Mara Shainheit

Assistant Professor

Name

Contact Information

PHONE
OFFICE
Smith Hall, Room No. 468A
E-MAIL
HOURS
Mon - Wed 12 p.m. - 2 p.m.
Thurs: 11 a.m.-3 p.m.

Education

B.S. Biology; Lafayette College, Easton, PA
Ph.D. Immunology; Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA

Areas of Expertise

Bacterial pathogenesis, host-pathogen interactions

Research Interests

Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium that typically colonizes the upper respiratory tract asymptomatically, but can also cause invasive diseases such as acute otitis media, pneumonia, meningitis and sepsis. As a consequence of these pneumococcal diseases, approximately one million children, primarily in developing parts of the world, die each year. My laboratory examines various aspects of pneumococcal disease pathogenesis with an emphasis on understanding the interface between this pathogen and the host immune response. Through our research, we hope to shed light on the biology of this potentially devastating bacterial pathogen and anticipate that our insights will inform the development of improved therapeutic interventions.

A first line host defense strategy against pneumococcal infection is the recruitment and action of innate immune cells. Neutrophils are a key component of this initial response. The primary means by which neutrophils kill invading pneumococci is through the concerted action of various serine proteases, although the underlying mechanisms of this process remain uncharacterized. Using a combination of genetic and biochemical approaches, my laboratory aims to address two main questions:
1) What factors does pneumococcus utilize to resist killing by neutrophil serine proteases (NSPs)?
2) What pneumococcal factors are targeted by NSPs that result in bacterial death?

In addition to neutrophils, the complement system is a critical component of the innate immune system required for killing blood-borne pathogens such as pneumococcus. An important first step in complement-mediated killing of pneumococcus is the deposition of a key protein, C3, on the bacterial cell surface. By using a complex pool of S. pneumoniae mutants and high-throughput sequencing coupled with phenotypic assays, we will identify novel pneumococcal factors required for resisting C3 deposition and characterize the role of the identified factors in antagonizing this key immune process.

Recent Publications

Shainheit MG, Valentino MD, Gilmore MS and Camilli A. Mutations in pneumococcal cpsE generated via in vitro serial passaging reveals a potential mechanism of reduced encapsulation utilized by a conjunctival isolate. J Bacteriol. 2015 March 16. pii: JB.20602-14.

Shainheit MG, Mulé M and Camilli A. The Core Promoter of the Capsule Operon of Streptococcus pneumoniae is Necessary for Colonization and Invasive Disease. Infect Immun. 2014 Feb; 82 (2):694-705.

Ponichtera HE, Shainheit MG, Liu C, Larkin BM, Raychowdhury R, Russo J, Salantes DB, Lai C, Parnell L, Cheong C, Bunnell SC, Hacohen N and Stadecker MJ. CD209a expression on dendritic cells is critical for the development of pathogenic Th17 cell responses in murine schistosomiasis. J Immunol. 2014 May 15;192(10):4655-65.

Liberman R, Bond S, Shainheit MG, Stadecker MJ and Forgac M. Regulated assembly of the V-ATPase is increased during cluster disruption-induced maturation of dendritic cells through a PI3K/mTOR-dependent pathway. J Biol Chem. 2014 Jan 17: 289 (3):1355-63.

Shainheit MG, Lasocki KW, Finger E, Larkin BM, Smith PM, Sharpe AH, Dinarello CA, Rutitzky LI, Stadecker MJ. The pathogenic Th17 cell response to major schistosome egg antigen is sequentially dependent on IL-23 and IL-1. J Immunol. 2011 Nov 15;187(10):5328-35.

Shainheit MG, Smith PM, Bazzone LE, Wang AC, Rutitzky LI, Stadecker MJ. Dendritic cell IL-23 and IL-1 production in response to schistosome eggs induces Th17 cells in a mouse strain prone to severe immunopathology. J Immunol. 2008 Dec 15;181(12):8559-67.

Shainheit MG, Saraceno R, Bazzone LE, Rutitzky LI, Stadecker MJ. Disruption of interlukin-27 signaling results in impaired gamma interferon production but does not significantly affect immunopathology in murine schistosome infection. Infect Immun. 2007 Jun;75 (6): 3169-77