Workshop Travel Fellowship Award
2013 Immune Epitope Database user workshop training
2008 Merinoff Symposium: Systemic Lupus: Bringing science to the patient
2008 Poster presentation award, poster title: “Origin of Constitutive pERK in Normal B-1 Cells”

Publications
  1. 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. *Corresponding Author
  2. 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  *Corresponding Author
  3. Holodick NE* and Rothstein TL. “Atypical Response of B-1 Cells to BCR Ligation: A Speculative Model.” Front Immunol.  2013 Dec 16;4:457. *Corresponding Author
  4. 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.
  5. 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. 
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.

View more at PubMed

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