Dr. Randis is a Neonatologist and Assistant Professor of Pediatrics at Columbia University whose current investigative efforts are directed towards elucidating the pathogenic mechanisms underlying the development of bacterial vaginosis (BV). BV, the most common vaginal infection worldwide, is associated significant adverse sequelae including preterm birth. The association of BV with the onset of preterm labor is of major public health importance as BV has been estimated to cause 90,000 excess preterm births per year. Recently, maternal vitamin D deficiency has been linked to the development of BV during the first trimester of pregnancy. Vitamin D is an important regulator of innate immune response and deficiencies of this critical vitamin have been associated with an increased susceptibility to other infectious diseases. The role of vitamin D in the pathogenesis of BV may be of particular relevance in explaining the striking racial disparities in the prevalence of BV. African-American populations, which are at highest risk for vitamin D-deficiency, also have the highest prevalence of BV and BV-associated preterm birth. Identification of potentially modifiable risk factors for BV represents a unique opportunity to reduce the burden of this exceedingly prevalent disease and its associated morbidities. These observations have led the candidate to formulate the primary hypothesis of this research proposal: that vitamin D deficiency is a significant risk factor for the development of BV in healthy adult women and that this effect is mediated by a deficiency of vitamin D-responsive immune mediators. The primary aims of this proposal are 1) to investigate the role of vitamin D status in the development of BV in a cohort of non-pregnant, healthy adult women, 2) to explore specific molecular mechanisms by which vitamin D signaling controls vaginal innate immune responses relevant to BV, and 3) to determine whether vitamin D-responsive antimicrobial peptides mediate the observed association between vitamin D deficiency and bacterial vaginosis in pregnant women. This research proposal represents a critical step in attaining the candidate's long-term goal: to transition to an independent research career focused on mechanistic and translational studies of preterm birth. Superb mentorship, participation in the Master's program in Patient Oriented Research, and continued access to the abundant resources and rich intellectual environment across departments and schools at Columbia University leave this candidate well-positioned to achieve this goal. This Career Development Award will serve as a driving force in Dr. Randis' success, providing the protected time and additional training required for this candidate to become an independent investigator.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HD065844-05
Application #
8878829
Study Section
Biobehavioral and Behavioral Sciences Subcommittee (CHHD)
Program Officer
Ilekis, John V
Project Start
2011-09-01
Project End
2015-10-31
Budget Start
2015-07-01
Budget End
2015-10-31
Support Year
5
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pediatrics
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Khatami, Ameneh; Randis, Tara M; Chamby, Anna et al. (2018) Improving the Sensitivity of Real-time PCR Detection of Group B Streptococcus Using Consensus Sequence-Derived Oligonucleotides. Open Forum Infect Dis 5:ofy164
Baker, Jacqueline A; Lewis, Emma L; Byland, Leah M et al. (2017) Mucosal vaccination promotes clearance of Streptococcus agalactiae vaginal colonization. Vaccine 35:1273-1280
Hooven, Thomas A; Catomeris, Andrew J; Akabas, Leor H et al. (2016) The essential genome of Streptococcus agalactiae. BMC Genomics 17:406
Hooven, Thomas A; Randis, Tara M; Daugherty, Sean C et al. (2014) Complete Genome Sequence of Streptococcus agalactiae CNCTC 10/84, a Hypervirulent Sequence Type 26 Strain. Genome Announc 2:
Randis, Tara M; Gelber, Shari E; Hooven, Thomas A et al. (2014) Group B Streptococcus ?-hemolysin/cytolysin breaches maternal-fetal barriers to cause preterm birth and intrauterine fetal demise in vivo. J Infect Dis 210:265-73
Randis, Tara M; Zaklama, Joanne; LaRocca, Timothy J et al. (2013) Vaginolysin drives epithelial ultrastructural responses to Gardnerella vaginalis. Infect Immun 81:4544-50
Kulkarni, Ritwij; Randis, Tara M; Antala, Swati et al. (2013) ?-Hemolysin/cytolysin of Group B Streptococcus enhances host inflammation but is dispensable for establishment of urinary tract infection. PLoS One 8:e59091
Hymes, Saul R; Randis, Tara M; Sun, Thomas Yang et al. (2013) DNase inhibits Gardnerella vaginalis biofilms in vitro and in vivo. J Infect Dis 207:1491-7
Hooven, Thomas A; Randis, Tara M; Hymes, Saul R et al. (2012) Retrocyclin inhibits Gardnerella vaginalis biofilm formation and toxin activity. J Antimicrob Chemother 67:2870-2
Rampersaud, Ryan; Randis, Tara M; Ratner, Adam J (2012) Microbiota of the upper and lower genital tract. Semin Fetal Neonatal Med 17:51-7